Women with BRCA1 or BRCA2 mutations who underwent adjuvant tamoxifen treatment for breast cancer were at reduced risk for contralateral disease, according to results of a pooled observational analysis.
The findings add to the evidence base regarding the potential of tamoxifen to prevent primary breast cancer in BRCA mutation carriers, according to Kelly-Anne Phillips, MD, consultant medical oncologist at Peter MacCallum Cancer Centre in Victoria, Australia.
“Women with a mutation in BRCA1 or BRCA2 should review their cancer risk management plan with their specialist and discuss whether they should consider taking tamoxifen to reduce their risk of breast cancer,” Phillips told HemOnc Today. “Cancer risk management decisions are complex. Research that ensures optimal integration of these research findings into clinical practice will be important.”
The researchers used the International BRCA1 and BRCA2 Carrier Cohort Study, the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer, and the Breast Cancer Family Registry to identify women with primary breast cancer who enrolled between 1993 and 2009. Exclusion criteria included the development of other invasive cancers, or tamoxifen treatment prior to first breast cancer.
The final analysis included 2,464 women (96% white). Of them, 1,583 had BRCA1 mutations and 881 had BRCA2 mutations. Median time since first breast cancer diagnosis was 6.6 years.
Researchers reported that 383 (24%) of the BRCA1 carriers and 454 (52%) of the BRCA2 carriers were treated with tamoxifen.
During 20,104 person-years of observation, researchers reported 520 incidences of contralateral breast cancer. Contralateral disease developed in 24% of BRCA1 carriers and 17% of BRCA2 carriers.
Among women treated with tamoxifen after first breast cancer diagnosis, adjusted HRs were 0.38 (95% CI, 0.27-0.55) for BRCA1 mutation carriers and 0.33 for BRCA2 carriers (95% CI, 0.22-0.50) compared with those who did not undergo tamoxifen treatment.
Researchers determined ER status for 44% of participants. Based on that sample, ER status did not affect the HRs.
Among BRCA1 mutation carriers who were premenopausal at first diagnosis, the reduction of risk for contralateral breast cancer associated with tamoxifen use was less apparent for those who underwent bilateral salpingo-oophorectomy compared with those who did not (HR=0.70; 95% CI, 0.32-1.53 vs. HR=0.26; 95% CI, 0.16-0.43). Researchers reported a similar trend among BRCA2 mutation carriers (HR=0.70; 95% CI; 0.27-1.82 vs. HR=0.21; 95% CI, 0.12-0.36).
"This study provides observational evidence that, for BRCA1 and BRCA2 mutation carriers, tamoxifen use for first breast cancer might reduce risk of contralateral breast cancer," Phillips and colleagues concluded. "Further follow-up of these cohorts will provide increased statistical power for prospective analyses and thus a more definitive answer to this important question."
Disclosure: The researchers report no relevant financial disclosures.