Breast series • CLINICAL PRACTICE Ductal carcinoma in situ Management update Kirsty Stuart, BSc (Med), MBBS, FRANZCR, is a radiation oncologist, NSW Breast Cancer Institute, Westmead Hospital, New South Wales. John Boyages, MBBS, FRANZCR, PhD, is Associate Professor, University of Sydney, and Executive Director and radiation oncologist, NSW Breast Cancer Institute, Westmead Hospital, New South Wales. Meagan Brennan, BMed, FRACGP, DFM, FASBP, is a breast physician, NSW Breast Cancer Institute, Westmead Hospital, New South Wales. [email protected] Owen Ung, MBBS, FRACS, is Clinical Associate Professor, University of Sydney, and Clinical Services Director and breast and endocrine surgeon, NSW Breast Cancer Institute, Westmead Hospital, New South Wales. This ninth article in our series on breast disease will focus on ductal carcinoma in situ of the breast – a proliferation of potentially malignant cells within the lumen of the ductal system. An overview of the management of ductal carcinoma in situ including pathology, clinical presentation and relevant investigations is presented, and the roles and dilemmas of surgery, radiotherapy and endocrine therapy are discussed. The incidence of ductal carcinoma in situ that may present as a single grade or a inflammation. Myoepithelial stains are used (DCIS) of the breast has risen over the past combination of high, intermediate or low to help identify a breach in the duct lining. 15 years. This is in part due to the introduction grades. There are various histological patterns However, if there is any doubt, a second of screening mammography. The diagnosis of DCIS and more than one of these may be pathological opinion may be worthwhile. The and management of DCIS still pose many present in a single case. The most common information that is expected from a pathology dilemmas (Table 1). are the comedo, solid, papillary, cribriform report on DCIS is listed in Table 2. and micro-papillary types. The biological Natural history of DCIS What is DCIS? potential for a subsequent invasive carcinoma Ductal carcinoma in situ is a noninvasive may differ among the types of DCIS. Cells Ductal carcinoma in situ is considered a abnormal proliferation of milk duct epithelial of the comedo type are cytologically more precursor of invasive breast cancer. There is cells without light microscopic invasion of malignant, more likely to be high grade a 30–50% risk of untreated DCIS progressing the periductal stroma. While the cells appear than other types of DCIS and have a higher to invasive carcinoma in the ipsilateral breast malignant they are still within the confines proliferative rate.5 The typical histological 10–20 years after initial diagnosis.6 The of the ductal system and therefore defined features of low grade and high grade DCIS cumulative risk of contralateral breast cancer as in situ. Although in situ carcinoma has are shown in Figure 2, 3. is low (less than 1% per annum).7 the potential of evolving into an invasive Although in the majority of cases the When there is occult invasion or lymph tumour (Figure 1) it is not clear how often, diagnosis of DCIS is straightforward, DCIS vessel or node involvement, the tumour is and at what rate such lesions occur.1–4 Ductal may be difficult to differentiate histologically considered to be an invasive carcinoma. carcinoma in situ is defined as stage 0 breast from (benign) atypical ductal hyperplasia Occult invasion may be present in up to 20% cancer and is designated TisN0M0 in the (ADH) at one end of the spectrum, and of cases; up to 50% when the tumour is 50 tumour, nodes, and metastasis (TNM) cancer invasive carcinoma at the other. Early stromal mm or more.8 staging classification. invasion, for example, may be missed Ductal carcinoma in situ may recur after The hallmark of DCIS is the proliferation because of sampling error or distortion of treatment. Factors increasing the risk of local of what appears to be a single cell population the surrounding tissue due to fibrosis and recurrence after breast conservation include: Reprinted from Australian Family Physician Vol. 34, No. 11, November 2005 4 949 Clinical practice: Ductal carcinoma in situ – management update ‘indeterminate.’ A decision must be made Table 1. Dilemmas in ductal carcinoma in situ as to whether a biopsy should be performed or if follow up at a short interval is required. Diagnosis – is it DCIS? Comparison with previous mammograms is Imaging – is there correlation between imaging and the pathology? critical in such cases; often the only hint that Surgery – what to decide: mastectomy or breast conservation? microcalcification is related to DCIS is that Radiotherapy – when should radiotherapy be used? the cluster is new or increasing. Axillary surgery – is surgery to the axilla ever necessary? Microcalcification in DCIS may be associated with a mass or architectural distortion, and Tamoxifen – should tamoxifen be used? the presence of these increases the level of Recurrence – what is the optimal treatment of a recurrence? suspicion. Age and breast density affect the diagnostic yield, with microcalcification and other features of DCIS generally being more Normal Hyperplasia Atypia cells DCIS cancer Invasive cancer difficult to diagnose in young women and those milk duct too many cells becoming cells inside cells spread with dense breast tissue.15 abnormal the duct out of the duct Breast ultrasound may not show the microcalcification and may therefore not contribute significant additional information. However, ultrasound may be helpful if the calcifications are associated with a mass. Ultrasound showing typical malignant features Figure 1. Progression from normal duct to DCIS (malignant cells contained within the duct) to invasive such as irregular margins, heterogeneity, and carcinoma (malignant cells invading though the wall of the duct into the parenchyma beyond) posterior shadowing raises the possibility of an area of invasion. • young age at diagnosis common for DCIS to present with a palpable Fine needle aspiration biopsy (FNAB) is a • increasing tumour size mass (detected by the patient or by her doctor cytological test that has the ability to detect • positive margins at clinical examination), nipple discharge or malignant cells, but is unable to differentiate • high grade tumours, and Paget disease of the nipple.14 Uncommonly, with certainty between DCIS and invasive • the omission of radiotherapy. DCIS may be an incidental finding following breast cancer. Core biopsy provides Previous reviews from the NSW Breast benign or prophylactic breast surgery. histopathology, the architecture of which Cancer Institute have examined these factors Ductal carcinoma in situ is usually may confirm a diagnosis of DCIS or invasive in more detail.7,9,10 After treatment for DCIS, detected as an area of microcalcification on disease. This may allow a surgeon to perform half the recurrences following surgery with mammography. However, microcalcification definitive one-step surgery, including axillary or without radiation are invasive carcinoma, is an extremely common finding in the breast surgery based on the presence of invasion. while half are DCIS.10,11 and usually has a benign cause. Magnification Note that the presence of DCIS alone in core views are usually required to fully characterise samples does not rule out the possibility of Clinical presentation and investigations the features. Microcalcification related to invasive disease elsewhere in the breast. DCIS is typically clustered, with a granular, The surgeon’s dilemma is to determine Before commencement of screening heterogeneous appearance. It is classically where the tumour is located and how mammography in Australia, DCIS made up in a ‘ductal’ distribution, often tracking extensive the lesion is. While DCIS is usually 2% of all newly diagnosed breast cancers.12 toward the nipple. The individual pieces of detected as an area of microcalcification, it It usually presented with a palpable mass calcification may be rod-shaped, or branching, is known that not all DCIS will calcify. The or was associated with another abnormality taking the shape of the duct (Figure 4a, b). size of a cluster of microcalcification on such as nipple discharge or Paget disease of Microcalcification related to benign processes, mammography may therefore underestimate the nipple, with or without a mass. It now on the other hand, tend to be scattered rather the true extent of the lesion. High grade DCIS represents around 18% of all newly diagnosed than clustered, and the individual ‘specks’ is more likely to calcify and there is better breast cancers detected by BreastScreen, are more likely to be uniform in size and correlation between imaging and pathology Australia’s national screening program.13 shape. Often microcalcification has many size in such lesions. Most patients with DCIS are now detected benign features combined with more There is a high correlation between the by screening mammography. It is less concerning features, making its appearance mammographic pattern of calcification and 950 3Reprinted from Australian Family Physician Vol. 34, No. 11, November 2005 Clinical practice: Ductal carcinoma in situ – management update the grade of DCIS.16 Specifically, there is a Table 2. Minimum requirements in a pathology report high correlation between radiological and pathological extent for high grade lesions Specimen (84% of cases with less than 20 mm • Size of specimen disparity), but a lesser correlation for low • Laterality grade lesions. Later it was