LAUSR

Abstract Background Breast cancer (BC) incidence increases after treatment for Hodgkin’s disease (HD). Over time, radiation techniques (RT) have reduced in dose and irradiated volume, and fewer alkylating (and gonadotoxic) chemotherapy (CT) agents used. We investigated BC incidence in the context of treatment changes over almost 4 decades and known risk factors. Methods PubMed abstracts were identified using search terms ‘Hodgkin disease’, ‘Breast neoplasm’ and ‘risk’. Articles in English between 01/01/1990-31/12/2018 reporting on risk of BC in HD survivors were included. Outcomes included relative risk (RR), standardized incidence ratio (SIR), absolute excess risk (AER), cumulative incidence (CI), hazard ratio (HR) and odds ratio (OR) of BC in HD survivors. Results 30/245 articles were included. 6 report BC incidence alone (n = 7573). Other factors were RT dose and volume, CT, age at HD and its proximity to menarche and menopause. 10 studies looked at 2 factors (n = 34637), 7 at 3 factors (n = 15253), 4 at 4 factors (n = 5763), and 2 at 5 factors (n = 6110). 1 study was on radiation volume only (n = 734). SIR of BC ranged from 2.4-75.3; AER from 9.2-83.6/10,000 years; RR was 1.9-10.6. Variation is due to differences in cohort characteristics, and incomplete follow-up. BC incidence peaks 11-35 years post HD. Risk remains high at age 50-59 (SIR 3.8), when women are no longer annually screened. BC risk increases if RT is given within 6 months menarche (OR 5.52 (1.97–15.46). Earlier menopause reduces BC risk. BC risk increases linearly with increasing radiation dose. The OR can increase 11-fold with breast doses >40Gy compared to 0Gy. Mantle vs. mediastinal RT doubles HR. CT reduces the BC risk compared with RT alone. Newer RTs reduce BC risk; as a result, some studies demonstrate lower BC incidence in more recent treatment periods (SIR 3.2 in 1970s vs. 1.3 1990-2007). Other studies show no temporal change in incidence. Conclusions Reduction in BC risk from lower doses and volumes of RT may be offset by reduced CT gonadotoxicity from newer regimens and, therefore, the impact of treatment changes over 4 decades on BC incidence requires further investigation. Current guidelines on screening HD survivors need to be adapted to reflect the changes in treatment regimens. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.