Young women who carry the BRCA1 and/or BRCA2 mutation and develop breast cancer appear to have outcomes similar to those who are BRCA-negative, according to the results of the Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH) trial, which were recently presented at the 2016 San Antonio Breast Cancer Symposium (SABCS).
The findings were different, however, for women with BRCA-positive, triple-negative breast cancer. Women in this group were found to have an 11% survival advantage compared with those with BRCA-negative breast cancer, an effect that was observed at 10-year follow-up. The researchers also discovered that immediate bilateral mastectomy within the first year of diagnosis did not affect survival, suggesting that patients can safely delay bilateral mastectomy.
“It’s important to know if BRCA has an independent prognostic effect to help patients make informed choices about their treatment, particularly the extent of surgery that may be necessary to manage presenting cancer,” said lead investigator Diana M. Eccles, MD, Professor of Cancer Genetics at the University of Southampton, UK.
“Even today, the literature remains conflicting, partially because the published studies are based on retrospective analyses with their inherent and multiple biases, and because on the whole, they have incomplete clinical data and incomplete BRCA testing data,” she said.
The POSH Trial
The POSH trial is a multicenter, prospective, observational cohort study designed to identify factors that may affect prognosis in young patients with breast cancer.
The trial enrolled 2956 British patients aged ≤40 years with a diagnosis of invasive breast cancer who were recruited from 127 oncology centers between 2000 and 2008. The researchers collected patient characteristics, family history, breast cancer risk factors, tumor pathology and treatment information, and blood DNA at the time of recruitment. Follow-up data, including risk recurrence data and risk-reducing surgery data, were collected at 6 and 12 months, then annually. The analysis presented at SABCS included 2759 patients, of whom 379 had either BRCA1 (n = 212) or BRCA2 (n = 170) mutations.
A preplanned subanalysis looked at patients with triple-negative breast cancer. At the time of the SABCS presentation, current BRCA1 data were available for 542 patients with triple-negative tumors.
Pathogenic BRCA1 mutations were identified in 122 patients (BRCA1-positive); 420 had no BRCA1 mutation (BRCA1-negative). BRCA1-positive women were younger than BRCA1-negative women (median age, 34 vs 36 years; P <.001) and were more likely to have a positive family history (P <.001).
There were no significant differences between BRCA1-positive and BRCA1-negative status in terms of median tumor size (20.8 mm vs 23.0 mm); tumor grade distribution (95.8% grade 3 vs 93.6%); nodal involvement (35.2% node-positive vs 39.9% node-negative); or presence of metastases at diagnosis (0.0% vs 1.0%).
No difference in survival was observed between BRCA carriers and non-BRCA carriers (or between BRCA1 or BRCA2 carriers and noncarriers)—at a median follow-up of 8.2 years. Ten-year survival rates were 69.74% for BRCA-negative patients and 72.85% for BRCA-positive patients.
Among the 511 patients with triple-negative breast cancer (19% of the whole sample), a clear 11% difference in survival favoring BRCA carriers was observed at 10 years. The maximum benefit among the BRCA carriers in this group occurred during the first 2 years on multivariate analysis (hazard ratio [HR], 0.45; P = .006). BRCA-positive and BRCA-negative patients with triple-negative disease had similar usage of breast conservation, unilateral mastectomy, and anthracyclines with or without taxanes, noted Dr Eccles. As expected, more patients who were BRCA carriers had bilateral mastectomy <1 year after diagnosis compared with the BRCA-negative population with triple-negative disease (15% vs 3%; P <.001). When excluding patients who had bilateral mastectomy from the analysis, the survival advantage among the BRCA carriers improved to 13% at 10 years, with an HR of 0.37 at 2 years (P = .002). “Bilateral mastectomy soon after diagnosis does not improve survival in young BRCA gene carriers,” Dr Eccles said.
“These are very small numbers and we have to be careful, but I think this is good news for patients because many patients believe that being a BRCA gene carrier or even having a family history is going to give them an adverse prognosis, and that’s clearly not true, and it’s also important for patients who are facing the difficult decisions around chemotherapy and breast cancer treatment don’t feel compelled to make a decision about bilateral mastectomy within that time shortly after their diagnosis, and can reasonably reserve judgment about the extent of surgery until a later date,” she added.