Germline BRCA Mutation Does Not Affect Survival in Young-Onset Breast Cancer


By Will Boggs MD

NEW YORK (Reuters Health) - Overall survival in women with young-onset breast cancer does not differ according to BRCA mutation status, researchers from the UK report.

"The cancer management was the same for BRCA carriers or non-carriers, so standard of care works fine in the same proportion of patients and the prognosis is dictated by the first primary (at least for the duration of our study),” Dr. Diane M. Eccles from the University of Southampton told Reuters Health by email. “However, looking at the hazard ratio for death over time, this was increasing for BRCA carriers at the later time points.”

Younger women with breast cancer are more likely to have a pathogenic BRCA1 or BRCA2 mutation compared with women whose breast cancer develops at an older age. But whether germline mutations in BRCA1/BRCA2 have independent prognostic implications after an initial cancer diagnosis remains unclear.

Dr. Eccles and colleagues, in the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study, sought to determine the effect of inherited BRCA1 or BRCA2 mutations on overall survival and other outcomes in 2,733 women with young-onset breast cancer.

During a median follow-up of 8.2 years, contralateral breast tumors arose in 6% of women, including 18% of BRCA1 mutation carriers, 12% of the BRCA2 mutation carriers, and 4% of BRCA-negative patients, the researchers report in The Lancet Oncology, online January 11.

At two years, overall survival did not differ significantly between BRCA-positive women (97.0%) and BRCA-negative women (96.6%). Overall survival rates were also similar at five years (83.8% vs. 85.0%, respectively) and at 10 years (73.4% vs. 70.1%).

Analyses of distant disease-free survival yielded similar results, as did separate analyses of women with BRCA1 and BRCA2 mutations.

Among women with triple-negative breast cancer (TNBC), overall survival at two years was significantly better for BRCA-positive patients (95%) than for BRCA-negative patients (91%), but overall survival no longer differed between the groups at five or 10 years.

Results persisted in a post hoc analysis that excluded women with TNBC who underwent bilateral mastectomy within the first year after diagnosis.

“Physicians (and patients) should understand that the decision about bilateral risk-reducing mastectomy (BRRM), in most cases, will not affect the likelihood of successful treatment for the breast cancer,” Dr. Eccles explained. “In a woman who gets a breast cancer diagnosis and shortly after discovers she also carries a pathogenic BRCA1 or BRCA2 gene variant, the physician should take into account tumor prognosis, tumor stage, subtype, and optimum oncological treatment, e.g., whether radiotherapy is going to be part of the treatment, whether she has mastectomy or not, clinical trial participation, etc.”

“Half our patients had breast-conserving treatment and half mastectomy - mastectomy did not avoid radiotherapy in the majority,” she said. “Physicians should assess prior knowledge, experience, educational level, cancer related anxiety, and understanding of the purpose of surgery and try and get a perspective on the risk of new primary breast cancer and the difference between secondary and primary cancers (patients really struggle to grasp this).”

“Reassure patients that extensive surgery is not a necessary part of their cancer treatment and will not improve the chance of curing the cancer - and is a choice for BRCA carriers that in some people may be easier to make once their cancer treatment is complete and she is fully recovered both physically and psychologically,” Dr. Eccles added.

“The report of this study is surely only the beginning of a better understanding of young patients with breast cancer,” writes Dr. Peter A. Fasching from Friedrich-Alexander University Erlangen-Nuremberg, in Erlangen, Germany, in a linked editorial. “The interaction between pregnancies at a young age, other genetic causes such as predisposition genes, and associated pathways such as RANK/RANKL1 are just some topics which could be addressed after the POSH study.”


Lancet Oncol 2018.

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