Roles of radiotherapy, chemotherapy, and hormonal factors in the risk of breast cancer following treatment for hodgkin's lymphoma

Background. Female patients treated with radiotherapy (RT) for Hodgkin's lymphoma (HL) at a young age have a strongly increased risk of breast cancer (BC). There are still many questions about the influence of reproductive and hormonal factors on BC risk in these patients. This study assesses the influence of radiation dose, and modification of this effect by chemotherapy (CT), menopausal age and hormonal factors for the risk of BC after HL treatment. Methods. We conducted a matched case-control study within a cohort of 1,011 female 5-year HL survivors diagnosed before age 41 between 1965 and 1995. We compared HL treatments and hormonal factors between 143 patients with and 368 controls without breast cancer after HL. Analyses were restricted to cases and controls who received chest irradiation. Results. Patients treated with RT and CT had a lower risk of developing BC compared with patients treated with RT alone (Odds ratio (OR) 0.57, (95% confidence interval (CI) 0.37-0.88)). Compared with women treated with RT only, the OR for BC was 0.43 (95%CI 0.22-0.85) for women treated with 4.2-8.4 g/m2 procarbazine and 0.30 (95%CI 0.10-0.89) for those treated with more than 8.4 g/m2 procarbazine. This association appeared to be due to the effect of CT on ovarian function: 14% of women treated with RT only became menopausal before age 41 compared to 93% of women treated with 4.2 g/m2 procarbazine or more. Reaching menopause before age 31 was associated with a lower risk of BC compared to women who reached menopause after age 50 (OR 0.35, 95%CI 0.13-1.46). Analyses concerning the influence of other hormonal factors and dosimetry are currently being performed. Conclusion. A procarbazine dose of 4.2 g/m2 or more reduces the risk of RT-induced BC due to CT-induced premature menopause. results Regarding other hormonal factors and radiation dosimetry will be presented.