Total body irradiation linked to long-term breast cancer risk
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Total body irradiation appeared to increase breast cancer risk later in life for women who underwent blood or marrow transplantation for hematologic malignancies — particularly those exposed at age 30 years or younger, study results showed.
Women exposed to alkylating agents prior to autologous transplantation also demonstrated an increased risk for breast cancer, according to the study, published in Journal of Clinical Oncology.
“The association between chest radiation and secondary breast cancer is clearly established — there is a strong dose-response relationship. This has prompted recommendations for screening for early detection. However, the association between total body irradiation and breast cancer was not well established. We undertook this study to address this gap in knowledge,” Smita Bhatia, MD, MPH, professor and vice chair of outcomes for pediatrics and director of the School of Medicine Institute for Cancer Outcomes and Survivorship at The University of Alabama at Birmingham, as well as a HemOnc Today Editorial Board Member, told Healio.
Bhatia and colleagues sought to examine the association between total body irradiation and subsequent risk for breast cancer among 1,464 women (median age, 58 years; range, 18-89) included in the BMT Survivor Study — a retrospective cohort study of women with hematologic malignancies who underwent allogeneic (n = 788) or autologous (n = 676) blood or marrow transplantation between 1974 and 2014 and survived at least 2 years after transplant.
Diagnoses included acute myeloid leukemia or myelodysplastic syndrome (27.5%), non-Hodgkin lymphoma (23.3%), plasma cell dyscrasias (18%) and chronic myelogenous leukemia (10.3%).
Participants were asked to complete a survey including questions on breast cancer diagnosis, and researchers reviewed pathology reports or physician notes to confirm subsequent breast cancer. Women with a prior history of breast cancer or who underwent chest radiation before blood or marrow transplantation were excluded from the study.
Researchers used Cox proportional hazards models to assess the association between total body irradiation and subsequent breast cancer risk and calculated standardized incidence ratios of the risk for subsequent breast cancer in comparison with the age-matched general population.
Median follow-up from blood or marrow transplant was 9.3 years (range, 2-39.9).
Nearly half of women (46%; n = 660) underwent total body irradiation. Of these, 37 women (allogeneic transplant, n = 19; autologous transplant, n = 18) developed breast cancer a median 9.1 years (range, 0.6-27.2) after transplant. Median age at breast cancer diagnosis was 53.9 years (range, 37.6-74.8).
The 10-year estimated cumulative probability of developing breast cancer was 1.1% (standard deviation [SD], 0.4%) after allogeneic transplant and 2.6% (SD, 0.8%) after autologous transplant.
The estimated cumulative probability of developing breast cancer among the overall cohort nearly doubled from 2.7% by age 60 years to 5.2% by age 70 years. The cumulative probability by age 60 years was 3.1% for women who underwent allogeneic transplant and 2.2% for those who underwent autologous transplant.
Results of a multivariable analysis showed associations between total body irradiation and an increased risk for subsequent breast cancer among women who underwent allogeneic transplant (HR = 3.7; 95% CI, 1.2-11.8) and those who underwent autologous transplant (HR = 2.6; 95% CI, 1-6.8).
Researchers additionally observed an increased risk for subsequent breast cancer among women who were exposed to alkylating agents before autologous transplant (HR = 3.3; 95% CI, 1-9). The overall SIR for subsequent breast cancer among all study participants compared with an age-matched general population was 1.3 (95% CI, 0.9-1.7).
Moreover, women who received total body irradiation had a 1.5-fold higher risk for breast cancer than the general population. Among women exposed to total body irradiation when aged younger than 30 years, those who underwent allogeneic transplant appeared at 4.4 times the risk for subsequent breast cancer compared with the general population and those who underwent autologous transplant appeared at 4.6 times the risk.
“These findings suggest that patients exposed to total body irradiation at age 30 years or younger are at increased risk for breast cancer, suggesting that we need to include this subgroup in our screening recommendations,” Bhatia told Healio. “Future research needs to focus on identifying subgroups of patients at higher risk for breast cancer based on their genetic makeup.”
For more information:
Smita Bhatia, MD, MPH, can be reached at The University of Alabama at Birmingham, 1600 7th Ave. South, Lowder 500, Birmingham, AL 35233; email: sbhatia@peds.uab.edu.
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