Young women who carry the BRCA1 and/or BRCA2 mutation and develop breast cancer seem to have similar survival compared with young women who have BRCA-negative breast cancer. However, women with BRCA-positive triple-negative breast cancer have an 11% survival advantage compared with those with BRCA-negative breast cancer, according to the results of a study presented at the 2016 San Antonio Breast Cancer Symposium.1 The study showed that patients with BRCA-positive breast cancer may safely delay bilateral mastectomy, since an immediate bilateral mastectomy within the first year of diagnosis did not affect survival.
The literature is conflicting…with incomplete data on BRCA testing [and its effect on outcomes]. These findings provide a good evidence base for helping patients who are BRCA carriers make informed decisions about treatment and extent of surgery.— Diana M. Eccles, MD
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“These findings provide a good evidence base for helping patients who are BRCA carriers make informed decisions about treatment and extent of surgery. There is no significant difference in survival between BRCA carriers and noncarriers in young breast cancer patients, but there is a consistent 11% difference in overall survival in favor of BRCA-gene carriers presenting with triple-negative breast cancer. Bilateral mastectomy soon after diagnosis does not improve survival in young BRCA-gene carriers with breast cancer. This study shows that for a newly diagnosed symptomatic patient with triple-negative cancer who discovers after diagnosis that she is a BRCA gene carrier, addition of a major surgical procedure during the cancer treatment period does not improve survival chances further. Consideration of risk-reducing surgery can be delayed until after all cancer treatment is complete,” stated Diana M. Eccles, MD, of the University of Southampton School of Medicine, UK.
“The effect of being a BRCA carrier on outcomes is an important question, but the literature is conflicting and includes retrospective studies with incomplete data on BRCA testing. We designed the Prospective Study of Outcomes in Sporadic and Hereditary Breast Cancer [POSH] to answer the question of the effect of carrier status on outcome,” Dr. Eccles explained.
The POSH investigators recruited 2,956 women younger than age 40 at diagnosis of invasive breast cancer from 126 National Health Service oncology clinics in the UK between 2000 and 2008. A total of 2,759 with BRCA test data were included in the final analysis.
Most patients had blood sampled during the primary treatment period. Oncology management was per national UK guidelines. The investigators gathered comprehensive diagnosis and treatment data, as well as long-term follow-up data, and they had DNA test results on 285 patients. Also, data were collected on whether or not patients were referred for genetic consultation and testing.
Of the 2,956 patients, 8 (0.3%) were known BRCA carriers prior to diagnosis; 314 patients (11%) were referred after diagnosis for genetic testing. Of these 314 patients, 131 (42%) had detectable BRCA mutations (84 with BRCA1 and 47 with BRCA2); 379 patients (about 14% of the entire sample) had either BRCA1 or BRCA2 mutations (212 had BRCA1, 170 had BRCA2, and a few had both mutations).
BRCA1 carriers were significantly younger than BRCA2 carriers, had larger tumors, and were more likely to have triple-negative breast cancer (53% vs 10%, respectively), whereas BRCA2 carriers were more likely to have node-positive (36% vs 59%, respectively), estrogen receptor–positive disease (27% vs 83%, respectively), and HER2-positive disease (9% vs 16%, respectively).
No difference in survival was observed between BRCA carriers and non-BRCA carriers or between just the 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. “The study was well powered to detect a significant survival difference,” Dr. Eccles told listeners.
The 511 patients with triple-negative breast cancer (19% of the whole sample) were analyzed separately. A clear 11% difference in survival favoring BRCA carriers was observed at 2 years, with this advantage sustained to 10 years.
Among the triple-negative patients, 128 had BRCA-positive disease and 383 had BRCA-negative disease; 55% of BRCA-positive and 60% of BRCA-negative triple-negative patients had breast-conserving surgery; 6% of all triple-negative patients had bilateral mastectomy: 19 (15%) of BRCA-positive patients and 10 (5%) of BRCA-negative patients; anthracycline was given to 70% and 67%, respectively; and anthracycline plus taxane was given to 26% and 31%, respectively.
A total of 29 patients (6%) with triple-negative disease had bilateral mastectomy within the first year of diagnosis (19 BRCA carriers [15%] vs 10 noncarriers [5%]). The percentages of patients having bilateral mastectomy in the overall trial were similar to those in the triple-negative subgroup.
There was no survival benefit associated with immediate bilateral mastectomy (within the first year of diagnosis), so this intervention did not explain the survival advantage in the triple-negative cohort.
Some audience members were surprised by the survival advantage in triple-negative BRCA-positive patients. ■
Disclosure: Dr. Eccles is an occasional consultant for AstraZeneca.
1. Eccles DM, Copson ER, Maishman T, et al: Does BRCA status affect outcome in young breast cancer patients? Results from the prospective study of outcomes in sporadic and hereditary breast cancer (POSH). 2016 San Antonio Breast Cancer Symposium. Abstract S2-03. Presented December 7, 2016.
The take-home message from the POSH trial is that by using treatment that is still standard of care, [patients with] BRCA-positive breast cancer have outcomes that are not worse than BRCA-negative patients.— Leif Ellisen, MD, PhD
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