Purpose: The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. Patients and Methods: We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). Results: Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer–specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. Conclusion: Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.

BACKGROUND: Many young adult female cancer survivors (YAFCS) are at risk of experiencing premature menopause. The current study characterized the posttreatment fertility information needs, reproductive concerns, and decisional conflict regarding future options for posttreatment fertility preservation (FP) among YAFCS.METHODS: Participants completed a Web‐based, anonymous survey between February and March 2015. The survey included investigator‐designed questions of perceived information needs, the Reproductive Concerns After Cancer Scale, and the Decisional Conflict Scale. Analyses included Pearson correlation coefficients, independent‐sample Student t tests, and multiple regression.RESULTS: There was a total of 346 participants with an average age of 29.9 years (SD = 4.1 years) who were 4.9 years from treatment (SD = 5.4 years [range, 0‐27 years]). The main analyses focused on a subgroup of YAFCS with uncertain fertility status who had not previously undergone/attempted FP and either wanted future children or were unsure (179 women). Across fertility information topics, 43% to 62% of participants reported unmet information needs. The greatest reproductive concerns were related to fertility potential and the health of future offspring. The regression model controlled for a priori covariates including current age, age at treatment completion, income, relationship status, nulliparity, and prior fertility evaluation. Greater unmet information needs were found to be related to greater decisional conflict (β = .43; p<.001); greater reproductive concerns were associated at the trend level (β = .14, p = .08; F[8,118] = 6.42, p<.001).CONCLUSIONS: YAFCS with limited awareness or knowledge of their risk of experiencing premature menopause and FP options reported higher levels of decisional conflict regarding future FP. Posttreatment survivorship care should include comprehensive reproductive health counseling, including posttreatment FP options and family‐building alternatives. Cancer 2016;122:2101–9. © 2016 American Cancer Society.

PURPOSE: As new evidence is available, the International Late Effects of Childhood Cancer Guideline Harmonization Group has updated breast cancer surveillance recommendations for female survivors of childhood, adolescent, and young adult cancer. METHODS: We used evidence-based methods to apply new knowledge in refining the international harmonized recommendations developed in 2013. The guideline panel updated the systematic literature review, developed evidence summaries, appraised the evidence, and updated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance interventions while attaining flexibility in implementation across different health care systems. The GRADE Evidence-to-Decision framework was used to translate evidence to recommendations. A survivor information form was developed to counsel survivors about the potential harms and benefits of surveillance. RESULTS: The literature update identified new study findings related to the effects of prescribed moderate-dose chest radiation (10 to 19 Gy), radiation dose-volume, anthracyclines and alkylating agents in non–chest irradiated survivors, and the effects of ovarian function on breast cancer risk. Moreover, new data from prospective investigations were available regarding the performance metrics of mammography and magnetic resonance imaging among survivors of Hodgkin lymphoma. Modified recommendations include the performance of mammography and breast magnetic resonance imaging for survivors treated with 10 Gy or greater chest radiation (strong recommendation) and upper abdominal radiation exposing breast tissue at a young age (moderate recommendation) at least annually up to age 60 years. As a result of inconsistent evidence, no recommendation could be formulated for routine breast cancer surveillance for survivors treated with any type of anthracyclines in the absence of chest radiation. CONCLUSION: The newly identified evidence prompted significant change to the recommendations formulated in 2013 related to moderate-dose chest radiation and anthracycline exposure as well as breast cancer surveillance modality.

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.

Endocrine complications, including diabetes and metabolic syndrome, are highly prevalent in childhood cancer survivors. These metabolic derangements may contribute to survivors’ risk of excess cardiovascular morbidity and premature mortality. This review summarizes existing knowledge on risk of diabetes and metabolic syndrome among childhood cancer survivors, focusing specifically on known risk factors, potential mechanisms, and screening recommendations. Early diagnosis via standardized risk-based screening can improve long-term outcomes in this population. Additional work is needed to elucidate the mechanisms underlying these metabolic complications and to inform the design of risk-reducing interventions and optimize long-term cardiometabolic health among survivors of childhood cancer.