Faculty Opinions recommendation of Radiation dose and breast cancer risk in the childhood cancer survivor study.

Purpose Little is known about the breast cancer risk among childhood cancer survivors who did not receive chest radiotherapy. We sought to determine the magnitude of risk and associated risk factors for breast cancer among these women. Patients and Methods We evaluated cumulative breast cancer risk in 3,768 female childhood cancer survivors without a history of chest radiotherapy who were participants in the Childhood Cancer Survivor Study. Results With median follow up of 25.5 years (range, 8 to 39 years), 47 women developed breast cancer at a median age of 38.0 years (range, 22 to 47 years) and median of 24.0 years (range, 10 to 34 years) from primary cancer to breast cancer. A four-fold increased breast cancer risk (standardized incidence ratio [SIR] = 4.0; 95% CI, 3.0 to 5.3) was observed when compared with the general population. Risk was highest among sarcoma and leukemia survivors (SIR = 5.3; 95% CI, 3.6 to 7.8 and SIR = 4.1; 95% CI, 2.4 to 6.9, respectively). By the age of 45 years, the cumulative incidence of breast cancer in sarcoma and leukemia survivors was 5.8% (95% CI, 3.7 to 8.4) and 6.3% (95% CI, 3.0 to 11.3), respectively. No other primary cancer diagnosis was associated with an elevated risk. Alkylators and anthracyclines were associated with an increased breast cancer risk in a dose-dependent manner (P values from test for trend were both < .01). Conclusions Women not exposed to chest radiotherapy who survive childhood sarcoma or leukemia have an increased risk of breast cancer at a young age. The data suggest high-dose alkylator and anthracycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.

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Mortality After Breast Cancer Among Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology ◽

10.1200/jco.18.02219 ◽

2019 ◽

Vol 37 (24) ◽

pp. 2120-2130 ◽

Cited By ~ 4

Author(s):

Chaya S. Moskowitz ◽

Joanne F. Chou ◽

Joseph P. Neglia ◽

Ann H. Partridge ◽

Rebecca M. Howell ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Survivors ◽

Childhood Cancer ◽

Cancer Survivor ◽

De Novo ◽

Childhood Cancer Survivors ◽

Childhood Cancer Survivor ◽

Malignant Neoplasms ◽

Childhood Cancer Survivor Study ◽

Survivors Of Childhood Cancer

PURPOSE Female survivors of childhood cancer have a high risk of subsequent breast cancer. We describe the ensuing risk for mortality and additional breast cancers. PATIENTS AND METHODS Female participants in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of cancer diagnosed between 1970 and 1986 before age 21 years, and subsequently diagnosed with breast cancer (n = 274; median age at breast cancer diagnosis, 38 years; range, 20 to 58 years) were matched to a control group (n = 1,095) with de novo breast cancer. Hazard ratios (HRs) and 95% CIs were estimated from cause-specific proportional hazards models. RESULTS Ninety-two childhood cancer survivors died, 49 as a result of breast cancer. Overall survival after breast cancer was 73% by 10 years. Subsequent risk of death as a result of any cause was higher among childhood cancer survivors than among controls (HR, 2.2; 95% CI, 1.7 to 3.0) and remained elevated after adjusting for breast cancer treatment (HR, 2.4; 95% CI, 1.7 to 3.2). Although breast cancer–specific mortality was modestly elevated among childhood cancer survivors (HR, 1.3; 95% CI, 0.9 to 2.0), survivors were five times more likely to die as a result of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (HR, 5.5; 95% CI, 3.4 to 9.0). The cumulative incidence of a second asynchronous breast cancer also was elevated significantly compared with controls ( P < .001). CONCLUSION Mortality after breast cancer was higher in childhood cancer survivors than in women with de novo breast cancer. This increased mortality reflects the burden of comorbidity and highlights the need for risk-reducing interventions.

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Chemotherapy and Risk of Subsequent Malignant Neoplasms in the Childhood Cancer Survivor Study Cohort

Journal of Clinical Oncology ◽

10.1200/jco.19.00129 ◽

2019 ◽

Vol 37 (34) ◽

pp. 3310-3319 ◽

Cited By ~ 10

Author(s):

Lucie M. Turcotte ◽

Qi Liu ◽

Yutaka Yasui ◽

Tara O. Henderson ◽

Todd M. Gibson ◽

...

Keyword(s):

Breast Cancer ◽

Childhood Cancer ◽

Cancer Survivor ◽

Dose Response ◽

Cumulative Incidence ◽

Alkylating Agents ◽

Childhood Cancer Survivor ◽

Malignant Neoplasms ◽

Linear Dose ◽

Childhood Cancer Survivor Study

PURPOSE Therapeutic radiation in childhood cancer has decreased over time with a concomitant increase in chemotherapy. Limited data exist on chemotherapy-associated subsequent malignant neoplasm (SMN) risk. PATIENTS AND METHODS SMNs occurring > 5 years from diagnosis, excluding nonmelanoma skin cancers, were evaluated in survivors diagnosed when they were < 21 years old, from 1970 to 1999 in the Childhood Cancer Survivor Study (median age at diagnosis, 7.0 years; median age at last follow-up, 31.8 years). Thirty-year SMN cumulative incidence and standardized incidence ratios (SIRs) were estimated by treatment: chemotherapy-only (n = 7,448), chemotherapy plus radiation (n = 10,485), radiation only (n = 2,063), or neither (n = 2,158). Multivariable models were used to assess chemotherapy-associated SMN risk, including dose-response relationships. RESULTS Of 1,498 SMNs among 1,344 survivors, 229 occurred among 206 survivors treated with chemotherapy only. Thirty-year SMN cumulative incidence was 3.9%, 9.0%, 10.8%, and 3.4% for the chemotherapy-only, chemotherapy plus radiation, radiation-only, or neither-treatment groups, respectively. Chemotherapy-only survivors had a 2.8-fold increased SMN risk compared with the general population (95% CI, 2.5 to 3.2), with SIRs increased for subsequent leukemia/lymphoma (1.9; 95% CI, 1.3 to 2.7), breast cancer (4.6; 95% CI, 3.5 to 6.0), soft-tissue sarcoma (3.4; 95% CI, 1.9 to 5.7), thyroid cancer (3.8; 95% CI, 2.7 to 5.1), and melanoma (2.3; 95% CI, 1.5 to 3.5). SMN rate was associated with > 750 mg/m2 platinum (relative rate [RR] 2.7; 95% CI, 1.1 to 6.5), and a dose response was observed between alkylating agents and SMN rate (RR, 1.2/5,000 mg/m2; 95% CI, 1.1 to 1.3). A linear dose response was also demonstrated between anthracyclines and breast cancer rate (RR, 1.3/100 mg/m2; 95% CI, 1.2 to 1.6). CONCLUSION Childhood cancer survivors treated with chemotherapy only, particularly higher cumulative doses of platinum and alkylating agents, face increased SMN risk. Linear dose responses were seen between alkylating agents and SMN rates and between anthracyclines and breast cancer rates. Limiting cumulative doses and consideration of alternate chemotherapies may reduce SMN risk.

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