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Hodgkin lymphoma survivors at increased risk for breast cancer

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January 24, 2018

Risk for ER-negative breast cancer appeared higher among survivors of Hodgkin lymphoma compared with the general population, according to a research letter published in JAMA Oncology.

Patients who received radiotherapy for treatment of their Hodgkin lymphoma also had an increased risk for ER-positive breast cancer.

Survivors of Hodgkin lymphoma have a high risk [for] developing a subsequent breast cancer, particularly after chest irradiation,” Diana R. Withrow, PhD, postdoctoral fellow in the radiation epidemiology branch of the NCI, and colleagues wrote. “Although breast cancer is a heterogeneous disease, the association between [Hodgkin lymphoma] treatment and the ER status of subsequent breast cancers has not been examined in large cohorts.”

Withrow and colleagues used SEER data to evaluate 7,355 women aged 10 to 39 years (mean age at diagnosis, 26 years) when diagnosed with primary Hodgkin lymphoma between 1973 to 2009.

Follow-up ended at breast cancer diagnosis, last known status, death or December 2014. Mean follow-up was 12 years (range, 5 to 38).

Researchers classified patients’ radiotherapy and/or chemotherapy status for their first course of Hodgkin lymphoma treatment as yes or no/unknown.

Withrow and colleagues identified 377 incidences of invasive breast cancer — 57% were ER positive, 34% were ER negative, and 9% had unknown or borderline ER status.

Researchers estimated standardized incidence ratios (SIRs) for ER-positive and -negative breast cancer using expected rates of each subtype based on age, race and calendar year in the SEER general population.

Survivors of Hodgkin lymphoma had a greater relative risk for developing ER-negative breast cancer (SIR = 5.8; 95% CI, 4.8-6.9) than ER-positive breast cancer (SIR = 3.1; 95% CI, 2.7-3.5; P < .001 for difference).

For ER-positive breast cancer, increased SIR only occurred among those who received radiotherapy (SIR = 3.9; 95% CI, 3.4-4.5). Relative risk did not vary significantly by treatment for ER-negative breast cancer.

Limitations of this study included lack of information on family history, reproductive factors, hormone replacement therapy, radiotherapy dose, fields, specific chemotherapeutic agents and subsequent therapy as part of the SEER registries.

“Despite changes in treatment recommendations, 40% of young women with [Hodgkin lymphoma] currently receive radiotherapy, which was associated with an increased risk [for] ER-positive breast cancer in our study,” the researchers wrote.

“Further investigation of the association between [Hodgkin lymphoma] treatment and breast cancer subtype in studies with comprehensive treatment records will lead to a better understanding of the risk [for] and etiology of subsequent breast cancers and can ultimately inform treatment and screening decisions to reduce morbidity and mortality among [Hodgkin lymphoma] survivors,” they added. – by Cassie Homer

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Disclosures: The authors report no relevant financial disclosures.

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PERSPECTIVE
Stefan K. Barta

Stefan K. Barta

It has long been known that second malignancies are more common among Hodgkin lymphoma survivors, reaching an incidence of close to 50% at 40 years. Specifically, breast cancer is one of the more common second cancers, especially among women who received radiation as part of their Hodgkin lymphoma treatment.

Although Withrow and colleagues confirmed the increased incidence of breast cancer among Hodgkin lymphoma survivors, the researchers also found that ER-negative breast cancer occurred more commonly than ER-positive breast cancer. Further, the likelihood of developing ER-positive breast cancer appeared only among patients who received radiation therapy, whereas the risk for developing ER-negative breast cancer increased similarly among women who did and did not receive radiation therapy as part of their treatment. These findings suggest that not only is prior radiation therapy responsible for the increased breast cancer risk among Hodgkin lymphoma survivors, but other factors — such as a general genetic predisposition or chemotherapy, specifically for the ER-negative breast cancer — also may increase risk. More work is needed to elucidate the exact mechanisms that lead to ER-negative breast cancers among Hodgkin lymphoma survivors. The findings highlight the need for close surveillance and aggressive cancer screening among Hodgkin lymphoma survivors to detect second malignancies early and limit the impact of late treatment complications.


Stefan K. Barta, MD, MS, MRCP

Fox Chase Cancer Center

Disclosures: Barta reports research funding from Celgene, Merck and Seattle Genetics, and a consultant role with Janssen.