scholarly journals Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2254
Author(s):  
Matteo Franchi ◽  
Roberta Tritto ◽  
Luigi Tarantini ◽  
Alessandro Navazio ◽  
Giovanni Corrao

Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.

2010 ◽  
Vol 28 (34) ◽  
pp. 5088-5096 ◽  
Author(s):  
Michael T. Milano ◽  
Huilin Li ◽  
Mitchell H. Gail ◽  
Louis S. Constine ◽  
Lois B. Travis

Purpose The increased risk of breast cancer (BC) among women receiving chest radiotherapy for Hodgkin's lymphoma (HL) is well-established. However, there are no large population-based studies that describe overall survival (OS) and cause-specific survival (CSS) compared with women with first primary BC. Methods For 298 HL survivors who developed BC (HL-BC group) and 405,223 women with a first or only BC (BC-1 group), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL, and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program. Results OS among patients with HL-BC was significantly inferior that of to patients with BC-1: 15-year OS was 48% versus 69% (P < .0001) for localized BC, and 33% versus 43% (P < .0001) for regional/distant BC. Patients with HL-BC had a significantly increased seven-fold risk (P < .0001) of death from other cancers (ie, not HL or BC) compared with patients with BC-1. Mortality from heart disease among patients with HL-BC with either localized or regional/distant disease was also significantly increased (hazard ratio = 2.22, P = .04; and hazard ratio = 4.28, P = .02, respectively) compared with patients with BC-1. Although 10-year BC-CSS was similar for patients with HL-BC and BC-1 with regional/distant disease, it was inferior for patients with localized BC (82% v 88%, respectively; P = .002). Conclusion Women with HL may survive a subsequent diagnosis of BC, only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in patients with HL-BC is warranted.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Anna-Karin Wennstig ◽  
Charlotta Wadsten ◽  
Hans Garmo ◽  
Mikael Johansson ◽  
Irma Fredriksson ◽  
...  

AbstractAdjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of later radiation-induced lung cancer (LC). We examined the risk of primary LC in a population-based cohort of 52300 women treated for BC during 1992 to 2012, and 253796 age-matched women without BC. Cumulative incidence of LC was calculated by the Kaplan–Meier method, and the risk of LC after BC treatment was estimated by Cox proportional hazards regression analyses. Women with BC receiving RT had a higher cumulative incidence of LC compared to women with BC not receiving RT and women without BC. This became apparent 5 years after RT and increased with longer follow-up. Women with BC receiving RT had a Hazard ratio of 1.59 (95% confidence interval 1.37–1.84) for LC compared to women without BC. RT techniques that lower the incidental lung doses, e.g breathing adaption techniques, may lower this risk.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Anna-Karin Wennstig ◽  
Charlotta Wadsten ◽  
Hans Garmo ◽  
Irma Fredriksson ◽  
Carl Blomqvist ◽  
...  

Abstract Background Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC. Methods The Breast Cancer DataBase Sweden (BCBaSe) includes all women diagnosed with BC from 1992 to 2012 (n = 60,217) and age-matched women without a history of BC (n = 300,791) in three Swedish health care regions. Information on comorbidity, educational level, and incidence of IHD was obtained through linkage with population-based registries. The risk of IHD was estimated by Cox proportional hazard regression analyses and cumulative incidence by the Kaplan-Meier method. Results Women with BC had a lower risk of IHD compared to women without BC with a hazard ratio (HR) of 0.91 (95% CI 0.88–0.95). When women with left-sided BC were compared to right-sided BC, an increased HR for IHD of 1.09 (95% CI 1.01–1.17) was seen. In women receiving RT, a HR of 1.18 (95% CI 1.06–1.31) was seen in left-sided compared to right-sided BC, and the HRs increased with more extensive lymph node involvement and with the addition of systemic therapy. The cumulative IHD incidence was increased in women receiving left-sided RT compared to right-sided RT, starting from the first years after RT and sustained with longer follow-up. Conclusions Women given RT for left-sided BC during 1992 to 2012 had an increased risk of IHD compared to women treated for right-sided BC. These women were treated in the era of three-dimensional conformal RT (3DCRT), and the results emphasize the importance of further developing and implementing RT techniques that lower the cardiac doses, without compromising the beneficial effects of RT.


Circulation ◽  
2020 ◽  
Vol 141 (7) ◽  
pp. 549-559 ◽  
Author(s):  
Farzin Khosrow-Khavar ◽  
Kristian B. Filion ◽  
Nathaniel Bouganim ◽  
Samy Suissa ◽  
Laurent Azoulay

Background: The association between aromatase inhibitors and cardiovascular outcomes among women with breast cancer is controversial. Given the discrepant findings from randomized controlled trials and observational studies, additional studies are needed to address this safety concern. Methods: We conducted a population-based cohort study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study population consisted of women newly diagnosed with breast cancer initiating hormonal therapy with aromatase inhibitors or tamoxifen between April 1, 1998, and February 29, 2016. We usedCox proportional hazards models with inverse probability of treatment and censoring weighting to estimate hazard ratios (HRs) with 95% CIs comparing new users of aromatase inhibitors with new users of tamoxifen for each of the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality). Results: The study population consisted of 23 525 patients newly diagnosed with breast cancer, of whom 17 922 initiated treatment with either an aromatase inhibitor or tamoxifen (8139 and 9783, respectively). The use of aromatase inhibitors was associated with a significantly increased risk of heart failure (incidence rate, 5.4 versus 1.8 per 1000 person-years; HR, 1.86 [95% CI, 1.14–3.03]) and cardiovascular mortality (incidence rate, 9.5 versus 4.7 per 1000 person-years; HR, 1.50 [95% CI, 1.11–2.04]) compared with the use of tamoxifen. Aromatase inhibitors were associated with elevated HRs, but with CIs including the null value, for myocardial infarction (incidence rate, 3.9 versus 1.8 per 1000 person-years; HR, 1.37 [95% CI, 0.88–2.13]) and ischemic stroke (incidence rate, 5.6 versus 3.2 per 1000 person-years; HR, 1.19 [95% CI, 0.82–1.72]). Conclusions: In this population-based study, aromatase inhibitors were associated with increased risks of heart failure and cardiovascular mortality compared with tamoxifen. There were also trends toward increased risks, although nonsignificant, of myocardial infarction and ischemic stroke. The increased risk of cardiovascular events associated with aromatase inhibitors should be balanced with their favorable clinical benefits compared with tamoxifen.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12016-12016
Author(s):  
Heather Greenlee ◽  
Carlos Iribarren ◽  
Romain Neugebauer ◽  
Jamal S Rana ◽  
Mai Nguyen-Huynh ◽  
...  

12016 Background: Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) following diagnosis, as compared to women without BC. To provide a population-based estimate of CVD risk in BC survivors, we compared risk of CVD events in women with and without BC history enrolled in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed between 2005-2013 were identified and matched 1:5 with non-BC controls on birth year, race/ethnicity and KPNC membership at date of BC diagnosis. Cox regression models were used to assess differences in the hazard of four major CVD events (ischemic heart disease (IHD), heart failure (HF), cardiomyopathy, and stroke). Models were adjusted for factors known to influence risk of breast cancer or CVD.Other CVD events included arrhythmia, cardiac arrest, carotid disease, myocarditis/pericarditis, transient ischemic attack, valvular disease, and venous thromboembolism (VTE). We additionally examined subgroups of cases who received chemotherapy, radiation, and endocrine therapy, and their controls. Results: A total of 14,942 women with a new diagnosis of invasive BC were identified and matched to 74,702 women without BC history. On average, women were 62.0 years, 28.3 kg/m2BMI, 64.9% non-Hispanic white. Among all cases and controls, there were no significant differences in hazard of developing IHD, cardiomyopathy, and stroke; there was a borderline difference in HF (HR: 1.08, 95% CI: 0.99, 1.19). Cases were more likely to have a cardiac arrest (HR: 1.39, 95% CI: 1.09, 1.78) and develop VTE (HR: 1.97, 95% CI: 1.74, 2.23). Women treated with chemotherapy were more likely than controls to develop HF (HR: 1.44, 95% CI: 1.21, 1.72), cardiomyopathy (HR: 2.01, 95% CI: 1.02, 3.98), and VTE (HR: 3.15, 95% CI: 2.62, 3.79). Women who received radiation therapy were more likely to develop carotid disease (HR: 5.49, 95% CI: 1.22, 24.66) and VTE (HR: 1.65, 95% CI: 1.35, 2.03) than controls. Women who received endocrine therapy were more likely to experience a cardiac arrest (HR: 1.49, 95% CI: 1.07, 2.09) and develop VTE (HR: 1.70, 95% CI: 1.42, 2.03) than controls. Conclusions: Women with BC were at increased risk of heart failure, cardiomyopathy, cardiac arrest, VTE and carotid disease. These risks varied by cancer treatment, with higher risk in those who received chemotherapy. Future studies should explore the effects of chemotherapy class and radiation dose exposure on diverse CVD endpoints in BC survivors.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hossein Farhadnejad ◽  
Karim Parastouei ◽  
Hosein Rostami ◽  
Parvin Mirmiran ◽  
Fereidoun Azizi

Abstract Background In the current study, we aimed to investigate the association of dietary inflammation scores (DIS) and lifestyle inflammation scores (LIS) with the risk of metabolic syndrome (MetS) in a prospective population-based study. Methods A total of 1625 participants without MetS were recruited from among participants of the Tehran Lipid and Glucose Study(2006–2008) and followed a mean of 6.1 years. Dietary data of subjects were collected using a food frequency questionnaire at baseline to determine LIS and DIS. Multivariable logistic regression models, were used to calculate the odds ratio (ORs) and 95 % confidence interval (CI) of MetS across tertiles of DIS and LIS. Results Mean ± SD age of individuals (45.8 % men) was 37.5 ± 13.4 years. Median (25–75 interquartile range) DIS and LIS for all participants was 0.80 (− 2.94, 3.64) and 0.48 (− 0.18, − 0.89), respectively. During the study follow-up, 291 (17.9 %) new cases of MetS were identified. Based on the age and sex-adjusted model, a positive association was found between LIS (OR = 7.56; 95% CI 5.10–11.22, P for trend < 0.001) and risk of MetS, however, the association of DIS and risk of MetS development was not statistically significant (OR = 1.30;95% CI 0.93–1.80, P for trend = 0.127). In the multivariable model, after adjustment for confounding variables, including age, sex, body mass index, physical activity, smoking, and energy intake, the risk of MetS is increased across tertiles of DIS (OR = 1.59; 95% CI 1.09–2.33, P for trend = 0.015) and LIS(OR = 8.38; 95% CI 5.51–12.7, P for trend < 0.001). Conclusions The findings of the current study showed that greater adherence to LIS and DIS, determined to indicate the inflammatory potential of diet and lifestyle, are associated with increased the risk of MetS.


Author(s):  
Khalaf Kridin ◽  
Jennifer E. Hundt ◽  
Ralf J. Ludwig ◽  
Kyle T. Amber ◽  
Dana Tzur Bitan ◽  
...  

AbstractThe association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.


2021 ◽  
pp. jmedgenet-2020-107471
Author(s):  
Pei Sze Ng ◽  
Rick ACM Boonen ◽  
Eldarina Wijaya ◽  
Chan Eng Chong ◽  
Milan Sharma ◽  
...  

BackgroundRare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.MethodsMutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.ResultsPTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.ConclusionDespite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1378
Author(s):  
Tú Nguyen-Dumont ◽  
James G. Dowty ◽  
Jason A. Steen ◽  
Anne-Laure Renault ◽  
Fleur Hammet ◽  
...  

Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein-truncating variant CHEK2 c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. We conducted a population-based case-control-family study of pathogenic CHEK2 variants (26 families, 1071 relatives) and estimated the age-specific cumulative risk of breast cancer using segregation analysis. The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5–9.5) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02–11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5–12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11–30%) and 33% (95% CI 21–48%) to age 60 and 80 years, respectively. These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.


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