Purpose The second International Consensus Conference on B3 lesions was held in Zurich, Switzerland, in March 2018, organized by the International Breast Ultrasound School to re-evaluate the consensus recommendations. Methods This study (1) evaluated how management recommendations of the first Zurich Consensus Conference of 2016 on B3 lesions had influenced daily practice and (2) reviewed current literature towards recommendations to biopsy. Results In 2018, the consensus recommendations for management of B3 lesions remained almost unchanged: For flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL) and radial scars (RS) diagnosed on core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB), excision by VAB in preference to open surgery, and for atypical ductal hyperplasia (ADH) and phyllodes tumors (PT) diagnosed at VAB or CNB, first-line open surgical excision (OE) with follow-up surveillance imaging for 5 years. Analyzing the Database of the Swiss Minimally Invasive Breast Biopsies (MIBB) with more than 30,000 procedures recorded, there was a significant increase in recommending more frequent surveillance of LN [65% in 2018 vs. 51% in 2016 ( p = 0.004)], FEA (72% in 2018 vs. 62% in 2016 ( p = 0.005)), and PL [(76% in 2018 vs. 70% in 2016 ( p = 0.04)] diagnosed on VAB. A trend to more frequent surveillance was also noted also for RS [77% in 2018 vs. 67% in 2016 ( p = 0.07)]. Conclusions Minimally invasive management of B3 lesions (except ADH and PT) with VAB continues to be appropriate as an alternative to first-line OE in most cases, but with more frequent surveillance, especially for LN.

ABCSG 8: NCT00291759.

No abstract

NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

International audienceMultigene assays have been developed and validated to determine the prognosis of breast cancer. In this study, we assessed the additional predictive value of the 70-gene MammaPrint signature for chemotherapy (CT) benefit in addition to endocrine therapy (ET) from pooled study series. For 541 patients who received either ET ( = 315) or ET + CT ( = 226), breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) at 5 years were assessed separately for the 70-gene high and low risk groups. The 70-gene signature classified 252 patients (47%) as low risk and 289 (53%) as high risk. Within the 70-gene low risk group, BCSS was 97% for the ET group and 99% for the ET + CT group at 5 years with a non-significant univariate hazard ratio (HR) of 0.58 (95% CI 0.07–4.98;  = 0.62). In the 70-gene high risk group, BCSS was 81% (ET group) and 94% (ET + CT group) at 5 years with a significant HR of 0.21 (95% CI 0.07–0.59;  < 0.01). DDFS was 93% (ET) versus 99% (ET + CT), respectively, in the 70-gene low risk group, HR 0.26 (95% CI 0.03–2.02;  = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17–0.71;  < 0.01). Results were similar in multivariate analysis, showing significant survival benefit by adding CT in the 70-gene high risk group. A significant and clinically meaningful benefit was observed by adding chemotherapy to endocrine treatment in 70-gene high risk patients. This benefit was not significant in low risk patients, who were at such low risk for recurrence and cancer-related death, that adding CT does not appear to be clinically meaningful

The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1–3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of the 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n = 219) and high-risk (n = 208) patients were 97.0% and 91.7%. The 5-year DRFI probabilities for AOL low-risk (n = 132) and high-risk (n = 295) patients were 96.7% and 93.4%. For 70-gene signature low-risk–AOL high-risk patients (n = 124), of whom 76% (n = 94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinicopathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.

557 Background: The ABCSG 28 Posytive trial compared primary surgery versus primary systemic therapy without surgery in stage IV breast cancer patients. The primary aim was to investigate whether immediate resection of the primary tumor followed by standard systemic therapy improves median survival compared with no surgical resection (NCT01015625). The trial had to be stopped early due insufficient recruitment. Methods: Untreated stage IV breast cancer patients with the primary in situ were randomly assigned to either surgery of the primary versus no surgery followed by systemic therapy between 2011 and 2015 in 15 breast health centers in Austria. Systemic therapy included endocrine therapy or chemotherapy. Patients were routinely followed every 3-6 months. Primary endpoint was median survival. Results: 90 patients (45 with surgery, 45 with primary systemic therapy without surgery) were randomized. Stratification criteria were age, endocrine responsiveness, her2 expression, planned first line therapy and bone only versus other metastases. Patients in the surgery arm had more cT3 breast cancer (22% versus 7%) and more cN2 staging (16% versus 4%) as well as more her2 positive breast cancer cases (27% versus 18%). The median follow up was 37.5 months and immunohistochemical subtype analysis showed 9% basal like, 22% her2 positive, 51% luminal A and 13% luminal B cancers. Both groups were well balanced regarding first line treatment (endocrine versus chemotherapy) however, there were more taxane treated patients in the no surgery group (24.4 versus 15.6%). The median survival in the surgery arm was 34.6 months versus 54.8 months in the no surgery arm without statistical significance (HR 0.691 CI 0.358 – 1.333; p=0.267). Time to distant progression was insignificantly longer in the no surgery arm (surgery arm 13.9 versus no surgery arm 29.0 months). Conclusions: This first analysis of the prospective randomized phase III trial POSYTIVE-ABCSG-28 demonstrated no benefit in overall survival for immediate surgery of the primary in de novo stage IV breast cancer patients. Clinical trial information: NCT01015625.

Purpose: To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrineresponsive breast cancer patients.Experimental Design: The PAM50 assay was performed on formalin-fixed paraffin-embedded wholetumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters.Results: PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: DLRc 2 15.32, P < 0.001; ROR-based risk groups: DLRc 2 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease. Conclusion: PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors. Clin Cancer Res; 20(5); 1298-305. Ó2014 AACR.