Doxorubicin treatment of Hodgkin lymphoma increases the risk of breast cancer many years later, regardless of age at exposure and in addition to the known risk from radiotherapy, a study has shown.
While the effects of radiotherapy on second cancer risk have been known for many years, the new findings from a 20-year follow up study of almost 2000 people treated for Hodgkin lymphoma indicate that exposure to doxorubicin should now also be factored in when it comes to risk mitigation and long term follow up of adolescent and adults patients with Hodgkin lymphoma, researchers say.
In a paper published in Journal of Clinical Oncology (link here), clinicians from the Netherlands said previous studies in childhood survivors of Hodgkin lymphoma had reported an increased risk of breast cancer in those exposed to chemotherapy with doxorubicin.
However, until now this effect has not been described in an older population where doxorubicin-containing regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) are the mainstay of first-line treatment.
Doxorubicin chemotherapy had become more widely used in recent years as an alternative to gonadotoxic chemotherapy regimens. It could potentially cause second cancers, they suggested, because it causes DNA damage by inducing double-strand breaks, and chromatin damage through histone eviction in the genome.
Their new study followed 1964 females aged 15-50 when first treated for Hodgkin lymphoma between 1975 and 2008 and who subsequently survived at least five years.
After a median of 21.6 years follow-up the key finding was that patients who received a total cumulative dose of doxorubicin 200mg/m2 had a 1.5-fold increased risk of breast cancer compared with those not exposed to doxorubicin.
Moreover, each additional cumulative dose of 100mg/m2 was associated with a further 1.18- fold increase in risk (Ptrend =0.004) and the risk increase associated with doxorubicin was not modified by age at first treatment or chest radiotherapy, reported Dr Suzanne Neppelenbroek and colleagues from the Netherlands Cancer Institute, Amsterdam.
The association of doxorubicin with breast cancer risk appeared to be present only after 20 years following treatment for Hodgkin lymphoma, and not in the five-19 years interval after treatment, possibly reflecting an anthracycline-associated induction period for breast cancer.
“Our study shows that it remains of great importance to follow patients for more than 20 years after their treatment has been completed,” the authors said.
“Our findings confirm the importance of risk-based long-term follow-up care for lymphoma survivors and possibly survivors of other cancers treated with doxorubicin.”