Tamoxifen May Lower Risk of Second Cancer in Women With Abnormal BRCA1 or BRCA2 Genes

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A study found that women with abnormal BRCA1 or BRCA2 genes who took tamoxifen after being diagnosed with breast cancer had fewer second cancers in the other breast than women who didn’t take tamoxifen. This suggests that tamoxifen may be a good option to reduce risk in these high-risk women, but more research is necessary.

The study was published online on Aug. 5, 2013 by the Journal of Clinical Oncology.

Read the abstract of “Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.”

Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two).

Everyone has BRCA1 and BRCA2 genes. The function of the BRCA genes is to repair cell damage and keep breast cells growing normally. But when these genes contain abnormalities or mutations that are passed from generation to generation, the genes don’t function normally and breast cancer risk increases. Abnormal BRCA1 and BRCA2 genes may account for up to 10% of all breast cancers.

Women with an abnormal BRCA1 or BRCA2 gene:

  • have up to an 85% lifetime risk of developing breast cancer
  • have a much higher-than-average lifetime risk of ovarian cancer; estimates range from 15% to 60%

Women who know they have an abnormal BRCA1 or BRCA2 gene can take steps to reduce their risk. You probably heard about Angelina Jolie’s decision to have a preventive double mastectomy because she learned that she had an abnormal BRCA1 gene. Preventive double mastectomy is a very aggressive, irreversible risk-reduction option. While it’s a good option for a number of women, it’s not right for every woman.

Tamoxifen is a type of hormonal therapy medicine called a SERM (selective estrogen receptor modulator). SERMs block the action of estrogen in breast cancer and certain other cells by sitting in the cells’ estrogen receptors. SERMs don’t affect all estrogen receptors the same way because they’re selective (as the name says). In bone cells, SERMs interact with the receptors the way estrogen does and strengthen bones. In breast cells, SERMs block the receptors’ interaction with estrogen and limit cell growth.

Besides being used to reduce the risk of early-stage, hormone-receptor-positive breast cancer coming back (recurring) and to treat advanced-stage, hormone-receptor-positive disease, tamoxifen also is used to reduce breast cancer risk in women who haven’t been diagnosed but have a higher-than-average risk for the disease. Still, tamoxifen hasn’t been widely used to reduce risk in women with an abnormal BRCA1 or BRCA2 gene because very little research (only one study) has been done specifically on tamoxifen and that group of women.

In this study, the researchers looked at information from the International BRCA1 and BRCA2 Carrier Cohort Study, the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and the Breast Cancer Family Registry:

  • 1,583 women had an abnormal BRCA1 gene
  • 881 women had an abnormal BRCA2 gene

All the women had been diagnosed with cancer in one breast since 1970. None of them had been diagnosed with breast cancer before and none of them had taken tamoxifen before.

After being diagnosed with breast cancer, the women self-reported whether they had taken tamoxifen:

  • 383 women (24%) with an abnormal BRCA1 gene took tamoxifen
  • 454 women (52%) with an abnormal BRCA2 gene took tamoxifen

The researchers found that women who took tamoxifen were less likely to be diagnosed with a new, second cancer in the other breast than women who didn’t take tamoxifen. Risk was:

  • 62% lower for women with an abnormal BRCA1 gene
  • 67% lower for women with an abnormal BRCA2 gene

The hormone receptor status of the first breast cancer didn’t affect the amount of risk reduction associated with taking tamoxifen.

While the results of this study are very promising, there are some limitations. This study wasn’t a randomized study. This means that the women weren’t randomly assigned to take tamoxifen or not. So there may have been some reason why certain women took tamoxifen and other women didn’t. Other factors such as age or other health issues also may have affected the women’s risk of developing a new, second cancer. Further follow-up of the women in this study and more research is needed before we can be sure that tamoxifen is a good risk-reduction choice for women with an abnormal BRCA1 or BRCA2 gene.

If you have an abnormal BRCA1 or BRCA2 gene and have been diagnosed with breast cancer, you and your doctor will carefully consider your risk of developing a new cancer as well as your preferences as you develop your treatment plan. Choosing to have the opposite healthy breast removed is one option you may consider. You also may consider having your ovaries preventively removed. Taking tamoxifen is another option. There are also lifestyle steps you can take, including maintaining a healthy weight, avoiding alcohol, and exercising regularly.

Each woman’s situation is unique. Talk to your doctor about your level of risk and ways to manage it that are best for you.

For more information on steps you can take to reduce your risk of being diagnosed with a first or second breast cancer if you have an abnormal BRCA1 or BRCA2 gene, visit the Genetics page in the Breastcancer.org Lower Your Risk section.

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