Breast Cancer Genes Don't Raise Tumor-Linked Death Risk

By Amanda Gardner
HealthDay Reporter

WEDNESDAY, July 11 (HealthDay News) -- Women with breast cancer who carry BRCA gene mutations have the same death rates from their malignancies as women without this DNA variant do, a new study finds.

These findings, published in the July 12 issue of the New England Journal of Medicine, run counter to much current medical thought.

"Our main finding of similar -- or even better -- survival of the carriers is in contrast to some, but not all, of the former publications on the subject," noted study author Dr. Gad Rennert, of the Clalit National Cancer Control Center and Carmel Medical Center in Haifa, Israel. "However, we employed a 'clean' design which was not possible for other research groups and therefore our study results come closer to 'truth' than any other study on the subject."

Practically speaking, the findings could impact the treatment decisions of women who have one of the two genetic mutations, called BRCA1 or BRCA2.

Many previous studies on the issue had suggested that cancer resulting from these mutations had a worse outcome than other types of breast tumors.

The BRCA mutations are more common among women of Ashkenazi Jewish descent, which may help account for why breast cancer is the leading cause of all deaths from cancer among Israeli women. Some 60 percent of Israeli Jews are Ashkenazi. About 2 percent of all Ashkenazi women and 12 percent of Ashkenazi women with breast cancer carry a mutation in one of these two genes.

BRCA1-associated breast cancers, especially, tend to occur in younger women, are high-grade and are not estrogen-receptor positive, all factors which are associated with a poorer outcome.

But information on how a woman's BRCA status might affect her prognosis has been "inconsistent," the authors stated.

To clarify the picture, the authors looked at all cases of invasive breast cancer diagnosed between Jan. 1, 1987 and Dec. 31, 1988, and recorded in the Israeli National Cancer Registry. This represented the majority of all women who had been diagnosed with breast cancer in Israel during this time period. The researchers examined patient tumor samples and analyzed DNA, and they also catalogued deaths occurring within 10 years of diagnosis.

The authors were able to look at tumor samples from 1,794 of 2,514 participants and obtained medical records for 1,545 of the women. Ten percent of participants who were of Ashkenazi Jewish ancestry had either a BRCA1 or BRCA2 mutation.

The risk of dying from breast cancer was not significantly different among carriers and non-carriers, the researchers found. Furthermore, both groups responded similarly well to chemotherapy.

"The main importance of the study is in demonstrating that in spite of the bad prognostic factors profile, [BRCA] carriers do well, which is of importance both to doctors as well as to the carrier women," Rennert said. "It also demonstrates that chemotherapy is very efficacious in the carriers and that oncologists should not spare carrier women, even with small tumors, the potential benefits of treatment."

The next step will be to individualize treatments, "as it seems that certain treatments probably work better for carriers, while they might be resistant to others," Rennert added.

SOURCES: Gad Rennert M.D., Ph.D., Clalit National Cancer Control Center and Carmel Medical Center, Haifa, Israel, and B. Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel; July 12, 2007, New England Journal of Medicine

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