scholarly journals Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report

2020 ◽  
Vol 38 (25) ◽  
pp. 2872-2882
Author(s):  
Andrew M. McDonald ◽  
Yanjun Chen ◽  
Jessica Wu ◽  
Lindsey Hageman ◽  
Liton Francisco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Alkylating Agents ◽  
Population Exposure ◽  
Pathology Report ◽  
Allogeneic Bmt ◽  
Increased Risk ◽  
Total Body

PURPOSE To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies. PATIENTS AND METHODS Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population. RESULTS A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; P = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; P = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; P = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors. CONCLUSION The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.

Total body irradiation (TBI) and risk of breast subsequent malignant neoplasm (SMN) after blood or marrow transplantation (BMT): A report from the BMT survivor study (BMTSS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11572-11572
Author(s):  
Andrew Michael McDonald ◽  
Yanjun Chen ◽  
Jessica Wu ◽  
Lindsey Hageman ◽  
Liton Francisco ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Malignant Neoplasm ◽  
Cox Proportional Hazards ◽  
Pathology Report ◽  
Screening Guidelines ◽  
Allogeneic Bmt ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Total Body ◽  
Study Participants

11572 Background: The association between TBI and breast SMN in BMT recipients is not clearly defined. We address this limitation to develop evidence for screening guidelines for those at risk. Methods: Study participants were drawn from BMTSS – a multi-site retrospective cohort of patients who had received BMT between 1974 and 2014 and survived ≥2y post-BMT. Participants completed the BMTSS survey that included sociodemographics and health conditions. Breast SMN was confirmed by pathology report review. Clinical characteristics, pre-BMT and BMT exposures were abstracted from medical records. Using multivariable Cox proportional hazards models, freedom from breast SMN was measured from birth and TBI was treated as a time-varying covariate in analyses stratified by type of BMT (allogeneic; autologous). Results: 1546 female participants (allogeneic 808; autologous 738) received BMT at a mean age of 43.1±17.6y and were followed for 9.4±7.7y; primary diagnoses: HL/NHL (28%), AML/MDS (27%), PCD (19%), other (28%). TBI was used in 671 patients (allogeneic 57%; autologous 30%). Patients with pre-BMT chest radiation (n = 45) were excluded from the analysis. A total of 38 cases of breast SMN were identified (allogeneic 19; autologous 19). Allogeneic BMT: exposure to TBI (HR = 3.4; 95%CI 1.1-10.9, p = 0.04) and age at BMT < 40y (HR = 4.0; 95%CI 1.3-12.8, p = 0.02) were associated with increased risk of breast SMN. Risk of breast SMN was higher and breast SMN developed earlier among those exposed to TBI before age 40y vs. those exposed after 40y (8.7% vs. 0% by attained age 50; 10.6% vs. 5.8% by attained age 60, p = 0.003). Autologous BMT: Age < 40y was associated with a 4.8-fold higher risk (95%CI 1.1-20.1, p = 0.03) of breast SMN. TBI was associated with a 2-fold higher risk (p = 0.2). The cumulative incidence of breast SMN among those exposed to TBI at age < 40y vs. age ≥40y was 5.1% vs. 2.4% by attained age 60 (p = 0.07). Conclusions: TBI is associated with breast SMN among allogeneic BMT recipients. The risk is especially high and occurs at a younger age, among those exposed at age < 40y. These findings provide evidence for initiating screening at a young age after exposure to TBI.

Total-body irradiation before bone marrow transplantation. Results of two randomized instantaneous dose rates in 157 patients

Cancer ◽  
1992 ◽  
Vol 69 (11) ◽  
pp. 2853-2865 ◽  
Author(s):  
Mahmuf Ozsahin ◽  
Francoise Pène ◽  
Emmanuel Touboul ◽  
Brigitte Gindrey-Vie ◽  
Claude Dominique ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Dose Rates ◽  
Total Body

Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study

2016 ◽  
Vol 34 (11) ◽  
pp. 1208-1216 ◽  
Author(s):  
Charlotte Näslund-Koch ◽  
Børge G. Nordestgaard ◽  
Stig E. Bojesen
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Population Study ◽  
Cell Cycle Checkpoint ◽  
Loss Of Function ◽  
General Population Study ◽  
Chek2 1100Delc ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Age And Sex

Purpose CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population. Patients and Methods We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests. Results Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer. Conclusion CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.

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