Differential effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins

2019 ◽  
Author(s):  
Alexander Stanoyevitch ◽  
Lei Zhang ◽  
Javier Sanz ◽  
Robert Follett ◽  
Douglas Bell
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Elderly Women ◽  
Menopausal Status ◽  
Previous History ◽  
Therapeutic Effects ◽  
Group 12 ◽  
Significant Difference

Abstract Background The risks of osteoporosis and breast cancer are increasing in elderly women, as well as menopausal status related hyperlipidemia. Bisphosphonates and denosumab, varying in drug mechanisms and therapeutic effects are recommended medications for treatment of osteoporosis. The pharmacodynamics of bisphosphonates and statin overlap in one signal pathway. We aim to assess different effects of bisphosphonates and denosumab on breast cancer, possibly modifiable by statins use. Methods This cohort study includes 97,671 women elder than 50 years without previous history of malignancy. Results Over an average of 3.6 years follow up, 3020 women have received either denosumab (n=778) or bisphosphonates (n=2326) for osteoporosis, among them, 84 (84/3020=2.8%) patients have combination medication of both. Our data demonstrated significant difference in breast cancer occurrence after first year latency between denosumab ever prescription group (12/778, 1.54%) and bisphosphonates group (12/2326, 0.52%), P=0.0046; this significance is also proved by Log-rank test (p=0.0004). Although the breast cancer risk in bisphosphonates ever use group (12/2326, 0.52%), statins ever use group (99/15287, 0.65%), hormone users for menopausal symptoms (20/7631, 0.26%) are significantly lower than control patients (1032/74867, 1.38%), p<=0.004, there is no significant difference in breast cancer risk between denosumab group and control patients (p=0.6965). Further subgroup analysis revealed that concurrent use of statins in denosumab prescribers lowered the breast cancer risk to 0.89% (2/224), but with no significantly change of breast cancer risk in bisphosphonates group (7/919, 0.762%). Conclusion Our data suggest superior protective effects of bisphosphonates over denosumab on breast cancer risk in elderly women. Statins could potentially exert breast cancer protective effect in denosumab users but no synergistic effect in patients taking bisphosphonates. Large scale study with long term follow up is needed

scholarly journals Differential protective effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins: a retrospective study using electronic health records

2020 ◽  
Author(s):  
Alexander Stanoyevitch ◽  
Lei Zhang ◽  
Javier Sanz ◽  
Robert Follett ◽  
Douglas Bell
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Elderly Women ◽  
Previous History ◽  
Bivariate Analysis ◽  
Control Group ◽  
Protective Effects ◽  
Significant Difference

Abstract Background: The risks of osteoporosis and breast cancer are increasing in elderly women, as well as hyperlipidemia. Bisphosphonates and denosumab are recommended for treatment of osteoporosis, and statins are used for hyperlipidemia. There are different and overlapping pharmacodynamics among bisphosphonates, denosumab and statins. We aim to assess effects of bisphosphonates and denosumab on breast cancer, possibly affected by statins use.Methods: This retrospective cohort is consisted of 97,671 women elder than 50 years with no previous history of malignancy and no cancer other than breast during follow-up, including 778, 2326, 15287 and 7631denosumab, bisphosphonates, statins and hormone for postmenopausal symptoms ever users. Univariate and bivariate analysis, and the Cox Proportional Hazards multi-variate model are performed.Results: Over an average of 3.6 years follow up, the breast cancer risks counted after 365 days of latency are 1.54% (12/778) for denosumab, 0.52% (12/2326) for bisphosphonates, compared to 0.65% (99/15287) in statins ever use group, 0.26% (20/7631) in hormone users for menopausal symptoms and 1.38% (1032/74867) in control group. The significant difference of breast cancer risk between denosumab and bisphosphonates group (p=0.0047) is supported by the Log-rank test (p=0.0004). The multivariate model is in partial agreement with the uni- and bivariate analysis. Further subgroup analysis revealed that concurrent use of statins in denosumab prescribers lowered the breast cancer risk to 0.89% (2/224), but with no significantly change of breast cancer risk in bisphosphonates group (7/919, 0.762%).Conclusion : Our data suggest superior protective effects of bisphosphonates over denosumab on breast cancer risk in elderly women. Statins could potentially exert breast cancer protective effect in denosumab users with no synergistic effect in patients taking bisphosphonates. A large scale study with long term follow up is needed.

scholarly journals Binge Drinking and Risk of Breast Cancer: Results from the SUN (‘Seguimiento Universidad de Navarra’) Project

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 731
Author(s):  
Rodrigo Sánchez-Bayona ◽  
Alfredo Gea ◽  
Itziar Gardeazabal ◽  
Andrea Romanos-Nanclares ◽  
Miguel Ángel Martínez-González ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Binge Drinking ◽  
Cox Regression ◽  
Menopausal Status ◽  
The Sun ◽  
Stratified Analysis ◽  
Incident Cases

Alcohol intake is associated with the risk of breast cancer. Different patterns of alcohol-drinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03–2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11–3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.

scholarly journals Dietary pattern and breast cancer risk in Japanese women: the Japan Public Health Center-based Prospective Study (JPHC Study)

2016 ◽  
Vol 115 (10) ◽  
pp. 1769-1779 ◽  
Author(s):  
Sangah Shin ◽  
Eiko Saito ◽  
Manami Inoue ◽  
Norie Sawada ◽  
Junko Ishihara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Dietary Patterns ◽  
Dietary Pattern ◽  
Menopausal Status ◽  
Japanese Women ◽  
Hazard Ratios ◽  
Increased Risk

AbstractEvidence that diet is associated with breast cancer risk is inconsistent. Most of the studies have focused on risks associated with specific foods and nutrients, rather than overall diet. In this study, we aimed to evaluate the association between dietary patterns and breast cancer risk in Japanese women. A total of 49 552 Japanese women were followed-up from 1995 to 1998 (5-year follow-up survey) until the end of 2012 for an average of 14·6 years. During 725 534 person-years of follow-up, 718 cases of breast cancer were identified. We identified three dietary patterns (prudent, westernised and traditional Japanese). The westernised dietary pattern was associated with a 32 % increase in breast cancer risk (hazard ratios (HR) 1·32; 95 % CI 1·03, 1·70; Ptrend=0·04). In particular, subjects with extreme intake of the westernised diet (quintile (Q) Q5_5th) had an 83 % increase in risk of breast cancer in contrast to those in the lowest Q1 (HR 1·83; 95 % CI 1·25, 2·68; Ptrend=0·01). In analyses stratified by menopausal status, postmenopausal subjects in the highest quintile of the westernised dietary pattern had a 29 % increased risk of breast cancer (HR 1·29; 95 % CI 0·99, 1·76; Ptrend=0·04). With regard to hormone receptor status, the westernised dietary pattern was associated with an increased risk of oestrogen receptor-positive/progesterone receptor-positivetumours (HR 2·49; 95 % CI 1·40, 4·43; Ptrend<0·01). The other dietary patterns were not associated with the risk of breast cancer in Japanese women. A westernised dietary pattern is associated with an increased risk of breast cancer in Japanese women.

scholarly journals Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

2021 ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Endogenous Hormones ◽  
Uk Biobank ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

scholarly journals Genotypes and haplotypes of the methyl-CpG-binding domain 2 modify breast cancer risk dependent upon menopausal status

2005 ◽  
Vol 7 (5) ◽  
Author(s):  
Yong Zhu ◽  
Heather N Brown ◽  
Yawei Zhang ◽  
Theodore R Holford ◽  
Tongzhang Zheng
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Menopausal Status ◽  
Binding Domain

scholarly journals Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis

2018 ◽  
Vol 48 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Xiang Shu ◽  
Lang Wu ◽  
Nikhil K Khankari ◽  
Xiao-Ou Shu ◽  
Thomas J Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mendelian Randomization ◽  
Menopausal Status ◽  
Inverse Association ◽  
Fasting Insulin

Abstract Background In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10–4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10–4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10–19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10–6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.

scholarly journals Using Whole Breast Ultrasound Tomography to Improve Breast Cancer Risk Assessment: A Novel Risk Factor Based on the Quantitative Tissue Property of Sound Speed

2020 ◽  
Vol 9 (2) ◽  
pp. 367 ◽  
Author(s):  
Neb Duric ◽  
Mark Sak ◽  
Shaoqi Fan ◽  
Ruth M. Pfeiffer ◽  
Peter J. Littrup ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Sound Speed ◽  
Menopausal Status ◽  
Surrogate Marker ◽  
Breast Ultrasound ◽  
Ultrasound Tomography ◽  
Breast Cancer Risk Assessment

Mammographic percent density (MPD) is an independent risk factor for developing breast cancer, but its inclusion in clinical risk models provides only modest improvements in individualized risk prediction, and MPD is not typically assessed in younger women because of ionizing radiation concerns. Previous studies have shown that tissue sound speed, derived from whole breast ultrasound tomography (UST), a non-ionizing modality, is a potential surrogate marker of breast density, but prior to this study, sound speed has not been directly linked to breast cancer risk. To that end, we explored the relation of sound speed and MPD with breast cancer risk in a case-control study, including 61 cases with recent breast cancer diagnoses and a comparison group of 165 women, frequency matched to cases on age, race, and menopausal status, and with a recent negative mammogram and no personal history of breast cancer. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the relation of quartiles of MPD and sound speed with breast cancer risk adjusted for matching factors. Elevated MPD was associated with increased breast cancer risk, although the trend did not reach statistical significance (OR per quartile = 1.27, 95% CI: 0.95, 1.70; ptrend = 0.10). In contrast, elevated sound speed was significantly associated with breast cancer risk in a dose–response fashion (OR per quartile = 1.83, 95% CI: 1.32, 2.54; ptrend = 0.0003). The OR trend for sound speed was statistically significantly different from that observed for MPD (p = 0.005). These findings suggest that whole breast sound speed may be more strongly associated with breast cancer risk than MPD and offer future opportunities for refining the magnitude and precision of risk associations in larger, population-based studies, including women younger than usual screening ages.

scholarly journals Association Between Organic Food Consumption and Breast Cancer Risk: Findings from the Sister Study (P18-038-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yong-Moon Mark Park ◽  
Alexandra White ◽  
Nicole Niehoff ◽  
Katie O'Brien ◽  
Dale Sandler
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Food Consumption ◽  
Menopausal Status ◽  
Organic Food ◽  
Organic Foods ◽  
Organic Food Consumption ◽  
Organic Produce ◽  
Diet Score

Abstract Objectives Diet is a source of exposure to pesticides. Organic food consumption may lower cancer risk, possibly due to decreased exposure to pesticides. Few studies have investigated the association between organic food consumption and cancer risk and evidence on the risk of breast cancer is limited. Methods We used data from 39,563 Sister Study participants aged 35 to 74 years who enrolled in 2003–2009 and had information available on frequency of organic food consumption. Participants reported their consumption of organic produce, meat, and dairy during the past 12 months as never, less than half the time, about half the time, and more than half the time. An organic diet score was calculated by assigning scores of 0, 1, 2 and 3 for increasing consumption proportions and summing across foods (maximum score 9). We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer associated with ever consuming organic foods and organic diet scores, adjusting for potential confounders, including known risk factors for breast cancer. Results At baseline, 61.8% of women reported ever eating organic produce, meat, or dairy. We identified 2336 incident breast cancers diagnosed at least 1 year after enrollment (mean follow-up 9.0 years). Any organic food consumption was inversely associated with breast cancer (HR: 0.87 [95% CI, 0.80–0.95]), especially estrogen receptor negative cancer (HR: 0.77 [95% CI, 0.61–0.98]). There was no trend with increasing organic diet score based on all organic food types. Consumption of organic produce half or more than half the time was associated with reduced risk of breast cancer compared to no organic produce consumption (HR: 0.87 [95% CI, 0.77–0.99]). There was no trend for organic dairy or meat consumption. In stratified analyses, associations did not differ by demographics, obesity, menopausal status, lifestyle characteristics, cancer screening, or degree of family history. Conclusions Although unmeasured factors associated with consuming organic foods may explain these results, organic produce consumption was associated with reduced breast cancer risk. Funding Sources National Institute of Environmental Health Sciences.

Sign in / Sign up

Export Citation Format

Share Document