Lumps, Bumps, Leaking and Pain I HAVE NO DISCLOSURES Management of Breast Conditions

Rebecca A. Jackson, MD Professor Department of Obstetrics, Gynecology and Reproductive Sciences University of California, San Francisco

Likelihood of Cancer in Dominant Plan by Age oPalpable breast mass 60% 50% 37% oNon‐Palpable breast mass 40% oMastalgia 30% 20% Nipple Discharge 9% o 10% 1% 0% <40 yo 41-55 >55 yo Of all discrete breast masses, about 10% are cancerous. (In contrast, 8% of abnormal mammos = cancer) Failure to diagnose breast cancer “Dominant Mass”? in a timely manner is a leading cause of malpractice claims o Discrete or dominant mass= stands out from adjoining breast tissue, definable Common reasons: borders, is measurable, not bilateral. o Unimpressive o Nodularity or thickening = ill‐defined, physical findings often bilateral, fluctuates with menstrual o Failure to f/u with pt cycle o Palpable mass with negative mammo o In women <40 referred for mass, only 1/3 had confirmed dominant mass

Breast Mass: Diagnostic Options Question 1 o Physical exam A 42 yr old woman with no family or personal history of breast cancer has o Ultrasound found a breast lump. She doesn’t know o Diagnostic Mammogram how long it has been there. It is not o Digital Breast Tomosynthesis (DBT) painful. o aspiration On exam, it is a discrete mass, 2 cm, o Fine needle aspiration relatively smooth, mobile and non‐tender. o Core needle biopsy She has no axillary lymphadenopathy. o Excisional biopsy What is your next step? Q1: Palpable mass in 42 yo Q1b: Palpable mass in 42 yo Next step (pick one)? A mammography was chosen and is A. Nothing now. Re‐examine in 1‐2 months negative. Next step (pick one)? B. Ultrasound A. Re‐examine in 1‐2 months C. Digital Mammography B. F/u 1 year for annual exam D. DBT: Digital Breast Tomosythesis C. Ultrasound E. Office aspiration D. Office aspiration F. FNAB (fine needle aspiration biopsy) E. FNAB G. Core biopsy F. Core biopsy

Q1c: Palpable mass in 42 yo Step 1: Palpable Breast Mass An ultrasound was chosen as the first step. It shows a cystic mass. Next step? oDetermine if mass is cystic or A. Re‐examine in 1‐2 months solid B. F/u 1 year for annual exam o Simple are benign and don’t C. Standard diagnostic mammogram require further evaluation D. DBT (digital breast tomosynthesis) o 20‐25% of palpable masses are simple E. Office aspiration cysts, most occurring in 40‐49 yo’s F. FNA o Options?: Ultrasound, office aspiration, FNA, core needle biopsy G. Core biopsy Breast Exam Ultrasound

o Nether sensitive (50‐60%) nor specific (60‐ o Primary Use: Classify mass as cystic or solid 90%) (even when done by experts) o Also can help to further classify mass via Bi‐ Cannot reliably distinguish cyst from solid (58% o Rads system for sono‐‐ but much less data on accuracy) risk of cancer assoc with each classification o Not reliable for determining if biopsy needed Guidance for cyst aspiration or biopsy o Nonetheless, it is important for determining if o mass is discrete (vs nodularity or thickening) o Adjunct to evaluate symmetric densities and for follow‐up of masses detected by mammography o Perform in 2 positions, methodical, spirals or strips Can be the first test performed & if cyst is o Mark mass prior to biopsy so others can find it o confirmed—the only test required

Fibroadenoma Cancer Cyst Cyst Aspiration o Simple office procedure: 20‐23 gauge needle and syringe, ultrasound guidance optional, specialized training not necessary o Primary Use: Confirm mass is cystic o Secondary use: Relieve pain/pressure due to Anechoic, well- symptomatic cyst circumscribed, Well-circumscribed, Irregular, deep superficial o Benefits: If cystic fluid obtained, establishes Ultrasound is 98-100% accurate for diagnosis of simple cysts. immediate diagnosis and provides However, for solid masses, it cannot reliably distinguish benign symptomatic relief from malignant. Cyst Aspiration (cont’d)

Adequate/reassuring if: 1. Cyst fully collapses (no residual mass) 2. Fluid is not brown/red (cloudy ok) 3. Does not re‐accumulate (i.e. frequent f/u) o If all are true, no need to send fluid. o F/u in 1‐3 months to ensure no reaccumulation or residual mass o If no fluid or if bloodyfurther workup

Fine Needle Aspiration: QUIZ Fine Needle Aspiration Biopsy o Primary Use: Diagnosis of solid masses o FNAB should be done by an experienced o Least invasive biopsy method cytopathologist or breast surgeon? ….TRUE OR o Sensitivity is operator dependent: FALSE? o For experienced personnel, 92‐98% o For untrained personnel, 75% Average (as low as 65%). o A diagnosis of FATTY TISSUE on FNA means o Experienced cytopathologist necessary to interpret what? o Cannot diagnose DCIS, atypical hyperplasia or infiltrating carcinoma. However, >90% there is o When should you FOLLOW‐UP a woman with a sufficient material to perform prognostic studies palpable mass and negative FNA and o A non‐diagnostic result in the setting of a discrete mammogram? mass requires further work‐up (possible sampling error) Palpable mass: Diagnostic Mammography Breast Cyst o Cannot accurately differentiate benign from malignant masses or cystic from solid Can’t distinguish cyst from solid on mammogram o Poor sensitivity in young women due to density o 15‐20% of mammos are normal in women with palpable mass o Primary Use: Screen opposite breast (in women >40 yo) and identify other non‐palpable suspicious areas o Secondary use: Further classification of the palpable mass EVEN IF THE MAMMO IS NORMAL, FURTHER WORK‐UP IS REQUIRED Cyst is anechoic on ultrasound

Breast Density Small Cancer

Spiculated mass Merriman’s: Waimea What about DBT? Digital Breast Tomosynthesis; “3D Mammography” o 3‐D depiction of breast using series of low‐dose digital mammograms at various angles o Better for delineating true lesions from spurious lesions caused by overlapping structures seen on routine mammography. o Higher radiation dose: sometimes twice as high b/c do both a digital mammogram and DBT are done o Newer techniques have lower radiation dose but upgrading is costly

Is Breast tomosynthesis (DBT) better than Pt with mass mammography for palpable mass? marked by BB. Difficult to see Too soon to say: Most studies have o well on mammo. been done in screening setting Distinct edges o But promising —especially in the on DBT. setting of dense breasts. U/S confirmed a o A few small studies show better cyst. characterization of lesions when used in diagnostic setting leading to fewer biopsies Conventional DBT Friedewald 2014 JAMA Radiol Clin North Am. 2010 Sep; 48(5): 917–929. Breast Tomosynthesis: Invasive ductal carcinoma: patient experience Subtle on mammo Spiculated edges well seen on DBT

Traditional Mammo DBT

Radiol Clin North Am. 2010 Sep; 48(5): 917–929.

Core Needle Biopsy o Primary Use: Diagnosis of solid Breast tomosynthesis: Radiology experience masses, f/u of non‐diagnostic FNAB o Can distinguish DCIS from invasive disease and because it is a tissue specimen, interpretation is easier (unlike FNA) o Few direct comparisons to FNAB for palpable lesions: o Preferred for Studies mixed for sensitivity‐ some biopsy non- showing FNA better and some with CNB better. Similar specificity. palpable lesions Question 1 So, what is the best first step? o First step = determine if cystic or solid. A 42 year old woman with no family or personal o How depends on your institution (availability and history of breast cancer has found a breast expertise of various services) and whether patient is lump. She doesn’t know how long it has been symptomatic there. It is not painful. o FNAB: Therapeutic, diagnostic and cost‐efficient On exam, it is a discrete mass, about 2 cm, o U/S: Similar in cost to FNAB, but FNAB more cost relatively smooth, mobile and non‐tender. She effective b/c 80% of masses are NOT cystic on U/S has no axillary lymphadenopathy. and will require FNAB to further evaluate o If FNAB not available: U/S first will eliminate What is your next step? need for core biopsy in 20% that do have cysts

Plate lunch, loco moco, and So, what is the best first step? malasadas o Office aspiration: Reasonable 1st step esp if symptomatic. If not cystic, will require biopsy o Mammography: not best 1st step b/c can’t reliably distinguish benign from malignant or cystic from solid (but is usually part of a complete evaluation) o F/U 1‐2 mos: Could be ok in young woman (<40) who will reliably follow‐up. Discuss options, get agreement, document well. If Honokaa, past Waimea on the mass persists, go to U/S or FNA. way to Hilo or Waipio Valley Step 2: for a cystic mass… Step 2: for a solid mass

o If symptomatic, aspirate Biopsy (FNA or core needle biopsy) o If diagnosed by ultrasound and no PLUS aspiration is done, f/u 1 year. Mammogram (to further characterize mass o If aspirated and fluid is not bloody, f/u 1‐ and to screen rest of breasts) 3 months to ensure no residual mass or o If both are negative, f/u 3‐6 months re‐accumulation If either is equivocal or results are not o For any patient >40, also get mammo for o screening (>50 recommend, >40 shared concordant, refer to breast surgeon for decision) further evaluation

Ultrasound F/u instead of Surveillance instead of biopsy for solid biopsy for solid mass? mass? o 2 small retrospective cohort studies—largest n=312 with palpable mass & U/S= “probably o Retrospective cohort study of 441 benign” patients with benign solid lesions by sono o Mostly young women so low pretest probability of (Birads 3 and 4A) cancer (avg age 34yo) o Excluded those with immediate biopsy o Strict criteria for calling lesion “probably benign” (300) leaving 141 who had surveillance. o 2 of 312 were cancer. NPV=0.6%. o 3 of 141 had cancer in f/u biopsy o Conclude ok to not biopsy and follow with q 6mo o Unacceptably high rate (but small u/s for 2 yrs (sim to f/u of birads3 mammo) retrospective study with incomplete f/u) o Caution: retrospective Park, Acta Radiologica, 2008 Giess, Ultrasound Med, 2012 How are we doing? Summary: Palpable Breast Mass o In a study of women with a palpable mass o Choice of work‐up often depends on and negative mammo, only 57% received availability and expertise of FNA, U/S and any subsequent evaluation. core needle biopsy o Latinas, obese and uninsured less likely to o None of these tests is 100% accurate, have any subsequent evaluation maintain a high index of suspicion o One study of delay in diagnosis found the o If any of test is discordant continue most common reason was inappropriate work‐up reassurance of women with a lump and o Frequent f/u even for masses thought to normal mammogram be benign to detect false negatives Haas, JGIM, 2005; Goodson, Arch Int Med 2002

Simple If aspirate and no Dominant U/S or residual lump, fluid Aspirate* cyst Breast Mass not bloody then do CBE 4-6 wks. If u/s, U/S or Aspirate* no further w/u. Solid or complex cyst Do FNA or core bx

Cancer Atypical, Benign Non- suspicious diagnostic Treat Positive Negative Mammo Mammo Core or Repeat FNA, core excisional More CBE 3-6 or excision biopsy imaging, core mos or excision bx biopsy Recommended Review: Kerlikowske, Annals Int Med, 2003 * Aspirate=office aspiration or FNAB Adapted from Kerlikowske, Ann Int Med, 2003 Q1b: Palpable mass in 42 yo Q1c: Palpable mass in 42 yo

A mammography was chosen and is negative. An ultrasound was chosen as the first step. Next step (pick one)? It shows a cystic mass. Next step? A. Re‐examine in 1‐2 months Mammo cannot A. Re‐examine in 1‐2 months B. F/u 1 year for annual exam distinguish cyst from B. F/u 1 year for annual exam C. Ultrasound solid and is negative in 15% with C. Office aspiration Simple cysts are benign D. Office aspiration palpable mass so D. FNA and no further work-up is E. FNA need to proceed with required. If the cyst is work-up from Step 1 E. Core biopsy symptomatic, may F. Core biopsy ie cyst vs solid aspirate in office.

Great Road Trip: Akaka Falls and/or Hawaii Tropical Botanical Work-up of non-palpable lesions Gardens

A few miles outside Hilo. Incredibly lush. Quintessential Hawaii BI-RADS: Breast Imaging Reporting and Data System Pre/Post Test Probability of cancer Follow-up of abnormal screening mammogram based on mammo results and age

If normal, repeat Consider breast exam screen 6 mos to see if lesion is Kerlikowske, Annals Int Med, 2003 then q 1-2 yrs palpable & biopsiable Kerlikowske, K. et. al. Ann Intern Med 2003;139:274-284

Breast Pain Kalopa State Park

o 2/3 -3/4 report it Short nature o > 1/2 of breast visits hike or up to 5 o Etiology unknown: not associated with prolactin, miles estrogen or progesterone levels Near o 2 types: cyclic & non-cyclic Honoka’a, 15 o Both types chronic, relapsing especially if severe miles past or early onset Waimea o Severe breast pain interferes with sex (46%), activity (36%), social (13%), work (6%) Mastalgia: Treatment Mastalgia: Treatment

Topical Proven in RCT’s: diclofenac No benefit (per RCT’s, NSAID’s (topical and oral) o Work‐up: goal is to reassure them its not very effective o though many are small and o Evening Primrose Oil likely underpowered) cancer; exam, mammo if >40 years Possibly o Iodine o Caffeine restriction effective, o Vitex agnus castus extract- o Vitamin E 1000 mg containing solution (VACS) o Vitamin B6 Determine effect on QOL bid-tid for o o Gestrinone (N/A in US) o Diuretics 2-3 months o Progesterone vaginal cream o Provera 60‐80% resolve spontaneously. o Bromocryptine o Most o Soya protein o Danazol effective o Isoflavones o Tamoxifen o Reassurance often sufficient but poorly tolerated Other: Supportive, well fitting bra, bra at night, trigger point injections for localized pain OCP’s—help some, make worse in others. If on OCP, try lower dose of Estradiol

Topical NSAID for mastalgia Mastalgia: Prescribing Guide

Diclofenac topical (Voltaren) q 8hr vs placebo Proven in RCT’s: cream. Randomized, double-blinded Very large decrease o **NSAID’s (topical diclofenac q 8hr very effective in in pain score 3 RCTs; oral NSAIDs—moderately effective in some but not all RCTS ) o Evening Primrose Oil: 1000mg tid for at least 1 mo trial, >$2/day, mild nausea. Recent meta-analysis showed no benefit o Bromocriptine: increase dose gradually to decrease side effects (nausea, dizziness, orthostatic hypotension, headache). 1.25 mg qhs, increase by 1.25 mg every week until 5 mg/day. o Danazol: best of the endocrine agents but virulizing side effects make it less desirable, teratogenic, expensive. Start at 200mg qd. Taper down as tolerated to 100mg every other day or qd during luteal phase.

Colac, Journal of the American College of Surgeons, April 2003 Mastalgia: Prescribing Guide Nipple Discharge

o Usually benign or malignant? benign Proven in RCT’s (continued): intraductal o Most common cause of unilateral discharge? papilloma o Tamoxifen: 10 mg qd, hot flashes, expensive o Other causes: duct ectasia, nipple eczema, Paget o Torimefin: 30 mg qd, vag d/c, irreg menses disease, breast cancer/DCIS o GnRH agonists: very expensive, menopausal side effects, can only use for 6 months due to bone loss. o If associated with mass, more likely to be cancer o Local Injections: trigger point injection of 1% (but cancer uncommonly presents with nipple d/c) lidocaine (1cc) and methyl prednisone (40mg). Half require second injection in 2-3 months. Paget’s Dz

Nice review: Bhavika, Am J Med 2015

Nipple Discharge Nipple Discharge: Diagnosis

Physiologic: Pathologic (Spont, unilat): Physiologic: o Isolate involved duct Pathologic: o History: running, o Due to galactorrhea (ie o Hemoccult to confirm o Papilloma, cancer breast stimulation increased prolactin) or blood, cytology not useful nipple stimulation o Prolactin, TSH o Mammography with With compression o Spontaneous o Meds: o retro-alveolar views o Multiple ducts o Single duct Psychotropics o Galactography vs MRI o Clear, yellow, white o Bloody o referral o No mass o Mass present Questions? Mastitis

o 2 types: lactating vs non‐lactating o Primary vs secondary (cellulitis, , hydradinitis, sebaceous cyst)

Cellulitis

Lactational Mastitis Non-Lactational Mastitis o Suspect in any breast-feeding o Difficult to treat woman with a fever and o Often chronic, recurrent malaise o Peri-areolar: young (avg o Often wedge shaped redness 32), 90% are smokers, over involved duct central pain, nipple o Staph, Strept—(community retraction and discharge, acquired MRSA becoming often assoc with more common so do culture o Peripheral: elderly, usually associated with of milk) underlying disease (diabetes) or trauma o Gram negatives, staph, strept, anaerobes Cancer can mimic mastitis Mastitis Treatment

Lactational Non-Lacatational o Increase feeding, o Include anaerobic warm compresses coverage o Keflex, Dicloxicillin o Clindamycin or o IV if not better Flagyl + Ancef or quickly Nafcillin o Septra or Clinda for community acquired MRSA Inflammatory ** Biopsy if recurrent or doesn’t resolve Cancer

Breast Abscess Core Needle Biopsy (cont’d)

o Suspect if “lump” on exam or if mastitis not o Like FNAB, requires responding to abx training to prevent false negatives due to Ultrasound to confirm o sampling error o Get culture o Used instead of FNAB by o Aspiration now consultant preference or preferred over I&D where cytopathology o Sometimes need service not skilled in repeated aspirations or interpretation drain o Also preferred for o I&D often assoc with poor cosmetic result or evaluation of non‐ fistula palpable lesions