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Effect of Tamoxifen on the Risk of Osteoporosis and Osteoporotic Fracture in Younger Breast Cancer Survivors: A Nationwide Study.

ABSTRACT: Background: Although international guidelines recommend bone screening for premenopausal breast cancer patients taking adjuvant tamoxifen, the effects of tamoxifen on osteoporosis and related risks remain controversial. The objective of this study was to investigate the incidence of and risk factors for osteoporosis and osteoporotic fractures in younger breast cancer patients. Methods: A nationwide retrospective cohort study was conducted using South Korea Health Insurance Review and Assessment Service claims data. The rates of osteoporosis and osteoporotic fracture were calculated as incident cases per person-year and disease-free probability rates were analyzed with the Kaplan-Meier method. To identify risk factors for osteoporosis and osteoporotic fracture, a multivariable Cox proportional hazard regression model was applied. Results: From January 2009 to December 2014, a total of 47,649 breast cancer patients were included. The incidence rates of osteoporosis and osteoporotic fracture were 23.59 and 2.40 per 1,000 person-years, respectively. In the overall population, tamoxifen was significantly associated with a decreased risk of osteoporosis and osteoporotic fractures 0.76). However, tamoxifen was not associated with the risk of osteoporosis (HR 1.24, CI 0.85-1.82) and osteoporotic fracture (HR 8.15, CI 0.36-186.70) in patients under age 40. In the 40-49 years subgroup, tamoxifen significantly decreased the risk of osteoporosis (HR 0.74, CI 0.65-0.84) and osteoporotic fracture (HR 0.49, CI 0.31-0.76). Conclusions: Tamoxifen is not associated with an increased risk of osteoporosis and osteoporotic fracture in premenopausal breast cancer patients. Tailored screening strategies for breast cancer survivors with different osteoporosis risks are needed. Precis: Tamoxifen is not associated with an increased risk of osteoporosis and osteoporotic fracture in premenopausal breast cancer patients. Tailored screening strategies for breast cancer survivors who are at different risks of developing osteoporosis are needed.

SUBMITTER: Lee J

PROVIDER: S-EPMC7098996 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBreast cancer survivors have a high incidence of osteoporosis-related fractures; the associated factors are understudied. We investigated incidence of bone fracture and its associations with soy food consumption, exercise, and body mass index among breast cancer survivors.MethodsThis prospective study included 4139 stage 0-III breast cancer patients and 1987 pre-/perimenopausal and 2152 postmenopausal patients. Fractures were assessed at 18 months and at 3, 5, and 10 years after cancer diagnosis. Osteoporotic fractures were defined as fractures caused by falls from standing height and at sites associated with osteoporosis. Exercise and soy isoflavone intake were assessed at 6 and 18 months postdiagnosis. Weight and height were measured at baseline. Lifetable and Cox regression analyses were employed. All statistical tests were two sided.ResultsThe 10-year incidence for osteoporotic fractures was 2.9% and 4.4% for pre-/perimenopausal and postmenopausal patients, respectively. High soy isoflavone intake was associated with reduced risk among pre-/perimenopausal patients (hazard ratio [HR] = 0.22, 95% confidence interval [CI] = 0.09 to 0.53, for soy isoflavone mg/d ≥56.06 vs <31.31; P trend < .001) but not among postmenopausal patients (P interaction < .01). Overweight (vs normal weight) was a risk factor for pre-/perimenopausal patients (HR = 1.81, 95% CI = 1.04 to 3.14) but not for postmenopausal patients (HR = 0.67, 95% CI = 0.43 to 1.03; P interaction = .01). Exercise was inversely associated with osteoporotic fractures in postmenopausal patients (HR = 0.56, 95% CI = 0.33 to 0.97, for metabolic equivalents hours ≥12.6 vs <4.5) following a dose-response pattern (P trend = .035), an association not modified by menopausal status.ConclusionsOur findings, especially the novel association of soy food intake with osteoporotic fractures in breast cancer survivors, if confirmed, can help guide future strategies for fracture risk reduction in this vulnerable population.

Project description:BackgroundAlthough the guidelines recommend gynecological assessment and close monitoring for symptoms of endometrial cancer in postmenopausal breast cancer survivors taking tamoxifen (TAM), the risk of endometrial cancer in young breast cancer survivors has not yet been fully assessed. This study aimed to investigate the risk of developing endometrial cancer and the frequencies of gynecological examinations in young breast cancer survivors taking TAM in South Korea.MethodsA nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment Service claims data. Kaplan-Meier analyses and log-rank tests were used to assess the probability of endometrial cancer, benign endometrial conditions, and the probability of invasive endometrial procedure. To analyze the risk of endometrial cancer and benign endometrial conditions, we used a multivariable Cox proportional hazards regression model.ResultsBetween 2010 and 2015, 60,545 newly diagnosed female breast cancer survivors were included. The total person-years were 256,099 and 140 (0.23%) patients developed endometrial cancer during the study period. In breast cancer survivors aged ≥60 years [hazard ratio (HR), 5.037; 95% confidence interval (CI), 2.185-11.613], 50-59 years (HR, 4.343; 95% CI, 2.122-8.891), and 40-49 years (HR, 2.121; 95% CI, 1.068-4.213), TAM was associated with an increased risk of endometrial cancer. In subjects aged below 40 years, TAM did not significantly increase the risk of endometrial cancer. However, among the TAM subgroups, breast cancer survivors aged below 40 years [1.61 per 1,000 person-years (PY); HR, 12.460; 95% CI, 2.698-57.522] and aged 40-49 years (2.22 per 1,000 PY; HR, 9.667; 95% CI, 4.966-18.819) with TAM-related endometrial diseases showed significantly increased risks of endometrial cancer. Among the TAM subgroup with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were higher in subjects under 40 than subjects aged 60 or more.ConclusionYoung breast cancer survivors with TAM-related benign endometrial diseases are at a higher risk of developing endometrial cancer. Gynecological surveillance should be tailored to the risk of endometrial cancer in young breast cancer survivors to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures.

Project description:BACKGROUND:Osteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies. OBJECTIVE:To assess the relationship between BMD and fracture and all common single-nucleotide polymorphisms (SNPs) in previously proposed osteoporosis candidate genes. DESIGN:Large-scale meta-analysis of genome-wide association data. SETTING:5 international, multicenter, population-based studies. PARTICIPANTS:Data on BMD were obtained from 19 195 participants (14 277 women) from 5 populations of European origin. Data on fracture were obtained from a prospective cohort (n = 5974) from the Netherlands. MEASUREMENTS:Systematic literature review using the Human Genome Epidemiology Navigator identified autosomal genes previously evaluated for association with osteoporosis. We explored the common SNPs arising from the haplotype map of the human genome (HapMap) across all these genes. BMD at the femoral neck and lumbar spine was measured by dual-energy x-ray absorptiometry. Fractures were defined as clinically apparent, site-specific, validated nonvertebral and vertebral low-energy fractures. RESULTS:150 candidate genes were identified and 36 016 SNPs in these loci were assessed. SNPs from 9 gene loci (ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and TNFSF11) were associated with BMD at either site. For most genes, no SNP was statistically significant. For statistically significant SNPs (n = 241), effect sizes ranged from 0.04 to 0.18 SD per allele. SNPs from the LRP5, SOST, SPP1, and TNFRSF11A loci were significantly associated with fracture risk; odds ratios ranged from 1.13 to 1.43 per allele. These effects on fracture were partially independent of BMD at SPP1 and SOST. LIMITATION:Only common polymorphisms in linkage disequilibrium with SNPs in HapMap could be assessed, and previously reported associations for SNPs in some candidate genes could not be excluded. CONCLUSION:In this large-scale collaborative genome-wide meta-analysis, 9 of 150 candidate genes were associated with regulation of BMD, 4 of which also significantly affected risk for fracture. However, most candidate genes had no consistent association with BMD.

Project description:Chemotherapy is a common treatment for breast cancer (BrCa) and can cause chemotherapy-induced peripheral neuropathy (CIPN). CIPN contributes to falls, and is thus a potential risk factor for nontraumatic fractures (NTFx); yet, the effect of CIPN on NTFx risk has not been examined for BrCa survivors. We therefore investigated the association between CIPN and NTFx in BrCa survivors. Data were extracted from Optum's Deidentified Clinformatics® Data Mart Database years 2010-2015 in this retrospective cohort study. Among women, three groups were derived based on BrCa and CIPN status: BrCa+/CIPN+ (primary group of interest), BrCa+/CIPN- (first comparison group), and BrCa-/CIPN- (second comparison group). After propensity score matching the comparison groups to BrCa+/CIPN+ at a ratio of 1:11 (BrCa:control) for demographics, osteoporosis, glucocorticoid medication, comorbidities, and cancer-related variables for BrCa+/CIPN-, 1-year incidence rate (IR) of NTFx was determined for each group. The incident rate ratio (IRR) determined if the IR for NTFx was different for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN-. Cox proportional hazards regression models estimated the hazard ratios (HRs) after adjusting for covariates that were unable to be matched for. The crude IR (95% confidence interval [CI]) of NTFx was 4.54 (2.32-6.77) for BrCa+/CIPN+ (n = 359), 2.53 (2.03-3.04) for BrCa+/CIPN- (n = 3949), and 1.76 (1.35-2.18) for BrCa-/CIPN- (n = 3949). The crude IRR of NTFx was significantly elevated for BrCa+/CIPN+ as compared to BrCa+/CIPN- (IRR = 1.80; 95% CI, 1.06-3.05) and BrCa-/CIPN- (IRR = 2.58; 95% CI, 1.50-4.44). The elevated rate of NTFx for BrCa+/CIPN+ remained unchanged after adjusting for aromatase inhibitors compared to BrCa+/CIPN- (HR = 1.79; 95% CI, 1.06-3.04). Female BrCa survivors have an increased 1-year IR of NTFx after the onset of CIPN, suggesting that CIPN is an additive burden on NTFx risk among BrCa survivors. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Effect of Tamoxifen on the Risk of Osteoporosis and Osteoporotic Fracture in Younger Breast Cancer Survivors: A Nationwide Study.

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