Originally published as JCO Early Release 10.1200/JCO.2008.19.9174 on August 10 2009

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Breast Cancer Risk in Female Survivors of Hodgkin's Lymphoma: Lower Risk After Smaller Radiation Volumes

From the Departments of Epidemiology and Radiotherapy and Division of Experimental Therapy, the Netherlands Cancer Institute; Department of Hematology, Vrije Universiteit Medical Center; Department of Paediatric Oncology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, Amsterdam; Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen; Departments of Hematology and Radiotherapy, Erasmus MC, Daniel den Hoed Cancer Center, Rotterdam; Department of Radiotherapy, Leiden University Medical Center, Leiden; and the Eindhoven Cancer Registry, Comprehensive Cancer Center South, Eindhoven, the Netherlands.

Corresponding author: Flora E. van Leeuwen, PhD, Department of Epidemiology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: F.v.Leeuwen{at}nki.nl.

Purpose We assessed the long-term risk of breast cancer (BC) after treatment for Hodgkin's lymphoma (HL). We focused on the volume of breast tissue exposed to radiation and the influence of gonadotoxic chemotherapy (CT).

Patients and Methods We performed a cohort study among 1,122 female 5-year survivors treated for HL before the age of 51 years between 1965 and 1995. We compared the incidence of BC with that in the general population. To assess the risk according to radiation volume and hormone factors, we performed multivariate Cox regression analyses.

Results After a median follow-up of 17.8 years, 120 women developed BC (standardized incidence ratio [SIR], 5.6; 95% CI, 4.6 to 6.8), absolute excess risk 57 per 10,000 patients per year. The overall cumulative incidence 30 years after treatment was 19% (95% CI, 16% to 23%); for those treated before age 21 years, it was 26% (95% CI, 19% to 33%). The relative risk remained high after prolonged follow-up (> 30 years after treatment: SIR, 9.5; 95% CI, 4.9 to 16.6). Mantle field irradiation (involving the axillary, mediastinal, and neck nodes) was associated with a 2.7-fold increased risk (95% CI, 1.1 to 6.9) compared with similarly dosed (36 to 44 Gy) mediastinal irradiation alone. Women with 20 years of intact ovarian function after radiotherapy at young ages (< 31 years) experienced significantly higher risks for BC than those with fewer than 10 years of intact ovarian function.

Conclusion Reduction of radiation volume appears to decrease the risk for BC after HL. In addition, shorter duration of intact ovarian function after irradiation is associated with a significant reduction of the risk for BC.

Supported by Grants No. NKI 98-1833 and NKI 04-3068 from the Dutch Cancer Society, Amsterdam, the Netherlands.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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