Doxorubicin Exposure and Risk of Breast Cancer in Survivors of Hodgkin Lymphoma

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In a Dutch study reported in the Journal of Clinical Oncology, Neppelenbroek et al found that doxorubicin treatment was associated with an increased risk of breast cancer among adolescent and adult Hodgkin lymphoma survivors.

Study Details

The study involved a cohort of 1,964 female 5-year Hodgkin lymphoma survivors treated at age 15 to 50 years in 20 Dutch hospitals between 1975 and 2008.

Key Findings

After a median follow-up of 21.6 years (interquartile range [IQR] = 15.8–27.1 years), 252 women had developed invasive breast cancer or ductal carcinoma in situ, with a 30-year cumulative breast cancer incidence of 20.8% (95% confidence interval [CI] = 18.2%–23.4%). The median interval between Hodgkin lymphoma treatment and breast cancer diagnosis was 19.9 years (IQR = 15.9–24.9 years) and the median age at breast cancer diagnosis was 45.8 years (IQR = 40.6–51.8 years).

Survivors who received a cumulative doxorubicin dose of > 200 mg/m2 had a significantly increased risk of breast cancer (hazard ratio [HR] = 1.5, 95% CI = 1.08–2.1) vs survivors not treated with doxorubicin. Risk of breast cancer increased by 1.18-fold (95% CI = 1.05–1.32) for each additional 100 mg/m2 doxorubicin received (P for trend = .004).

The risk increase associated with doxorubicin exposure vs no exposure was not modified by age at first treatment of < 21 years (HR = 1.5, 95% CI = 0.9–2.6) or ≥ 21 years (HR = 1.3, 95% CI = 0.9–1.9). Risk was also not modified by receipt of chest radiotherapy: hazard ratios were 1.9 (95% CI = 1.06–3.3) without mantle/axillary field radiotherapy and 1.2 (95% CI = 0.8–1.8) with mantle/axillary field radiotherapy.

The investigators concluded, “This study shows that treatment with doxorubicin is associated with increased breast cancer risk in both adolescent and adult Hodgkin lymphoma survivors. Our results have implications for breast cancer surveillance guidelines for Hodgkin lymphoma survivors and treatment strategies for patients with newly diagnosed Hodgkin lymphoma.”

Michael Schaapveld, PhD, of the Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Dutch Cancer Society. For full disclosures of the study authors, visit

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