Breast cancer risk following radiotherapy for Hodgkin lymphoma: Modification by other breast cancer risk factors.
Authors: Deirdre A. Hill, Ethel Gilbert, Graca Dores, Mary Gospodarowicz, Flora E. Van Leeuwen, Eric Holowaty, Bengt Glimrliud, Michael Andersson, Tom Wiklund, Charles F. Lynch, Mars Van’t Veer, Ingrid Glimelius, Hans Storm, Eero Pukkala, Marilyn Stovall, Rochelle Curtis, John D. Boice, Lois B. Travis
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3130 

Background Young women treated for Hodgkin lymphoma (HL) with high doses of radiotherapy (RT) to the breast have a significantly increased risk of breast cancer. However, risk is reduced almost in half by HL treatment with selected alkylating agent (AA) chemotherapy, or radiation doses to the ovary > 5 gray (Gy), each of which may induce early menopause. Objective We sought to determine whether the risk of breast cancer associated with HL radiotherapy is modified by established breast cancer risk factors. Methods A cohort of 3,817 female one-year survivors of HL diagnosed at age 30 or less between 1965 and 1994 were followed in six population-based cancer registries. Breast cancer developed in 105 women, who were matched to 266 controls. Since almost all women received RT to the chest, radiation dose to the site where breast cancer developed (median 22 Gy; range .07- 56.0 Gy in exposed controls) was modeled as a continuous variable. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for confounders and other HL treatments. Results Mean age at breast cancer diagnosis was 41 years, and 78% of cases and 62% of controls with known menopausal status were pre- or peri-menopausal at study end. Breast cancer risks in relation to established risk factors were consistent with those reported in previous studies among young women, including a negligible effect of parity on risk. Overall, breast cancer risk increased 1.04-fold (95% CI 1.01-1.07) for each 1 Gy increment in breast dose. Among women who did not receive AA or ovarian radiation > 5 Gy (treatments associated with ovarian suppression), parous women experienced an increase in breast cancer risk with increasing breast radiation dose (OR 1.05 per Gy; 95% CI 1.02-1.08; n=50 cases, 91 controls), which was less evident among nulliparous women (OR 1.0 per Gy; 95% CI 0.96-1.04; 17 cases, 29 controls). Breast cancer risk also increased with increasing breast dose among women without a known first degree family history of breast or ovarian cancer (OR 1.08 per Gy; 95% CI 1.03-1.13; 59 cases, 135 controls), and the corresponding odds ratio among women with such history was 0.98 per Gy (95% CI 0.92-1.05; n=14 cases, 14 controls). On a multiplicative scale, the RT dose-response did not appear to be modified by other established breast cancer risk factors, including age at menarche, age at first birth, number of live births, and body mass index. Discussion Breast cancer risk following RT for HL may be modified by a few established breast cancer risk factors, although data were sparse in some subgroups. HL treatment may involve large breast radiation doses, thus our findings may not be generalizable to all settings.