Researchers at Moffitt Cancer Center and colleagues in Toronto and at Yale University studied the long-term survival of women with a BRCA1 or BRCA2 gene mutation who were diagnosed with invasive ovarian cancer. They found that the short-term benefit to having either mutation does not lead to a long-term survival benefit.
The study appeared in the Jan. 16 issue of the Journal of the National Cancer Institute.
Overall, 13 percent of patients with ovarian cancer carry an inherited BRCA gene mutation. Those with mutations have a lifetime risk of up to 44 percent for developing ovarian cancer, compared to 2 percent in the general population.
According to the authors, some studies have suggested that the five-year survival of women with ovarian cancer and BRCA gene mutations is better than expected. However, this study was aimed at determining whether there was any longer-term survival benefit associated with those gene mutations, and included 1,626 women diagnosed with invasive ovarian cancer. The group was followed for a period of up to 15 years.
Many other studies involving BRCA mutations and survival time, the authors noted, followed patients for a much shorter period. In addition to the long-term follow-up, the authors said that additional strengths in their study were the large number of participants, as well as the number of women in the mutation positive subset.
"Of those women diagnosed with invasive ovarian cancer in the United States and Canada, approximately 35 percent are expected to be long-term survivors and ultimately cured," said Thomas A. Sellers, Ph.D., M.P.H., center director of Moffitt. "We sought to estimate the 10-year survival for women with ovarian cancer -- with and without the mutations -- to determine whether or not the observed short-term survival benefit for those with the mutations was associated with a better prospect for cure."
The researchers found that during a three-year period after an invasive ovarian cancer diagnosis, the presence of a BRCA gene mutation was associated with a better prognosis, but at 10 years after diagnosis there was no survival benefit. Peak mortality occurred two years after diagnosis for non-BRCA carriers, but approximately 3.5 years after diagnosis for BRCA mutation carriers, potentially indicating a short-term survival advantage for mutation carriers.
"Our results on long-term survival differed somewhat from those in earlier studies that found a short-term survival advantage for women with BRCA mutations," said Tuya Pal, M.D., associate member of the Cancer Epidemiology Program at Moffitt. "However, our results for short-term survival were similar to previous studies. Our study found the survival advantage at five years for women with stage III cancers at 55 percent for BRCA1 and BRCA2 mutation carriers combined, versus 39 percent for noncarriers."
The study concluded that the short-term benefit of carrying a BRCA mutation is not reflected over the long-term. The authors also noted that in their study, there was only one death among the 309 women who survived more than 12 years after diagnosis and suggested that a 12-year survival "seems a reasonable surrogate for cure."
"We believe there is insufficient evidence to counsel women with ovarian cancer and a BRCA mutation that they should expect their long-term survival to be better than that of noncarriers, or that tailored treatments reflect the differences in survival," concluded the authors. However, new targeted treatment trials have recently emerged for BRCA mutation carriers, thus it will be important to assess their impact on long-term survival in carriers with ovarian cancer.
This work was supported by the Canadian Institutes of Health Research; by grants from the National Cancer Institute (R01 CA 63682; 01 CA 63678; and R01CA111914); and by the Florida Biomedical Grant (IBG09-34198).
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