Breast cancer risk after radiotherapy for Hodgkin lymphoma: influence of gonadal hormone exposure

Publication date: Available online 18 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Inge M. Krul, Annemieke W.J. Opstal – van Winden, Berthe M.P. Aleman, Cécile P.M. Janus, Anna M. van Eggermond, Marie L. De Bruin, Michael Hauptmann, Augustinus D.G. Krol, Michael Schaapveld, Annegien Broeks, Karen R. Kooijman, Sandra Fase, Marnix L. Lybeert, Josée M. Zijlstra, Richard W.M. van der Maazen, Ausrele Kesminiene, Ibrahima Diallo, Florent de Vathaire, Nicola S. Russell, Flora E. van Leeuwen
BackgroundYoung 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.MethodsWe 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.ResultsWe 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.ConclusionBC 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.

Teaser

It is unknown whether gonadal hormone exposure affects the risk of radiation-associated breast cancer in female Hodgkin lymphoma survivors. We performed a nested-case control study to assess the separate and joint effects of radiation dose to the breast and hormone exposure on breast cancer risk. Risk increased linearly with radiation dose, decreased with shorter duration of ovarian function, and did not appear to be influenced by hormone use among women with treatment-induced early menopause.


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