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BRCA status, age at first breast cancer affects risk of developing contralateral breast cancer, study shows

Tuesday, December 22 2009 | Comments

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What's This? Women with unilateral breast cancer who carry a BRCA1 mutation and who had their breast cancer at a younger age have a greater risk of developing contralateral breast cancer than do women who carry the BRCA2 mutation or develop initial breast cancer at an older age, according to recently published study results.

If women carry a deleterious BRCA1 or BRCA2 mutation, they not only have a higher risk of breast and ovarian cancer, but they also have a greater risk of developing a second breast cancer, with the majority of these cases occurring in the contralateral breast, the authors explained.

To estimate the risk of contralateral breast cancer in members of BRCA1- and BRCA2-positive families, the researchers conducted a retrospective cohort study of 2,020 women with unilateral breast cancer (index patients, n=978; relatives, n=1,042) from 978 families who had a BRCA1 or BRCA2 mutation.

The association of age at first breast cancer with time from first to contralateral breast cancer was assessed using Cox regression analysis. Analyses were also stratified by the affected BRCA gene.

The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8%-56.0%) for patients from families with either type of mutation.

The risk of developing contralateral breast cancer was 1.6 fold (95% CI, 1.2 fold-2.3 fold) for the members of families with BRCA1 mutations as compared with the member of families with BRCA2 mutations.

For the patients with BRCA1 mutations, younger age (<40 years) at the time of first breast cancer was associated with a significantly higher risk of developing contralateral breast cancer as compared with older age (P<. 001). Specifically, 62.9% (95% CI, 50.4%-75.4%) of the patients from BRCA1 families who were aged younger than 40 years at their first breast cancer developed contralateral breast cancer, versus 43.7% (95% CI, 24.9%-62.5%) of those who developed their first breast cancer between the age of 41 and 50 years and 19.6% (95% CI, 5.3%-33.9%) of the women who developed their first breast cancer after the age of 50 years.

A similar trend was seen for the women from BRCA2 families, but it was not statistically significant.

"While data from prospective studies are lacking, we consider these risk estimates an appropriate approximation of the true risks for contralateral breast cancer during up to 20 years of follow-up," the authors concluded. (Graeser MK, et al. J Clin Oncol 2009;27:5887-5892.)

In an accompanying editorial, Judy Garber and Mehra Golshan of the Dana Farber Cancer Institute and Brigham and Women's Hospital, said the findings from this study provide cancer care teams with compelling data to indicate that women with BRCA1/BRCA2 mutations who receive a diagnosis at a young age should be considered for management of the opposite breast. At the same time, the lower risk seen for older patients with BRCA1/BRCA2 mutations provides a less-compelling rationale for management of the opposite breast. (J Clin Oncol 2009;27:5862-5864.)

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