Breast Cancer after Childhood Cancer

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Background: Survivors of childhood cancer are at risk for secondary breast cancer. Other than previous chest radiation therapy, risk factors for secondary breast cancer have not been established.

Objective: To identify risk factors for breast cancer among female survivors of childhood cancer.

Design: Retrospective cohort study.

Setting: The Childhood Cancer Survivor Study (CCSS), a multicenter study of persons who survived more than 5 years after childhood cancer diagnosed from 1970 to 1986.

Participants: Among 6068 women in the CCSS, 95 women had 111 confirmed cases of breast cancer.

Measurements: Standardized incidence ratios for breast cancer were calculated by using age-specific incidence rates in the general population. Breast cancer incidence was evaluated with respect to primary cancer diagnosis and therapy, age at and time since primary diagnosis, menstrual and reproductive history, and family history of cancer.

Results: Breast cancer risk was increased in survivors who were treated with chest radiation therapy (standardized incidence ratio, 24.7 [95% CI, 19.3 to 31.0]) and survivors of bone and soft-tissue sarcoma who were not treated with chest radiation therapy (standardized incidence ratios, 6.7 and 7.6, respectively). Family history of breast cancer (relative rate, 2.7 [CI, 1.3 to 5.0]) and history of thyroid disease (relative rate, 1.7 [CI, 1.1 to 2.6]) were independently associated with increased risk, and exposure to pelvic radiation was protective (relative rate, 0.6 [CI, 0.4 to 0.9]). Age at primary cancer diagnosis and menstrual and reproductive histories did not statistically significantly modify risk.

Limitations: This cohort has not yet attained an age at which breast cancer risk is greatest.

Conclusion: Survivors of childhood sarcomas and those who received chest radiation therapy are at risk for secondary breast cancer. When assessing a survivor’s risk, clinicians should consider primary diagnosis, previous radiation therapy, family cancer history, and history of thyroid disease.

Editors’ Notes

Context

• Adult survivors of childhood cancer are at risk for developing breast cancer and other secondary cancer. Knowing the risk factors for breast cancer in these women may help to formulate screening policies for them.

  Contribution

• Among 6068 women who survived childhood cancer, 95 developed breast cancer at a median age of 35 years. Childhood sarcoma, chest irradiation, family history of breast cancer, and personal history of thyroid disease increased the risk for breast cancer.

  Implications

• Women who survived childhood cancer and had sarcoma, chest irradiation, family history of breast cancer, or personal history of thyroid disease should consider early, vigilant screening for breast cancer.

Requests for Single Reprints: Lisa B. Kenney, MD, David B. Perini, Jr. Quality of Life Clinic, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115; e-mail, .

Current Author Addresses: Drs. Kenney and Diller: David B. Perini, Jr. Quality of Life Clinic, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Dr. Yasui: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, PO Box 19024, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024.

Mr. Inskip: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Executive Plaza South, Room 7052, Bethesda, MD 20892.

Dr. Hammond: Anatomic Pathology, Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205.

Dr. Neglia: Division of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, University of Minnesota, MMC 484, 420 Delaware Street SE, Minneapolis, MN 55455.

Dr. Mertens: Department of Pediatrics, University of Minnesota, MMC 715, 420 Delaware Street SE, Minneapolis, MN 55455.

Dr. Meadows: The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104.

Dr. Friedman: Children’s Hospital and Regional Medical Center, Division of Hematology/Oncology, Mailstop 6D1, 4800 Sand Point Way NE, Seattle WA 98105.

Dr. Robison: Cancer Center, University of Minnesota, MMC 422, Minneapolis, MN 55455.

Lisa B. Kenney, MD; Yutaka Yasui, PhD; Peter D. Inskip, ScD; Sue Hammond, MD; Joseph P. Neglia, MD; Ann C. Mertens, PhD; Anna T. Meadows, MD; Debra Friedman, MD; Leslie L. Robison, PhD; and Lisa Diller, MD

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