Breast cancer risk after radiotherapy for Hodgkin lymphoma : influence of gonadal hormone exposure
Menée à l'aide de questionnaires et à partir de données de registres médicaux portant sur 466 témoins et 174 patientes atteintes avant 41 ans d'un lymphome hodgkinien traité par radiothérapie, cette étude évalue l'effet des hormones ovariennes d'origine endogène ou exogène (traitement hormonal substitutif) sur l'association entre radiothérapie et risque de cancer du sein
Background : Young women treated with chest radiotherapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. Methods : We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC cases and 466 controls. Radiation dose to breast tumor location was estimated based on RT charts, simulation films and mammography reports. Results : We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gray (95%CI:2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR:0.13, 95%CI:0.03-0.51) than women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<0.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR:0.86, 95%CI:0.32-2.32), while this risk was non-significantly increased among women without early menopause (OR:3.69, 95%CI:0.97-14.0, P for interaction:0.06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. Conclusion : BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship.