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Background: Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed., Methods: Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2-) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1-3 based on observed mitoses., Results: A total of 1292 ER+, HER2- invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0-14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009)., Conclusions: First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.

Background: The significance of androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is unclear, and published studies so far have been inconclusive., Methods: A tissue microarray was constructed using tissue obtained from 119 patients with primary TNBC and stained for AR expression. Other tissue types obtained included recurrent TNBC, normal breast tissue, adjacent ductal carcinoma-in situ (DCIS), lymph node (LN) and distant metastases. Positive AR expression was defined as ≥10% nuclear staining., Results: Epithelial tissue was present and evaluable in 94 TNBC patients with a total of 177 tissue cores. AR expression in TNBC was 22 of 94 (23%). AR expression was higher in normal breast tissue (88%) and adjacent DCIS (73% overall). All LN metastases from AR-positive TNBC patients were also AR positive; in addition, no AR-negative TNBC patient had AR-positive LNs. AR expression was associated with older patient age (63 vs. 57 years, respectively, p = 0.051) and LN metastases (p = 0.033). Locoregional recurrence and overall/disease-specific survival were similar between AR-positive and AR-negative patients, although AR-positive patients had more advanced disease. On multivariate analysis, the presence of LN metastases was associated with poorer recurrence-free survival in AR-positive patients (hazard ratio, 4.34) (p = 0.031)., Conclusions: The AR is expressed in normal breast tissue, and expression decreases with advancement to DCIS and invasive cancer. AR-positive TNBC was more common in older patients and had a higher propensity for LN metastases. AR-positive TNBC may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapies.

Excisional biopsy has been recommended for papillary lesions diagnosed on core needle biopsy (CNB) because a significant proportion of cases are upstaged to in situ/invasive cancer after surgical excision. The study goals were to identify patients at lowest risk of upstaging in whom excisional biopsy may potentially be avoided. We retrospectively evaluated 46 patients with a papillary lesion on CNB. Six patients were upstaged overall (13%), to intraductal papillary carcinoma (7%), invasive papillary carcinoma (4%), and mixed invasive ductal/lobular carcinoma (2%). The upstaging rate for patients with atypia on CNB was higher than for patients without atypia (33 vs 3%, P = 0.011). No patient younger than 65 years was upstaged to in situ or invasive carcinoma, and the mean lesion size was also higher among patients who were upstaged (P > 0.05). Patients younger than 65 years with small papillary lesions lacking atypia on CNB may therefore represent a low-risk group that may be offered close clinical and radiologic follow-up.

Introduction: Excisional biopsy is currently recommended for atypical ductal hyperplasia (ADH) diagnosed on core needle breast biopsy (CNB), due to risk of upstaging to invasive or in situ carcinoma (DCIS). The study goal was to identify patients who may potentially forego excisional biopsy if the risk of upstaging is low., Methods: We conducted a retrospective review of patients diagnosed with ADH on CNB who underwent excisional biopsy at one institution (5/2000-5/2011). We evaluated the upstaging rate and clinicopathologic factors associated with increased upstaging risk., Results: A total of 114 cases of ADH were diagnosed on CNB. The median patient age was 64 years. On mammography, a mass/density/area of distortion was present in 23 % of cases; calcifications were present in 77 %. Most biopsies (79 %) were performed stereotactically. Twenty lesions (18 %) were upstaged to infiltrating carcinoma (5 %) or DCIS (13 %). Residual ADH was present in 43 biopsies (38 %). On univariate analysis, significant variables associated with upstaging included age >50 years, a mass lesion on mammography, and shorter length of biopsy core (p < 0.05). No patient ≤50 years of age was upstaged. Three patients who were not upstaged (3 %) developed ipsilateral disease (2 DCIS and 1 infiltrating ductal carcinoma) at a median time of 37 months., Conclusions: The rate of upstaging when ADH is diagnosed on CNB at our institution is 18 %, and routine excisional biopsy is currently recommended for all patients. However, patients <50 years old with focal atypia only and no residual calcifications postbiopsy may represent a low-risk group who could potentially avoid excisional biopsy.

Background: Triple-negative (TN) breast cancers lack estrogen receptor (ER), progesterone receptor (PR), and HER2/neu amplification (HER2). Few studies have been dedicated to characterizing this subset of cancer., Materials and Methods: Retrospective review of a prospectively collected database of patients treated for invasive breast cancer at a single institution. Three tumor marker groups were compared: TN [ER-/PR-/HER2-], HER2+ [ERx/PRx/HER2+], and ER+ [ER+/PRx/HER2-]., Results: Over 8 years, 123 TN, 210 HER2+, and 728 ER+ patients were identified. On average, TN patients were younger (mean age TN 59.7, HER2+ 62.0, ER+ 64.5 years, P = 0.0001). They were referred for genetic testing more frequently (17% TN, 10% HER2+, 10% ER+, P = 0.055) and were most likely to have a BRCA mutation identified if tested (24% TN, 10% HER2+, 4% ER+, P = 0.019). TN tumors were larger (mean size 2.1 cm TN, 2.0 cm HER2+, 1.8 cm ER+, P = 0.031) and most commonly detected by breast exam (54% TN, 43% HER2+, 42% ER+, P = 0.025). Lymph node involvement was least common with TN tumors (21% TN, 37% HER2+, 32% ER+, P = 0.013), and angiolymphatic invasion was less common for TN than HER2+ (18% TN, 24% HER2+, 15% ER+, P = 0.006). TN patients had significantly higher local or regional recurrence (5.7% TN, 2.9% HER2+, 1.0% ER+, P = 0.001), and the worst 5-year overall survival, although this did not reach statistical significance (85% ± 6% TN, 94% ± 2% HER2+, 91% ± 2% ER+)., Conclusions: TN breast cancers are associated with unique patient presentations, tumor characteristics, and clinical outcomes of which clinicians and investigators should be aware.