title: Risk factors for subsequent endocrine-related cancer in childhood cancer survivors.
abstract: Long-term adverse health conditions, including secondary malignant neoplasms, are common in childhood cancer survivors. Although mortality attributable to secondary malignancies declined over the past decades, the risk for developing a solid secondary malignant neoplasm did not. Endocrine-related malignancies are among the most common secondary malignant neoplasms observed in childhood cancer survivors. In this systematic review, we describe risk factors for secondary malignant neoplasms of the breast and thyroid, since these are the most common secondary endocrine-related malignancies in childhood cancer survivors. Radiotherapy is the most important risk factor for secondary breast and thyroid cancer in childhood cancer survivors. Breast cancer risk is especially increased in survivors of Hodgkin lymphoma who received moderate- to high-dosed mantle field irradiation. Recent studies also demonstrated an increased risk after lower-dose irradiation in other radiation fields for other childhood cancer subtypes. Premature ovarian insufficiency may protect against radiation-induced breast cancer. Although evidence is weak, estrogen-progestin replacement therapy does not seem to be associated with an increased breast cancer risk in premature ovarian-insufficient childhood cancer survivors. Radiotherapy involving the thyroid gland increases the risk for secondary differentiated thyroid carcinoma, as well as benign thyroid nodules. Currently available studies on secondary malignant neoplasms in childhood cancer survivors are limited by short follow-up durations and assessed before treatment regimens. In addition, studies on risk-modifying effects of environmental and lifestyle factors are lacking. Risk-modifying effects of premature ovarian insufficiency and estrogen-progestin replacement therapy on radiation-induced breast cancer require further study.
authors.affiliation: Department of Pediatric Oncology/HematologyErasmus MC - Sophia Children's Hospital, Rotterdam, the Netherlands Department of MedicineSection Endocrinology, Erasmus University Medical Center, Rotterdam, the Netherlands m.wijnen.1@erasmusmc.nl.
authors.forename: M
authors.initials: M
authors.lastname: Wijnen
authors.affiliation: Department of Pediatric Oncology/HematologyErasmus MC - Sophia Children's Hospital, Rotterdam, the Netherlands Princess Maxima Center for Pediatric OncologyUtrecht, the Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Department of MedicineSection Endocrinology, Erasmus University Medical Center, Rotterdam, the Netherlands Rotterdam Thyroid CenterErasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Medici
authors.affiliation: Department of MedicineSection Endocrinology, Erasmus University Medical Center, Rotterdam, the Netherlands Rotterdam Thyroid CenterErasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Peeters
authors.affiliation: Department of MedicineSection Endocrinology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.affiliation: Department of Pediatric Oncology/HematologyErasmus MC - Sophia Children's Hospital, Rotterdam, the Netherlands Department of MedicineSection Endocrinology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: S J C M M
authors.initials: SJ
authors.lastname: Neggers
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology; D000073116:Cancer Survivors; D006801:Humans; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000453:epidemiology
keywords: breast cancer; childhood cancer survivors; endocrine-related cancer; secondary malignant neoplasms; thyroid cancer