Selecting postoperative adjuvant systemic therapy for early-stage breast cancer: An updated assessment and systematic review of leading commercially available gene expression assays.

Gene expression assays (GEAs) can guide treatment for early-stage breast cancer. Several large prospective randomized clinical trials, and numerous additional studies, now provide new information for selecting an appropriate GEA. This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®). The comprehensive dataset available provides a contemporary opportunity to assess each GEA's utility as a prognosticator and/or predictor of adjuvant therapy benefit.

Intraoperative ultrasound margin evaluation as a tool to reduce positive superficial margins in nipple and skin sparing mastectomy in breast cancer patients.

BACKGROUND: Intraoperative ultrasound (IOUS) guided conservative surgery has been shown to reduce rates of positive margins in breast cancer. The aim of the study is to evaluate the feasibility of using IOUS to assess superficial/anterior margins in nipple and skin sparing mastectomy (NSM/SSM) and its impact on reducing rates of positive margins. METHODS: This prospective study includes all breast cancer patients who had an indication for NSM/SSM at our Institution. Superficial margin width was measured by IOUS before surgery and the area marked on the skin. Same measurement was performed afterwards in the mastectomy specimen. Any superficial margin < 5 mm was re-excised intraoperatively following the mark on the skin. RESULTS: Fifty-nine patients were included, 47 patients (79.7%) underwent NSM, and 12 patients (20.3%) a SSM. Of the 59 patients, 23 (38.98%) had margins ≥5 mm and 36 patients (61.02%) had margins of ≤5 mm. Of the 36 patients with superficial margins ≤5 mm, 20 had margins <2 mm, and 6 of them had intraoperative involved superficial margins in final pathology. However, after IOUS-guided re-excision, final pathology showed no involved margins. A 2 mm margin was set as the cut-off point for performing an intraoperative re-excision. IOUS guided re-excisions for intraoperative margins ≤2 mm significantly reduced the risk of close/positive margins in final pathology, p < 0.0001. CONCLUSION: The results showed that IOUS margin evaluation significantly reduced the rate of superficial positive margins in NSM/SSM. It is feasible and effective and may avoid challenging reoperations and/or additional radiation therapy for positive margins.

Intraoperative assessment of sentinel lymph node by one-step nucleic acid amplification in breast cancer patients after neoadjuvant treatment reduces the need for a second surgery for axillary lymph node dissection.

PURPOSE: Sentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). Intraoperative assessment of SLN by frozen sections can produce false negative results. The aim of this study was to compare two different techniques of intraoperative assessment of SLN in breast cancer patients treated with NAC: frozen section (FS) and molecular assay (OSNA). METHODS: A multicenter cohort of 320 consecutive breast cancer patients treated with NAC between 2010 and 2014 was analyzed. FS was performed intraoperatively in 166 patients (H&E cohort) and OSNA in 154 patients (OSNA cohort). RESULTS: A mean of 2.15 SLNs by FS and 1.22 SLNs by OSNA was assessed (p = 0.03). SLN metastasis was found in 44 patients (26.5%) by FS and in 48 (31.2%) by OSNA (p = 0.4). There was no statistical significance in rates of macrometastasis (75%), micrometastasis (20.5%) or ITCs (4.5%) when assessed by FS compared to OSNA (52.3%, 36.3% and 11.4%, respectively) (p = 0.06). There were 10 patients in the H&E cohort with positive-SLN in the definitive pathology assessment with negative intraoperative FS. When OSNA and definitive pathology were compared, there were no differences in rates of macrometastasis (61.1%), micrometastasis (33.3%) nor ITCs (5.6%) (p = 0.5). Fifty-four patients in the H&E cohort and 44 in the OSNA cohort had ALND after positive-SLNs. ALND was performed in a second surgery in 10 patients (18.5%) in the H&E cohort for intraoperative FS false negative results, 90% being micrometastasis. 42 out of 44 patients (95.5%) in the OSNA cohort had an ALND in the same surgery (p = 0.03). CONCLUSIONS: OSNA assay detects SLNs metastases as accurately as conventional pathology in the NAC setting. Intraoperative definitive assessment of the SLN by OSNA reduces the need for a second surgery for ALND in 18.5% of breast cancer patients with a positive-SLN after NAC.

Different Prognostic Implications of Residual Disease After Neoadjuvant Treatment: Impact of Ki 67 and Site of Response.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) can be used as an independent prognostic factor in neoadjuvant trials. The objective of this study was to determine the impact of Ki 67 expression and site of response on overall survival (OS) and disease-free survival (DFS) across different molecular subtypes of breast cancer following NAC. METHODS: Records from 357 patients who received NAC from 2004 to 2011 were reviewed. Univariate and multivariate analyses were performed to analyze clinical and pathological factors that influence pCR and DFS. RESULTS: Mean follow-up time was 45 months (range 12-112). pCR was achieved in 82 patients (23 %). According to molecular subtypes, rates of pCR were significantly higher for patients with HER2-positive and triple-negative tumors (69.4 and 32.7 %, respectively; p < 0.001) compared with other molecular subtypes. pCR was a predictive factor of longer OS and DFS. The hazard ratio for DFS in patients with positive lymph nodes (ypN1) after NAC was 2.48 (95 % confidence interval 1.47-4.19). Multivariate analysis showed that molecular subtype, changes in Ki 67 expression, and axillary lymph node response were significantly predictors of OS and DFS. CONCLUSIONS: pCR in the axilla and posttreatment changes in Ki 67 after NAC are associated with improved survival. Depending on axillary staging before NAC, detection of minimal residual disease-defined as the presence of isolated tumor cells in the SLN after NAC-may confer different prognosis. Further studies are needed to tailor treatments for patients with residual disease after NAC.