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e-Journal Club

Tamoxifen and Breast Cancer Incidence Among Women with Inherited Mutations in BRCA1 and BRCA2

December 20, 2001

Reviewed by:

Bruce K. Lin and Paula Yoon
Office of Genomics and Disease Prevention, 
Centers for Disease Control and Prevention

The Health Outcome

As many as 192,200 new cases of invasive breast cancer will be diagnosed among women in the United States in 2001, making it the most common form of cancer in women this year. Three to five percent of these breast cancer cases will be associated with mutations within the BRCA1 or BRCA2 genes. Despite declining mortality rates among women during 1990-1997, breast cancer remains the second-leading cause of cancer deaths among women. In addition to mutations found in the breast cancer susceptibility genes, several environmental, physical and behavioral risk factors have been identified that place some women at increased risk of developing breast cancer. Current research suggests that estrogen-receptor (ER) modulators, specifically tamoxifen, reduce breast cancer risk (1).

The Finding

King et al. (2001) reports gene-environment interaction results from a controlled clinical trial that examined the risk for breast cancer among women with BRCA1 and BRCA2 mutations associated with the use of tamoxifen vs. placebo (2). A detailed abstraction of this article is available online as part of the HuGENet™ e-Journal club (3). Among a cohort of previously healthy women (aged 35 years and older) who developed breast cancer during the course of the clinical trial and who could be genotyped (n=288), 19 (6.6%) carried mutations within BRCA1 and BRCA2. In this study, tamoxifen did not appear to decrease breast cancer incidence among healthy BRCA1 carriers; however, the finding was not statistically significant. Based on this result for BRCA1 carriers, the authors clarify that it is unclear whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women who have BRCA1 mutations. In contrast, the incidence of breast cancer among patients with BRCA2 mutations who received tamoxifen decreased by 62% (again, statistically insignificant) compared with placebo. The authors point out that the reduction is similar to the reduction in incidence of ER-positive breast cancer among all women in the clinical trial. In addition, the authors report that for this study, tumors of women with inherited BRCA1 mutations are more frequently ER negative than tumors with BRCA2 mutations.

Public Health Implications

Currently, screening the general population for BRCA1 and BRCA2 mutations for breast cancer is not recommended (1). In the context of studies that examine the treatment of breast cancer and identify BRCA1 and BRCA2 mutations as susceptibility genes, King et al. (2001) addressed a specific issue in their study- whether chemoprevention using tamoxifen would reduce the incidence of invasive breast cancer among previously healthy women who were either BRCA1 and BRCA2carriers. The results suggest that for their study group, having BRCA1 and BRCA2 mutations can affect the expected effect of tamoxifen in reducing the incidence of breast cancer. In fact, results of the King et al. study show that tamoxifen’s effectiveness is reduced in cancer-free women with BRCA1 mutations. The authors note that because of the small sample size, inferences from the genetic data cannot completely answer their study hypothesis (2). King et al. state that additional research into the efficacy of tamoxifen among younger, cancer-free women with BRCA1 mutations is needed to further clarify the issue. For the purposes of this HuGE eJournal club, we could not comment further on gene prevalence or conduct a proper incidence-based analysis because no person-year information (or denominator data) was presented with this publication.

References

  1. American Cancer Society. Cancer facts and figures 2001. Atlanta : The American Cancer Society; 2001
  2. King M-C, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2. JAMA 2001;286:2251-6
  3. King M-C et al. e-Journal Club abstraction template

 

Last Updated August 27, 2004