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- Borgquist, Signe, et al.
(författare)
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Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study
- 2017
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 35:11, s. 1179-1188
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor-positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-freesurvival, breast cancer-free interval, and distant recurrence-free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer-free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence-free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor-positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.
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- Borgquist, Signe, et al.
(författare)
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Statin Use and Breast Cancer Risk in the Nurses' Health Study.
- 2016
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 25:1, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies support an anticancer effect of statin drugs, yet epidemiologic evidence remains inconsistent regarding their role in breast cancer primary prevention. Here, we report an updated analysis of the association between statin use and breast cancer incidence in the Nurses' Health Study (NHS) cohort. Postmenopausal NHS participants without a cancer history were followed from 2000 until 2012 (n = 79,518). Data on statin use were retrieved from biennial questionnaires. We fit Cox regression models to estimate associations between longitudinal statin use and breast cancer incidence. Over 823,086 person-years of follow-up, 3,055 cases of invasive breast cancer occurred. Compared with never users, both former and current statin users had similar rates of invasive breast cancer incidence [former users: HRadj, 0.96; 95% confidence interval (CI), 0.82-1.1; current users: HRadj, 1.1; 95% CI, 0.92-1.3]. Associations did not differ by estrogen receptor (ER) status or histology (ductal vs. lobular carcinoma). Statin use was not associated with risk of invasive breast cancer, irrespective of histologic subtype and ER status. Statin drugs do not appear to modify processes involved in breast cancer initiation. Cancer Epidemiol Biomarkers Prev; 25(1); 201-6. ©2016 AACR.
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- Harborg, Sixten, et al.
(författare)
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Circulating lipids and breast cancer prognosis in the Malmö diet and cancer study
- 2022
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 191:3, s. 611-621
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods: Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results: We enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13–4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68–2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70–2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61–2.05]). Conclusion: High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes.
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- Harborg, Sixten, et al.
(författare)
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Obesity and Risk of Recurrence in Patients with Breast Cancer Treated with Aromatase Inhibitors
- 2023
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Ingår i: JAMA Network Open. - 2574-3805. ; 6:10, s. 2337780-2337780
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Clinical studies confirm that obesity is a risk factor for recurrence in postmenopausal women with hormone receptor-positive (HR+) breast cancer. Evidence suggests that women with obesity do not obtain similar protection from aromatase inhibitors as women with healthy weight. Objective: To examine the associations of body mass index (BMI) with recurrence. Design, Setting, and Participants: The cohort study was conducted using data from the Danish Breast Cancer Group and enrolled postmenopausal women diagnosed with stage I to III HR+ breast cancer from 1998 through 2016. Data analysis was conducted from November 2022 to April 2023. Exposures: BMI was classified as (1) healthy weight (18.5-24.9), (2) overweight (25.0-29.9), (3) obesity (30.0-34.9), and (4) severe obesity (≥35.0) using the World Health Organization guidelines. Healthy weight was considered the reference group in statistical analyses. Main Outcomes and Measures: Follow-up began 6 months after breast cancer surgery and continued until the first event of recurrence, contralateral breast cancer, new primary malignant neoplasm, death, emigration, end of clinical follow-up at 10 years, or September 25, 2018. Cox regression was used to estimate crude and adjusted hazard ratios with 95% CIs, adjusting for patient, tumor, and treatment characteristics. Results: A total of 13230 patients (median [IQR] age at diagnosis, 64.4 [58.6-70.2] years) with information on BMI were enrolled. There were 1587 recurrences with a median (IQR) potential estimated follow-up of 6.2 (3.6-8.5) years. Multivariable analyses revealed increased recurrence hazards associated with obesity (adjusted hazard ratio, 1.18 [95% CI, 1.01-1.37]) and severe obesity (adjusted hazard ratio, 1.32 [95% CI, 1.08-1.62]) vs patients with healthy weight. Patients with overweight had a greater risk, but the results were not statistically significant (adjusted hazard ratio, 1.10 [95% CI, 0.97-1.24]). Conclusions and Relevance: In this study, obesity was associated with an increased risk of breast cancer recurrence among postmenopausal patients with HR+ early-stage breast cancer treated with aromatase inhibitors. Physicians should be aware of the significance of obesity on breast cancer outcomes to secure optimal treatment benefit in all patients..
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| 7. |
- Harborg, Sixten, et al.
(författare)
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Statin use and breast cancer recurrence in postmenopausal women treated with adjuvant aromatase inhibitors : a Danish population-based cohort study
- 2020
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 183:1, s. 153-160
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the association between statin use and risk of breast cancer recurrence in a national Danish cohort of postmenopausal breast cancer patients receiving aromatase inhibitors (AI) in the adjuvant setting. Patients and methods: We enrolled all postmenopausal patients diagnosed with stage I–III estrogen receptor positive breast cancer during the years 2007–2017, assigned adjuvant AI treatment, and registered in both the Danish Breast Cancer Group database and the Danish Cancer Registry. We ascertained incident statin exposure (≥ 1 prescription post-diagnosis) from the Danish National Prescription Registry and modeled statins as a time-varying exposure lagged by 6 months. Follow-up began 7 months after diagnosis and continued to the first event of recurrence, death, emigration, 5 years elapsed, or 25th September 2018. We estimated incidence rates of recurrence at 5 years and used Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing statin exposure with non-exposure. Results: We enrolled 14,773 eligible patients. During the 5 years of follow-up, there were 32 recurrences in 3163 person-years of follow-up among statin-exposed patients, and 612 recurrences in 45,655 person-years among unexposed patients (incidence rate per 1000 person-years: 10.12 [95% CI 6.92–14.28] and 13.40 [95% CI 12.36–14.51], respectively). In multivariable models, any statin exposure was associated with a reduced rate of 5-year breast cancer recurrence (adjusted HR 0.72 [95% CI 0.50–1.04]). Considering only lipophilic statins as exposure the results were similar (adjusted HR 0.70 [95% CI 0.48–1.02]). Conclusions: Statin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received adjuvant AI therapy.
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| 8. |
- Lucht, Sarah A., et al.
(författare)
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Circulating lipids, mammographic density, and risk of breast cancer in the Nurses’ Health Study and Nurses’ Health Study II
- 2019
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 30:9, s. 943-953
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Epidemiologic evidence supports an association between high mammographic density and increased breast cancer risk yet etiologic mechanisms remain largely unknown. Mixed evidence exists as to whether circulating lipid levels influence mammographic density and breast cancer risk. Therefore, we examined these associations in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII), two large prospective cohorts with information on PMD and circulating lipid measures, long follow-up, and breast cancer risk factor and outcome data. Methods: We conducted a nested case–control study among women in the NHS and NHSII. Percent mammographic density (PMD) was measured using Cumulus software, a computer-assisted method, on digitized film mammograms. Cross-sectional associations between circulating lipids [total cholesterol (n = 1,502), high-density lipoprotein (HDL-C; n = 579), and triglycerides (n = 655)] and PMD were evaluated among controls. All analyses were stratified by menopausal status at time of mammogram. Relative risks for breast cancer by lipid and PMD measures were estimated among postmenopausal women in the full nested case–control study (cases/controls for cholesterol, HDL-C, and triglycerides were 937/975, 416/449, and 506/537, respectively). Results: There were no significant associations between circulating lipid levels and PMD among healthy women, irrespective of menopausal status. The association between PMD and breast cancer risk among postmenopausal women was not modified by circulating lipid levels (p interaction = 0.83, 0.80, and 0.34 for total cholesterol, HDL-C, and triglycerides, respectively). Conclusion: Overall, no association was observed between lipid levels and PMD, and there was no evidence that lipid levels modified the association between PMD and breast cancer risk.
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