medwireNews: Dutch research indicates that women who survive Hodgkin’s lymphoma diagnosed during adolescence or adulthood have a higher risk for developing breast cancer if they receive doxorubicin than if they do not.
The researchers explain that doxorubicin exposure has been linked to increased breast cancer risk in childhood cancer survivors, but theirs is the first study to evaluate the association in Hodgkin’s lymphoma survivors treated at adult ages.
They continue: “Our findings corroborate the carcinogenic potential of doxorubicin and suggest that the increased use of doxorubicin may partly explain why [Hodgkin’s lymphoma] survivors treated in more recent years do not experience lower [breast cancer] risk than survivors treated before the 1990s, when [mantle field] irradiation was widely used.”
The team analyzed data on 1964 female 5-year survivors who had Hodgkin’s lymphoma as their first malignancy and received treatment at age 15–50 years in 20 Dutch centers between 1975 and 2008. The majority (69.8%) received chemotherapy plus radiotherapy and 11.4% received chemotherapy alone. Over half (56.7%) of the patients received doxorubicin.
During a median follow-up of 21.6 years, 252 women developed breast cancer (invasive or ductal carcinoma in situ), and the 30-year cumulative incidence was 20.8% versus the expected incidence of around 5.0% in the Dutch general population.
Use of doxorubicin was associated with a significant 1.4-fold increased risk for breast cancer compared with no use, after adjustment for age at Hodgkin’s lymphoma diagnosis, chest radiotherapy, and gonadotoxic treatment.
When stratified by doxorubicin dose, the association remained significant for doses greater than 200 mg/m2, with a hazard ratio of 1.5 versus no use, but not for lower doses.
And each 100 mg/m2 increase in doxorubicin dose correlated with a significant 1.18-fold increase in breast cancer risk, report Michael Schaapveld (Netherlands Cancer Institute, Amsterdam) and co-researchers in the Journal of Clinical Oncology.
Of note, the risk increase with doxorubicin exposure was not modified by either age at first treatment or receipt of chest radiotherapy, they add.
The investigators also highlight that the findings were similar in sensitivity analyses that excluded individuals with ductal carcinoma in situ and those with missing data on treatment variables.
And they conclude: “In balancing treatment efficacy and toxicity, studies have focused on omitting [radiotherapy] and trying to cure patients with early-stage [Hodgkin’s lymphoma] with chemotherapy alone.
“Doxorubicin-associated [breast cancer] risk may be an additional late effect that needs to be considered when weighing risks and benefits of chemotherapy only versus combined modality in primary treatment.”
Writing in an accompanying editorial, John Radford, from the University of Manchester in the UK, describes the study as “intriguing and thought provoking.”
He continues: “These results, which will inform conversations with patients about the late consequences of their treatment and prompt a review of screening guidelines, once again emphasize the importance of long-term follow-up of patients treated for curable cancers.”
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J Clin Oncol 2024; doi:10.1200/JCO.23.01386
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