Clinicopathologic features of breast cancers diagnosed in females treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.

Abstract

567 Background: Childhood and young adult survivors of Hodgkin Lymphoma are at an increased risk of developing breast cancer, although little data exist on the characteristics and biologic subtype of breast cancers that develop in this high-risk population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all histologically confirmed breast cancers diagnosed between 1990-2016 in women treated with prior radiation therapy for Hodgkin Lymphoma ≤ 30 years of age. Clinicopathologic features of subsequent breast cancers (BC-HL) were examined and compared to breast cancers diagnosed in women with no prior malignancy (BC-NPM). The association between prior chemotherapy use and biologic subtype of BC-HL was evaluated. Results: We identified 321 breast cancers diagnosed in 257 women with a history of radiation therapy for Hodgkin Lymphoma. The median age at Hodgkin Lymphoma diagnosis was 22 years (range, 12-30 years), and nearly all BC-HL (97.9%) were diagnosed 8 or more years after radiation therapy. Overall, 56 (21.8%) BC-HL patients developed bilateral breast cancer, of which 28 (50%) were synchronous. When compared to women with BC-NPM, women with BC-HL were significantly younger at time of diagnosis (median age, 43 years vs. 60 years, p<0.001) and less likely to present with ductal carcinoma in situ (8.4% vs. 14.9%, p=0.001). Patients with invasive BC-HL were more likely to have high grade (43.8% vs. 32.9%, p<0.001), estrogen receptor (ER) negative breast cancer (27.7% vs. 18.2%, p<0.001), although pathologic tumor size, nodal status, and stage were not significantly different from those with BC-NPM. Compared to women with BC-NPM, the majority of operable BC-HL patients underwent surgical management with mastectomy (86.5% vs. 42.5%, p<0.001). In subset analysis of 102 women for which HER2 status was available, BC-HL were HER2+ in 18.7% of patients. Distribution of biologic subtype between BC-HL and BC-NPM are shown in the table below. In BC-HL patients, prior chemotherapy exposure was not associated with substantial differences in the proportion of ER+HER2- breast cancers (65.8% vs. 63.5%, p=0.82). Conclusions: Breast cancers in women treated with radiation therapy for Hodgkin Lymphoma are characterized by earlier onset and more aggressive biologic features, although the majority remain estrogen sensitive and early stage at presentation. Further studies are warranted to evaluate the use of preventive strategies in this high-risk patient population.[Table: see text]