Combined effect of radiotherapy and anthracyclines on risk of breast cancer among female childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10053-10053
Author(s):  
Lene H. S. Veiga ◽  
Rochelle E. Curtis ◽  
Lindsay M. Morton ◽  
Diana Withrow ◽  
Rebecca M. Howell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Radiation Dose ◽  
Cancer Risk ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Conditional Logistic Regression ◽  
Childhood Cancer Survivors ◽  
Combined Effect ◽  
Increased Risk

10053 Background: Breast cancer is a common late-effect for female childhood cancer survivors and chest radiotherapy is an established risk factor. Recent findings showed that treatment with anthracyclines also increases breast cancer risk. However, the risk from the combined effect of radiotherapy and anthracyclines is unknown. Methods: We conducted a matched case-control study of 271 subsequent breast cancer and 1044 controls nested within the CCSS - a North-American cohort of five-year survivors of childhood cancer, diagnosed from 1970-1986 and followed-up through 2016. Detailed treatment records were abstracted to estimate radiation dose (Gy) to the breast cancer location and ovaries and calculate cumulative chemotherapy doses (mg/m2). Multivariable conditional logistic regression was used to estimate Odds ratios (OR) and 95% confidence intervals (CI). Results: Breast cancer risk increased linearly with radiation dose to the breast (OR per 10Gy = 3.9, 95%CI:2.5-6.5) and decreased with increasing ovarian dose (p < 0.01). Adjusted for radiation dose, the highest quartile of dose (455+mg/m2) of anthracyclines was associated with a 3.8-fold increased risk of breast cancer (95%CI:1.8-8.2) compared to no anthracyclines. This risk increased with cumulative anthracycline dose (p-trend < 0.01) and was non-significantly higher for ER+ than ER- breast cancers. For a breast dose of 10+Gy, the OR was 19.1 (95%CI:7.6-48.0) with anthracyclines versus 9.6 (95%CI:4.4-20.7) without anthracyclines, compared to 0- < 1Gy breast dose and no anthracyclines (p-additive interaction = 0.04). Conclusions: The combination of anthracyclines and radiotherapy doses to the breast can markedly increase breast cancer risk compared to those who receive neither treatment. Our results can be used to inform risk management for childhood cancer patients treated in the past, as well as project potential breast cancer risk from current treatment protocols.

Development and Validation of a Breast Cancer Risk Prediction Model for Childhood Cancer Survivors Treated With Chest Radiation: A Report From the Childhood Cancer Survivor Study and the Dutch Hodgkin Late Effects and LATER Cohorts

2021 ◽  
pp. JCO.20.02244
Author(s):  
Chaya S. Moskowitz ◽  
Cécile M. Ronckers ◽  
Joanne F. Chou ◽  
Susan A. Smith ◽  
Danielle Novetsky Friedman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Risk Prediction ◽  
Area Under The Curve ◽  
Childhood Cancer Survivors ◽  
Degree Relative ◽  
Childhood Cancer Survivor Study

PURPOSE Women treated with chest radiation for childhood cancer have one of the highest risks of breast cancer. Models producing personalized breast cancer risk estimates applicable to this population do not exist. We sought to develop and validate a breast cancer risk prediction model for childhood cancer survivors treated with chest radiation incorporating treatment-related factors, family history, and reproductive factors. METHODS Analyses were based on multinational cohorts of female 5-year survivors of cancer diagnosed younger than age 21 years and treated with chest radiation. Model derivation was based on 1,120 participants in the Childhood Cancer Survivor Study diagnosed between 1970 and 1986, with median attained age 42 years (range 20-64) and 242 with breast cancer. Model validation included 1,027 participants from three cohorts, with median age 32 years (range 20-66) and 105 with breast cancer. RESULTS The model included current age, chest radiation field, whether chest radiation was delivered within 1 year of menarche, anthracycline exposure, age at menopause, and history of a first-degree relative with breast cancer. Ten-year risk estimates ranged from 2% to 23% for 30-year-old women (area under the curve, 0.63; 95% CI, 0.50 to 0.73) and from 5% to 34% for 40-year-old women (area under the curve, 0.67; 95% CI, 0.54 to 0.84). The highest risks were among premenopausal women older than age 40 years treated with mantle field radiation within a year of menarche who had a first-degree relative with breast cancer. It showed good calibration with an expected-to-observed ratio of the number of breast cancers of 0.92 (95% CI, 0.74 to 1.16). CONCLUSION Breast cancer risk varies among childhood cancer survivors treated with chest radiation. Accurate risk prediction may aid in refining surveillance, counseling, and preventive strategies in this population.

scholarly journals Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

2016 ◽  
Vol 34 (9) ◽  
pp. 910-918 ◽  
Author(s):  
Tara O. Henderson ◽  
Chaya S. Moskowitz ◽  
Joanne F. Chou ◽  
Angela R. Bradbury ◽  
Joseph Phillip Neglia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Childhood Cancer Survivors ◽  
Primary Cancer ◽  
History Of ◽  
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.

scholarly journals Risk factors for subsequent endocrine-related cancer in childhood cancer survivors

2016 ◽  
Vol 23 (6) ◽  
pp. R299-R321 ◽  
Author(s):  
M Wijnen ◽  
M M van den Heuvel-Eibrink ◽  
M Medici ◽  
R P Peeters ◽  
A J van der Lely ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
Malignant Neoplasms ◽  
Ovarian Insufficiency ◽  
Radiation Induced

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.

A novel association between GSTM1 null variant and anthracycline-induced cardiac dysfunction (ACD) in childhood cancer survivors (CCS): A COG ALTE03N1 report.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10030-10030
Author(s):  
Purnima Singh ◽  
Xuexia Wang ◽  
Lindsey Hageman ◽  
Yanjun Chen ◽  
Tarek Magdy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Expression Profiles ◽  
Conditional Logistic Regression ◽  
Gene Expression Profiles ◽  
Childhood Cancer Survivors ◽  
Differentially Expressed ◽  
Gstm1 Null Genotype ◽  
Increased Risk

10030 Background: ACD is a leading cause of mortality in CCS. Previous studies have identified genomic variants that moderate the ACD risk. An agnostic evaluation of differential gene expression between those with and without ACD has not been explored, and could provide insights into the mechanism of cardiotoxicity. Methods: Gene expression profiles in leukocyte RNA from anthracycline-exposed non-Hispanic white (NHW) CCS (20 with ACD [cases]; 20 without ACD [controls]) used Illumina HumanHT-12 v4.0 Expression Beadchips. Gene expression profiles in h uman iPSC-derived cardiomyocytes (hiPSC-CMs – Day 30) from 6 childhood cancer patients (3 each with and without CD) treated with 1μM doxorubicin or vehicle for 24 h, used RNA-seq. Genotyping in leukocyte DNA from anthracycline-exposed NHW CCS (65 cases; 76 controls) to determine if the differentially-expressed genes mapped to genetic variants that modified ACD risk, used conditional logistic regression analysis adjusted for sex, age at cancer diagnosis, chest radiation and anthracycline dose. Patient characteristics are in Table. Results: Gene-expression in survivors:Glutathione S transferase mu 1 ( GSTM1) was differentially-expressed; RT q-PCR showed significant downregulation of GSTM1 in cases (0.67±0.57 vs. 1.33±1.33, p=0.049). hiPSC-CMs gene expression: GSTM1 was downregulated in patients with ACD (logFC = -1.4). Genotyping: Using PCR for GSTM1 null, we observed a significant association between CD risk and GSTM1 null genotype (OR=3.0; 95%CI, 1.4-6.2, p=0.003). Conclusions: We report an association between GSTM1 null genotype and ACD, previously unreported likely because GWAS studies did not examined gene deletions. GSTM1 is involved in detoxification of anthracyclines. This finding could facilitate identification of childhood cancer survivors at increased risk of ACD. [Table: see text]

scholarly journals Association of Breast Cancer Risk After Childhood Cancer With Radiation Dose to the Breast and Anthracycline Use

2019 ◽  
Vol 173 (12) ◽  
pp. 1171 ◽  
Author(s):  
Lene H. Veiga ◽  
Rochelle E. Curtis ◽  
Lindsay M. Morton ◽  
Diana R. Withrow ◽  
Rebecca M. Howell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Radiation Dose ◽  
Cancer Risk ◽  
Childhood Cancer

scholarly journals Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk

2019 ◽  
Vol 111 (10) ◽  
pp. 1059-1067 ◽  
Author(s):  
Katherine W Reeves ◽  
Mary Díaz Santana ◽  
JoAnn E Manson ◽  
Susan E Hankinson ◽  
R Thomas Zoeller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Conditional Logistic Regression ◽  
Postmenopausal Breast Cancer ◽  
Consumer Products ◽  
Control Subjects ◽  
Increased Risk ◽  
Nested Case Control

Abstract Background Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. Methods We conducted a nested case-control study within the Women’s Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up. Results Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years. Conclusions In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.

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