Breast cancer after hodgkin's disease: Retrospective analysis of 30 cases

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin’s disease in relation to age at treatment and other factors. PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin’s disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete. RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3.3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55.9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy). CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin’s disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin’s disease require detailed investigation.

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Current perspectives on radiation-induced breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.1.338 ◽

1998 ◽

Vol 16 (1) ◽

pp. 338-347 ◽

Cited By ~ 69

Author(s):

P E Goss ◽

S Sierra

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Secondary Prevention ◽

Radiation Exposure ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Prospective Trial ◽

Brca1 And Brca2 ◽

Published Evidence ◽

Radiation Induced

PURPOSE An approach to screening and detection of radiation-induced breast cancer is offered. Primary and secondary prevention strategies are suggested and the need for prospective clinical trials is emphasized. METHODS Data are reviewed from published evidence of radiation-induced breast cancer secondary to atomic bomb radiation, occupational, and therapeutic exposure, especially that incurred during successful treatment of Hodgkin's disease (HD). Preclinical studies are reviewed to explore potential risk factors. RESULTS Risk factors evident in the link between radiation and breast cancer include the differentiation of breast tissue as mediated by age and hormonal influence. Evidence is presented exploring the link between genetics and breast cancer, including specific genes such as the BRCA1 and BRCA2 genes, the p53 gene, the ataxia telangiectasia (AT) gene, and other nonspecific alterations in DNA repair proficiency. In light of these findings, steps toward primary prevention are discussed, including avoiding radiation exposure, genetic screening, and manipulation of the hormonal milieu. Secondary prevention may also be possible with the use of tamoxifen, low-fat diets, and/or the consumption of flaxseed. CONCLUSION Our current recommendations for patients irradiated before 30 years of age for Hodgkin's disease include breast self-examination (BSE) monthly, yearly mammography 8 years postirradiation, and regular physical examinations every 6 months. Given the clear link between radiation exposure and breast cancer, we strongly recommend a prospective trial randomize patients to different levels of intensity of surveillance to monitor the efficacy of such screening efforts.

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