Breast Cancer in Young Women after Treatment with Irradiation for Hodgkin’s Lymphoma.
Authors: Lee Linda , Pintilie Melania , Hodgson David , Crump Michael 
Published: October 2019

Abstract
BACKGROUND: Women who are survivors of Hodgkin’s Lymphoma (HL) are at increased risk of developing breast cancer (BCa) as a long-term complication due to the use of extended field (mantle) irradiation (RT) of disease above the diaphragm. Many young women are at significantly increased risk of BCa prior to the age at which routine screening mammography is recommended for the general population. The sensitivity of mammography is lower in these women, in part due to increased breast tissue density characteristic of young pre-menopausal women. Currently, there is a paucity of information on the optimal screening modality and surveillance frequency for these women.
METHODS: We reviewed the current BCa screening strategies used for this high risk group at our centre and described the incidence, method of detection, and characteristics of secondary BCas in a cohort of 115 women who received supradiaphragmatic RT for HL before age 30 between 1965 and 2000 at Princess Margaret Hospital (PMH) and who subsequently accepted long-term follow-up in a high-risk screening clinic.
RESULTS: Median age at treatment was 22 (range 9–30). Radiation fields were mantle in 106 women, modified mantle in 6, and involved field in 3 (median dose delivered: 35 Gy, range 15–60). RT alone was used for 44 patients while 71 received combined modality therapy, of which 45 (65%) received MOPP. Treatment induced amenorrhea occurred in 15 women (median age 38); hormone replacement therapy was subsequently used by 9. Of the 107 women who participated in annual radiographic BCa screening, 95 were screened with mammogram alone, 1 with breast MRI alone, 8 with mammogram and MRI, and 3 with mammogram and ultrasound. Median age at first mammogram was 36; however, median age decreased with more recent year of HL diagnosis (age 40 for women diagnosed before 1985 compared to age 33 for women diagnosed after 1985, p<0.0001). Women with high breast density received MRI screening more often (p=0.02); however, breast density was not significantly associated with previous breast radiation dose or age at last follow-up. Twelve women were diagnosed with BCa in this cohort, following active breast surveillance for a median of 5 years (representing 584 person-years). The 20-year cumulative incidence of breast cancer was 10.9% (95% CI 5.3–18.8%) in this group of women. This was comparable to the 20-year cumulative incidence of breast cancer of 12% (95% CI 8–17%) in all 448 women with HL treated with supradiaphragmatic radiation before age 30 at PMH during the same time period. BCa occurred after a median of 17 years after treatment for HL (range 13–28). Median age at BCa diagnosis was 40 (range 31–51). Seven cancers were detected by physical exam (6 node-positive invasive BCas, 1 in-situ BCa) and 5 were detected on annual mammograms (1 node-positive invasive BCa, 4 in-situ BCas).
CONCLUSIONS: Although women in the more recent treatment cohort are receiving their first mammogram at a younger age, the majority of BCas were still detected clinically, and these BCas had less favorable pathological characteristics. More frequent breast imaging should be considered in women who have had supradiaphragmatic RT for HL. Prospective evaluation of breast MRI as a screening strategy for HL survivors has been initiated at PMH in an effort to detect BCa at an earlier stage.