Breast cancer patients carrying a BRCA1 mutation had significantly worse recurrence and survival rates than patients without BRCA mutations or with a BRCA2 mutation, research said.

Data from a large Dutch study found that women with a BRCA1 mutation were 1.5 times more likely to see a breast cancer recurrence, and 1.4 times more likely to die from breast cancer at 15 years’ follow-up compared with noncarriers, according to Marjanka K. Schmidt, PhD, of the Netherlands Cancer Institute in Amsterdam, and colleagues.

Survival rates were no different among patients with a BRCA2 mutation (who respond better to treatment than those with a BRCA1 mutation), nor was there a difference among noncarriers, Schmidt reported at the American Association for Cancer Research annual meeting.

Previous studies investigating survival differences between women with BRCA1 or BRCA2 mutations and those without a BRCA mutation, or noncarriers, have been inconsistent, Schmidt said.

“Patients are treated on the basis of their tumor characteristics, not on their BRCA status,” she said. “If we could show that BRCA status, independent of tumor characteristics, is predictive of prognosis, this could be taken into account in prediction models and could facilitate treatment decisions.”

Schmidt and colleagues evaluated BRCA status, recurrence, and survival among 5,518 breast cancer patients who were diagnosed before age 50. All patients were treated at cancer clinics in the Netherlands.

The researchers tested patients’ samples for 78 different inherited BRCA1 or BRCA2 mutations and linked those to long-term outcome during a mean follow-up of 11.3 years. They found that 3.6% of the patients had a BRCA1 mutation and 1.2% had a BRCA2 mutation.

Among BRCA1 patients, only 29% had estrogen-receptor (ER)-positive breast cancers. But in non-BRCA patients and BRCA2 patients, the ER positive rates were 68% and 81% respectively.

BRCA1 mutation carriers had worse overall survival rates that other participants after adjustment for grade, size, nodal status, estrogen reception, adjuvant treatment, and age. The hazard ratio was 1.2 (95% CI 1 to 1.5 P=0.12).

The rate of recurrence-free survival was also worse, with an adjusted hazard ratio of 1.2 (95% CI 0.9 to 1.5 P=0.295).

Schmidt said the study was limited by the DNA technique (DNA samples were extracted from archival, paraffin-embedded tissue), which did not permit sequencing of complete BRCA genes.

“We are also seeing in the most recent analyses that BRCA2 carriers are doing worse, but we have less power for that analysis and still need to investigate in more detail what exactly is going on in this group,” Schmidt told MedPage Today.

“BRCA1 carriers as compared to BRCA2 carriers are also possibly doing worse because they are more likely to be estrogen-receptor-negative, which are known to have poorer prognosis.”

“My guess is this is a very well-done study, but I’m wondering what could be going on here?” said Alice Whittemore, PhD, of Stanford University. “Because we know for women with ovarian cancer who also carry the BRACA1 mutation that they seem to survive better.”

Whittemore said that conventional thinking is that with “one disabled copy of a repair gene, a DNA repair gene, chemotherapy is more effective for [BRACA1 mutation carriers] because their cancer cells cannot repair the damage that the chemotherapy does.”

“What could explain what they’re seeing in BRACA2? Why are the BRACA1 carriers doing worse when the BRACA2 [carriers] are not doing worse?” she said. “A possible explanation for the findings is that the breast cancers of BRCA1 carriers are more likely than those of noncarriers to be estrogen-receptor-negative, which are known to have poorer prognosis.”

Studies in ovarian breast cancer patients have shown that BRCA-carriers do better.

Schmidt said that the difference in treatment regimens could explain this survival difference. Ovarian cancer patients often get platinum-based cancer treatments, which is different from what breast cancer patients receive, particularly when this cohort was diagnosed between 1970 and 2002.

“I do think there is some effect of adjuvant treatment, which I have adjusted for in the analyses,” she said. “But almost none of these women received platinum-based therapy.”

The authors had no financial disclosures.

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Primary source: American Association for Cancer Research
Source reference: Schmidt MK, et al “Breast cancer survival of BRCA 1/2 carriers compared to non-BRCA 1/2 carriers in a large breast cancer cohort” AACR 2013; Abstract 1338.