Radiation therapy for Hodgkin’s lymphoma associated with increased risk for bilateral breast cancer

Elkin EB. J Clin Oncol. 2011;doi:10.1200/JCO.2010.32.4079.

Results of a study of nearly 1,000 women found that those treated with radiation for Hodgkin’s lymphoma were more likely to develop bilateral breast cancer and had a higher incidence of all-cause mortality.

Researchers enrolled 253 women in North America diagnosed with Hodgkin’s lymphoma and treated with radiation from 1980 and 2006. The median cumulative radiation dose was 39 Gy, and 90% of patients received more than 30 Gy.

Those women were matched with 741 women who had sporadic breast cancer and no history of lymphoma.

Compared with patients diagnosed with sporadic breast cancer, patients treated for Hodgkin’s lymphoma were more likely to present with bilateral disease (6% vs. 2%), more likely to have breast cancer detected by screening mammography (40% vs. 33%) and more likely to be diagnosed at an earlier stage (61% vs. 42%). Conversely, survivors of lymphoma were less likely to have axillary lymph node involvement (25% vs. 39%) and less likely to be premenopausal at diagnosis (49% vs. 69%).

Researchers found that breast cancer event-free survival and breast cancer-specific survival were similar between the groups. However, all-cause mortality was significantly higher in patients treated for lymphoma. In adjusted analysis, rates of locoregional and metastatic failure and breast cancer mortality were elevated, but these differences were not statistically significant.

Multivariate analysis showed that the patients with lymphoma had poorer survival. After controlling for patient and disease characteristics and breast cancer treatment, the risk for all-cause mortality for patients with lymphoma was almost twice that of the control group (HR=1.9; 95% CI, 1.1-3.3).

Meena S. Moran, MD

This multi-institutional retrospective study analyzed breast cancer detection and outcomes in female patients treated with radiation to the mediastinal area for Hodgkin's disease several decades ago, compared to matched breast cancer patients who did not have Hodgkin's disease. The authors demonstrated several important differences: Patients with a history of Hodgkin's were more likely to be detected by screening (and not physical exam), were diagnosed at earlier stages of disease, and were more likely to have bilateral breast cancers and develop metachronous contralateral breast cancers.

While this study also found that overall survival was less in women with Hodgkin's disease, the breast cancer-specific survival did not differ. What this means is that Hodgkins patients have a higher risk of death, but it is not due to developing breast cancers with worse outcomes, and it remains unclear whether the worse survival is secondary to additional malignancies such as lung cancer, cardiac disease (which may have been potentiated by the previous mediastinal radiation) or some other cause. But it is important to note that the way we treat Hodgkin's today is very different than the way we did in the era in which the patients in this study were treated, in that the current regimens use chemotherapy more often with a trend to significantly decrease radiation doses and field volumes (if not completely eliminate radiation).

Thus, these data are not applicable to the patients undergoing radiation treatment for Hodgkin's in the current era, but are important for patients treated several decades ago (and their managing physicians). As the authors mention in their discussion, awareness of these findings can allow for measures to be taken (by the patient and physicians) to reduce risks and provide earlier detection and treatment for the potential long-term sequela of mediastinal radiation, for example earlier breast cancer screening, smoking cessation and management of risk factors for cardiovascular disease.

- Meena S. Moran, MD
Medical Director of Radiation Oncology at William W. Backus Hospital, Norwich, Conn.

Disclosure: Dr. Moran reported no relevant disclosures.

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