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      Steroidal aromatase inhibitors have a more favorable effect on lipid profiles than nonsteroidal aromatase inhibitors in postmenopausal women with early breast cancer: a prospective cohort study

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          Abstract

          Background:

          Aromatase inhibitors (AIs) influence blood lipid profiles. However, relatively few studies have directly compared the treatment effects of steroidal and nonsteroidal AIs.

          Methods:

          A prospective single-center cohort study was conducted to investigate the effects of steroidal and nonsteroidal AIs on lipid profiles during the first 24 months of endocrine therapy in hormone receptor-positive postmenopausal patients with early breast cancer. The primary endpoint was the cumulative incidence of lipid events, while the secondary endpoints were changes in lipid profiles and lipid event-free survival.

          Results:

          Comparison of the lipid profiles of the two groups showed that triglycerides (TGs) and total cholesterol (TC) levels were significantly higher in the nonsteroidal AI group over 24 months ( p < 0.05), whereas low-density lipoprotein cholesterol (LDL-C) was significantly higher only at 3 months ( p = 0.017) and 6 months ( p = 0.026). High-density lipoprotein cholesterol (HDL-C) was significantly lower in the steroidal group at all time points ( p < 0.05), except at 18 months ( p = 0.085). The cumulative incidence of lipid events in the steroidal and nonsteroidal groups at 24 months was 25.3% and 37.0%, respectively. Multivariate analysis results indicated that TG, LDL-C, and steroidal AIs were independently associated with blood lipid events.

          Conclusion:

          This trial showed that a significantly higher cumulative incidence of lipid events occurred in the nonsteroidal AI group than in the steroidal AI group, which indicated that steroidal AIs exerted a protective effect against blood lipid events in postmenopausal women receiving an AI as adjuvant therapy for breast cancer.

          ClinicalTrials.gov identifier:

          NCT02765373

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          Most cited references26

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          Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older.

          Postmenopausal women aged 55 years and older have 66% of incident breast tumors and experience 77% of breast cancer mortality, but other age-related health problems may affect tumor prognosis and treatment decisions. To document the comorbidity burden of postmenopausal breast cancer patients and evaluate its relationship with age on disease stage, treatment, and early mortality. Data were collected on breast cancer patients' comorbidities by retrospective hospital medical records review and merged with information on patients' tumor characteristics collected from 6 regional National Cancer Institute Surveillance, Epidemiology, and End Results cancer registries. Patients were followed up until death or for 30 months from breast cancer diagnosis. Population-based random sample of 1800 postmenopausal breast cancer patients diagnosed in 1992 stratified by 3 age groups: 55 to 64 years, 65 to 74 years, and 75 years and older. Extent of disease, therapy received, comorbidity, cause of death, and survival. Seventy-three percent (1312 of 1800) of the sample was diagnosed with stage I and II breast cancer, 10% (n = 188) with stage III and IV breast cancer, and 17% (n = 300) did not have a stage assignment. Of the 1017 patients with stage I and stage II node-negative breast cancer, 95% received therapy in agreement with the National Institutes of Health consensus statement recommendation for early-stage breast cancer. Patients in older age groups were less likely to receive therapy consistent with the consensus statement (P<.001), and women aged 70 years and older were significantly less likely to receive axillary lymph node dissection as determined by logistic regression analysis (P<.01). Diabetes, renal failure, stroke, liver disease, a previous malignant tumor, and smoking were significant in predicting early mortality in a statistical model that included age and disease stage. Breast cancer was the underlying cause of death for 135 decedents (51.3%). Heart disease (n = 45, 17.1%) and previous cancers (n = 22, 8.4%) were the next major underlying causes. In the 30-month follow-up period, 263 patients (15%) died. Patient care decisions occur in the context of breast cancer and other age-related conditions. Comorbidity in older patients may limit the ability to obtain prognostic information (ie, axillary lymph node dissection), tends to minimize treatment options (eg, breast-conserving therapy), and increases the risk of death from causes other than breast cancer.
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            Early breast cancer therapy and cardiovascular injury.

            Although recent advances in curative-intent therapies are beginning to produce significant survival gains in early breast cancer, these improvements may ultimately be attenuated by increased risk of long-term cardiovascular mortality. This paper reviews emerging evidence on the cardiovascular effects of breast cancer adjuvant therapy and proposes a new entity that we have labeled the "multiple-hit" hypothesis. The evidence that lifestyle modification, especially exercise therapy, may mitigate these adverse effects is also reviewed. These issues are of considerable practical importance for cardiovascular clinicians, as identification and intervention in those at high risk for cardiovascular complications may reduce a major cause of mortality in women with early breast cancer.
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              Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial.

              Tamoxifen has been the standard adjuvant treatment for postmenopausal women with hormone-responsive early breast cancer for more than 20 years. However, the third-generation aromatase inhibitor anastrozole has proven efficacy and tolerability benefits compared with tamoxifen when used as initial adjuvant therapy. We investigate whether women who have received a period of adjuvant tamoxifen would benefit from being switched to anastrozole. We present a combined analysis of data from two prospective, multicentre, randomised, open-label trials with nearly identical inclusion criteria. Postmenopausal women with hormone-sensitive early breast cancer who had completed 2 years' adjuvant oral tamoxifen (20 or 30 mg daily) were randomised to receive 1 mg oral anastrozole (n=1618) or 20 or 30 mg tamoxifen (n=1606) daily for the remainder of their adjuvant therapy. The primary endpoint was event-free survival, with an event defined as local or distant metastasis, or contralateral breast cancer. Analysis was by intention to treat. 3224 patients were included in analyses. At a median follow-up of 28 months, we noted a 40% decrease in the risk for an event in the anastrozole group as compared with the tamoxifen group (67 events with anastrozole vs 110 with tamoxifen, hazard ratio 0.60, 95% CI 0.44-0.81, p=0.0009). Both study treatments were well tolerated. There were significantly more fractures (p=0.015) and significantly fewer thromboses (p=0.034) in patients treated with anastrozole than in those on tamoxifen. These data lend support to a switch from tamoxifen to anastrozole in patients who have completed 2 years' adjuvant tamoxifen.
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                Author and article information

                Contributors
                Journal
                Ther Adv Med Oncol
                Ther Adv Med Oncol
                TAM
                sptam
                Therapeutic Advances in Medical Oncology
                SAGE Publications (Sage UK: London, England )
                1758-8340
                1758-8359
                26 May 2020
                2020
                : 12
                : 1758835920925991
                Affiliations
                [1-1758835920925991]Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [2-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [3-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [4-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [5-1758835920925991]Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [6-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [7-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [8-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [9-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [10-1758835920925991]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [11-1758835920925991]Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, 100021, China
                Author notes
                Article
                10.1177_1758835920925991
                10.1177/1758835920925991
                7252381
                32518597
                9fff0adf-846f-48ca-a51a-c17c72e28a20
                © The Author(s), 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 14 January 2020
                : 3 April 2020
                Categories
                Original Research
                Custom metadata
                January-December 2020
                ts1

                breast cancer,aromatase inhibitors,exemestane,postmenopausal women,lipid profile,low-density lipoprotein cholesterol

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