Non-mammary metastases to the breast and axilla are rare occurrences. However, they are important diagnostic considerations as their treatment and prognosis differ significantly from primary breast cancer. Between 1990 and 2010, we identified a total of 85 patients, 72 women and 13 men, with non-mammary malignancies involving the breast, axilla, or both. The tumor types consisted of carcinoma (58%), melanoma (22%) and sarcoma (20%). Ovary was the most common site of origin for carcinoma, and metastatic high-grade ovarian serous carcinoma was most frequently misdiagnosed as a primary breast carcinoma. Melanoma was the single most common non-carcinomatous tumor type to involve the breast and/or axilla, and uterine leiomyosarcoma was the most common type of sarcoma. Most patients (77%) had other metastases at the time of diagnosis of the tumor, but in 11% the breast or axillary lesion was the first presentation. Without a clinical history, non-mammary metastases were difficult to diagnose because the majority of cases presented with a solitary nodule and lacked pathognomonic pathologic features. There were, however, certain recurrent histological findings identified, such as the often relatively well-circumscribed growth pattern of the metastatic lesion surrounded by a fibrous pseudocapsule, and the absence of an in situ carcinoma. Overall, these patients had poor survival; 96% of patients with follow-up available are dead of disease, with a median survival of 15 months after the diagnosis of the breast or axillary lesion. This finding emphasizes the need to accurately identify these tumors as metastases in order to avoid unnecessary procedures and treatments in these patients. Keywords: axilla; breast; extramammary Metastases to the breast and axilla are rare and account for approximately 2% of all mammary malignancies. 1,2 The most common metastatic lesion to involve the breast is a metastasis from a contralateral mammary cancer. 1,2 If hematologic malignancies are also excluded, the number of non-mammary metastases drops to well below 1%. 1,3 Owing to the frequency of primary breast cancers and the rarity of non-mammary tumors involving the breast, a newly discovered lesion in the breast or axilla is usually presumed to be a primary or metastatic breast carcinoma. However, the recognition of non-mammary metastases to the breast and axilla is very important, as both the treatment and prognosis differ significantly. Materials and methodsAfter obtaining approval by our Institutional Review Board, we searched the pathology database of Memorial Sloan-Kettering Cancer Center between the years 1990-2010 for patients with non-mammary metastases to the breast and axilla. Hematologic malignancies were excluded, as they are systemic diseases. The medical records and pathology slides, when available, were reviewed and the clinicopathologic characteristics were recorded. Patient age, gender, primary tumor site, the presence of other metastases, laterality, number of lesions, interval from primary tumor diagnosis to breast/ a...

Mesothelin is a cell surface associated antigen expressed on mesothelial cells and in some malignant neoplasms. Mesothelin-targeted therapies are in phase I/II clinical trials. The clinicopathologic and prognostic significance of mesothelin expression in triple negative breast carcinomas (TNBC) has not been fully assessed. We evaluated the expression of mesothelin and of basal markers in tissue microarrays of 226 TNBC and 88 non-TNBC and assessed the clinicopathologic features of mesothelin-expressing breast carcinomas. Furthermore, we investigated the impact of mesothelin expression on the disease-free and overall survival of patients with TNBC. We found that mesothelin expression is significantly more frequent in TNBC than in non-TNBC (36% vs 16%, respectively; p = 0.0006), and is significantly correlated with immunoreactivity for basal keratins, but not for EGFR. Mesothelin-positive and mesothelin-negative TNBC were not significantly different by patients’ race, tumor size, histologic grade, tumor subtype, lymphovascular invasion and lymph node metastases. Patients with mesothelin-positive TNBC were older than patients with mesothelin-negative TNBC, developed more distant metastases with a shorter interval, and had significantly lower overall and disease-free survival. Based on our results, patients with mesothelin-positive TNBC could benefit from mesothelin-targeted therapies.

Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor (ER)-positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions.

Early-stage breast cancer patients with minimal sentinel node disease experience excellent outcomes without ALND, whether they undergo BCS or TM.

Background Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. Design We searched the 1992–2012 pathology database for FELs in females 18 years old or younger (F≤18y). Seven FELs from 1975–83 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records. Results Forty-eight F≤18y had 54 FELs with available slides. Thirty (67%) pts were Caucasian, 12 (27%) African-American, two (4%) Hispanic, one (2%) Asian; three were of unknown race/ethnicity. Median age at diagnosis was 16 y. Median age at menarche was 12 y; most (96%) FELs occurred after menarche (median interval 48 months). All pts underwent lumpectomy; one required subsequent mastectomy. The FELs were 34 fibroadenomas (FAs) (11 usual, 23 juvenile), and 20 phyllodes tumors (PTs) (16 benign, one borderline and three malignant). Eight (35%) juvenile FAs showed slight intratumoral heterogeneity. The mean mitotic rate was 1.3 mitoses/10 high-power fields (HPFs) (range, 0–6) in usual FAs, 1.8/10 HPFs in juvenile FAs, 3.1/10 HPFs in benign PTs, 10/10 HPFs in the borderline PT and 17/10 HPFs in malignant PTs. The mean follow-up for 29 pts with 33 FELs was 44 months. Two (10%) PTs recurred locally (a benign PT at 18 months, and a borderline PT at 11 months). Both recurrent PTs had microscopic margins <1 mm. Conclusion Mitotic activity in FAs from adolescents can be substantial and this finding should be interpreted cautiously. Awareness of the morphologic features of FELs in adolescents is important to avoid overdiagnosis of PTs, which can lead to additional unnecessary and potentially disfiguring surgery.

Background The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are very different. Yet there are “borderline” breast lesions that have characteristics of both ADH and DCIS. We examined interobserver diagnostic variability for such lesions and correlated pathologic features of the lesions with clinical outcomes. Methods We identified all cases of borderline ADH/DCIS lesions treated at our center from 1997 to 2010. Five specialized breast pathologists blinded to clinical outcomes independently reviewed all available slides from each case and were instructed to classify each as benign, ADH, or DCIS. A majority diagnosis (MajDx) was defined as a diagnosis agreed upon by ≥3 pathologists. Results A total of 105 women with borderline ADH/DCIS and slides available for review were identified. The MajDx was ADH in 84 (80%), and DCIS in 18 (17%). There were split diagnoses in 3 (3%). MajDx of DCIS correlated significantly with lesion size and nuclear grade. There was diagnostic agreement by all 5 pathologists in 30% of cases, 4 pathologists in 42%, and 3 pathologists in 25%. At a median follow-up of 37 months, 4 (3.8%) patients developed subsequent ipsilateral breast carcinoma (2 invasive, 2 DCIS); all 4 cases had MajDx of ADH. Conclusions Borderline ADH/DCIS represents an entity for which reproducible categorization as ADH or DCIS cannot be achieved. Furthermore, histologic features of borderline lesions resulting in MajDx of ADH vs. DCIS are not prognostic for risk of subsequent breast carcinoma.

BACKGROUND: Randomized data suggest that axillary clearance is not necessary in select, clinically lymph nodenegative women with positive sentinel lymph node (SLN) biopsies (SLNBs) who undergo breast-conserving surgery or receive whole-breast radiotherapy and systemic therapy. The additional value of axillary radiotherapy in these patients is unknown. METHODS: The authors identified 326 patients with positive SLNBs who underwent breast-conserving surgery without axillary lymph node dissection from 1997 to 2009. SLN tumor deposits measured 0.2 mm in 58% of patients, 0.3 to 2.0 mm in 35% of patients, and >2 mm in 7% Patients. Ninety-three percent of patients received adjuvant radiotherapy. Radiation fields were categorized as standard tangents, high tangents, comprehensive (tangents plus supraclavicular), or partial breast to reflect coverage of the axilla. Standard tangents included both prone and supine positions. Regional failure was defined as recurrence in the ipsilateral supraclavicular, axillary, or internal mammary lymph nodes. RESULTS: The median follow-up was 55 months (range, 1-158 months). The 4-year rates of regional control, local control, disease-free survival, and overall survival were 99%, 98%, 95%, and 91%, respectively. Three patients had regional recurrences. Two of those patients received adjuvant radiotherapy with standard supine tangents, and 1 patient did not receive radiotherapy. No regional recurrences occurred among 66 patients who received radiotherapy in the prone position. CONCLUSIONS: Regional control was high (99% at 4 years) in patients who had low-volume SLN disease who did not undergo axillary dissection, regardless of whether the axilla was irradiated. Whole-breast radiation alone, including in the prone position, is sufficient treatment after breast-conserving surgery for select patients with tumor-containing SLNs who omit axillary dissection.

Purpose Breast carcinoma in young women aged less than 40 years attracts a disproportionate level of mainstream media coverage, and there is a gap between societal perceptions of the disease as a growing problem, and epidemiologic trends. Several population studies have suggested that the overall incidence of breast carcinoma in young women is stable, while one study suggested that the relative proportion of breast carcinoma in young women that is metastatic at diagnosis is growing. We sought to establish whether these trends were apparent at our institution. Methods In this study, the clinical database at a breast carcinoma tertiary center was reviewed in terms of clinicopathologic data on patient age, diagnosis, clinical and pathologic stage, hormone receptor status and HER2 overexpression status for the period 2000–2011. Results Over the study period, young patients represented a decreasing proportion of all breast carcinoma cases (10.8% [2000–2003] to 8.7% [2008–2011]; p <0.0001). Young patients were more likely than patients aged forty years or older to present with metastatic disease (6.1% vs 4.4%; p = 0.0004), to be triple negative (21.6% vs 13 %; p < 0.001) or to be HER2 positive (HER2+) (24.3% vs 14.8%, p <0.01). Young patients with HER2+ cancers were significantly more likely to present with metastatic disease (8.3% vs 5%; p = 0.001). Conclusions This study showed no demonstrable increase in the relative proportion of breast cancer occurring in patients aged < 40 years over the twelve year period 2000–2011 and no increase in the proportion of young patients presenting with metastatic disease.