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NCCN Breast Cancer Treatment Guidelines Version VIII

Breast Treatment Guidelines for Patients

Version VIII/ September 2006 Current ACS/NCCN Treatment Guidelines for Patients

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Version VIII/ September 2006

The mutual goal of the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS) partnership is to provide patients with state- of-the-art cancer treatment information in an easy to understand language. This information, based on the NCCN’s Clinical Practice Guidelines, is intended to assist you in a discussion with your doctor. These guidelines do not replace the expertise and clinical judgment of your doctor. NCCN Clinical Practice Guidelines were developed by a diverse panel of experts. The guidelines are a statement of consensus of its authors regarding the scientific evidence and their views of currently accepted approaches to treatment. The NCCN guidelines are updated as new significant data become available. The Patient Information version is updated accordingly and available on-line through the American Cancer Society and NCCN Web sites. To ensure you have the most recent version, you may contact the American Cancer Society at 1-800-ACS-2345 or the NCCN at 1-888-909-NCCN.

©2006 by the American Cancer Society (ACS) and the National Comprehensive Cancer Network. All rights reserved. The information herein may not be reprinted in any form for commercial purposes without the expressed written permission of the ACS. Single copies of each page may be reproduced for personal and non- commercial uses by the reader. Contents

Introduction ...... 5 Making Decisions About Breast Cancer Treatment ...... 5 Inside Breast Tissue ...... 6 Types of Breast Cancer ...... 6 Breast Cancer Work Up ...... 9 Breast Cancer Stages ...... 14 Breast Cancer Treatment ...... 16 Treatment of Breast Cancer During ...... 28 Treatment of Pain and Other Symptoms ...... 28 Complementary and Alternative Therapies ...... 28 Other Things to Consider During and After Treatment ...... 29 Clinical Trials ...... 30 Work-Up (Evaluation) and Treatment Guidelines ...... 33 Decision Trees Stage 0 in Situ ...... 34 Stage 0 ...... 36 Stage I, II, and Some Stage III Breast Cancer ...... 40 Axillary ...... 46 Additional Treatment () After Surgery ...... 48 Invasive Ductal, Lobular, Mixed, or Metaplastic with Small Tumors ...... 50 Invasive Ductal, Lobular, Mixed, or Metaplastic Cancers with Larger Tumors or Lymph Node Spread ...... 52 Tubular or Colloid Breast Cancers ...... 54 Adjuvant Treatment ...... 56 Treatment of Large Stage II or Stage IIIA Breast Cancers ...... 60 Stage III Locally Advanced Breast Cancers ...... 66 Follow-up and Treatment of Stage IV Disease or Recurrence of Disease . . . 70 Breast Cancer in Pregnancy ...... 80 Glossary ...... 82 Member Institutions

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University City of Hope Cancer Center Dana-Farber/Partners CancerCare Duke Comprehensive Cancer Center Fox Chase Cancer Center Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida Huntsman Cancer Institute at the University of Utah Memorial Sloan-Kettering Cancer Center Robert H. Lurie Comprehensive Cancer Center of Northwestern University Roswell Park Cancer Institute The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine St. Jude Children’s Research Hospital/ University of Tennessee Cancer Institute Stanford Comprehensive Cancer Center UCSF Comprehensive Cancer Center University of Alabama at Birmingham Comprehensive Cancer Center University of Michigan Comprehensive Cancer Center The University of Texas M.D. Anderson Cancer Center UNMC/Eppley Cancer Center at The Nebraska Medical Center Introduction • Does my cancer contain hormone receptors? What does this mean for me? With this booklet, women with breast cancer • Is my cancer positive for HER-2? have access to information on the way breast What does this mean for me? cancer is treated at the nation’s leading • Is breast-conserving treatment an cancer centers. Originally developed for cancer option for me? specialists by the National Comprehensive • In addition to surgery, what other treat- Cancer Network (NCCN), these treatment ment do you recommend? ? guidelines have now been translated for the ? ? public by the American Cancer Society. • What are the side effects? Since 1995, doctors have looked to the • Are there any clinical trials that I NCCN for guidance on the highest quality, should consider? most effective advice on treating cancer. For more than 90 years, the public has relied on the American Cancer Society for information Making Decisions About about cancer. The Society’s books and Breast Cancer Treatment brochures provide comprehensive, current, and understandable information to hundreds On the pages after the general information of thousands of patients, their families and about breast cancer, you’ll find flow charts friends. This collaboration between the that doctors call decision trees. The charts NCCN and ACS provides an authoritative and represent different stages of breast cancer. understandable source of cancer treatment Each one shows you step-by-step how you information for the public. These patient and your doctor can arrive at the choices you guidelines will help you better understand need to make about your treatment. your cancer treatment and your doctor’s Here you will find background information counsel. We urge you to discuss them with on breast cancer with explanations of cancer your doctor. To make the best possible use of stage, work-up, and treatment—all categories this information, you might begin by asking used in the flow charts. We’ve also provided a your doctor the following questions: glossary at the end of the booklet. Words in • How large is my cancer? Do I have the glossary will appear in italics when first more than one tumor in the breast? mentioned in this booklet. • What is my cancer’s grade (how Although breast cancer is a very serious abnormal the cells appear) and histology disease, it can be treated, and it should be (type and arrangement of tumor cells) treated by a team of health care professionals as seen under a microscope? with experience in treating women with breast • Do I have any lymph nodes with cancer cancer. This team may include a surgeon, (positive lymph nodes, i.e. nodal status)? radiation oncologist, medical oncologist, If yes, how many? radiologist, pathologist, nurse, • What is the stage of my cancer? social worker, and others. But not all women

5 with breast cancer receive the same treat-

ment. Doctors must consider a ’s Lobular cells Lobule specific medical situation and the patient’s preferences. This booklet can help you and your doctor decide which choices best meet your medical and personal needs. cells Breast cancer can occur in men. Since the is very low, this booklet is for Duct women with breast cancer. To learn more Ducts about breast cancer in men, speak with your Areola doctor and contact the American Cancer Society at 1-800-ACS-2345 or visit our Web Lobules site at www.cancer.org. Fatty connective tissue

Inside Breast Tissue Diagram of Breast

Source: American Cancer Society, 2006 The main parts of the female breast are lobules (milk producing glands), ducts (milk passages Lymph nodes are small, bean shaped col- that connect the lobules and the nipple), and lections of immune system cells important in stroma (fatty tissue and ligaments surround- fighting . When breast cancer cells ing the ducts and lobules, blood vessels, and reach the , they can lymphatic vessels). Lymphatic vessels are continue to grow, often causing swelling of similar to veins but carry lymph instead of the lymph nodes in the armpit or elsewhere. blood. Most breast cancer begins in the ducts If breast cancer cells have spread to the (ductal), some in the lobules (lobular), and axillary lymph nodes, it makes it more likely the rest in other breast tissues. that they have spread to other organs of the Lymph is a clear fluid that has tissue waste body as well. products and immune system cells. Most lymphatic vessels of the breast lead to under- arm (axillary) lymph nodes. Some lead to Types of Breast Cancer lymph nodes above the collarbone (called supraclavicular) and others to internal mam- Breast cancer is an abnormal growth of cells mary nodes which are next to the breastbone that normally line the ducts and the lobules. (or sternum). Cancer cells may enter lymph Breast cancer is classified by whether the vessels and spread along these vessels to cancer started in the ducts or lobules, reach lymph nodes. Cancer cells may also whether the cells have “invaded” (grown or enter blood vessels and spread through the spread) through the duct or lobule, and the bloodstream to other parts of the body. way the cancer cells look under a microscope.

6 lobule walls. Breast cancer specialists do not think that LCIS itself becomes an Lymph nodes invasive cancer, but women with this condition do run a higher risk of devel- oping an invasive cancer in either breast. • Ductal carcinoma in situ (DCIS): This

Lymph is the most common type of noninvasive vessels breast cancer. In DCIS, cancer cells

Axillary inside the ducts do not spread through lymph nodes the walls of the ducts into the fatty

Internal tissue of the breast. DCIS is treated mammary with surgery and sometimes radiation, lymph node which are usually curative. If not treated, DCIS may grow and become an invasive cancer. Normal Lymph Drainage

Source: American Cancer Society, 2006 Invasive Breast Cancers Invasive cancer describe those cancers that Breast cancers are broadly grouped into those have started to grow and have spread beyond that are still in the breast lobules or ducts the ducts or lobules. These cancers are (referred to as “noninvasive” or “carcinoma in divided into different types of invasive breast situ”) and those that have spread beyond the cancer depending on how the cancer cells walls of the ducts or lobules (referred to as look under the microscope. They are also “infiltrating” or “invasive”). It is not unusual for grouped according to how closely they look a single breast tumor to have combinations of like normal cells. This is called the grade these types, and to have a mixture of invasive which helps predict whether the woman has and non-invasive cancer. a good or less favorable outlook. Outlook is referred to as prognosis. Carcinoma In Situ Carcinoma is another word for cancer and Invasive (also called Infiltrating) carcinoma in situ (CIS) means that the cancer Ductal Carcinoma (IDC) is a very early cancer and it is still confined to The cancer starts in a milk passage, or the ducts or lobules where it started. It has duct, of the breast, but then the cancer cells not spread into surrounding fatty tissues in break through the wall of the duct and spread the breast or to other organs in the body. into the fatty tissue. Cancer cells can then There are 2 types of breast carcinoma in situ: spread into lymphatic channels or blood ves- • Lobular carcinoma in situ (LCIS): Also sels of the breast and to other parts of the called lobular neoplasia. It begins in the body. About 80% of all breast cancers are lobules, but has not grown through the invasive ductal carcinoma.

7 Invasive (also called Infiltrating) Inflammatory Breast Cancer (IBC) Lobular Carcinoma (ILC) Inflammatory breast cancer is a special This type of cancer starts in the milk- type of breast cancer in which the cancer cells producing glands. Like IDC, this cancer can have spread to the lymph channels in the skin spread beyond the breast to other parts of the of the breast. Inflammatory breast cancer body. About 10% to 15% of invasive breast accounts for about 1% to 3% of all breast cancers are invasive lobular carcinomas. cancers. The skin of the affected breast is red, swollen, may feel warm, and has the appear- Mixed Tumors ance of an orange peel. The affected breast may Mixed tumors describe those that contain become larger or firmer, tender, or itchy. IBC a variety of cell types, such as invasive ductal is often mistaken for in its early stages. combined with invasive lobular breast Inflammatory breast cancer has a higher cancer. With this type, the tumor is usually chance of spreading and a worse outlook treated as if it were an invasive ductal cancer. than typical invasive ductal or lobular cancer. Inflammatory breast cancer is always staged Medullary Cancer as stage IIIB unless it has already spread to This special type of infiltrating ductal other organs at the time of diagnosis which cancer has a fairly well-defined boundary would then make it a stage IV. (See discussion between tumor tissue and normal breast tis- of stage on page 14). sue. It also has a number of special features, including the presence of immune system Colloid Carcinoma cells at the edges of the tumor. It accounts for This rare type of invasive ductal breast about 5% of all breast cancer. It can be diffi- cancer, also called mucinous carcinoma, is cult to distinguish medullary breast cancer formed by mucus-producing cancer cells. from the more common invasive ductal breast Colloid carcinoma has a better outlook and a cancer. Most cancer specialists think that lower chance of than invasive lob- medullary cancer is very rare, and that cancers ular or invasive ductal cancers of the same size. that are called medullary cancer should be treated as invasive ductal breast cancer. Tubular Carcinoma Tubular carcinoma is a special type of Metaplastic Tumors invasive ductal breast carcinoma. About 2% Metaplastic tumors are a very rare type of of all breast cancers are tubular carcinomas. invasive ductal cancer. These tumors include Women with this type of breast cancer have a cells that are normally not found in the better outlook because the cancer is less likely breast, such as cells that look like skin cells to spread outside the breast than invasive (squamous cells) or cells that make . lobular or invasive ductal cancers of the same These tumors are treated similarly to invasive size. The majority of tubular cancers are hor- ductal cancer. mone positive and HER-2 negative. (See discussion of tumor tests, on page 12.)

8 Breast Cancer Work Up After completing the physical examination Evaluating a Breast Lump or and medical history, the doctor will recommend Abnormal Mammogram Finding tests to look at the breast. A mammogram will An evaluation of a breast lump or an abnormal likely be done first, unless this has already mammogram finding includes a thorough been done or if the woman is very young. medical history, a physical examination, and Women with a lump in the breast, other breast imaging (such as x-rays). A is suspicious symptoms, or with a change found needed for a suspicious finding, though often on a mammogram, will often have these suspicious areas prove to be benign (not a procedure called a diagnostic mammogram. cancer). If cancer is found, other x-rays and A diagnostic mammogram includes more blood tests are needed. Exactly which tests mammogram images of the area of concern are helpful depends on the type of cancer, and to give more information about the size and if and where it has spread. These sections character of the area. A breast ultrasound or provide a summary of the steps, tests, and sonogram also may be done. Ultrasound types of biopsy that may be suggested. examination uses high frequency sound waves to further evaluate a lump or mammogram Doctor Visit and Examination finding. Most importantly, ultrasound helps A women’s first step in having a new breast determine if the area of concern is a fluid- lump, symptom, or mammogram change filled simple , which is usually not cancer, evaluated is to meet with her doctor. The or is solid tissue that may be cancer. doctor will take a medical history, including Some women may have a breast magnetic asking a series of questions about symptoms resonance imaging (MRI) procedure in addition and factors that may be related to breast to a diagnostic mammogram and ultrasound. cancer risk (such as family history of cancer). In some cases, breast MRI may help define The physical examination should include a the size and extent of cancer within the breast general examination of the woman’s body as tissue. It can also spot other tumors. It may be well as careful examination of her especially useful in women who have dense (called palpation). The doctor will examine: breast tissue that makes it more difficult to • the breasts, including texture, size, find tumors with a mammogram. relationship to skin and chest muscles, and the presence of lumps or masses • the and skin of the breasts If a woman or her doctor finds a suspicious • lymph nodes under the armpit and breast lump, or if imaging studies show a above the collarbone suspicious area, the woman must have a • other organs to check for obvious biopsy. This procedure takes a tissue sample spread of breast cancer and to help to be examined under the microscope to see evaluate the general condition of the if cancer is present. woman’s health

9 There are several different types of breast needle during the biopsy. The mammogram- . Biopsy may be done by a needle, directed technique is called stereotactic nee- where the doctor removes a piece of breast dle biopsy. In this procedure, a computerized tissue by placing a needle through the skin view of the mammogram helps the doctor into the breast. With a surgical biopsy a sur- guide the tip of the needle to the right spot. geon uses a scalpel to cut through the skin Ultrasound can be used in the same way to and remove a larger piece of breast tissue. guide the needle. The choice between a Each type of biopsy has advantages and dis- mammogram directed stereotactic needle advantages. The type of biopsy procedure biopsy and ultrasound guided biopsy depends used is tailored to each woman’s situation on the type and location of the suspicious and the experience of her health care team. area, as well as the experience and preference In most cases, a needle biopsy is preferred of the doctor. over a surgical biopsy as the first step in Some patients need a surgical (excisional) making a cancer diagnosis. A needle biopsy biopsy. The surgeon generally removes the provides a diagnosis quickly and with little entire lump or suspicious area and includes a discomfort. In addition, it gives the woman a zone of surrounding normal appearing breast chance to discuss treatment options with her tissue called a margin. If the tumor cannot be doctor before any surgery is done. In some felt, then the mammogram or ultrasound is patients, a surgical biopsy may still be needed used to guide the surgeon through a technique to remove all or part of a lump for microscopic called wire localization. After numbing the area examination after a needle biopsy has been with a local anesthetic, x-ray or ultrasound done, or it may be necessary to do a surgical pictures are used to guide a small hollow biopsy instead of needle biopsy. needle to the abnormal spot in the breast. A Several types of needle biopsies are used thin wire is inserted through the center of the to diagnosis breast cancer. The most common needle, the needle is removed, and the wire is is a core needle biopsy that removes a small used to guide the surgeon to the right spot. cylinder of tissue. A suction device attached Most breast biopsies cause little discomfort. to the needle can also be used to remove Only local (numbing of the skin) breast tissue. Another type of biopsy is fine is necessary for needle biopsies. For surgical needle aspiration biopsy (FNA). FNA uses a biopsies, most surgeons use a local anesthetic smaller needle than a core biopsy and plus some intravenous medicines to make the removes a small amount of cells for evaluation patient drowsy. A general anesthetic is not under the microscope. FNA also is used to needed for most breast biopsies. remove fluid from a suspicious cyst. A doctor can do a core needle or FNA Tissue examination and pathology report biopsy in the office, without the aid of breast After a breast biopsy, the biopsy tissue is x-rays to guide the needle, if the lump can be sent to a pathology lab where a doctor trained felt. If a lump cannot be felt easily, ultrasound to diagnose cancer (pathologist) examines it or mammograms can be used to guide the under the microscope. This process may take

10 several days. This examination of the breast symptoms of spread to the bone, including tissue determines if cancer is present. new pains or changes on blood tests, a bone The pathology report is a key part of your scan is not recommended except in patients cancer care. This report tells your doctor what with advanced cancer. To do a bone scan, a type of cancer you have, and includes many small dose of a radioactive substance is facts that will determine the best treatment injected into your vein. The radioactive sub- for you. stance collects in areas of new bone formation. Your doctor should give you your pathology These areas can be seen on the bone scan results. You can ask for a copy of your pathology image. Other than the needle stick for the report and to have it explained carefully to you. injection, a bone scan is painless. If you want, you can obtain a second opinion Computerized tomography (CT) scans: of the pathology of your tissue by having the CT scans are done when symptoms or other microscope slides from your tissue sent to a findings suggest that cancer has spread to consulting breast pathologist at an NCCN other organs. For most women with an early cancer center or other laboratory suggested stage breast cancer, a CT scan is not needed. by your doctor. But if the cancer appears more advanced, a CT of the abdomen and/or chest may be done Other Tests after Cancer Has to see if the cancer has spread. CT scans take Been Diagnosed multiple x-rays of the same part of the body If the breast biopsy results show that cancer from different angles to provide detailed is present, the doctor may order other tests pictures of internal organs. Except for the to find out if the cancer has spread and to injection of intravenous dye, necessary for help determine treatment. For most women most patients, this is a painless procedure. with breast cancer, extensive testing provides Magnetic resonance imaging (MRI): no benefit and is not necessary. There is no MRI scans use radio waves and magnets to test that can completely reassure you that the produce detailed images of internal organs cancer has not spread. The NCCN Guidelines without any x-rays. MRI is useful in looking at describe which tests are needed based on the the brain and spinal cord, and in examining extent (spread) of the cancer and the results any specific area in the bone. A special MRI of the history and physical examination. Tests procedure called a breast MRI with dedicated that may be done include: breast coils can also be used to look for tumors Chest x-ray: All women with invasive in the breast. Routine MRIs for all patients with breast cancer should have a chest x-ray before breast cancer are not helpful and not needed. surgery and to see if there is evidence that the Positron emission tomography (PET): breast cancer has spread to the lungs. PET scans use a form of sugar (glucose) that Bone scan: This may provide information contains a radioactive atom. A small amount about spread of breast cancer to the bone. of the radioactive material is injected into a However, many changes that show up on a vein. Then you are put into the PET machine bone scan are not cancer. Unless there are where a special camera can detect the

11 radioactivity. Because of the high amount of many breast cancers. Cancer cells energy that breast cancer cells use, areas of respond to these through cancer in the body absorb large amounts of the receptors (ER) and prog- the radioactive sugar. Newer devices combine esterone receptors (PR). ER and PR are PET scans and CT scans. cells’ “welcome mat” for these hormones Blood Tests: Some blood tests are needed circulating in the blood. The tumor is to plan surgery, to screen for evidence of tested for these receptors in a test cancer spread, and to plan treatment after called a hormone receptor assay. If a surgery. These blood tests include: cancer does not have these receptors, • Complete blood count (CBC). This it is referred to as hormone receptor determines whether your blood has the negative (estrogen-receptor negative correct type and number of blood cells. and -receptor negative). Abnormal test results could reveal other If the cancer has these receptors, it is health problems including anemia, and referred to as hormone receptor positive could suggest the cancer has spread to (estrogen- receptor positive and/or the bone marrow. Also, if you receive progesterone-receptor positive) or just chemotherapy, doctors repeat this test ER-positive or PR-positive. because chemotherapy often affects the The hormone receptors are impor- blood forming cells of the bone marrow. tant because cancer cells that are ER • Blood chemicals and enzyme tests. or PR-positive often stop growing if the These tests are done in patients with woman takes drugs that either block invasive breast cancer (not needed with the effect of estrogen and progesterone in situ cancer). They can sometimes tell or decrease the body’s levels of estrogen. if the cancer has spread to the bone or These drugs lower the chance that the liver. If these test results are abnormal, cancer will come back (recur) and your doctor will order imaging tests, improve the changes of living longer. such as bone scans or CT scans. Most women whose breast cancer is ER-positive or PR-positive will take Tumor tests (, proges- these drugs as part of their treatment. terone receptors, and HER-2/neu): Testing However, these hormone-active drugs the tumor itself for certain features is an are not effective if the cancer does not important step in deciding what treatment contain these receptors. options are best for your particular cancer. All breast cancers, with the exception The pathology lab tests the cancer tissue that of lobular carcinoma in situ, should be is removed, either from a biopsy or the final tested for hormone receptors. Each surgery. woman should ask her doctor for these • Estrogen and Progesterone Receptors: test results, and if hormone-like drugs Two hormones in women—estrogen and or blocking her own hormones should progesterone—stimulate the growth of be part of the treatment. normal breast cells and a role in 12 • HER-2/neu: About 15-25% of breast chemotherapy. At the present time more cancers have too much of a growth- studies are needed on this new strategy before promoting protein called HER-2/neu specific recommendations can be made. and too many copies (more than 2) of Breast Cancer Grade: Pathologists look the gene that instructs the cells to at breast cancers under a microscope and produce that protein. Tumors with determine how much they look like normal increased levels of HER-2/neu are breast tissue. This is called the grade of the referred to as “HER-2 positive.” tumor. Cancers that closely resemble normal HER-2 positive tumors tend to grow breast tissue get a lower number grade and and spread more rapidly than other tend to grow and spread more slowly. In gen- breast cancers. They can be treated with eral, a lower grade number indicates a cancer a drug called that prevents that is slightly less likely to spread, and a higher the HER-2/neu protein from stimulating number indicates a cancer that is slightly breast growth. Recent studies more likely to spread. have shown that trastuzumab given Grade is based on the arrangement of the after breast cancer surgery for HER-2 cells in relation to each other; whether they positive tumors reduces the risk of form tubules, how closely they resemble recurrence when the tumor measures normal breast cells (nuclear grade), and how larger than 1 cm in diameter or when many of the cancer cells are in the process of the cancer has spread to the lymph dividing (mitotic count). A low grade (Grade 1) nodes. Studies also suggest that chemo- cancer may also be called “well-differentiated” therapy containing certain drugs (such because it more closely resembles normal breast as or epirubicin) may be cells. Similarly a high grade tumor (Grade 3) especially effective against breast may also be called “poorly differentiated,” cancers that are HER-2 positive. since the cells have lost their resemblance to normal breast cells. A moderate grade Genetic Analysis of Tumor: Treatment (Grade 2) cancer is in between low grade and decisions today are primarily based on hor- high grade. mone receptor status, HER-2/neu status, The tumor grade is most important in appearance of the cancer under the micro- patients with small tumors without lymph node scope, size of the breast cancer, and extent of involvement. Patients with well-differentiated spread of the breast cancer. Recently, there tumors may require no further treatment, has been interest in studying the genes in while patients with moderately or poorly dif- breast cancers to see if the tumors can be ferentiated tumors usually receive additional divided into good prognosis and poor prog- hormonal therapy or chemotherapy. nosis tumors. This information has the Ductal carcinoma in situ (DCIS) is graded potential to identify those patients whose in a different way. DCIS is given a nuclear breast cancers have not spread to the lymph grade, which describes how abnormal the nodes and who may not need additional

13 part of the cancer cells that contain the genetic Each woman’s outlook with breast cancer material appears. Sometimes other features differs, depending on the cancer’s stage and of DCIS are also used by the pathologist to other factors such as hormone receptors, her determine the grade. general state of health, and her treatment. You should talk frankly with your doctors about your cancer stage and prognosis, and Breast Cancer Stages how they affect treatment options.

Cancers are divided into different groups, System to Define Cancer Stage called stages, based on whether the cancer is The system most often used to describe the invasive or non-invasive, the size of the extent of breast cancer is the TNM staging tumor, how many lymph nodes are involved, system. In TNM staging, information about and whether there is spread to other parts of the tumor (T-Stage), nearby lymph nodes (N- the body. Stage), and distant metastases (M-Stage) is Staging a cancer is the process of finding combined and a stage is assigned to specific out how far the cancer has progressed when TNM groupings. The TNM stage groupings it is diagnosed. Doctors determine the stage are described using Roman numerals from 0 of a cancer by gathering information from to IV. physical examinations and tests on the tumor, The clinical stage is determined by what the lymph nodes, and distant organs. doctor learns from the physical examination A breast cancer’s stage is one of the most and tests. The pathologic stage includes the important factors that may predict prognosis findings of the pathologist after surgery. Most (outlook for cure versus the chance of cancer of the time, pathologic stage is the most coming back or spreading to other organs). important stage since involvement of the lymph A cancer’s stage, therefore, is an important nodes can only be accurately determined by factor in choosing the best treatment. examining them under a microscope.

Tumor Sizes

1 cm 2 cm 3 cm 5 cm

2.5 centimeters (cm) = 1 inch 1 cm = 10 mm

Source: American Cancer Society, 2006 14 T stands for the size of the cancer (meas- N0 Pathological: The cancer has not ured in centimeters: 2.5 centimeters = 1 inch) spread to lymph nodes, based on examining and whether it is growing directly into them under the microscope. nearby tissues. N stands for spread to nearby N1 Clinical: The cancer has spread to lymph nodes and M is for metastasis (spread lymph nodes under the arm on the same side to other parts of the body). as the breast cancer. Lymph nodes are not attached to one another or to the surrounding Categories of T, N, and M tissue. N1 Pathological: The cancer is found in 1 T Categories to 3 lymph nodes under the arm. T categories are based on the size of the N2 Clinical: The cancer has spread to breast cancer and whether it has spread to lymph nodes under the arm on the same side nearby tissue. as the breast cancer and are attached to one Tis: Tis is used only for carcinoma in situ another or to the surrounding tissue. Or the or noninvasive breast cancer such as ductal cancer can be seen to have spread to the carcinoma in situ (DCIS) or lobular carcinoma internal mammary lymph nodes (next to the in situ (LCIS). sternum), but not to the lymph nodes under T1: The cancer is 2 cm in diameter (about the arm. 3 ⁄4 inch) or smaller. N2 Pathological: The cancer has spread to T2: The cancer is more than 2 cm but not 4 to 9 lymph nodes under the arm. more than 5 cm in diameter. N3 Clinical: The cancer has spread to T3: The cancer is more than 5 cm in lymph nodes above or just below the collar- diameter. bone on the same side as the cancer, and may T4: The cancer is any size and has spread or may not have spread to lymph nodes under to the chest wall or the skin. the arm. Or the cancer has spread to internal mammary lymph nodes and lymph nodes N Categories under the arm, both on the same side as the The N category is based on which of the cancer. lymph nodes near the breast, if any, are affected N3 Pathological: The cancer has spread to by the cancer. There are 2 classifications used to 10 or more lymph nodes under the arm or also describe N. One is clinical—before surgery— involves lymph nodes in other areas around i.e. what the doctor can feel or see on imaging the breast. studies. The other is pathological—what the pathologist can see in lymph nodes removed M Categories at surgery. The M category depends on whether the N0 Clinical: The cancer has not spread to cancer has spread to any distant tissues and lymph nodes, based on clinical exam. organs. M0: No distant cancer spread. M1: Cancer has spread to distant organs.

15 Breast Cancer Stages

Overall Stage T category N category M category Stage 0 Tis N0 M0

Stage I T1 N0 M0

Stage IIA T0 N1 M0 T1 N1 M0 T2 N0 M0

Stage IIB T2 N1 M0 T3 N0 M0

Stage IIIA T0 N2 M0 T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0

Stage IIIB T4 Any N M0

Stage IIIC Any T N3 M0

Stage IV Any T Any N M1

Stage Grouping for Breast Cancer see if the breast cancer has spread. The treat- Once the T, N, and M categories have been ment for cancer cells that may have spread assigned, this information is combined to beyond the breast and lymph nodes in the assign an overall stage of 0, I, II, III or IV as armpit is a combination of either hormone seen in the table. The stages identify tumor therapy and/or chemotherapy. types that have a similar outlook and thus are treated in a similar way. Treatment of the Breast Most women with breast cancer will have surgery. The 2 common types of surgery are Breast Cancer Treatment breast-conserving surgery and .

Breast cancer treatment includes treatment Breast-Conserving Surgery of the breast and treatment for cancer cells removes only the breast lump that may have spread to other parts of the and a rim of normal surrounding breast tissue. body. The breast itself is treated by surgery, Partial or segmental mastectomy or quadran- often in combination with radiation. The tectomy removes more breast tissue than a lymph nodes in the armpit are also studied to lumpectomy (up to one-quarter of the breast).

16 If cancer cells are present at the outside edge • women whose tumors are larger than of the removed breast tissue (the margin), 5 centimeters (2 inches) and can’t be more surgery is usually needed to remove any shrunk by treatment before surgery remaining cancer. Most often this additional as a part of breast- surgery is a repeat lumpectomy, but some- conserving therapy for invasive cancer can times it requires removal of the entire breast sometimes be omitted. Women who may (mastectomy). consider lumpectomy without radiation Radiation therapy is usually given after therapy have all of the following: these types of surgery. Side effects of these • age 70 years or older; and operations include temporary swelling and • a tumor 2 cm or less that has been tenderness and hardness due to scar tissue completely removed; and that forms in the surgical site. • a tumor that contains hormone For most women with stage I or II breast receptors; and cancer, breast conservation therapy (lumpec- • no lymph node involvement; and tomy and radiation therapy) is as effective as • who receive treatment with hormone mastectomy. Survival rates of women treated therapy with these 2 approaches are the same. However, breast conservation therapy is not an option Mastectomy for all women with breast cancer (see section, Mastectomy is removal of the entire breast, “Choosing Between Breast-Conserving Surgery including the nipple. Mastectomy is needed and Mastectomy” on page 18.) Those who may for some cases, and some women choose not have breast-conserving therapy include: mastectomy rather than lumpectomy. (See • prior radiation therapy of the affected discussion on next page, Choosing Between breast or chest Breast-Conserving Surgery and Mastectomy.) • suspicious or malignant appearing Different words are used to describe abnormalities that are widespread mastectomy depending on the extent of the throughout the breast surgery in the armpit and the muscles under • women whose lumpectomy, including the breast. In a simple or total mastectomy the any possible repeat lumpectomy when entire breast is removed, but no lymph nodes needed, cannot completely remove from under the arm or muscle tissue from their cancer with a satisfactory beneath the breast is removed. In a modified cosmetic result , the entire breast and some • women with active connective tissue axillary (underarm) lymph nodes are removed. disease involving the skin (especially In a radical mastectomy, all the muscle under scleroderma or lupus) that makes body the breast is also removed. Radical mastec- tissues especially sensitive to the side tomy is rarely used today, and for most effects of radiation women, this surgery is not more effective • pregnant women who would require than more limited forms of mastectomy. radiation while still pregnant

17 Choosing Between Breast-Conserving Reconstructive Surgery Surgery and Mastectomy If a woman has a mastectomy, she may want The advantage of breast-conserving surgery to consider having the breast rebuilt; this is (lumpectomy) is that it preserves the appear- called . This requires ance of the breast. A disadvantage is the need additional surgery to create the appearance for several weeks of radiation therapy after of a breast after mastectomy. The breast can surgery. Some women who have a mastectomy be reconstructed at the same time the mas- will still need radiation therapy. Women who tectomy is done (immediate reconstruction) choose lumpectomy and radiation can expect or at a later date (delayed reconstruction). the same chance of survival as those who Surgeons my use saline-filled implants or tissue choose mastectomy. from other parts of your body. Although most women and their doctors How do a woman and her doctor decide prefer lumpectomy and radiation therapy, your on the type of reconstruction and when she choice will depend on a number of factors, should have the procedure? The answer such as: depends on the woman’s personal preferences, • how you feel about losing your breast the size and shape of her breasts, the size and • whether you want to devote the addi- shape of her body, her level of physical exer- tional time and travel for radiation cise, details of her medical situation (such as therapy how much skin is removed), and if she needs • whether you would want to have more chemotherapy or radiation. surgery to reconstruct your breast after If you are thinking about breast recon- having a mastectomy struction, please discuss this with your doctor • your preference for mastectomy as a way when you are planning your treatment. to “take it all out as quickly as possible” Lymph Node Surgery In determining the preference for lumpec- In the treatment of invasive cancer, whether tomy or mastectomy, be sure to get all the a woman has a mastectomy or lumpectomy, facts. Though you may have a gut feeling for she and her doctor usually need to know if mastectomy to “take it all out as quickly as the cancer has spread to the lymph nodes. possible,” the fact is that in most cases doing When the lymph nodes are affected, there is so does not provide any better chance of long an increased likelihood that cancer cells have term control or a better outcome of treatment. spread through the bloodstream to other Large research studies with thousands of parts of the body. women participating, and over 20 years of Doctors once believed that removing as information show that when lumpectomy can many lymph nodes as possible would reduce be done, mastectomy does not provide any the risk of developing spread of breast cancer better chance of survival from breast cancer and improve a woman’s chances for long-term than lumpectomy plus radiation. It is because survival. We now know that removing the of these facts that most women do not have lymph nodes probably does not improve the their breast removed. 18 chance for long-term survival. But knowing If there are enlarged lymph nodes with whether lymph nodes are involved is impor- apparent spread of the cancer, or the lymph tant in selecting the best treatment to prevent nodes are otherwise found to be involved cancer recurrence. with cancer, then complete axillary lymph The only way to accurately determine if dissection is necessary. However, in many lymph nodes are involved is to remove and cases, the lymph nodes are not enlarged and examine them under the microscope. This are not likely to contain cancer. In such cases, means removing some or all of the lymph the more limited biopsy nodes in the armpit. In the standard operation, procedure can be performed. called an axillary lymph node dissection, all In the sentinel lymph node biopsy proce- the lymph nodes are removed. This is often dure the surgeon finds and removes the necessary. In many cases, lymph node testing “sentinel nodes,” the first few lymph nodes into may be done with a more limited surgery that which a tumor drains. These are the lymph only removes a few lymph nodes with fewer nodes most likely to contain cancer cells. To side effects. This is called sentinel lymph node find these so-called “sentinel lymph nodes,” the biopsy, and is discussed further below. surgeon injects a radioactive substance and/ For some women with invasive cancer, or a blue dye under the nipple or into the area removing the underarm lymph nodes can be around the tumor. Lymphatic vessels carry considered optional. This includes: these substances into the sentinel lymph • women with tumors so small and with nodes and provide the doctor with a “lymph such a favorable outlook that lymph node map.” The doctor can either see the blue node spread is unlikely dye or detect the radioactivity with a Geiger • instances where it would not affect counter. The surgeon then removes the marked whether adjuvant treatment is given nodes for examination by the pathologist. • elderly women If the sentinel node contains cancer, the • women with serious medical conditions surgeon removes more lymph nodes in the armpit (axillary dissection). This may be done Lymph node surgery is not necessary with at the same time or several days after the pure ductal carcinoma in situ or pure lobular original sentinel node biopsy. If the sentinel carcinoma in situ. A sentinel node biopsy (see node is cancer-free, the patient will not need below) may be done if the woman is having more lymph node surgery and can avoid the surgery (such as mastectomy) that would make side effects of full lymph node surgery. This it impossible to do the sentinel node biopsy limited sampling of lymph nodes is not procedure if invasive cancer were found in appropriate for some women. A sentinel the tissue removed during the surgery. lymph node biopsy should be considered The surgical technique used to remove only if there is a team experienced with this lymph nodes from under the armpit depends technique. on the personal circumstances of the patient.

19 Side Effects of Lymph Node Surgery • If your arm or hand feels tight or Side effects of lymph node surgery can be swollen, don’t ignore it. Tell your bothersome to many women. The side effects doctor immediately. can occur with either the full axillary lymph • If needed, wear a well-fitted node dissection or sentinel lymph node biopsy. compression sleeve. Side effects are much less common and less • Wear gloves when gardening or severe with the sentinel lymph node procedure. doing other things that are likely to Side effects of lymph node surgery include: lead to cuts. • temporary or permanent numbness in For more information on , call the skin on the inside of the upper arm the American Cancer Society at 1-800-ACS-2345 • temporary limitation of arm and and ask for Lymphedema: What Every Women shoulder movements With Breast Cancer Should Know. • swelling of the breast and arm called lymphedema Radiation Therapy Lymphedema is the most significant of these Radiation therapy uses a beam of high-energy side effects. If it develops it may be permanent. rays (or particles) to destroy cancer cells left Most women who develop lymphedema find behind in the breast, chest wall, or lymph it bothersome but not disabling. No one can nodes after surgery. Radiation may also be predict which patients will develop this con- needed after mastectomy in cases with either dition or when it will develop. Lymphedema a larger breast tumor, or when cancer is found can develop just after surgery, or even months in the lymph nodes. or years later. Significant lymphedema occurs This type of treatment can be given in in about 10% of women who have axillary several ways. lymph node dissection and in up to 5% of • External beam radiation delivers radia- women who have sentinel lymph node biopsy. tion from a machine outside the body. With care, patients can take steps to help This is the typical radiation therapy avoid lymphedema or at least keep it under given after lumpectomy and is given to control. Talk to your doctor for more details. the entire breast with an extra dose Some of the steps to take to help avoid (“boost”) to the site of the tumor. It is lymphedema include: usually given 5 days a week for a • Avoid having blood drawn from or IVs course of 6 to 7 weeks. inserted into the arm on the side of the • , also called internal lymph node surgery. radiation or interstitial radiation, • Do not allow a blood pressure cuff to describes the placement of radioactive be placed on that arm. If you are in the materials in or near where the tumor hospital, tell all health care workers was removed. They may be placed in about your arm. the lumpectomy site to “boost’ the radiation dose in addition to external beam radiation therapy. 20 Recently there has been interest in limiting a rib fracture or second cancer may be radiation therapy only to the site of the caused by the radiation. lumpectomy, referred to as partial breast irradiation. This is based on the observation Systemic Treatment that when breast cancer recurs in the breast, To reach cancer cells that may have spread the most common place is in the site of the beyond the breast and nearby tissues, doctors original tumor. Brachytherapy is one technique use drugs that can be given by pills or by of partial breast irradiation. External beam injection. This type of treatment is called sys- radiation therapy also can be used to deliver temic therapy. Examples of systemic treatment partial breast irradiation. include chemotherapy, hormone therapy, The extent of radiation depends on and monoclonal therapy. Hormone whether or not a lumpectomy or mastectomy therapy is only helpful if the tumor is hormone was done and whether or not lymph nodes receptor positive, and trastuzumab (the mono- are involved. If a lumpectomy was done, the clonal antibody therapy) is only effective if entire breast receives radiation with an extra the tumor is HER-2 positive. boost of radiation to the area in the breast Even in the early stages of the disease, where the cancer was removed to prevent it cancer cells can break away from the breast from coming back in that area. and spread through the bloodstream. These If the surgery was mastectomy, radiation is cells usually don’t cause symptoms, they don’t given to the entire area of the skin and muscle show up on an x-ray, and they can’t be felt where the mastectomy was done if the tumor during a physical examination. But if they are was over 5 cm in size, or if the tumor is close allowed to grow, they can establish new to the edge of the removed mastectomy tissue. tumors in other places in the body. Systemic In patients who have had lumpectomy or treatment given to patients who have no evi- mastectomy, further radiation may be rec- dence of spread of cancer, but who are at risk ommended if the cancer has spread to the of developing spread of the cancer is called lymph nodes. Radiation may be given to the adjuvant therapy. The goal of adjuvant therapy area just above the collarbone and along the is to kill undetected cancer cells that have breastbone, depending on the number and traveled from the breast. location of involved lymph nodes. Women who have invasive breast cancer Side effects most likely to occur from radi- should receive adjuvant therapy, except those ation include swelling and heaviness in the with very small or well-differentiated tumors. breast, sunburn-like skin changes in the treated For example, women with hormone receptor area, and fatigue. Changes to the breast tissue positive disease will receive hormone therapy, and skin usually go away in 6 to 12 months. In and women with HER-2 positive tumors greater some women, the breast becomes smaller than 1 cm in diameter or with involvement of and firmer after radiation therapy. There may lymph nodes will receive also be some aching in the breast, and rarely therapy with trastuzumab. Chemotherapy may also be recommended based on the size of

21 the tumor, grade of the tumor, and presence When chemotherapy is given after surgery or absence of lymph node involvement. For for early stage breast cancer, it is called women with breast cancers with hormone adjuvant chemotherapy. Sometimes chemo- receptor negative tumors, hormone therapy therapy is given before surgery. This is called is not effective and in women with HER-2 neoadjuvant chemotherapy. In most cases, negative tumors, trastuzumab is not effective. adjuvant or neoadjuvant chemotherapy is In women with tumors that are hormone and most effective when combinations of drugs HER-2 negative, the only decision is whether are used together. Chemotherapy may also be or not to receive chemotherapy. given to treat breast cancer that has spread to In most cases, systemic treatment is given places other than the breast or lymph nodes. soon after surgery using the results of the Both single drugs and combinations of drugs surgery and pathology evaluation to deter- are often used in the treatment of breast cancer mine the best choice treatment. In some that has spread. Clinical research studies cases, the systemic therapy is given to over the last 30 years have determined which patients after a needle biopsy but before chemotherapy drugs are most effective. With lumpectomy or mastectomy. This is called continued research, better combinations may neoadjuvant treatment. Oncologists give be discovered. patients neoadjuvant treatment to try to Below are listed common combinations of shrink the tumor enough to make surgical adjuvant chemotherapy drugs, divided into removal easier. This may allow women who combinations for women with HER-2 positive would otherwise need mastectomy to have tumors and HER-2 negative tumors. There are breast-conserving surgery. also lists of common chemotherapy options For women whose breast cancer has spread for women who have recurrent or metastatic to other organs in the body (metastases), sys- breast cancer. temic treatment is the main treatment. This treatment may be chemotherapy, hormone Chemotherapy Drugs Commonly Used to Treat Breast Cancer therapy, trastuzumab, or combined therapy. Brand Name Generic Name Chemotherapy Adriamycin Doxorubicin Chemotherapy uses medicines that are toxic Cytoxan to cancer cells and that often kill the cancer cells. Usually these cancer-fighting drugs are Ellence Epirubicin given intravenously (injected into a vein) or as Navelbine a pill by mouth. Either way, the drugs travel Taxol through the bloodstream to the entire body. Taxotere Doctors who prescribe these drugs (medical oncologists) sometimes use only a single drug Xeloda and other times use a combination of drugs. Gemzar

22 Adjuvant Chemotherapy Options

ADJUVANT CHEMOTHERAPY OPTIONS FOR HER-2 NEGATIVE TUMORS

FAC/CAF /doxorubicin/cyclophosphamide or FEC/CEF cyclophosphamide/epirubicin/fluorouracil AC doxorubicin/cyclophosphamide with or without paclitaxel EC epirubicin/cyclophosphamide TAC docetaxel/doxorubicin/cyclophosphamide with filgrastim support A→CMF doxorubicin followed by cyclophosphamide//fluorouracil E→CMF epirubicin followed by cyclophosphamide/methotrexate/fluorouracil CMF cyclophosphamide/methotrexate/fluorouracil AC x 4 doxorubicin/cyclophosphamide followed by sequential paclitaxel x 4, every 2 week regimen with filgrastim support A→T→C doxorubicin followed by paclitaxel followed by cyclophosphamide, every 2 week regimen with filgrastim support FEC→T flourouracil/epirubicin/cyclophosphamide followed by docetaxel

ADJUVANT CHEMOTHERAPY OPTIONS FOR HER-2 POSITIVE TUMORS Adjuvant: AC→T + Trastuzumab doxorubicin/cyclophosphamide followed by paclitaxel with trastuzumab

Neoadjuvant: T + Trastuzumab→ paclitaxel plus trastuzumab followed by CEF + Trastuzumab cyclophosphamide/epirubicin/fluorouracil plus trastuzumab

Doctors give chemotherapy in cycles, with or combination of drugs. Adjuvant chemo- each period of treatment followed by a rest therapy usually lasts for a total time of 3 to 6 period. The chemotherapy is given on the first months depending on the drugs used. day of each cycle, and then the body is given The side effects of chemotherapy depend on time to recover from the effects of chemo- the type of drugs used, the amount taken, and therapy. The chemotherapy drugs are then the length of treatment. Some women have repeated to start the next cycle. The time many side effects while other women have few between giving the chemotherapy drugs varies side effects. according to the specific chemotherapy drug

23 Chemotherapy Regimens for Recurrent or

PREFERRED SINGLE AGENTS • Doxorubicin • Paclitaxel • Vinorelbine • Epirubicin • Docetaxel • Gemcitabine • Pegylated liposomal doxorubicin • Capecitabine • Albumin-bound paclitaxel

PREFERRED COMBINATIONS • CAF/FAC (cyclophosphamide/doxorubicin/fluorouracil) • CMF (cyclophosphamide/methotrexate/ • FEC (fluorouracil/epirubicin/cyclophosphamide) fluorouracil • AC (doxorubicin/cyclophosphamide) • Docetaxel/capecitabine • EC (epirubicin/cyclophosphamide) • GT (gemcitabine/paclitaxel • AT (doxorubicin/docetaxel; doxorubicin/paclitaxel)

PREFERRED AGENTS WITH Paclitaxel

OTHER ACTIVE AGENTS • • Vinblastine • Carboplatin • Fluorouracil continuous IV infusion • Etoposide (in pill form)

• Doxorubicin and epirubicin may cause • Lowering of the blood counts from heart damage but this is uncommon in chemotherapy is the most common people who do not have a history of serious side effect of chemotherapy. heart disease. If you know you have Chemotherapy does this by damaging heart disease or there is concern you the blood producing cells of the bone might have heart disease, your doctor marrow. A drop in white blood cells may suggest special heart tests before can raise a patient’s risk of infection; a you use these drugs and may suggest shortage of blood platelets can cause other chemotherapy drugs if your bleeding or bruising after minor cuts heart function is weakened. or injuries; and a decline in red blood • Temporary side effects often include cells can lead to fatigue. loss of appetite, nausea and vomiting, There are treatments for these side effects. fatigue, mouth sores, and hair loss. There are excellent drugs that prevent or at • Chemotherapy may cause menstrual least reduce nausea and vomiting. A group of cycles to stop either temporarily or drugs called growth factors that stimulate permanently. the production of white blood cells or red

24 Preferred Chemotherapy Regimens in Combination with Trastuzumab (for HER-2 positive metastatic disease)

• Paclitaxel with or without carboplatin • Docetaxel with or without carboplatin • Vinorelbine

blood cells can help bone marrow recover Monoclonal Antibody Therapy after chemotherapy and prevent problems Trastuzumab (Herceptin) is an antibody resulting from low blood counts. Although directed against the HER-2/neu receptor that these drugs are often not necessary, doctors is on the surface of the breast cancer cells of have been using them to allow them to give some patients. Trastuzumab is an important the chemotherapy more often. Talk with your treatment option for some patients with doctor about which treatment will be right HER-2 positive tumors. It may be used as for you. adjuvant therapy with chemotherapy to Premenopausal women will often develop reduce the risk of recurrence, as neoadjuvant early and infertility from chemo- therapy combined with chemotherapy to therapy drugs. The older a woman is when shrink the size of the tumor before surgery, she receives chemotherapy, the more likely it and as treatment for metastatic breast cancer. is she will stop menstruating or lose her ability Trastuzumab can cause heart damage and to become pregnant. Some are should be used cautiously when combined more likely to do this than others. However, with other heart damaging drugs such as you cannot depend on chemotherapy to doxorubicin and epirubicin. prevent pregnancy, and getting pregnant Bevacizumab (Avastin) is another mono- while receiving chemotherapy could lead to clonal antibody that may be used in patients birth defects and interfere with treatment. with metastatic breast cancer. It is used in Therefore, premenopausal women should combination with the chemotherapy drug consider using while receiving paclitaxel. Bevacizumab works by preventing chemotherapy. It is safe to have children after the growth of new blood vessels that supply chemotherapy, but it’s not safe to get pregnant tumor cells with the blood, oxygen, and other while on treatment. nutrients they need to grow. Ask you doctor or call the American Cancer Society and ask for a copy of specific Hormone Therapy guidelines for treating many of the side Estrogen, a hormone produced mostly by the effects caused by chemotherapy, such as , but also from hormones produced by Nausea and Vomiting Treatment Guidelines for the adrenal glands and tissue in a woman’s Patients With Cancer and Fever and Neutropenia body, causes some breast cancers to grow. Treatment Guidelines for Patients With Cancer.

25 Several approaches can be used to block the Anti-Estrogen Drugs effect of estrogen or to lower estrogen levels. is the drug used These approaches can be divided into two most often. Taking tamoxifen as adjuvant main groups: therapy after surgery, usually for 5 years, • Drugs that block the effect of estrogen reduces the chance of hormone receptor on cancer cells, called anti-. positive breast cancer coming back. Tamoxifen These medicines do not decrease is also used to treat metastatic breast cancer. estrogen levels; instead, they prevent In many women, tamoxifen causes the estrogen from causing the breast cancer symptoms of menopause, including hot cells to grow. flashes, vaginal discharge, and mood swings. • Drugs or treatments that lower the Tamoxifen has two rare, but more serious side production of estrogen in the body. effects. These are a slightly increased risk of developing cancer of the lining of the uterus These treatments are used in two situations: () and uterine sarcoma, • Women who have hormone receptor and a slightly increased risk of developing positive breast cancers that appear to blood clots. For most women with breast have been completely removed by cancer, the benefits of taking the drug far surgery. This adjuvant therapy reduces outweigh the risks. the risk of recurrence or spread. Toremifene is another antiestrogen closely Adjuvant therapy may also include related to tamoxifen. It may be an option for chemotherapy or trastuzumab. postmenopausal women with metastatic • Women with hormone receptor posi- breast cancer. tive breast cancer that has spread to is a newer drug that reduces other parts of the body or in whom the the number of estrogen receptors. It is often cancer comes back. effective in postmenopausal women, even if Hormone drugs are only effective in the breast cancer is no longer responding to women whose cancer contains increased tamoxifen. Hot flashes, mild nausea and levels of estrogen or . fatigue are the major side effects of fulvestrant. Every breast cancer should be tested for these receptors, and you should ask your doctor Drugs that Lower Estrogen Levels – the results of this test on your cancer. If the Inhibitors cancer is negative for both these receptors, Aromatase inhibitors stop estrogen pro- then the hormone drugs are of no benefit. duction in postmenopausal women. Three Often a combination of hormone therapy drugs in this category have been approved and chemotherapy are used in the treatment for treatment of breast cancer, , of breast cancer. , and . They work by blocking an enzyme that makes estrogen in postmenopausal women. They cannot stop the ovaries of premenopausal women from

26 making estrogen. For this reason they are and FSH may be required to make sure that a only effective in postmenopausal women. For woman is truly postmenopausal. premenopausal women, tamoxifen remains the best drug to use. Ovarian Ablation The aromatase inhibitors have been com- The ovaries are the source of most estro- pared with tamoxifen as adjuvant hormone gen in premenopausal women. Destroying therapy. They have fewer side effects than the ability of the ovaries to produce estrogen tamoxifen because they don’t cause cancer of (ablation) may be an effective hormone ther- the uterus and very rarely cause blood clots. apy to treat premenopausal women with They can, however, cause and cancers that are positive for the estrogen or bone fractures because they remove all progesterone receptors. Destruction of the estrogen from a postmenopausal woman. production of estrogen can be done in They also cause side effects of hot flashes and a number of ways: sometimes joint pain. • The ovaries can be removed by surgery The aromatase inhibitors are more effective (). than tamoxifen alone in preventing breast • Radiation therapy can be given to the cancer from coming back in postmenopausal ovaries. women. Based on recent studies, many doctors • Drugs called luteinizing hormone- recommend including an releasing hormone (LHRH) agonists or in the adjuvant hormone therapy in post- antagonists block estrogen production menopausal women with hormone receptor by the ovaries. positive breast cancer. Hormone Therapy and Menopause Bisphosphonates are used in breast cancer As discussed above, the aromatase treatment to strengthen that have been inhibitors are not recommended for pre- weakened by invading breast cancer cells. menopausal women. Therefore, determining The most commonly used bisphosphonates whether the patient is menopausal is impor- in breast cancer treatment are pamidronate tant in making treatment decisions. This is not and zoledronate. These drugs are not used as simple as it may sound, because menstrual unless cancer has spread to the bone. periods can stop as a side effect of treatment Hormonal treatment with the aromatase while the ovaries continue to make estrogen. inhibitors may also weaken the bones by Also, sometimes chemotherapy stops the causing loss of calcium from the bone (called ovaries from making estrogen for a short period osteoporosis) and thus increase the risk of a of time, but when the ovaries recover from fracture. Therefore, patients treated with an the chemotherapy they start making estrogen aromatase inhibitor should have their bone again. Therefore, if the use of an aromatase strength tested (called a bone density test) to inhibitor is considered in young women, determine if medication to strengthen their monitoring of hormone levels such as bones would be appropriate. Some patients

27 may go into early menopause due to the side your cancer care team. There are effective and effects of chemotherapy. Menopause is asso- safe ways to treat pain, other symptoms of ciated with bone loss, too. These patients may breast cancer, and most of the side effects also undergo a bone density test to evaluate the caused by breast cancer treatment. If you presence of osteoporosis. There are a number don’t tell you health care team, they may have of medications, including some oral forms of no way of knowing about your problems. bisphosphonates, to treat the loss of calcium from bone that is not caused by direct breast cancer in the bone. Talk with your doctor Complementary and about whether one of these medications is Alternative Therapies right for you. Complementary and alternative medicines are a group of different types of health care Treatment of Breast Cancer practices, systems, and products that are not During Pregnancy part of your usual medical treatment. They may include herbs, special supplements, Breast cancer is diagnosed in about 1 pregnant acupuncture, massage, and a host of other woman out of 3,000. Radiation therapy during types of treatment. You may hear about dif- pregnancy is known to increase the risk of ferent treatments from your family and birth defects, so it is not recommended for friends. People will offer all sorts of things, pregnant women with breast cancer. such as vitamins, herbs, stress reduction, and For this reason, breast conservation ther- more as a treatment for your cancer or to apy (lumpectomy and radiation therapy) is help you feel better not considered an option if radiation cannot The American Cancer Society defines be delayed until it is safe to deliver the baby. complementary medicine or methods as those However, breast biopsy procedures and even that are used in addition to your regular modified radical mastectomy are safe for the medical care. If these treatments are carefully mother and fetus. managed, they may add to your comfort and well-being. Alternative medicines are defined as those that are used instead of your regular Treatment of Pain and medical care. Some of them have been proven Other Symptoms harmful, but are still promoted as “cures.” If you choose to use these alternatives, they may Most of this booklet discusses ways to remove reduce your chance of fighting your cancer by or destroy breast cancer cells or to slow their delaying or replacing regular cancer treatment. growth. But helping you feel as well as you There is a great deal of interest today in can and continuing to do the things you enjoy complementary and alternative treatments doing are important goals. Don’t hesitate to for cancer. Many are being studied to find out discuss your symptoms or how you feel with if they are truly helpful to people with cancer.

28 Before changing your treatment or adding deep faith, and these strengths may make a any of these methods, it is best to discuss this difference in how you respond to cancer openly with your doctor or nurse. Some treatment. There are also experienced pro- methods can be safely used along with stan- fessionals in mental health services, social dard medical treatment. Others, however, work services, and pastoral services who may can interfere with standard treatment or assist you in coping with your illness. cause serious side effects. That is why it’s You can also help in your own recovery important to talk with your doctor. More from cancer by making healthy lifestyle information about complementary and alter- choices. If you use tobacco, stop now. Quitting native methods of cancer treatment is avail- will improve your overall health and the full able through the American Cancer Society’s return of the sense of smell may help you toll-free number at 1-800-ACS-2345 or on our enjoy a healthy diet during recovery. If you Web site at www.cancer.org. use alcohol, limit how much you drink. Have no more than 1 drink per day. Good nutrition can help you get better after treatment. Eat a Other Things to Consider nutritious and balanced diet, with plenty of During and After Treatment fruits, vegetables, and whole grain foods. If you are being treated for cancer, be During and after your treatment for breast aware of the battle that is going on in your cancer you may be able to speed up your body. Radiation therapy and chemotherapy recovery and improve your quality of life by add to the fatigue caused by the disease itself. taking an active role in your care. Learn To help you with the fatigue, plan your daily about the benefits and risks of each of your activities around when you feel your best. Get treatment options, and ask questions of your plenty of sleep at night. And ask your cancer cancer care team if there is anything you do care team about a daily exercise program to not understand. Learn about and look out for help you feel better. side effects of treatment, and report these A woman’s choice of treatment will likely right away to your cancer care team so they be influenced by her age, the image she has of can take steps to ease them. herself and her body, her hopes and fears, Remember that your body is as unique as and her stage in life. For example, many your personality and your fingerprints. women select breast-conserving surgery with Although understanding your cancer’s stage radiation therapy over a mastectomy for and learning about your treatment options body image reasons. On the other hand, can help predict what health problems you some women who choose mastectomy may may face, no one can say for sure how you want the affected area removed, regardless of will respond to cancer or its treatment. the effect on their body image, and others You may have special strengths such as a may be more concerned about the side history of excellent nutrition and physical effects of radiation therapy than body image. activity, a strong family support system, or a

29 Other issues that concern women include get to the point where you feel overwhelmed, loss of hair from chemotherapy and the consider attending a meeting of a local support changes of the breast from radiation therapy. group. If you need help in other ways, contact Women on chemotherapy tend to gain your hospital’s social service department or weight and it is important to continue to eat call the American Cancer Society who can help a healthy diet and exercise as much as your you find resources in your area. We are avail- energy level will permit. In addition to these able anytime day or night at 1-800-ACS-2345. body changes, women may also be concerned about the outcome of their treatment. These are all factors that affect how a woman will Clinical Trials make decisions about her treatment, how she views herself, and how she feels about her The Purpose of Clinical Trials treatment. Studies of promising new or experimental Concerns about sexuality are often very treatments in patients are known as clinical worrisome to a woman with breast cancer. trials. Researchers conduct studies of new Some treatments for breast cancer can change treatments to answer the following questions: a woman’s hormone levels and may have a • Is the treatment helpful? negative impact on sexual interest and/or • How does this new type of treatment response. A diagnosis of breast cancer when work? a woman is in her 20s or 30s is especially • Does it work better than other treatment difficult because choosing a partner and already available? childbearing are often very important during • What side effects does the treatment this period. Relationship issues are also cause? important because the diagnosis can be very • Are the side effects greater or less than distressing for the partner, as well as the the standard treatment? patient. Partners are usually concerned • Do the benefits outweigh the side effects? about how to express their love physically • In which patients is the treatment most and emotionally during and after treatment. likely to be helpful? Suggestions that may help a woman adjust to changes in her body image include Types of Clinical Trials looking at and touching her body; seeking the A new treatment is normally studied in three support of others, preferably before surgery; phase of clinical trials. involving her partner as soon as possible after surgery; and openly talking about the feelings, Phase I Clinical Trials needs, and wants created by her changed The purpose of a phase I study is to find image. the best way to give a new treatment and how A cancer diagnosis and its treatment is a much of it can be given safely. Doctors watch major life challenge, with an impact on you patients carefully for any harmful side effects. and everyone who cares for you. Before you The treatment has been well-tested in labo-

30 ratory and animal studies, but the side effects their progress very carefully. The study is in patients are not completely known. especially designed to pay close attention to Although doctors are hoping to help patients, participating patients. However, there are the main purpose of a phase I study is to test some risks. While most side effects will dis- the safety of the drug. appear in time, some can be permanent or even life threatening. Keep in mind, though, Phase II Clinical Trials that even standard treatment have side These are designed to see if the drug works. effects. Depending on many factors, you may Patients are usually given the highest dose that decide to enroll in a clinical trial doesn’t cause severe side effects (determined from the phase I study) and closely observed Deciding to Enter a Clinical Trial for an effect on the cancer. The doctor will also Enrollment in a clinical trial is completely up look for side effects. to you. Your doctors and nurses will explain the risks and possible benefits of the study to Phase III Clinical Trials you in detail and will give you a form to read Phase III studies involve large numbers of and sign indicating your understanding of the patients. Some phase III clinical trials may study and your desire to take part. You should enroll thousands of patients and are read the consent form very carefully and be designed to compare the results of the group certain that all of your questions about the given the new or experimental treatment clinical trial are answered before you sign it. with the group that is given the standard Even after signing the form and after the treatment. Patients are randomly assigned to clinical trial begins, you are free to leave the one of the two groups, which means that the study at any time, for any reason. Taking part patient and the doctor will not know before in the study will not prevent you from getting the study starts which treatment will be given. other medical care you may need. One group (the control group) will receive To find out more about clinical trials, ask the standard (most accepted) treatment. The your cancer care team. Among the questions other group will receive the new treatment. you should ask are: Phase III studies are done when researchers • What is the purpose of the study? believe that the two treatments are effective, • What kinds of tests and treatments but that the experimental treatment may offer does the study involve? some advantages. This cannot be proven until • What does this treatment do? the results of the two groups are compared • What is likely to happen in my case with each other. The study will be stopped if with or without this new research the side effects of the new treatment are too treatment? severe or if one group has had much better • What are my choices and their results than the others. advantages and disadvantages? All patients in a clinical trial are closely • How could the study affect my daily life? watched by a team of experts to monitor

31 • What side effects can I expect from the The American Cancer Society offers a study? Can the side effects be controlled? clinical trials matching service that will help • Will I have to be hospitalized? If so, you find a clinical trial that is right for you. how often and for how long? Simply go to our Web site (www.cancer.org) • Will the study cost me anything? or call us at 1-800-ACS-2345. You also can get Will any of the treatment be free? a list of current National Cancer Institute • If I am harmed as a result of the research, sponsored clinical trials by calling the NCI what treatment would I be entitled to? Cancer Information Service toll free at 1-800- • What type of long-term follow-up care 4-CANCER or visiting the NCI clinical trials is part of the study? Web site (www.cancer.gov/ clinical_trials/). • Has the treatment been used to treat other types of cancers?

NOTES

32 Work-Up (Evaluation) and Treatment Guidelines

Decision Trees The decision trees on the following pages represent different stages of breast cancer. Each one shows you step-by-step how you and your doctor can arrive at the choices you need to make about your treatment.

Keep in mind, this information is not meant to be used without the expertise of your own doctor who is familiar with your situation, medical history, and per- sonal preferences.

Participating in a clinical trial is an option for women at any stage of breast cancer. Taking part in a study does not prevent you from getting other medical care you may need.

The NCCN guidelines are updated as new, significant data become available. To ensure you have the most recent version, consult the Web sites of the American Cancer Society (www.cancer.org) or NCCN (www.nccn.org). You may also call the NCCN at 1-888-909-NCCN or the ACS at 1-800-ACS-2345 for the most recent information on these guidelines. If you have questions about your cancer or cancer treatment, please call the American Cancer Society anytime day or night at 1-800-ACS-2345.

33 Treatment Guidelines for Patients

Stage Work-Up (Evaluation) Treatment

Stage 0 • Medical history and physical exam Lobular carcinoma • Diagnostic mammogram (both breasts) Observation in situ (LCIS) • Pathology review of biopsy sample

Stage 0 Lobular Carcinoma in Situ women who are diagnosed with LCIS The work up for lobular carcinoma in situ because LCIS is not an invasive cancer, nor (LCIS) includes a complete medical history does it normally become one. But women and physical examination. A diagnostic with LCIS have an increased risk of develop- mammogram of both breasts is done to see if ing invasive breast cancer in either breast. there are any other abnormal areas in either Ways to reduce the risk of breast cancer have breast. Pathology review (another pathologist become an important option. to look at the biopsy sample) is suggested to There is evidence that two drugs—ralox- be certain you have LCIS and not an invasive ifene and tamoxifen—can lower the risk of cancer or another condition. developing a future invasive breast cancer in LCIS is usually not treated with surgery women diagnosed with LCIS. This risk is other than the initial biopsy procedure. lowered when the drug is taken for a full 5 years. Observation (careful follow-up without mas- A of both breasts tectomy) is the preferred option for most may be an option for women with LCIS who

34 Stage 0 Lobular Carcinoma in Situ

Risk Reduction Follow-Up

Consider taking tamoxifen • Medical history and physical exam for 5 years every 6 to 12 months In special circumstances, • Yearly mammogram unless there double mastectomy, with or was a double mastectomy without breast reconstruction • Yearly pelvic exam for women is an option. taking tamoxifen

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have a very high risk of developing invasive If you and your doctor decide on observa- breast cancer—for example, women who tion as the primary treatment for LCIS, the have many family members with breast follow-up includes a medical history and cancer. Your doctor can help you decide physical exam every 6 to 12 months. You should whether to consider this treatment. You have a mammogram every year. Because should also consider genetic counseling to tamoxifen increases endometrial cancer risk see if you have a gene that increases your risk in postmenopausal women, women taking of developing breast cancer before deciding to this drug should have a pelvic exam each year have a preventive (prophylactic) mastectomy. and postmenopausal women should report After mastectomy, breast reconstruction is an any bleeding from the vagina right away. option at the same time as the mastectomy These precautions are not needed if the or later on. uterus has been removed ().

35 Treatment Guidelines for Patients

Stage Work-Up (Evaluation)

• Medical history and physical exam Stage 0 • Diagnostic mammogram (both breasts) Ductal carcinoma • Pathology review of biopsy sample in situ (DCIS) • Measure hormone receptor of tumor

Complete surgical excision

Patient preferred mastectomy

Stage 0 Ductal Carcinoma in Situ have DCIS and not an invasive cancer or The work up for ductal carcinoma in situ other condition. The tumor should also be (DCIS) begins with a complete medical his- tested for hormone receptors. If any evidence tory and physical examination. Diagnostic of invasive cancer is seen in the biopsy, the mammograms of both breasts should be woman’s treatment should be according to done to help estimate how far DCIS has the decision trees for invasive cancer. (See spread within the ducts of the breast and to page 40.) check whether the opposite breast contains The NCCN recommends that the margin any abnormal areas. The NCCN recommends of normal tissue removed around the DCIS a pathology review (another pathologist to should be at least greater than 1 mm. If DCIS look at the biopsy sample) to be certain you is present in only one area and no cancer is

36 Stage 0 Ductal Carcinoma in Situ

Findings

Widespread DCIS in two or more separate areas of the breast

Margins positive

Primary Treatment (see next page) Reexcision

Margins negative

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found at the edges of the first surgical excision, tumor, and the woman’s preference. The NCCN the surgical options are either a total mastec- guidelines recommend that patients interested tomy or a lumpectomy. Lymph node surgery in partial breast irradiation participate in a (lymph node dissection or sentinel node clinical trial. biopsy) is generally not done with DCIS. If a Mastectomy provides the most certain lumpectomy is chosen, then radiation therapy local control of DCIS. But studies have shown to the whole breast with a boost to the site of that women with DCIS who are treated with the tumor may or may not be done depending lumpectomy and radiation are in no greater on several factors, such as woman’s age, other danger of dying of breast cancer than those health problems, certain characteristics of the who have a mastectomy. They do have a risk

37 Treatment Guidelines for Patients

Findings Primary Treatment

Widespread disease OR Total mastectomy without Margins positive after more surgery lymph node removal with or OR without breast reconstruction Patient prefers mastectomy

Lumpectomy without lymph node removal followed by radiation OR Margins negative Total mastectomy without lymph node removal and with or without breast reconstruction

Lumpectomy followed by radiation OR Margins negative and Total mastectomy without lymph tumor is low grade and node removal and with or without 1 small (less than ⁄5 inch) breast reconstruction OR Lumpectomy without radiation

of the cancer coming back in the breast, which or more separate areas of the breast contain would require a mastectomy. Mastectomy is DCIS, mastectomy is recommended. With recommended if the margins of the excision mastectomy, sentinel lymph node biopsy contain cancer and even with repeat surgery may be done to be certain there is no invasive the DCIS cannot be completely removed. cancer present, but an axillary lymph node Radiation is not needed if a mastectomy is dissection is not needed. done unless the DCIS is at the margin of the After lumpectomy, a mammogram is sug- mastectomy. If the mammogram, physical gested to ensure that the entire tumor has examination or biopsy results show that two been removed.

38 Stage 0 Ductal Carcinoma in Situ (continued)

Treatment After Surgery Follow-Up

• Medical history and physical exam every Consider tamoxifen for 5 years 6 months for 5 years, then every year; for patients with ER-positive • Mammogram every year DCIS treated with lumpectomy with or without radiation • Yearly pelvic exam for women taking tamoxifen

©2006 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes without the expressed written permission of the NCCN and the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.

Women with DCIS who are treated with Follow-up for women with DCIS includes mastectomy can choose to have either imme- a medical history and physical exam every 6 diate or delayed breast reconstruction. months for 5 years, then every year there- Women with DCIS treated with lumpectomy after. They should have yearly mammograms. with or without radiation and who have Because tamoxifen increases endometrial estrogen receptor positive tumors should cancer risk in postmenopausal women, consider taking tamoxifen for 5 years. In patients taking this drug should have a pelvic women who have had lumpectomy for DCIS, exam every year and should promptly report tamoxifen can lower the risk of developing an any abnormal . These pre- invasive breast cancer in the same breast. cautions are not needed if the uterus was removed.

39 Treatment Guidelines for Patients

Clinical Stage Work-Up (Evaluation)

If tumor is larger than 2 cm (0.8 inches), and breast- conserving therapy is an option, consider preoperative • Medical history and physical exam therapy (see page 61) • Blood counts and chemical tests • Chest x-ray • Diagnostic mammogram (both breasts), ultrasound as needed Stages I and II • Breast MRI with dedicated breast and Stage IIIA coil may be considered for breast- Lumpectomy and sentinel with tumor conserving surgery node biopsy (see page 46) larger than 5 • Pathology review of biopsy sample OR cm and limited lymph node • Estrogen/progesterone receptor Removal of underarm spread and HER-2/neu test of tissue lymph nodes (T3, N1, M0) • Bone scan (only done if or tests suggest cancer has spread to bones) • Abdominal CT, US, or MRI – optional for stage II, recommended if blood chemistry tests abnormal or Stage IIIA – T3, N1, M0 Mastectomy and sentinel node biopsy or removal of underarm nodes with or without breast reconstruction (see page 44)

Stage I, II, and Some Stage III • chest x-ray Breast Cancer • diagnostic mammograms of both breasts The guidelines for women with stage I and II • breast ultrasound and MRI if needed tumors, and those stage IIIA tumors larger than • pathology review of biopsy sample 5 centimeters (2 inches) with breast cancer in • tests for the presence of hormone the lymph nodes, but not attached to each receptors other (T3, N1, M0), recommend the following: • HER-2/neu test • medical history and physical Bone scan may be ordered and is recom- examination mended if there is bone pain or abnormal • complete blood count, platelet count, blood tests. and liver function tests

40 Stage I, II, and Some Stage III Breast Cancer

Stage I, II, and Some Stage III (T3, N1, M0)

See Treatment for Large Stage II Breast Cancers or Stage IIIA (page 61)

Radiation to the whole breast (with Cancer spread added boost to tumor site) and to 4 or more supraclavicular (above the collarbone) lymph nodes area; consider radiation therapy to lymph nodes next to the breastbone

Additional Cancer spread Radiation to the whole breast (with Treatment to 1, 2, or 3 added boost to tumor site). Possible After Surgery lymph nodes radiation to supraclavicular (above (see page 48) the collarbone) area and to lymph nodes next to the breastbone

No cancer Radiation to the whole breast (with spread to added boost to former tumor site) lymph nodes

See Mastectomy (page 44)

©2006 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes without the expressed written permission of the NCCN and the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.

Abdominal CT scan, ultrasound, or MRI removal of the breast (mastectomy). This may be ordered for stage II and is recom- decision tree only addresses lumpectomy, mended if the blood tests are abnormal or while mastectomy is addressed on page 44. the stage is IIIA (T3,N1, M0). Lumpectomy as the surgical treatment is For patients with Stage I or II breast cancer, possible in most women with stage I or II the surgery can either be a lumpectomy breast cancer. If the tumor is large (i.e. greater (removing only the cancer and a margin of than 2 cm in diameter), breast-conserving surrounding normal tissue) or complete surgery is sometimes done after chemotherapy

41 Treatment Guidelines for Patients

(see page 61). Radiation to the whole breast contain cancer. There are 2 choices for exam- is recommended as part of the treatment ining the lymph nodes—complete axillary following lumpectomy in most cases. Extra lymph node dissection or sentinel lymph node radiation should be given to the area of the biopsy (see discussion in the first part of this breast where the tumor was removed. Breast booklet). This is further described on page 46. irradiation may be omitted in some patients Not all patients need lymph node evaluation; over 70 years old with small, hormone recep- these include patients with favorable tumors, tor positive tumors that do not have lymph where selection of additional treatment will node involvement and who are treated with not be based on whether or not the lymph hormone therapy. The NCCN guidelines rec- nodes are involved, or in patients with other ommend that patients interested in partial serious medical conditions. These specific breast irradiation should participate in a circumstances should be discussed with your clinical trial. doctor. If the cancer has spread to lymph In addition to removing the cancer by nodes, radiation to these areas may be given, lumpectomy or mastectomy, the lymph nodes depending on the number of involved nodes. under the arm are examined to see if they

NOTES

42 Stage I, II, and Some Stage III Breast Cancer (continued)

In choosing breast-conserving surgery • women whose lumpectomy, including versus mastectomy, women must understand any possible repeat lumpectomy when that as long as lumpectomy can be done satis- needed, cannot completely remove factorily (based on the factors that follow), their cancer with a satisfactory the chances of successful treatment and sur- cosmetic result vival are the same with lumpectomy and • women with active connective tissue radiation as with mastectomy. The reasons disease involving the skin (especially for choosing lumpectomy and mastectomy scleroderma or lupus) that makes body are discussed in the first part of this booklet. tissues especially sensitive to the side Lumpectomy and radiation therapy are not effects of radiation appropriate in the following women: • pregnant women who would require • prior radiation therapy of the affected radiation while still pregnant breast or chest • women whose tumor is larger than • suspicious or malignant appearing 5 centimeters (2 inches) and can’t be abnormalities that are widespread shrunk by treatment before surgery throughout the breast

NOTES

43 Treatment Guidelines for Patients

Cancer spread to 4 or more lymph nodes

Cancer spread to 1, 2, or 3 lymph nodes Mastectomy and sentinel node biopsy or removal of underarm nodes with or without breast reconstruction No cancer in lymph nodes, but tumor larger than 5 cm or positive margins

Tumor smaller than 5 cm and no cancer spread to nodes

If a woman and her doctor choose a mas- • If the cancer has spread to 1 to 3 lymph tectomy as her breast cancer treatment, the nodes, there should be consideration guidelines recommend radiation after surgery given to using radiation for the area in the following situations: that the breast was removed from (the • If the cancer has spread to 4 or more chest wall), the area above the collar- lymph nodes, radiation should be given bone, and perhaps the part of chest to the area that the breast was removed near the breastbone. from (the chest wall), the area above • Even if there is no spread to lymph the collarbone and perhaps the part of nodes, if the tumor is larger than 5 cm the chest near the breast bone or the margins are positive, radiation

44 Stage I, II, and Some Stage III Breast Cancer (continued)

Stage I, II, and Some Stage III (T3, N1, M0)

After chemotherapy, radiation to the chest wall and supraclavicular (above the collar- bone) area; possible radiation therapy to lymph nodes next to the breastbone

After chemotherapy, possible radiation to the chest wall and supraclavicular lymph nodes and perhaps lymph nodes next to the breastbone Adjuvant Treatment (see page 48) After chemotherapy, radiation to the chest wall and supraclavicular (above the collarbone) area and perhaps lymph nodes next to the breastbone

No radiation therapy unless margins are very close – then radiation to the chest wall

©2006 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes without the expressed written permission of the NCCN and the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.

should be given to the area that the No radiation is needed if the tumor is breast was removed from (the chest smaller than 5 centimeters, with good margins, wall) and possibly the area above the and no spread to lymph nodes. collarbone and near the breastbone. In all cases where both radiation and • If the tumor is less than 5 cm and the chemotherapy are used, the radiation is given margins are very close, radiation should after chemotherapy unless the chemotherapy be given to the area that the breast was regimen is CMF. CMF and radiation can be removed from (the chest wall). given together.

45 Treatment Guidelines for Patients

Stage Procedure

No Sentinel node procedure can be done if: • There has been no previous Clinical chemotherapy or hormonal therapy Stage I/II AND • There is a team of doctors experienced in the sentinel node procedure Yes

Axillary Lymph Node Surgery of this booklet. The choices are complete In addition to the surgery for the cancer in removal of the lymph nodes (axillary lymph the breast, the lymph nodes under the arm node dissection) or removal of a few lymph are examined in most cases. This provides nodes in the sentinel lymph node biopsy information to guide further treatment and is procedure. In a mastectomy, the lymph nodes usually done at the same time as the breast are removed through the same incision (cut surgery. in the skin). In a lumpectomy, it is usually The types of surgery for lymph nodes under done through an incision separate from the the arm are fully discussed in the first section lumpectomy incision.

46 Axillary Lymph Node Surgery

Usual axillary lymph node surgery

Lymph nodes likely contain cancer as determined by physical examination Usual axillary lymph node Sentinel node No further surgery contains no surgery Lymph nodes cancer are not thought OR to be involved with cancer Sentinel node mapping and excision Sentinel node contains cancer Usual axillary lymph node surgery Sentinel node not identified

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Sentinel lymph node biopsy is not appro- on physical exam, it can be first assessed with priate for all women. It should only be used if a needle biopsy and examined under the the woman has not yet had any chemotherapy microscope. If this biopsy shows no evidence or hormone therapy, and when the nodes are of cancer, a sentinel node biopsy is still con- not enlarged and are not thought to contain sidered appropriate. A sentinel node biopsy cancer based on physical examination at the should only be done if the team of doctors time of diagnosis. If a suspicious node is found has proven experience with this procedure.

47 Treatment Guidelines for Patients

Additional Treatment (Adjuvant • hormone receptor negative and HER-2 Therapy) After Surgery positive tumors Decisions about adjuvant chemotherapy or • hormone receptor positive and HER-2 hormonal treatment for the most common negative tumors types of cancer (with the exception of tumors • hormone receptor negative and HER-2 with good prognosis cell types, such as negative tumors. tubular or colloid) are based on the status of Hormone therapy is used only in tumors the hormone receptors and whether or not that are hormone receptor positive, and the tumor is HER-2 positive. This creates 4 trastuzumab is used only for tumors that are different groups of tumors based upon the HER-2 positive. Chemotherapy is used when hormone receptor and HER-2 status: there is a higher risk of tumor spread based • hormone receptor positive and HER-2 on tumor stage and grade, or if the tumor is positive tumors hormone receptor negative. Patients are

NOTES

48 Additional Treatment (Adjuvant Therapy) After Surgery

often treated with combinations of these The decision trees on the following pages therapies—hormone therapy, trastuzumab divide patients into three broad groups: and chemotherapy, depending on the status • those with small invasive ductal or of the hormone receptors, HER-2 status, and lobular cancers (and its variants) with the risk for recurrence. minimal or no lymph node involvement Specific recommendations regarding • those with larger invasive ductal or type of hormone therapy are discussed on lobular cancers, or cancers involving page 56. Not enough data exists to make lymph nodes strong recommendations regarding adjuvant • those with cancers with a more favorable chemotherapy for those over the age of 70. outlook, i.e. tubular or colloid subtypes. Decisions regarding chemotherapy in this group should take into consideration other health conditions.

NOTES

49 Treatment Guidelines for Patients

Breast Cancer Type Size of Tumor

• Tumor less than or equal to 0.5 cm; or • Microinvasive; or • Tumor 0.6–1.0 cm, well-differentiated

Cancer type is: • Ductal • Tumor doesn’t invade chest wall or skin; and • Lobular • No or minimal spread • Mixed to lymph nodes • Metaplastic

Tumor 0.6–1.0 cm, moderate/poorly differentiated or unfavorable features

Invasive Ductal, Lobular, Mixed, or • If the tumor is smaller than 0.5 cm, or Metaplastic Cancers with Small Tumors is a well-differentiated tumor and is This decision tree describes patients with no larger than 1 cm, or the tumor is invasive ductal, lobular, mixed or metaplastic considered microinvasive, then no cancer that measures up to 1 cm in diameter. adjuvant treatment is needed. If there is The tumor has not spread to the chest wall or lymph node spread smaller than 2 mm, skin and the lymph nodes are either not hormone therapy may be given if the involved, or only one lymph node shows a tumor is hormone receptor positive very small deposit of cancer: and chemotherapy may be given if the tumor is hormone receptor negative.

50 Additional Treatment for Invasive Ductal, Lobular, Mixed, or Metaplastic Cancers with Small Tumors

Hormone Systemic Adjuvant Responsiveness Treatment

No lymph node spread when examined by a No adjuvant therapy pathologist

Consider adjuvant Hormone receptor positive hormone therapy Lymph node spread smaller than 2mm when examined by a pathologist Consider adjuvant Hormone receptor negative chemotherapy

Adjuvant hormone with or without chemotherapy Hormone receptor positive or ovarian suppression or ablation if premenopausal

Hormone receptor negative Consider chemotherapy

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• When the tumor measures 0.6 to 1 cm, Whenever chemotherapy is given, it is moderately or poorly differentiated should be given before hormone therapy. or has unfavorable features (such as • Ovarian ablation using surgery, radiation looking aggressive under the micro- therapy, or drugs (LHRH agonists or scope), hormone therapy with or antagonists) may be recommended in without chemotherapy is given if the premenopausal women, although the tumor is hormone receptor positive. benefit is uncertain in those who have Chemotherapy alone is given if the received adjuvant chemotherapy. tumor is hormone receptor negative.

51 Treatment Guidelines for Patients

Breast Cancer Type Size of Tumor

Tumor greater than 1 cm

Cancer type is: • Ductal • Lobular • Mixed • Metaplastic

Cancer has spread to lymph nodes, measuring greater than 2 mm

Invasive Ductal, Lobular, Mixed, or • Chemotherapy is recommended for all Metaplastic Cancers with Larger Tumors patients in this category. Hormone or Lymph Node Spread therapy and/or trastuzumab are also This decision tree focuses on tumors that used depending upon the features of are greater than 1 cm in diameter and/or with the tumor. Hormone therapy is recom- positive lymph nodes. The HER-2 and hormone mended if the tumor is hormone receptor status of the tumor are also important receptor positive, and trastuzumab is in choosing therapy. recommended if the tumor is HER-2 52 Additional Treatment for Invasive Ductal, Lobular, Mixed, or Metaplastic Cancers with Larger Tumors or Lymph Node Spread

HER-2/neu and Systemic Adjuvant Hormone Responsiveness Treatment

Adjuvant chemotherapy Hormone receptor positive, plus hormone therapy HER-2/neu positive plus trastuzumab

Hormone receptor positive, Adjuvant chemotherapy HER-2/neu negative plus hormone therapy

Hormone receptor negative, Adjuvant chemotherapy HER-2/neu positive plus trastuzumab

Hormone receptor negative, Adjuvant chemotherapy HER-2/neu negative

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positive. Whenever chemotherapy is be able to estimate the likelihood that given, it should be given before hormone they will improve your outcome. Along therapy. with your doctors, you should balance • The decision to take chemotherapy, the benefits and the side effects of the hormone therapy, and/or trastuzumab is treatment to decide if the treatments an important decision in the treatment are right for you. of breast cancer. Your doctor should

53 Treatment Guidelines for Patients

Breast Cancer Type Size of Tumor

Less than 1 cm

Tumor does not invade chest wall or skin, and no spread to lymph 1–2.9 cm nodes or spread is smaller than 2 mm to a single node

Cancer type is: • Tubular Greater than or equal to 3 cm • Colloid

Cancer spread to lymph node and is larger than 2 mm

Tubular or Colloid Breast Cancers lymph node status, as well as the status of This decision tree addresses tubular or hormone receptors. NCCN recommends the colloid breast cancers, which have a more following: favorable outlook than other types of breast • For tumors smaller than 1 cm with no cancer. The hormone receptor status is an or a very small amount of spread in one important factor in deciding treatment in lymph node, no treatment is needed these tumors, but HER-2 status is not, since after surgery, although hormone therapy these tumors are usually HER-2 negative. In may be considered if the tumor is fact, the diagnosis of tubular cancer should hormone receptor positive. be questioned if the tumor is either hormone • If the tumor is between 1 and 2.9 cm in receptor negative or HER-2 positive. The size, with no or a very small amount of treatment options for tubular and colloid spread in one lymph node, adjuvant tumors are based on the size of tumor and chemotherapy may be considered,

54 Additional Treatment for Tubular or Colloid Breast Cancers

Hormone Responsiveness Systemic Adjuvant Treatment

No adjuvant therapy. May consider hor- mone therapy if hormone receptor positive

Consider adjuvant hormone Hormone receptor positive therapy plus chemotherapy

Hormone receptor negative Consider adjuvant chemotherapy

Adjuvant hormone therapy Hormone receptor positive plus chemotherapy

Hormone receptor negative Adjuvant chemotherapy

Adjuvant hormone therapy Hormone receptor positive plus chemotherapy

Hormone receptor negative Adjuvant chemotherapy

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with the addition of hormone therapy The benefits of chemotherapy and hormone for those whose tumor has positive therapy are additive. However, the benefit of hormone receptors. chemotherapy may be minimal in patients • Adjuvant chemotherapy is more over 60 years-old with good prognosis strongly recommended for tumors 3 tumors who are already receiving hormone cm in diameter or larger, or those with therapy. In these patients, the decision to add positive lymph nodes. Hormone therapy chemotherapy to hormone therapy should be is added if the tumor is hormone individualized. receptor positive.

55 Treatment Guidelines for Patients

Menopausal Adjuvant Treatment Status

Premenopausal

Tamoxifen for 2 to 3 years with or without ovarian Premenopausal suppression (LHRH) or ablation (radiation, surgery)

Postmenopausal Anastrozole or letrozole for 5 years

Tamoxifen for 2 to 3 years

Postmenopausal

Tamoxifen for 4.5 to 6 years

Tamoxifen for 5 years if woman can’t take aromatase inhibitor

Adjuvant Hormone Treatment letrozole or exemestane) in postmenopausal This describes the options for adjuvant hor- women. Although all aromatase inhibitors are monal treatment after breast surgery in women probably equally effective, they are specifically whose cancers contained hormone receptors. named in this decision tree, based on the In the past, tamoxifen has been the standard results of clinical trials. therapy. Results of recent clinical trials have Tamoxifen is the recommended hormone pointed to new treatments, particularly the treatment for premenopausal patients. use of aromatase inhibitors (anastrozole, Treatment with tamoxifen followed by an

56 Additional (Adjuvant) Hormone Treatment

Tamoxifen for full 5 years Letrozole for 5 years

Exemestane or anastrozole to complete 5 year adjuvant therapy

Now postmenopausal Letrozole for 5 years

Tamoxifen for full 5 years

No further Still premenopausal hormone therapy Exemestane or anastrozole to complete 5 year adjuvant therapy

Letrozole for 5 years

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aromatase inhibitor, or an aromatase inhibitor at the time of her diagnosis of breast cancer, alone is recommended for postmenopausal she should monitored for hormone levels women. Treatment with tamoxifen followed such as estradiol and FSH to make sure that by an aromatase inhibitor is an option for she is truly postmenopausal. premenopausal women who become post- For premenopausal women, tamoxifen for menopausal during tamoxifen treatment. 2 to 3 years is recommended. While tamoxifen If use of an aromatase inhibitor is con- alone is often recommended, another option sidered in a woman who was premenopausal is to combine tamoxifen with efforts to

57 Treatment Guidelines for Patients

decrease ovarian production of estrogen exemestane or anastrozole for the remaining using surgery, radiation, or a medicine called 2 to 3 years. If the woman remains pre- an LHRH (leutinizing hormone releasing menopausal during the 2 to 3 years of treat- hormone) agonist or antagonist. If the ment with tamoxifen, the tamoxifen should woman becomes postmenopausal during be continued for a total of 5 years. If she then treatment, the tamoxifen should be continued becomes postmenopausal, the tamoxifen for a total of 5 years and followed by 5 years of should be stopped and letrozole for 5 years letrozole. Another option would be stopping should be added. the tamoxifen after 2 to 3 years and taking

NOTES

58 Additional (Adjuvant) Hormone Treatment (continued)

For women who are postmenopausal at letrozole for 5 years. If a woman can’t take an the beginning of therapy, one choice is an aromatase inhibitor, then tamoxifen for 5 years aromatase inhibitor, either anastrozole or is an acceptable option. Aromatase inhibitors letrozole, for 5 years. A second option is to take may weaken bones. Therefore, women taking tamoxifen for 2 to 3 years and then complete these drugs may have periodic checks of their 5 years of treatment with either anastrozole bone strength to determine if they would or exemestane. A third choice is to take benefit from bone strengthening drugs. tamoxifen for 4.5 to 6 years and then take

NOTES

59 Treatment Guidelines for Patients

Clinical Stage Work-Up

Wants to preserve • Medical history and physical breast (Consider examination needle biopsy of • Blood counts and chemistry tests enlarged lymph • Chest imaging nodes or sentinel node procedure. • Diagnostic mammograms (both The cancer is larger than Tumor should be breasts) 2 cm and doesn’t invade marked so it can chest wall or skin. Lymph • Breast MRI with dedicated be located after nodes can be enlarged but breast coil may be considered chemotherapy.) are movable. Diagnosed by • Pathology review of biopsy needle biopsy not excision. sample Breast-conserving surgery • Hormone receptor tests not possible because too large a tumor in the breast. • HER-2/neu test • Bone scan and CT, MRI, or ultra- sound of abdomen if symptoms or abnormal blood tests or tumor over 5 cm with lymph node spread Doesn’t want to preserve breast

Treatment of Large Stage II or that allows some women with large tumors Stage IIIA Breast Cancers (larger than 2 cm) that have not spread to the Breast-conserving treatment is usually not skin or chest wall to have breast-conserving recommended for women with large tumors. treatment if they want it. However, chemotherapy may shrink the The work-up recommended before starting tumor enough to permit a lumpectomy that preoperative chemotherapy includes: completely removes the main tumor and still • medical history and physical keeps the size and shape of the breast accept- examination able. Preoperative chemotherapy is an option • blood counts and chemical tests

60 Treatment of Large Stage II or Stage IIIA Breast Cancers

Primary Treatment

Tumor either doesn’t shrink, or grows even after trying different chemotherapy Presurgical therapy: Mastectomy with removal of underarm nodes, with • Chemotherapy or without reconstruction • Hormone ther- Tumor shrinks (Continued on next page) apy, if hormone but still too large receptor positive for lumpectomy, even after trying • Trastuzumab different if HER-2/neu chemotherapy positive Lumpectomy and removal of underarm lymph nodes Tumor shrinks (If lymph nodes not enough for involved pre-chemotherapy lumpectomy by biopsy, no further lymph node surgery is necessary.) (Continued on next page)

Treat with mastectomy and sentinel node biopsy or removal of underarm nodes, with or without reconstruction (see next page)

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• CT scan of the chest or chest x-ray • bone scan and CT, MRI or ultrasound • diagnostic of both of the abdomen if the tumor is larger breasts than 5 cm (2 inches) with lymph node • breast ultrasound and MRI if needed spread, or if there are symptoms of • pathology review of biopsy sample bone spread, such as pain or abnormal • hormone receptor test of the tumor blood tests. • HER-2/neu test of the tumor

61 Treatment Guidelines for Patients

If there are enlarged lymph nodes, a needle The same drugs used as adjuvant treatment biopsy can be done before chemotherapy. If the in Stage I or II breast cancer are also used lymph nodes are not enlarged, a sentinel node before surgery to shrink the tumors to permit procedure may be done before chemotherapy. a mastectomy or lumpectomy. If the tumor is It is recommended that the tumor be marked HER-2 positive, trastuzumab should be added before chemotherapy so that the area can be to the chemotherapy. If the tumor is hormone located in the event that the tumor completely receptor positive, then hormone therapy is disappears on physical examination and sometimes used instead of chemotherapy. If mammogram. hormone therapy is used instead of chemo-

NOTES

62 Treatment of Large Stage II or Stage IIIA Breast Cancers (continued)

therapy, the preferred hormone therapy is If the tumor doesn’t shrink enough to an aromatase inhibitor in postmenopausal permit a lumpectomy, another type of chemo- women. therapy may be given, but a mastectomy will If the tumor shrinks from the chemother- be needed if there isn’t enough shrinkage in the apy or hormone therapy, the next step is tumor to allow a lumpectomy. Mastectomy lumpectomy and removal of underarm lymph may be followed by breast reconstruction. The nodes unless a sentinel lymph node biopsy underarm lymph nodes should be removed done before the chemotherapy finds no unless a sentinel lymph node biopsy done cancer in the sentinel lymph nodes. before the chemotherapy found no cancer in the sentinel lymph nodes.

NOTES

63 Treatment Guidelines for Patients

Primary Treatment (Local) Adjuvant (Additional) Treatment

Mastectomy with underarm lymph node removal, with or without reconstruction. Possible additional Removal of underarm nodes chemotherapy may be omitted if sentinel node (before radiation) biopsy done pre-chemotherapy finds no cancer.

Lumpectomy with underarm lymph node removal, with or without reconstruction. Possible additional Removal of underarm nodes chemotherapy may be omitted if sentinel node (before radiation) biopsy done pre-chemotherapy finds no cancer.

After mastectomy or lumpectomy, more be followed by radiation therapy to the whole chemotherapy may be recommended, depend- breast and sometimes to the surrounding ing on the tumor size and number of positive lymph nodes. The decision to treat the lymph lymph nodes. If the tumor was hormone nodes with radiation, or the decision to treat receptor-positive, hormone therapy should the skin after mastectomy is based on the same be given. If a lumpectomy was done, it should principles as in Stage I and II on page 44.

64 Treatment of Large Stage II or Stage IIIA Breast Cancers (continued)

Radiation Therapy

Radiation therapy (after surgery) depending on tumor size and lymph node status (see page 44) AND Hormonal therapy if hormone receptor-positive.

See follow-up care on page 70

Radiation therapy (after surgery) depending on tumor size and lymph node status (see page 44) AND Hormonal therapy if hormone receptor-positive.

©2006 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes without the expressed written permission of the NCCN and the ACS. Single copies of each page may be reproduced for personal and non-commercial uses by the reader.

NOTES

65 Treatment Guidelines for Patients

Clinical Stage Work-Up Preoperative Chemotherapy

• Medical history and physical examination • Doxorubicin- or epirubicin- based • Blood count and chemistry tests or docetaxel-based • Chest CT scan with or without x-ray preoperative • Diagnostic mammograms (both chemotherapy Stage III preferred (Tumor growing breasts), ultrasound, as needed into chest wall or • Breast MRI with dedicated breast • Patients with skin, or enlarged coil if needed for breast-conserving tumors over- lymph nodes can surgery expressing HER- 2/neu should be be felt) • Pathology review of biopsy sample considered for • Pre-chemotherapy hormone receptor neoadjuvant tests, HER-2/neu test chemotherapy • Bone scan incorporating trastuzumab • CT, MRI, or ultrasound of abdomen

Stage III Locally Advanced Breast • chest CT scan and perhaps chest x-ray Cancers • diagnostic mammograms of both These are advanced cancers that are growing breasts into the skin or chest wall or have enlarged • breast ultrasound test and/or breast lymph nodes that are matted together. There MRI (if needed) is no evidence of spread anywhere else in the • pathology review (second opinion on body. The recommended work-up for these the biopsy samples) stage III breast cancers includes: • hormone receptor test of the biopsy • medical history and physical sample examination • HER-2/neu test of the biopsy sample • blood counts and blood tests to measure • bone scan liver function • CT, MRI, or ultrasound of the abdomen

66 Stage III Locally Advanced Breast Cancers

Primary Treatment

Mastectomy and removal of underarm lymph nodes, radiation to the chest wall and lymph nodes above the collarbone More chemotherapy and perhaps internal nodes next to and hormone therapy breastbone, with or without delayed if hormone receptor Tumor breast reconstruction present or unknown, shrinks OR and trastuzumab if Possible lumpectomy or removal of tumor is HER-2/neu underarm lymph nodes, radiation to positive (see follow- the breast and lymph nodes above the up on page 70) collarbone and perhaps internal nodes Tumor next to breastbone does not shrink

Tumor

Consider additional chemotherapy and/or preoperative radiation Individualized Tumor does treatment to not shrink be discussed with doctor

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The treatment for locally advanced breast and should include trastuzumab if the tumor cancer starts with chemotherapy given before is HER-2 positive. Patients whose tumors surgery. The should shrink enough to be surgically removed have contain an (doxorubicin or epi- 3 options: rubicin) or a (paclitaxel or docetaxel)

67 Treatment Guidelines for Patients

• Mastectomy and removal of underarm • Lumpectomy with removal of lymph lymph nodes. This is followed by nodes, if the cancer has shrunk enough, radiation therapy to the chest wall, followed by radiation therapy to the the lymph nodes above the collarbone, breast and the lymph nodes above the and, if they are enlarged, internal nodes collarbone, and, if they are enlarged, next to the sternum or breastbone. internal nodes next to the sternum or Breast reconstruction can be done breastbone. later if desired. • High dose radiation alone to the breast and usual dose radiation to the lymph

NOTES

68 Stage III Locally Advanced Breast Cancers (continued)

nodes. Among breast cancer specialists, Women with stage IIIA or IIIB breast this option is controversial. cancer that doesn’t shrink with their first treatment can be treated with another For these patients the guidelines recom- chemotherapy regimen and/or radiation. If mend adding more chemotherapy after surgery. the tumor shrinks, the patient can be treated If the cancer is hormone receptor positive or as outlined above. If the tumor does not the status is unknown, hormone therapy is shrink, the patient should discuss treatment recommended. If the tumor is HER-2 positive, for her specific situation with her doctor. trastuzumab is also recommended.

NOTES

69 Treatment Guidelines for Patients

Routine Follow-Up Work-Up for Stage IV or Suspected Recurrence

• Medical history and physical examination • Blood count, chemistry tests, • History and physical exam every 4 to and liver function tests 6 months for 5 years, then every year • Chest imaging • Mammograms every year. For • Bone scan lumpectomy patients, the first one should be 6 months after radiation • X-rays of bones that hurt and weight-bearing bones that • Women taking tamoxifen: pelvic are abnormal on bone scan exam every year if the uterus is present • CT or MRI of chest and abdomen and/or PET scan • Women on aromatase inhibitor or may be recommended who have gone through early menopause with chemotherapy • Biopsy of suspected should have bone density monitored. recurrence if possible • ER/PR and HER-2/neu testing if not known, hormone receptor previously negative, or HER-2/neu negative

Follow-up and Treatment of Stage Women who have had a mastectomy IV Disease or Recurrence of Disease should have a yearly mammogram of the Routine follow-up for all patients who have had remaining breast after the surgery. Because invasive breast cancer includes the following: tamoxifen increases a woman’s risk of devel- a medical history and physical exam every 4 oping cancer of the uterus, women taking to 6 months for 5 years, then once a year. this drug should have a yearly pelvic exam Women who have had a lumpectomy and should promptly tell their doctor if there should have a mammogram of the treated is any abnormal bleeding from the vagina. breast 6 months after radiation therapy, and Women on an aromatase inhibitor or who then mammograms of both breasts every year. went through early menopause on treatment

70 Follow-up and Treatment of Stage IV Disease or Recurrence of Disease

Treatment of Recurrence

If possible, remove For patient cancer, followed by initially treated radiation therapy if with mastectomy none given before Local recurrence (cancer came back in breast, underarm lymph nodes, or nearby tissues) For patient initially Continued treated with on page 74 Mastectomy lumpectomy and radiation therapy

Systemic recurrence or presenting with advanced cancer (Stage IV cancer spread to distant organs)

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should have their bones tested for strength • complete medical history and physical using a test called a bone mineral density test. examination If there is a suspected recurrence or if the • blood counts and chemistry tests cancer had spread away from the breast • liver function tests when it was diagnosed, the work-up includes: • chest imaging • bone scan

71 Treatment Guidelines for Patients

Weight-bearing bones that are painful or done if there are symptoms or blood tests showed abnormalities on the bone scan suggesting a recurrence in these areas. should also be x-rayed, and CT or MRI scans Another option is a PET scan. A biopsy should of the abdomen, chest, or head should be be done to confirm the first recurrence

NOTES

72 Follow-up and Treatment of Stage IV Disease or Recurrence of Disease (continued)

whenever possible. If HER-2/neu testing specimen if possible. Likewise, if hormone was not done on the original cancer or was receptor tests were not done or were negative, negative, it should be done on a new biopsy testing for these should be done.

NOTES

73 Treatment Guidelines for Patients

Recurrence Site

Prior mastectomy

Recurrence is local Prior lumpectomy or radiation

Antiestrogen therapy taken Cancer contains within last year hormone receptors with none or limited spread to Postmenopausal organs such as liver and lungs No antiestrogen therapy taken within last year Recurrence is systemic (distant) Premenopausal OR Stage IV (distant metastasis) when Cancer doesn’t first diagnosed contain hormone receptors, or does HER-2/neu positive not respond to hormone therapy, or has spread extensively to HER-2/neu negative internal organs causing symptoms

A recurrence may be local, meaning that surgery (if possible). The area of the recur- cancer has returned to the area of the breast, rence and surrounding tissues should receive underarm lymph nodes, or nearby tissue. Or radiation therapy, if it has not been given it may be systemic, which means that cancer before. If the cancer cannot be removed with has spread to distant organs. If the recurrence surgery, the woman should have radiation is local and the woman has had a mastectomy, therapy if it was not given before. In either the recurrent cancer should be removed by case, the NCCN recommends considering

74 Follow-up and Treatment of Stage IV Disease or Recurrence of Disease (continued)

Treatment of Recurrence or Stage IV

Surgery to remove recurrence if possible, Hormone treatment or radiation if not given before trastuzumab or chemotherapy may be recommended after Mastectomy surgery and radiation

Try different hormone therapy

Aromatase inhibitor or an antiestrogen

Ovarian ablation or suppression and either aromatase inhibitor or antiestrogen OR Antiestrogen alone

Trastuzumab with or If no response to 3 different without chemotherapy chemotherapy regimens in a row Supportive care focused OR on relieving Very weak and spending most of symptoms Chemotherapy time in bed

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75 Treatment Guidelines for Patients

ovarian ablation is appropriate for the fol- and whether or not she is premenopausal or lowing patients: postmenopausal. For example, if an anti- • The tumor is hormone receptor estrogen such as tamoxifen has been given positive; or within the past year, then a different hormone • There is spread only to the bones or therapy should be offered. If the patient has soft tissues; or not received an antiestrogen within the past • The cancer has spread to other organs year, the treatment options are based on such as the liver or lungs, but the whether the patient is pre or postmenopausal. organs are still working well. For postmenopausal women, an aromatase inhibitor or antiestrogen would be the first The specific treatment is based on what type choice. Premenopausal women may be of treatment the patient has received before treated with an antiestrogen alone. Another

NOTES

76 Follow-up and Treatment of Stage IV Disease or Recurrence of Disease (continued)

treatment option for premenopausal women In patients whose tumor is hormone- is to block the ovaries from making estrogen receptor negative, treatment options depend and then use hormone therapy similar to on whether or not the tumor is HER-2 posi- postmenopausal patients. The ovaries may tive. If the tumor is HER-2 positive, then be blocked with a medicine that decreases trastuzumab may be given, either alone or estrogen production in the ovary, with radia- combined with chemotherapy. If the tumor is tion therapy to the ovary, or by surgically HER-2 negative, chemotherapy alone is rec- removing the ovaries. If there is spread to ommended. If the tumor does not shrink after bone, either pamidronate or , 3 different chemotherapy regimens, stopping along with calcium citrate and vitamin D, chemotherapy and providing supportive care should be given to strengthen the bones. to relieve symptoms should be considered.

NOTES

77 Treatment Guidelines for Patients

Primary Response Treatment Treatment

Cancer shrinks or If cancer grows Try different is stable for 6 or cancer invades hormone therapy months or longer other organs, or side effects not tolerated

Hormone treatment

Cancer doesn’t Chemotherapy shrink

If the hormone therapy causes the cancer trying at least 3 different hormone treatments to shrink or at least not grow for a while, it until there is no longer any benefit or the would be continued until the cancer begins cancer has spread extensively to internal to grow. At that time another hormone treat- organs with associated symptoms. At that ment may be tried. The NCCN recommends point chemotherapy is recommended.

78 Follow-up and Treatment of Stage IV Disease or Recurrence of Disease (continued)

Response Treatment

If no benefit after 3 different hormone regimens or Chemotherapy extensive spread to internal organs causing symptoms

If no benefit after 3 different chemotherapy regimens Supportive care focused OR on relieving symptoms Very weak and spending most of time in bed

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Hormone therapy is not recommended in • When the tumor has not responded to 3 situations: three prior hormone therapies; or • When the tumor is hormone receptor • When the tumor has spread extensively negative; or to organs such as the lungs or liver, and is causing the organs to not work well.

79 Treatment Guidelines for Patients

Clinical Primary Treatment Presentation

Discuss Mastectomy and axillary 1st trimester pregnancy lymph node dissection termination

Mastectomy or lumpectomy and axillary lymph node dissection Pregnant patient with 2nd trimester OR breast cancer or early 3rd and no distant trimester spread Preoperative chemotherapy followed by mastectomy or lumpectomy with axillary node dissection

Late 3rd Mastectomy or lumpectomy and trimester axillary lymph node dissection

Breast Cancer in Pregnancy months (first trimester), second 3 months Breast cancer sometimes occurs during (second trimester), and third 3 months (third pregnancy. In this special situation, it is often trimester). Women who are diagnosed with necessary to try and find a treatment program breast cancer during the first trimester that helps the mother, but doesn’t hurt the should consider the option of having the fetus. This is not always possible. pregnancy terminated. This is because the The treatment recommendations depend use of drug treatments during the early part upon how long the woman has been pregnant. of pregnancy may cause damage to the fetus. Doctors divide pregnancy into the first 3 In general, the treatment options for women

80 Breast Cancer in Pregnancy

Adjuvant Treatment

Begin with adjuvant chemotherapy in 2nd trimester, with or without adjuvant radiation after birth, with or without adjuvant hormone therapy after birth

Adjuvant chemotherapy, with or without adjuvant radiation after birth, with or without adjuvant hormone therapy after birth

Possible adjuvant radiation after birth, with or without adjuvant hormone therapy after birth

Adjuvant chemotherapy, with or without adjuvant radiation after birth, with or without adjuvant hormone therapy after birth

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who are pregnant are similar to those recom- part of breast-conserving therapy must be mended in non-pregnant woman except that postponed until after the patient has given chemotherapy should not be given during the birth. Hormone therapy should not be first trimester of pregnancy, some chemother- started until after the patient has given birth. apies (such as methotrexate) need to be It is important that the cancer doctors of avoided, and radiation therapy should not be a woman who have breast cancer while preg- administered at any point during pregnancy. nant communicate and work closely with the For this reason, the radiation therapy that is woman’s obstetrician.

81 Glossary

Adjuvant therapy calcium. These include pamidronate and Treatment that is added to increase the effec- zoledronate. tiveness of a primary therapy. It usually refers Breast-conserving treatment or therapy to hormonal therapy, chemotherapy, or radi- Surgery to remove a breast cancer and a small ation therapy added after surgery to kill any amount of benign tissue around the cancer, remaining cancer cells and increase the without removing any other part of the breast. chances of curing the disease or keeping it in This procedure is also called lumpectomy, check. segmental excision, or limited breast surgery. Antiestrogen The method may require an axillary dissection A substance that blocks the effects of estrogen and usually requires radiation therapy after on tumors (for example, the drug tamoxifen). the surgery. are used to treat breast cancers Breast reconstruction that depend on estrogen for growth. Surgery that rebuilds the breast contour after Aromatase inhibitors mastectomy. A breast or the woman’s Drugs that block production of estrogens own tissue provides the contour. If desired, from hormones made by the adrenal gland. the nipple and areola may also be re-created. They are used to treat hormone-sensitive Reconstruction can be done at same time as breast cancer in postmenopausal women. the mastectomy or any time later. Examples are anastrozole, letrozole, and Carcinoma in situ exemestane. An early stage of cancer, in which the tumor Axillary lymph node dissection is still only in the structures of the organ A surgical procedure in which the lymph where it first developed—the disease does nodes in the armpit (axillary nodes) are not invade other parts of the organ or spread removed and examined to find out if breast to distant sites. Most in situ carcinomas are cancer has spread to those nodes. This is also highly curable. done to remove any cancerous lymph nodes. Chemotherapy Biopsy Treatment with drugs to destroy cancer cells. The removal of a sample of tissue to see Chemotherapy is often used in addition to whether cancer cells are present. surgery or radiation to treat cancer when spread (metastasis) is proven or suspected, Bisphosphonates when the cancer has come back (recurred), Drugs that help strengthen bones weakened or when there is a strong likelihood that the by cancer by encouraging the deposition of cancer could recur. 82 Clinical stage Duct Stage includes evaluation of the size and A hollow passage for gland secretions. In the extent of the cancer, the presence or absence breast, a passage through which milk passes of spread to lymph nodes, and the presence from the lobule (which makes the milk) to the or absence of spread to other body organs. nipple. These ducts are the starting point for Clinical stage is the stage determined only by most breast cancers. physical examination and x-ray or other Ductal carcinoma in situ imaging studies. This includes determination The most common type of non-invasive of the size of the cancer and evaluation of breast cancer. Cancer cells have not spread lymph nodes by the doctor’s examination of beyond the ducts. the armpit. The final stage is the pathological stage which is determined from microscopic Estrogen examination of the tumor and lymph nodes. A female sex hormone produced primarily by Clinical stage is used for initial treatment the ovaries, and in smaller amounts from planning. hormones produced by the adrenal gland and fat cells. In breast cancer, estrogen may Clinical trial help the growth of breast cancer cells. Research studies test new drugs or treatments and compare them to current, standard treatments. Before a new treatment is used on A type of benign breast tumor made of people, it is studied in the lab. If lab studies fibrous tissue and glandular tissue. On clinical suggest the treatment works, it is tested for examination or breast self-examination, it patients. These human studies are called usually feels like a firm, round, smooth lump. clinical trials. These usually occur in young women. Cyst Fibrocystic changes A fluid-filled mass that is usually not cancer A term that describes certain benign changes (benign). The fluid can be removed for testing. in the breast; also called fibrocystic disease. Symptoms of this condition are breast Diagnostic mammogram swelling or pain. The breasts often feel lumpy or Screening mammograms are performed on nodular. Because these signs sometimes mimic women with no evidence of lumps or other breast cancer, a diagnostic mammogram, symptoms. This includes 2 x-ray views of each ultrasound, or even a biopsy may be needed breast (top to bottom; side-to-side). Diagnostic to show that there is no cancer. mammograms include additional x-ray views of areas of concern (found on physical exam- Fibrosis ination or on the screening mammogram) to Formation of fibrous (scar-like) tissue. This provide more information about the size and can occur anywhere in the body. character of the abnormality.

83 Fulvestrant Hormone receptor A drug that reduces the number of estrogen These are the cells’ “welcome mat” for hor- receptors. mones circulating in the blood. The receptor is a protein located on a cell’s surface (or within Grade the cell cytoplasm) that binds to a hormone. Cancer cells are graded by how much they Tumors can be tested for hormone receptors look like normal cells. Grade 1 (also called to see if they can be treated with hormones well-differentiated) means the cancer cells or anti-hormones. See also, hormone receptor look like the normal cells. Grade 3 (poorly assay. differentiated) cancer cells do not look like normal cells at all. Grade 1 cancers aren’t Hormone receptor assay considered aggressive. In other words, they A test to see whether a breast tumor has hor- tend to grow more slowly and metastasize mone receptors and is affected by hormones slower. Grade 3 cancers are more likely to or can be treated with hormones. grow fast and metastasize. A cancer’s grade, Hormone therapy along with its stage, is used to determine Can be treatment with hormones, treatment treatment. with drugs that interfere with hormone pro- HER-2/neu duction or hormone action, or surgical removal A gene that produces a type of receptor that of hormone-producing glands to kill cancer helps cells grow. Breast cancer cells with too cells or slow their growth. The most common many HER-2/neu receptors tend to be fast- hormone therapy for breast cancer is the drug growing and may respond to treatment with tamoxifen. Other hormonal therapies include a monoclonal antibody called trastuzumab. aromatase inhibitors, androgens and surgical removal of the ovaries (oophorectomy). Histology The way the cancer cells look under the In situ microscope (described as type and arrange- Cancer in situ is localized in its original place ment of tumor cells). and confined to one area. This describes a very early stage of cancer. Hormone A chemical substance released into the body Internal mammary lymph nodes by glands, such as the thyroid, pituitary, or Lymph nodes located inside the chest, next ovaries. The substance travels through the to where the sternum (breastbone) and the bloodstream and sets in motion various body ribs come together. functions. For example, prolactin, which is Intraductal papillomas produced in the pituitary gland, begins and Small, finger-like, polyp-like, non-cancerous sustains the production of milk in the breast growths in the breast ducts that may cause a after childbirth. bloody . These are most often found in women 45 to 50 years of age. When

84 many papillomas exist, breast cancer risk is of tissue removed and is usually a sign that slightly increased. some cancer remains in the body. LHRH (luteinizing hormone-releasing Mastectomy hormone) agonists or antagonists Removal of the entire breast. In a simple or Drugs that block the ovaries from producing total mastectomy surgeons do not cut away estrogen. any lymph nodes or muscle tissue; in a modi- fied radical mastectomy, surgeons remove the Lobular carcinoma in situ breast and some armpit lymph nodes; in a Also called lobular neoplasia. Non-invasive radical mastectomy (now rarely performed) cancer that has not spread beyond the lobules. surgeons remove the breast, armpit lymph The lobules are the milk-producing parts of nodes, and chest wall muscles under the the breast at the distant end of the ducts. breast. Lumpectomy Menopause Surgery to remove the breast tumor and a The time in a woman’s life when monthly small amount of surrounding normal tissue. cycles of menstruation stop forever and the Lymph nodes level of hormones produced by the ovaries Small, bean-shaped collections of immune decreases. Menopause usually naturally occurs system tissue located along lymphatic vessels. in a woman’s late 40s or early 50s, but it can They remove waste and fluids from lymph and also be caused by surgical removal of both help fight infections. Also called lymph glands. ovaries (oophorectomy), or by chemotherapy, which often destroys ovarian function. Lymphedema A possible complication after breast cancer Metastasis treatment. Swelling in the arm is caused by The spread of cancer cells to distant areas of excess fluid that collects after lymph nodes the body by way of the lymph system or and vessels are removed by surgery or treated bloodstream. with radiation. Monoclonal antibody therapy Magnetic resonance imaging (MRI) Monoclonal (MABs) are made in A method of taking pictures of the inside of the lab and designed to target specific sub- the body. Instead of using x-rays, MRI uses a stances called antigens. MABs which have powerful magnet and transmits radio waves been attached to chemotherapy drugs or through the body; the images appear on a radioactive substances are being studied to computer screen and on film. see if they can seek out antigens unique to cancer cells and deliver these treatments Margin directly to the cancer, thus killing the cancer The edge of the tissue removed during surgery. cells without harming healthy tissue. A negative margin is a sign that no cancer Trastuzumab is the MAB used to treat HER-2 was left behind. A positive margin indicates positive breast cancers. that cancer cells are found at the outer edge 85 Neoadjuvant treatment PET (positron emission tomography) scan Used to describe systemic therapy, such as A total body scan that uses a radioactive form chemotherapy or hormone therapy, given of glucose to detect cancer. before surgery. This type of therapy can shrink Preoperative chemotherapy some tumors, so that they are easier to remove. Chemotherapy given before surgery to shrink Nodal status some breast tumors, so they can be removed Indicates whether a breast cancer has spread with less extensive surgery than would other- (node-positive) or has not spread (node-nega- wise be needed. Also called neoadjuvant tive) to lymph nodes in the armpit (axillary chemotherapy. nodes). The number and site of positive lymph Progesterone nodes can help predict the risk of cancer A female sex hormone released by the ovaries recurrence. during every to prepare the Oophorectomy uterus for pregnancy and the breasts for milk Surgery to remove the ovaries. production (lactation). Ovary Prognosis Reproductive organ in the female pelvis. A prediction of the course of disease—or the Normally a woman has two ovaries. They outlook for the cure of the patient. For exam- contain the eggs (ova) that, when joined with ple, women with breast cancer that is small, sperm, result in pregnancy. Ovaries produce does not involve the lymph nodes, and is most of a premenopausal woman’s estrogen. promptly treated have a good prognosis. Palpation Quadrantectomy Using the hands to examine. A palpable mass A type of breast-conserving surgery that in the breast is one that can be felt. removes more breast tissue than a lumpec- tomy (up to one-quarter of the breast). It is Partial mastectomy also called a partial or segmental mastectomy. A type of breast-conserving surgery that removes more breast tissue than a lumpec- Radiation tomy (up to one-quarter of the breast). It is Treatment with high-energy rays (or particles) also called a segmental mastectomy or a to kill or shrink cancer cells. The radiation quadrantectomy. may come from outside of the body (external radiation) or from radioactive materials Pathologic stage placed directly in the tumor (internal or Includes the findings of the pathologist after implant radiation called brachytherapy). surgery. Most of the time, pathologic stage is Radiation therapy may be used to reduce the the most important stage since involvement size of a cancer before surgery, to destroy any of the lymph nodes can only be accurately cancer cells left behind after surgery, or, in evaluated by examining them under a micro- some cases, as the main treatment. scope.

86 Segmental mastectomy located by touch. Computerized equipment A type of breast-conserving surgery that maps the location of the mass and this is removes more breast tissue than a lumpectomy used as a guide to place the needle. (up to one-quarter of the breast). It is also called Supportive care a partial mastectomy or a quadrantectomy. Measures taken to relieve symptoms and Sentinel node mapping and biopsy improve quality of life, but that are not In a sentinel lymph node mapping and biopsy, expected to destroy the cancer. Pain medica- the surgeon injects a radioactive substance tion is an example of supportive care. and/or a blue dye into the area around the Supraclavicular lymph nodes tumor. Lymphatic vessels carry these materials Lymph nodes located in the area just above to the sentinel lymph node (also called the the collarbone. sentinel node). The doctor can see the blue dye or detect the radioactivity (with a Geiger Systemic therapy counter) in the sentinel node, which is cut out Treatment that reaches and affects cells and examined. If the sentinel node contains throughout the body; for example, chemo- cancer, more axillary lymph nodes are therapy. removed. But if it is free of cancer, the patient Tamoxifen can avoid additional axillary surgery and its This antiestrogen drug blocks the effects of potential side effects. estrogen on many organs, such as the breast. Side effects Blocking estrogen is desirable in some cases Unwanted effects of treatment, such as hair of breast cancer because estrogen promotes loss caused by chemotherapy or fatigue their growth. Recent research suggests that caused by radiation therapy. tamoxifen may lower the risk of developing breast cancer in women with certain risk Sonogram factors. During an ultrasound the computer trans- forms the echoes into a picture called a Toremifene sonogram. See ultrasound. Another antiestrogen drug, similar to tamoxifen. Stage A method of describing the size and location Ultrasound of cancer based upon characteristics of the High frequency sound waves used to produce tumor, the lymph nodes, and whether there is images of the breast. See sonogram. involvement of other organs. For a more comprehensive glossary, you may Stereotactic needle biopsy visit the American Cancer Society Web site at A method of needle biopsy that is useful in www.cancer.org some cases in which calcifications or a mass can be seen on mammogram, but cannot be

87 NOTES

88 The Breast Cancer Treatment Guidelines for Patients were developed by a diverse group of experts and were based on the NCCN clinical practice guidelines. These patient guidelines were translated, reviewed, and published with help from the following individuals:

Terri Ades, MS, APRN-BC, AOCN Dorothy Shead, MS Joan McClure, MS American Cancer Society National Comprehensive National Comprehensive Cancer Network Cancer Network Elizabeth Brown, MD National Comprehensive Kimberly Stump-Sutliff, MS, RN Cancer Network American Cancer Society

The original NCCN Breast Cancer Clinical Practice Guidelines were developed by the following NCCN Panel Members:

Robert W. Carlson, MD/Chair Elizabeth C. Reed, MD Daniel F. Hayes, MD Stanford Hospital and Clinics UNMC Eppley Cancer Center at University of Michigan The Nebraska Medical Center Comprehensive Cancer Center Benjamin O. Anderson, MD Fred Hutchinson Cancer Research Samuel M. Silver, MD, PhD Clifford Hudis, MD Center/Seattle Cancer Care Alliance University of Michigan Memorial Sloan-Kettering Comprehensive Cancer Center Cancer Center Harold J. Burstein, MD, PhD Dana-Farber/Partners CancerCare Mary Lou Smith, JD, MBA Mohammad Jahanzeb, MD Consultant St. Jude Children’s Research W. Bradford Carter, MD Hospital/University of Tennessee H. Lee Moffitt Cancer Center & George Somlo, MD Cancer Institute Research Institute at the University City of Hope Cancer Center of South Florida Britt-Marie Ljung, MD Richard Theriault, DO, MBA UCSF Comprehensive Cancer Center Stephen B. Edge, MD The University of Texas Roswell Park Cancer Institute M. D. Anderson Cancer Center Lawrence B. Marks, MD Duke Comprehensive Cancer Center William B. Farrar, MD John H. Ward, MD Arthur G. James Cancer Hospital & Huntsman Cancer Institute Beryl McCormick, MD RichardJ. Solove Research Institute at the University of Utah Memorial Sloan-Kettering at The Ohio State University Cancer Center Eric P. Winer, MD Lori J. Goldstein, MD Dana-Farber/Partners CancerCare Lisle M. Nabell, MD Fox Chase Cancer Center University of Alabama at Birmingham Antonio C. Wolff, MD Comprehensive Cancer Center William J. Gradishar, MD The Sidney Kimmel Comprehensive Robert H. Lurie Comprehensive Cancer Center at Johns Hopkins Lori J. Pierce, MD Cancer Center of Northwestern University University of Michigan University Comprehensive Cancer Center ©2006, American Cancer Society, Inc. No.940508

Reading Grade Level: 10th

1.800.ACS.2345 1.888.909.NCCN www.cancer.org www.nccn.org

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