Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.
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ABSTRACT:
SUBMITTER: Donnelly LS
PROVIDER: S-EPMC3974072 | biostudies-other | 2014 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundDetrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause.MethodsWe conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case's diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression.ResultsAfter multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the >90th (≥2.94 ng/mgCr) to <25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5-24.9 kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m (OR: 0.98, CI: 0.39, 2.5, 138 cases).ConclusionsTogether with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk.
| S-EPMC5580344 | biostudies-literature
Project description:PurposeTo evaluate factors associated with endometrial pathology during tamoxifen use in premenopausal breast cancer (BC) patients.Materials and methodsWe reviewed the medical records of premenopausal BC patients treated with tamoxifen who underwent endometrial biopsy with or without hysteroscopy. Clinical characteristics were compared between women with endometrial pathology (endometrial hyperplasia or cancer) and those with normal histology or endometrial polyps.ResultsAmong 284 endometrial biopsies, endometrial hyperplasia was diagnosed in 7 patients (2.5%), endometrial cancer was diagnosed in 5 patients (1.8%), normal histology was noted in 146 patients (51.4%), and endometrial polyp was present in 114 patients (40.1%). When comparing women with endometrial cancer (n=5) to women with normal histology, abnormal uterine bleeding was more common (p=0.007), and endometrial thickness was greater (p=0.007) in women with endometrial cancer. Chemotherapy for BC was also more common in patients with endometrial cancer (p=0.037). When comparing women with endometrial polyps and those with endometrial hyperplasia or cancer, the presence of abnormal uterine bleeding was more common in patients with endometrial hyperplasia or cancer (p<0.001); however, tamoxifen duration and endometrial thickness did not differ significantly between the two groups.ConclusionIn premenopausal BC patients treated with tamoxifen, abnormal uterine bleeding, increased endometrial thickness, and chemotherapy for BC were associated with the occurrence of endometrial cancer. These findings may provide useful information for gynecologic surveillance and counseling during tamoxifen treatment in premenopausal BC patients.
| S-EPMC7105402 | biostudies-literature
Project description:Window studies are gaining traction to assess (molecular) changes in short timeframes. Decreased tumor cell positivity for the proliferation marker Ki67 is often used as a proxy for treatment response. Immunohistochemistry (IHC)-based Ki67 on tissue from neo-adjuvant trials was previously reported to be predictive for long-term response to endocrine therapy for breast cancer in postmenopausal women, but none of these trials enrolled premenopausal women. Nonetheless, the marker is being used on this subpopulation. We compared pathologist assessed IHC-based Ki67 in samples from pre- and postmenopausal women in a neo-adjuvant, endocrine therapy focused trial (NCT00738777), randomized between tamoxifen, anastrozole, or fulvestrant. These results were compared with (1) IHC-based Ki67 scoring by AI, (2) mitotic figures, (3) mRNA-based Ki67, (4) five independent gene expression signatures capturing proliferation, and (5) blood levels for tamoxifen and its metabolites as well as estradiol. Upon tamoxifen, IHC-based Ki67 levels were decreased in both pre- and postmenopausal breast cancer patients, which was confirmed using mRNA-based cell proliferation markers. The magnitude of decrease of Ki67 IHC was smaller in pre- versus postmenopausal women. We found a direct relationship between post-treatment estradiol levels and the magnitude of the Ki67 decrease in tumors. These data suggest IHC-based Ki67 may be an appropriate biomarker for tamoxifen response in premenopausal breast cancer patients, but anti-proliferative effect size depends on estradiol levels.
| S-EPMC8528844 | biostudies-literature
Project description:Body mass index (BMI) is inversely related to the risk of premenopausal breast cancer, but the underlying biological mechanisms of this association are poorly understood. Leptin, a peptide hormone produced primarily by adipocytes, is a potential mediator of the BMI association because BMI and total body fat are positively associated with circulating leptin levels and leptin and its receptor are overexpressed in breast tumors. We conducted a prospective case-control study nested within the Nurses' Health Study II cohort examining the association between plasma leptin levels in premenopausal women and breast cancer risk. Leptin was measured in blood samples collected between 1996 and 1999. The analysis included 330 incident breast cancer cases diagnosed after blood collection and 636 matched controls. Logistic regression models, controlling for breast cancer risk factors, were used to calculate ORs and 95% CIs. After adjustment for BMI at age 18, weight change since age 18 to blood draw, and other breast cancer risk factors, plasma leptin levels were inversely associated with breast cancer risk (OR for top vs. bottom quartile = 0.55; 95% CI = 0.31-0.99; P(trend) = 0.04). Adjustment for BMI at blood draw attenuated the association (OR = 0.69; 95% CI = 0.38-1.23; P(trend) = 0.26). Our results suggest that leptin may be inversely associated with breast cancer risk, but it is unclear whether any part of this association is independent of BMI.
| S-EPMC3168067 | biostudies-literature
Project description:Background A decrease in breast density due to tamoxifen preventive therapy might indicate greater benefit from the drug. It is not known whether mammographic density continues to decline after 1 year of therapy, or whether measures of breast density change are sufficiently stable for personalised recommendations. Methods Mammographic density was measured annually over up to 5 years in premenopausal women with no previous diagnosis of breast cancer but at increased risk of breast cancer attending a family-history clinic in Manchester, UK (baseline 2010-2013). Tamoxifen (20 mg/day) for prevention was prescribed for up to 5 years in one group; the other group did not receive tamoxifen and were matched by age. Fully automatic methods were used on mammograms over the 5-year follow-up: three area-based measures (NN-VAS, Stratus, Densitas) and one volumetric (Volpara). Additionally, percentage breast density at baseline and first follow-up mammograms was measured visually. The size of density declines at the first follow-up mammogram and thereafter was estimated using a linear mixed model adjusted for age and body mass index. The stability of density change at 1 year was assessed by evaluating mean squared error loss from predictions based on individual or mean density change at 1 year. Results Analysis used mammograms from 126 healthy premenopausal women before and as they received tamoxifen for prevention (median age 42 years) and 172 matched controls (median age 41 years), with median 3 years follow-up. There was a strong correlation between percentage density measures used on the same mammogram in both the tamoxifen and no tamoxifen groups (all correlation coeficients > 0.8). Tamoxifen reduced mean breast density in year 1 by approximately 17–25% of the inter-quartile range of four automated percentage density measures at baseline, and from year 2, it decreased further by approximately 2–7% per year. Predicting change at 2 years using individual change at 1 year was approximately 60–300% worse than using mean change at 1year. Conclusions All measures showed a consistent and large average tamoxifen-induced change in density over the first year, and a continued decline thereafter. However, these measures of density change at 1 year were not stable on an individual basis.
| S-EPMC7523310 | biostudies-literature
Project description:PurposeThe Suppression of Ovarian Function trial showed improved disease control for tamoxifen plus ovarian function suppression (OFS) compared with tamoxifen alone for the cohort of premenopausal patients who received prior chemotherapy. We present the patient-reported outcomes.Patients and methodsThe quality-of-life (QoL) analysis includes 1,722 of 2,045 premenopausal patients with hormone receptor-positive breast cancer randomly assigned to receive adjuvant treatment with 5 years of tamoxifen plus OFS or tamoxifen alone. Chemotherapy use before enrollment was optional. Patients completed a QoL form consisting of global and symptom indicators at baseline, every 6 months for 24 months, and annually during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6, 24, and 60 months with mixed models for repeated measures with and without chemotherapy and overall.ResultsPatients on tamoxifen plus OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months, by loss of sexual interest and sleep disturbance at 6 months, and by vaginal dryness up to 60 months. Without prior chemotherapy, patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen plus OFS. Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy. Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period.ConclusionOverall, OFS added to tamoxifen resulted in worse endocrine symptoms and sexual functioning during the first 2 years of treatment, with variable magnitudes of treatment differences. Short-term differences in symptom-specific QoL, treatment burden, and coping effort between treatment groups were less pronounced for patients with prior chemotherapy, the cohort that benefited most from OFS in terms of disease control.
| S-EPMC4872319 | biostudies-literature
Project description:Increased breast density decreases mammographic sensitivity due to masking of cancers by dense tissue. Tamoxifen exposure reduces mammographic density and, therefore, should improve screening sensitivity. We modelled how low-dose tamoxifen exposure could be used to increase mammographic sensitivity. Mammographic sensitivity was calculated using the KARMA prospective screening cohort. Two models were fitted to estimate screening sensitivity and detected tumor size based on baseline mammographic density. BI-RADS-dependent sensitivity was estimated. The results of the 2.5 mg tamoxifen arm of the KARISMA trial were used to define expected changes in mammographic density after six months exposure and to predict changes in mammographic screening sensitivity and detected tumor size. Rates of interval cancers and detection of invasive tumors were estimated for women with mammographic density relative decreases by 10-50%. In all, 517 cancers in premenopausal women were diagnosed in KARMA: 287 (56%) screen-detected and 230 (44%) interval cancers. Screening sensitivities prior to tamoxifen, were 76%, 69%, 53%, and 46% for BI-RADS density categories A, B, C, and D, respectively. After exposure to tamoxifen, modelled screening sensitivities were estimated to increase by 0% (p = 0.35), 2% (p < 0.01), 5% (p < 0.01), and 5% (p < 0.01), respectively. An estimated relative density decrease by ≥20% resulted in an estimated reduction of interval cancers by 24% (p < 0.01) and reduction in tumors >20 mm at detection by 4% (p < 0.01). Low-dose tamoxifen has the potential to increase mammographic screening sensitivity and thereby reduce the proportion of interval cancers and larger screen-detected cancers.
| S-EPMC7830894 | biostudies-literature
Project description:PurposeAdipokines are linked to obesity and insulin sensitivity and have recently been related to breast cancer risk and prognosis. We investigated the associations of plasma leptin and adiponectin with mammographic density and disease status and assessed their prognostic effect on recurrence-free survival in premenopausal women at risk for breast cancer.Patients and methodsWe measured circulating lipids, insulin-like growth factor 1, glucose, insulin and insulin sensitivity (calculated by homeostasis model assessment [HOMA] index), leptin, adiponectin, and leptin-to-adiponectin ratio in 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), intraepithelial neoplasia (n = 160), or 5-year Gail risk of 1.3% or greater (n = 54) who participated in a 2 × 2 trial of low-dose tamoxifen, fenretinide, both agents, or placebo over a 2-year period.ResultsAt baseline, adiponectin levels were directly associated with mammographic density and HDL cholesterol and negatively associated with leptin, leptin-to-adiponectin ratio, body mass index (BMI), and HOMA index. Median adiponectin levels were lower in affected than in unaffected women (P = .006). After a median of 7.2 years and total of 57 breast neoplastic events, there was a 12% reduction in the risk of breast neoplastic events per unit increase of adiponectin (adjusted hazard ratio, 0.88; 95% CI, 0.81 to 0.96; P = .03). There was no interaction between treatment and adiponectin levels.ConclusionLow adiponectin levels are associated with a history of prior intraepithelial neoplasia or pT1mic/pT1a breast cancer and higher risk of second breast neoplastic events in premenopausal women. The associations are independent of BMI, mammographic density, and treatment. Our findings support the role of adiponectin as a potential target for premenopausal breast cancer prevention and treatment.
| S-EPMC3255561 | biostudies-literature
Project description:The purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women. To do so, we assessed change in proliferation in benign breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) as a primary endpoint, along with changes in other risk biomarkers and objective and subjective side effects as secondary endpoints. Twenty-five women with cytologic hyperplasia ± atypia and ≥2% of breast epithelial cells staining positive for Ki-67, received 20 mg acolbifene daily for 6-8 months, and then had benign breast tissue and blood risk biomarkers reassessed. Ki-67 decreased from a median of 4.6% [interquartile range (IQR), 3.1%-8.5%] at baseline to 1.4% (IQR, 0.6%-3.5%) after acolbifene (P < 0.001; Wilcoxon signed-rank test), despite increases in bioavailable estradiol. There were also significant decreases in expression (RT-qPCR) of estrogen-inducible genes that code for pS2, ERα, and progesterone receptor (P ≤ 0.026). There was no significant change in serum IGF1, IGFBP3, IGF1:IGFBP3 ratio, or mammographic breast density. Subjective side effects were minimal with no significant increase in hot flashes, muscle cramps, arthralgias, or fatigue. Objective measures showed a clinically insignificant decrease in lumbar spine bone density (DEXA) and an increase in ovarian cysts but no change in endometrial thickness (sonography). In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen-inducible gene expression but minimal side effects, suggesting a phase IIB placebo-controlled trial evaluating it further for breast cancer prevention.
| S-EPMC4670810 | biostudies-literature
Project description:Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer, in this study, we evaluated gene expression changes induced by parity in the breast of premenopausal women. Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers were performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted analysis of gene expression differences in P vs. NP women as a function of time since last FTP.
2019-03-19 | GSE112825 | GEO