When BRCA Mutations Run in the Family, Should Noncarriers Worry?

Home>
Specialties>
Women's Health>
Summary and Comment

When BRCA Mutations Run in the Family, Should Noncarriers Worry?

Population-based study shows that noncarriers are not at excess risk for breast cancer attributable to familial mutations.

A key rationale of BRCA mutation testing is to guide counseling and recommendations for family members of women with breast cancer who test positive. Some studies have suggested that relatives of women who carry deleterious BRCA mutations but who themselves test negative are at excess risk for breast and ovarian cancer; however, other findings conflict. Investigators used data from population-based cancer registries in Australia, Canada, and Northern California to assess breast cancer risk in first-degree relatives (FDRs) of women with the disease. Registry participants with breast cancer were tested for BRCA1 and BRCA2 mutations; FDRs of identified mutation carriers also were tested (FDRs of women with breast cancer who tested negative for BRCA mutations were considered to be noncarriers).

Among 3047 families, BRCA1 and BRCA2 mutations were detected in 160 and 132 families, respectively. Among FDRs who tested negative for family-specific BRCA mutations, risk for breast cancer was not significantly higher than that in FDRs from families without BRCA mutations. FDRs of women with non-BRCA breast cancer were at excess risk for this form of malignancy, implying a role for the aggregate contribution of polygenic (i.e., combined action of multiple genes with modest effects), as well as nongenetic risk factors within families.

Comment: Often, a primary motivation in women who undergo BRCA mutation testing is to provide information that could help their relatives. This report confirms that noncarrier first-degree relatives of BRCA mutation–positive women are not themselves at excess risk for the disease and, therefore, can pursue breast cancer screening consistent with that in the general population.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health November 17, 2011

Citation(s):

Kurian AW et al. Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: Findings from the Breast Cancer Family Registry. J Clin Oncol 2011 Oct 31; [e-pub ahead of print]. (http://dx.doi.org/10.1200/JCO.2010.34.4440)

Robson M. Do women remain at risk even if they do not inherit a familial BRCA 1/2 mutation? J Clin Oncol 2011 Oct 31; [e-pub ahead of print]. (http://dx.doi.org/10.1200/JCO.2011.37.6483)

Your Remark:

Reader Remarks are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

The editors of Journal Watch may respond to Reader Remarks, but we cannot promise to respond to a particular remark.

Remark subject:*

Your remark:*

Fields marked with an * are required.

Name as you'd like it to appear:
First & middle initial:*

Last:*

Email address (will not
be published):*

Professional specialty:*

Place of work (optional):

Submitting a comment indicates you have read and agreed to the remark guidelines and declare:*

No competing interests

Or, the following competing interests (for example, financial stakes or professional relationships):

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.

CLEAR erases anything you've added in any part of the form. CONTINUE allows you to check your entire post (and edit it if necessary) before submitting.

To ensure that your Reader Remark is not formatted as one long paragraph, precede new paragraphs with either a blank line or an indentation.