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ICARE Newsletter Winter 2015

Ask the Expert

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The following question was addressed to Dr. Steven Narod who is a Tier I Canada Research Chair in Breast Cancer and a senior scientist at Women’s College Research Institute in Toronto, Canada. Dr. Narod is a world-leader in the field of breast and ovarian cancer genetics. Over the course of his career, he has profoundly shaped current knowledge about cancer risks, prevention and screening amongst carriers of BRCA1 and BRCA2 mutations.

Q. As a BRCA mutation carrier, how much does Tamoxifen reduce my chance of developing contralateral breast cancer?

A. Following an initial breast cancer diagnosis in BRCA mutation carriers, the annual risk for developing contralateral breast cancer (i.e., breast cancer in the other breast) is 3%.1 We have mainly relied on studies evaluating contralateral breast cancer risk reduction with Tamoxifen. These studies have suggested that in women with breast cancer and a BRCA mutation, Tamoxifen reduces the lifetime risk of contralateral breast cancer by ~50%, particularly among those who still have their ovaries.3, 4, 5 Only one study to date with fewer than 20 carriers evaluated Tamoxifen for primary breast cancer prevention and showed risk reduction in BRCA2; however, risk reduction was not confirmed in BRCA1 (but it is important to note that this was a small sample size because there might not have been enough women to find an effect).2 Consequently, Tamoxifen may be considered in BRCA carriers with at risk breast tissue, especially among those who are premenopausal and have their ovaries.

More recently, we evaluated how the duration of Tamoxifen use affected contralateral breast cancer risk.6 We found that the risk of contralateral breast cancer was reduced by about half in those who used Tamoxifen for a short time (less than one year). These results do not imply any changes to the recommended course of Tamoxifen in the context of a breast cancer diagnosis because the primary goal in this situation would be to reduce risk of recurrence. However these results may be relevant for women without a breast cancer diagnosis who are considering Tamoxifen for primary prevention. In these women, consideration of a short course of Tamoxifen may be preferred over the recommended 5-year course, particularly given that many women are reluctant to take the drug because of the fear of side effects.7

Ultimately, we urge women to have a balanced discussion of the potential benefits and harms of Tamoxifen with their healthcare providers to enable them to make an informed decision about using this medication.

1. Metcalfe K, et al. British Journal of Cancer. Apr 26 2011;104(9):1384-1392. 2. King MC, et al. Jama. Nov 14 2001;286(18):2251-2256. 3. Gronwald J, et al. International Journal of Cancer.May 1 2006;118(9):2281-2284. 4. Narod SA, et al. Lancet. Dec 2 2000;356(9245):1876-1881. 5. Phillips KA, et al. J Clin Oncol. Sep 1 2013;31(25):3091-3099. 6. Gronwald J, et al. Breast Cancer Res Treat. Jul 2014;146(2):421-427. 7. Cuzick J, et al. Lancet. Mar 22 2014;383(9922):1041-1048.

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