Breast Cancer Risk Highlighted After Total Body Irradiation For BMT

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: A study of patients given a blood or bone marrow transplantation (BMT) for haematological malignancy has uncovered a significant increased risk for breast cancer among young women who receive total body irradiation (TBI). 

“Women who were exposed to TBI at age <30 years and those who received alkylating agents before BMT should be strongly considered for enhanced breast cancer screening”, recommend Smita Bhatia, from the University of Alabama at Birmingham in the USA, and co-investigators.

The team reports in the Journal of Clinical Oncology that 37 of the 1464 female participants of the BMT Survivor Study developed breast cancer over a median 9.3 years of follow-up, including 19 of the 788 patients who received allogeneic BMT and 18 of the 676 who received autologous BMT.

The patients had all undergone transplantation between 1974 and 2014 and survived for at least 2 years; 45% underwent TBI but none of the patients had received chest radiotherapy before BMT or had a history of breast cancer.

Multivariable analysis demonstrated a significantly increased risk of breast cancer for patients who underwent TBI versus those who did not, and this was true for both allogeneic (hazard ratio [HR]=3.7) and autologous (HR=2.6) BMT survivors.

Although TBI dose was not significantly associated with breast cancer risk, the researchers say that this finding “should be interpreted with caution because few patients received doses outside of the narrow range of 12–13.2 Gy.”

Patients given alkylating agents before autologous BMT were also significantly more likely to be diagnosed with breast cancer than those who did not take these agents, with a multivariable HR of 3.0, whereas no such increase in risk was found among allogeneic BMT patients.

“That an association between pre-BMT alkylating agents/anthracyclines and subsequent breast cancer was observed only within the autologous BMT group is likely because of the higher doses used for the diseases requiring autologous BMT”, the authors suggest.

When compared with age-matched individuals from the general population, the standardised incidence ratio (SIR) of breast cancer in study participants over 16,315.8 patient–years of follow-up was a nonsignificant 1.3.

A significant increase in risk was found among the TBI cohort (SIR=1.5) and for allogeneic BMT patients who received TBI (SIR=1.8), but not among their autologous BMT TBI-treated counterparts.

However, the largest excess risk of breast cancer was sustained by patients who received TBI before age 30 years (SIR=4.5) and this was true for both allogeneic BMT (SIR=4.4) and autologous BMT (SIR=4.6) patients.

Indeed, the cumulative probability of breast cancer diagnosis for women given TBI for BMT before the age of 30 years was 1.0% by age 40 years and 13.9% by age 50 years, the researchers say.

“These findings provide a framework for screening for breast cancer among TBI-exposed BMT recipients with respect to the age at initiation of screening, and they also provide a rationale for the use of screening strategies similar to those used in other chest-irradiated cancer survivors at an elevated risk of breast cancer”, Smita Bhatia and co-authors write.

They suggest that future research could focus on the contribution of familial breast cancer risk and better assessment of the TBI dose–response relationship in this patient population. 

Reference 

McDonald AM, Chen Y, Wu J, et al. Total body irradiation and risk of breast cancer after blood or bone marrow transplantation: A blood or marrow transplantation survivor study report. J Clin Oncol; Advance online publication 16 July 2020. DOI: 10.1200/JCO.20.00231