in Chest-irradiated Female Cancer Survivors at risk for Breast Cancer

Adolescent and young adult females treated with chest radiation for their primary cancer are at risk for breast cancer; the cumulative incidence of radiation-related breast cancer exceeds 35% by age 50. This risk is as high as that observed in BRCA mutation carrier. Mortality rates are higher after radiation-related breast cancer than after primary breast cancer. These findings present an urgent yet unmet need to develop breast cancer risk-reduction strategies for radiation-exposed cancer survivors.

The risk of radiation-related breast cancer is lower in survivors who also received ovarian radiation. These findings suggest a role for endogenous estrogens in radiation-related breast carcinogenesis, making tamoxifen a viable risk-reducing option for pre- and post-menopausal cancer survivors. While effective in reducing the risk of primary breast cancer, the possibility of severe adverse events (AEs), such as venous thromboembolism and endometrial cancer, have contributed to the low uptake of tamoxifen at 20mg/d. Low-dose tamoxifen (5mg/d) appears to retain the efficacy in reducing breast cancer risk, but with a safer AE profile. These findings make low-dose tamoxifen an attractive breast cancer risk-reducing strategy for chest-irradiated cancer survivors.

Radiation-related breast cancer has a latency of 8-10 years after exposure, necessitating use of a biomarker as a surrogate endpoint for assessing efficacy of breast cancer prevention. Mammographic density is an established biomarker of breast cancer risk. We hypothesized that tamoxifen at a dose of 5mg/d for 2y would be an efficacious and safe option for reducing mammographic dense area in young female cancer survivors at risk for radiation-related breast cancer.

Participating Institutions

University of Alabama at Birmingham, Birmingham, AL
City of Hope, Duarte, CA
The University of Texas MD Anderson Cancer Center, Houston, TX
University of Minnesota, Minneapolis, MN
University of Chicago, Chicago, IL
University of Toronto, Toronto, ON
St. Jude Children’s Research Hospital, Memphis, TN
Seattle Cancer Care Alliance, Seattle WA
Wake Forest School of Medicine, Winston-Salem, NC
University of Michigan, Ann Arbor, MI
University of Colorado, Denver, CO
Mayo Clinic, Rochester, MN
Dana Farber Cancer Institute, Boston, MA.

Funding

P30 CA046592/CA/NCI NIH HHS/United States
R01 CA140245/CA/NCI NIH HHS/United States

Publications

Bhatia S, Palomares MR, Hageman L, Chen Y, Landier W, Smith K, Umphrey H, Reich CA, Zamora KW, Armenian SH, Bevers TB, Blaes A, Henderson T, Hodgson D, Hudson MM, Korde LA, Melin SA, Merajver SD, Overholser L, Pruthi S, Wong FL, Garber JE. A Randomized Phase IIb Study of Low-dose Tamoxifen in Chest-irradiated Cancer Survivors at Risk for Breast Cancer. Clin Cancer Res. 2021 Feb 15;27(4):967-974. doi: 10.1158/1078-0432.CCR-20-3609. Epub 2020 Dec 3. PMID: 33272980; PMCID: PMC7887034.