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Discovering the causes of cancer and the means of prevention

Multiple Primary Cancer Monograph

The last three decades have seen dramatic improvements in cancer survival, mainly due to advances in treatment and the increased detection of cancer at an early stage. With more than 15 million cancer survivors in the U.S. alone, concern has turned to potential late effects, particularly the development of a new malignancy. To identify groups of cancer survivors who are at increased risk for multiple primary cancers, investigators in the Radiation Epidemiology Branch (REB) led a collaborative effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., published in 2006 as a monograph entitled New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000 (PDF, 3.1MB), Curtis RE, Freedman DM, Ron E, Ries LAG, Hacker D, Edwards B, Tucker P, Fraumeni JF, Jr., editors. 

The 500-page monograph utilized data from nine cancer registries participating in the Surveillance, Epidemiology, and End Results (SEER) Program from 1973 to 2000. The monograph describes the patterns of subsequent cancer risk for over 50 adult first primary cancers and 19 types of childhood cancers, by gender, age at initial diagnosis, time since diagnosis, initial treatment by radiation, and histologic type. Each chapter focuses on a specific initial cancer, presents the risk of subsequent cancers, and discusses potential causal mechanisms. The monograph provides a resource that will be useful to clinicians, researchers, policy makers, and cancer survivors, especially in tailoring appropriate guidelines and strategies for prevention and early detection of new malignancies. Other studies have evaluated risk of subsequent cancers for individual cancer types or groups of cancers, usually related to the late effects of treatment, but this report provides the first complete evaluation of subsequent cancer risk in the U.S.

The survey of 2 million cancer survivors (including 76,000 20-year survivors) revealed that 9.1% (n = 186,000) developed a new malignancy. Development of a second cancer was likely dependent on multiple factors, including tobacco use, alcohol use, hormonal influences, viral infections, genetic predisposition, and the adverse effects of treatment. Risks of developing a new malignancy were substantially higher among children (relative risks of 6-fold) than among adults. Expanded use of aggressive cancer treatments, particularly combined modality radiotherapy and chemotherapy, likely contributed to the increased incidence of second malignancies. The highest treatment-related risks were apparent for children and young adults. Overall, radiotherapy for most adult-onset cancers (at age 50 or older) was not associated with a large increase in subsequent cancer risk, except in specific patient subgroups (e.g., 10-year survivors of breast cancer treated with high dose radiotherapy to the chest wall and lymph nodes had excess subsequent cancers of the esophagus, bone, soft tissue, and lung).

The monograph’s results reveal variation in the burden of second cancers among cancer survivors. Combined tobacco and alcohol use likely accounted for a substantial excess of subsequent cancers following initial upper aerodigestive and respiratory tract cancers. Because of shared reproductive risk factors, cancers of the breast, uterine corpus, and ovary tended to cluster as multiple tumors within individual survivors. Increased risks of certain subsequent malignancies among younger patients (e.g., colon, ovarian, or breast cancer following initial breast cancer) suggested possible genetic predisposition. Evidence of virally-related second tumors was noted for initial cancers of the cervix and anus and for Kaposi sarcoma. The monograph’s identification of patient groups at increased risk for secondary malignancy should lead to the implementation of early diagnosis programs and reduction of morbidity and mortality associated with late cancer occurrence.

Learn more about second primary research in DCEG.