Tamoxifen cuts second cancer risk in BRCA carriers

Taking tamoxifen is tied to a sharply reduced risk of a second breast cancer among women who carry the BRCA1 or BRCA2 “breast cancer genes,” new research shows.

Women with mutations of those genes are much more likely to develop breast and ovarian cancer than other women. Some - like Angelina Jolie - will opt to have their breasts removed preemptively, which reduces breast cancer risk by more than 95 percent.

Other women may choose to have their ovaries removed, which cuts breast cancer risk in half. The new findings suggest taking tamoxifen may be another breast-cancer-preventing option for those women, whether or not they have already had cancer once, researchers said.

“In light of our finding, women with a BRCA1 or BRCA2 mutation should review their cancer risk management options with their specialist clinician,” Dr. Kelly-Anne Phillips of the Peter MacCallum Cancer Centre in Victoria, Australia, the study’s lead author, told Reuters Health.

Many breast cancer patients have tumors that grow and spread when exposed to estrogen. Women with these hormone-responsive cancers are typically prescribed tamoxifen, which blocks estrogen and reduces their risk of cancer recurrence by 40 percent.

But women with breast cancer who have BRCA1 or BRCA2 gene mutations are not typically offered tamoxifen treatment.

“There were very few BRCA1 and BRCA2 mutation carriers in previous studies of tamoxifen for breast cancer prevention, so there has been inadequate information about whether tamoxifen is useful in that specific group of women,” Phillips said in an email.

To investigate whether the drug might help these high-risk women, Phillips and her colleagues analyzed the results of three studies including a total of 1,583 BRCA1 mutation carriers and 881 BRCA2 carriers who had developed cancer in one breast. Twenty-four percent of the BRCA1 carriers and 52 percent of the BRCA2 carriers began taking tamoxifen after being diagnosed.

During an average of eight years of follow-up, 520 women - 24 percent of the BRCA1 carriers and 17 percent of the BRCA2 carriers - developed cancer in the opposite breast.

Women with the BRCA1 mutation were 62 percent less likely to develop a second cancer if they took tamoxifen, while BRCA2 carriers had a 67 percent lower risk with the drug. Tamoxifen was tied to fewer second cancers whether or not women’s original tumors had been estrogen-responsive, according to findings published in the Journal of Clinical Oncology.

“Our study suggests tamoxifen should now be considered for all BRCA1 and BRCA2 mutation carriers who have had breast cancer… if they have chosen not to have all their breast tissue removed,” Phillips said.

PREVENTING FIRST CANCERS

Women who carry the BRCA1 or BRCA2 mutation who have not developed breast cancer may want to consider taking tamoxifen as well, Phillips added.

“For BRCA1 and BRCA2 mutation carriers, tamoxifen should be considered while they are young and pre-menopausal because these women are at risk of breast cancer at an early age,” she said.

The American Society of Clinical Oncology says a 5-year course of tamoxifen should be discussed for women age 35 and older at increased risk of breast cancer.

“The most common side-effect is menopausal symptoms such as hot flushes,” Phillips said. “Most women find these tolerable but many women like to make a plan to try tamoxifen for a month or two to see how it feels, before finalizing a plan to use it for the recommended 5 years.”

Generic tamoxifen can be bought for about $100 per month or less.

Dr. Steven Narod, a professor at the Women’s College Research Institute at the University of Toronto, said he frequently prescribes tamoxifen to prevent breast cancer among women with BRCA1 or BRCA2 mutations who do not choose to have their breasts removed.

“I’ve been recommending tamoxifen in that sense for many years to prevent breast cancer,” Narod, who did not take part in the new study, told Reuters Health. “Very few doctors do. I think that this paper gives some pretty good support for the position that we should be using tamoxifen to prevent breast cancer in BRCA1 and BRCA2 carriers.”

Tamoxifen makes less sense as a treatment for BRCA1 or BRCA2 carriers who have already had breast cancer, he added. For these women, Narod said, the main treatment options are removal of the breasts or ovaries and chemotherapy.

“Tamoxifen has a role to play, but only I’d say a secondary one,” he said.

SOURCE: Journal of Clinical Oncology, online August 5, 2013

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Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases).

Conclusion This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.


  Kelly-Anne Phillips,
  Roger L. Milne,
  Matti A. Rookus,
  Mary B. Daly,
  Antonis C. Antoniou,
  Susan Peock,
  Debra Frost,
  Douglas F. Easton,
  Steve Ellis,
  Michael L. Friedlander,
  Saundra S. Buys,
  Nadine Andrieu,
  Catherine Noguès,
  Dominique Stoppa-Lyonnet,
  Valérie Bonadona,
  Pascal Pujol,
  Sue Anne McLachlan,
  Esther M. John,
  Maartje J. Hooning,
  Caroline Seynaeve,
  Rob A.E.M. Tollenaar,
  David E. Goldgar,
  Mary Beth Terry,
  Trinidad Caldes,
  Prue C. Weideman,
  Irene L. Andrulis,
  Christian F. Singer,
  Kate Birch,
  Jacques Simard,
  Melissa C. Southey,
  Håkan L. Olsson,
  Anna Jakubowska,
  Edith Olah,
  Anne-Marie Gerdes,
  Lenka Foretova and
  John L. Hopper

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