BRCA-Negative Breast Cancer Does Not Raise Ovarian Risk


Women from families with hereditary breast cancer who do not carry the BRCA1 or BRCA2 genetic mutations are not at increased risk for ovarian cancer, a prospective study has shown.

If validated by additional studies, the findings by Noah D. Kauff, M.D., and colleagues at New York's Memorial Sloan-Kettering Cancer Center may allow physicians to better tailor ovarian cancer risk-reduction strategies.

Using records from the Sloan-Kettering clinical genetics service, investigators identified more than 1,700 patients who underwent genetic testing for BRCA mutations from August 1996 through July 2002 and who had consented to participate in follow-up studies. Those kindred with site-specific breast cancer who were BRCA mutation-negative and who had a living female proband received detailed questionnaires to provide clinical follow-up information and information on new cancers in themselves and their first- and second-degree relatives.

For the study, probands were defined as the youngest living BRCA mutation-negative women with breast cancer whose lineage included at least three cases of breast cancer—at least one of which must have been diagnosed before age 50—and no ovarian cancer, the investigators said (J. Natl. Cancer Inst. 2005;97:1382–4).

Probands whose heritage was exclusively Ashkenazi Jewish were included if they tested negative for the three Ashkenazi founder mutations because such testing has been shown to identify approximately 95% of detectable BRCA mutations, Dr. Kauff and associates stated.

Of 207 living female probands identified, 165 completed the study questionnaires. During a mean follow-up of 40.6 months, 19 new cases of breast cancer were diagnosed in the families, which included the 165 probands and 583 first- or second-degree female relatives. The disease incidence was more than three times greater than expected in age-matched women from the general population.

During the same follow-up period, one case of ovarian cancer was diagnosed, which is consistent with expectations for an average-risk population.

Dr. Kauff and associates advised caution with respect to revising ovarian cancer risk-reduction strategies for women from families with site-specific hereditary breast cancer kindred and mutation-negative status until the findings can be confirmed through additional studies.

The authors wrote that “two-thirds of the women in the cohort were Ashkenazi Jewish, and it is possible that BRCA mutation testing in this group more effectively excludes the possibility of a deleterious mutation than in non-Ashkenazi populations.”

Also, the study was powered to detect a 3.5- to 4-fold increase in ovarian cancer risk, compared with the general population, but detection of a 2.5- to 3-fold increase would require 3,800–7,600 women-years of follow-up, compared with the 2,534 women-years of follow-up represented by the current study.

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