Gene mutations were not a prognostic factor for women with breast cancer

Among Ashkenazi women with breast cancer, rates of death were similar for carriers and noncarriers.

Issue: August 1, 2007

Results from a recent study indicate that the rates of breast cancer–specific death among Israeli women were similar between carriers and noncarriers of a BRCA founder mutation.

Researchers in Israel examined the role of BRCA1 and BRCA2 mutations in the prognosis of women of Ashkenazi Jewish ancestry with breast cancer. The results were published in The New England Journal of Medicine.

“Our results were surprising, to an extent,” Gad Rennert, MD, PhD, told Hem/Onc Today. Rennert is chairman of the department of community medicine and epidemiology at the Carmel Medical Center, and director of the Clalit Health Services at the National Cancer Control Center in Haifa, Israel.

“Previous literature was split between papers suggesting worse survival [for women who carry these mutations], and papers suggesting equal survival,” he said. “Carrier women do appear with tumors that look more aggressive. However, our study, which is ‘cleaner’ than the others, shows that carrier women ‘ignore’ these bad prognostic factors.”

Similar outcomes

Rennert and colleagues collected data from the Israel National Cancer Registry on invasive breast cancer diagnoses from Jan. 1, 1987, to Dec. 31, 1988. They linked the women to the Israel Population Register to determine the ethnic origin.

Of the 2,729 women identified with breast cancer, pathological samples were available for 1,794 (71%). The researchers extracted DNA to analyze for three BRCA1 and BRCA2 mutations common to Ashkenazi women.

In the group of Ashkenazi women, 10% carried BRCA1 or BRCA2 mutations. The prevalence of the mutation was 18% among women diagnosed before age 50, and 7% in women diagnosed after age 50.

All of the women were followed for at least 10 years. Among the Ashkenazi women, a BRCA mutation did not influence the overall 10-year survival rate. Among mutation carriers, 89% of the deaths were attributed to cancer, compared with 72% of the deaths among noncarriers (P=.002). The adjusted hazard ratios for death from any cause did not differ between the groups.

The 10-year survival rate was 67% for BRCA1 carriers, 56% for BRCA2 carriers and 67% for noncarriers. The adjusted HRs for death from breast cancer did not differ between groups. For BRCA1, the HR was 0.76 (95% CI, 0.45-1.30). For BRCA2, the HR was 1.31 (95% CI, 0.80-2.15).

There was also no difference in 10-year survival between women who received chemotherapy after surgery and women who did not. Tumor size was also not a predictor of the probability of death.

Treatment decisions

The presence of BRCA mutations is still considered a risk for developing breast cancer. However, the results of this study show that despite increased risk, the disease progression is similar.

“It’s an interesting biological question that comes up fairly frequently,” said Douglas Yee, MD, director of the University of Minnesota Cancer Center in Minneapolis, and an editorial board member of Hem/Onc Today’s Breast Cancer section. “The question really is should we be treating women with BRCA1 or BRCA2 mutations differently, and the answer to that basically is no. They don’t have any comparative higher risk compared with those matched patients without the mutations.”

Rennert also said that all women should be treated with chemotherapy, regardless of mutation status.

“Carrier women tend to ignore these bad prognostic markers,” Rennert said. “Small and/or low-stage tumors tend to behave like large tumors, and carriers respond beautifully to chemotherapy.”

Rennert also recommended genetic testing for triple negative tumors in young women, or if there is a strong family history of breast and/or ovarian tumors.

Yee said treatment for patients with BRCA mutations or triple-negative tumors is a prominent topic in breast oncology, and there are several trials underway to test the effectiveness of different chemotherapy drugs on these tumors.

“Today, these mutations do not help you decide what treatment to give, but tomorrow, they may,” Yee said. “We don’t have strategies directed at the molecular signals for BRCA tumors like we do for estrogen receptor or HER2 expressing tumors. Several groups are working hard to understand if different drugs are more effective at treating patients with these mutations. At the moment, do not change your treatment plans based on presence of these mutations. But if your center is open to clinical trials, patients should be encouraged to participate.” – by Emily Shafer

For more information:

Rennert G, Bisland-Naggan S, Barnett-Griness O, et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med. 2007;357:115-123.