Postmenopausal Breast Cancer Research Articles

Assessing the Factor Structure and Measurement Invariance of the Pittsburgh Sleep Quality Index Between Postmenopausal Breast Cancer Survivors and Controls.

Background and Purpose: This study evaluates the Pittsburgh Sleep Quality Index (PSQI) in terms of factor structure and measurement invariance (MI). The sample included postmenopausal breast cancer (BC) survivors (n = 101) and matched healthy controls (n = 60). Methods: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed on PSQI's seven component scores. MI was tested between groups and across time using Bayes factor (BF). Results: Two factors were identified: sleep efficiency and perceived sleep quality. MI is evidenced between groups (BF < 0.007) and over time (BF > 150). Conclusions: PSQI scores with two subscales are comparable between postmenopausal BC survivors and controls over a 1-year period, providing some validation of PSQI for researching sleep quality in this population.

Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study

BackgroundChemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S. cohort. MethodsWe used the U.S. Environmental Protection Agency’s Toxics Release Inventory to estimate historical airborne emissions (1987–1995) of 19 known and probable carcinogens for participants enrolled (1995–1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status. ResultsWe observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34–3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92–1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94–1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89–1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01–1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status. ConclusionsAn increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.

Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole.

ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes. MA.27 (ClinicalTrials.gov identifier: NCT00066573) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤-1; (-1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05. Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS (P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated (P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS (P = .001) in models with ER. Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤-1.

Adverse Event Profiles of the Third-Generation Aromatase Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS.

The third-generation aromatase inhibitors (AIs), represented by letrozole, anastrozole, and exemestane, have been used as a standard first-line adjuvant therapy for postmenopausal breast cancer patients with positive hormone receptor. However, their safety in the real world has not been systematically analyzed. We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate adverse event (AE) profiles of the three AIs, covering the period from Q1 2004 to Q3 2023. The time-to-event onset profiles and cumulative incidence were analyzed by Weibull shape parameter test and Kaplan-Meier method, respectively. The disproportionality analysis was utilized to assess drug toxicity risk. Based on the FAERS database, 18,035, 8242, and 7011 reports listing letrozole, anastrozole, and exemestane as primary suspected drugs were extracted, respectively. AEs associated with anastrozole displayed the latest onset (p < 0.0001); meanwhile, WSP test showed that all three AIs had early failure-type profiles. At the preferred term level, we acquired 95, 59, and 42 significant signals associated with letrozole, anastrozole, and exemestane, which involved 18, 13, and 15 system organ classes, respectively. The three AIs all reported that their strongest AE signal was trigger finger. Neutropenia was the most frequent AE for letrozole, while the highest occurrences of anastrozole and exemestane were arthralgia. We also found that interstitial lung disease, a rare but serious AE, showed strong signal intensity in all three AIs. Additionally, letrozole was also associated with lots of other rare but serious AEs in hematologic, respiratory, and hepatic systems, which were not recorded in the instructions. Our analysis of safety warning signals of the third-generation AIs from the FAERS database provided reference for clinical safe and rational drug use.

Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes

Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear. To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin. This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024. Prescription of GLP-1RAs, insulins, or metformin. Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates. In the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87). In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.

Anastrozole Dose Escalation for Optimal Estrogen Suppression in Postmenopausal Early-Stage Breast Cancer: A Prospective Trial.

We previously reported that postmenopausal women with estrogen receptor-α-positive breast cancer receiving adjuvant anastrozole 1 mg/day (ANA1) with estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL [inadequate estrogen suppression (IES)] had a threefold increased risk of a breast cancer event. The objective of this study was to determine if increasing anastrozole to 10 mg/day (ANA10) could result in adequate estrogen suppression (AES: E1 <1.3 pg/mL and/or E2 <0.5 pg/mL) among those with IES on ANA1. Postmenopausal women with estrogen receptor-α-positive breast cancer planning to receive adjuvant ANA1 were eligible. E1 and E2 were assessed pre- and post-8 to 10 weeks of ANA1. Those with IES were switched to 8- to 10-week cycles of ANA10 followed by letrozole 2.5 mg/day. E1 and E2 were assessed after each cycle. Anastrozole concentrations were measured post-ANA1 and post-ANA10. Primary analyses included patients who documented taking at least 80% of the planned treatment (adherent cohort). In total, 132 (84.6%) of 156 eligible patients were ANA1 adherent. IES occurred in 40 (30.3%) adherent patients. Twenty-five (78.1%) of 32 patients who began ANA10 were adherent, and AES was achieved in 19 (76.0%; 90% confidence interval, 58.1%-89.0%) patients. Anastrozole concentrations post-ANA1 and post-ANA10 did not differ by estrogen suppression status among adherent patients. AES was maintained/attained in 21 (91.3%) of 23 letrozole-adherent patients. Approximately 30% of ANA1-adherent patients had IES. Among those who switched to ANA10 and were adherent, 76% had AES. Further studies are required to validate emerging data that ANA1 results in IES for some patients and to determine the clinical benefit of switching to ANA10 or an alternative aromatase inhibitor.

Sensitivity of BMI for the Screening of Obesity in Postmenopausal Breast Cancer Survivors

Sensitivity of BMI for the Screening of Obesity in Postmenopausal Breast Cancer Survivors

A Mediation Analysis of Obesity and Adiponectin Association with Postmenopausal Breast Cancer Risk: A Nested Cohort Study in the International Breast Cancer Intervention Study II (IBIS-II) Prevention Trial.

Obesity is a risk factor for postmenopausal breast cancer (BC), and evidence suggests a role for adiponectin in the relationship between obesity and BC. We investigated whether adiponectin or other biomarkers mediate the effect of body mass index (BMI) on postmenopausal BC risk in a cohort study nested in the IBIS-II Prevention Trial. We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering baseline BMI as an exposure and the 12-month adiponectin increase as a mediator after adjustment for the Tyrer-Cuzick score and the lipid-lowering medications/supplements use. In the multivariable Cox model, both the 12-month adiponectin increase (HR, 0.60; 95%CI, 0.36-1.00) and BMI were associated with BC risk (HR, 1.05; 95%CI, 1.00-1.09), with a 40% reduction in women with a 12-month increase in adiponectin. A significantly higher cumulative hazard of BC events was observed in obese women (BMI > 30) with decreased adiponectin (p = 0.0087). No mediating effect of the adiponectin increase on the total effect of BMI on BC risk was observed (natural indirect effect: HR, 1.00; 95%CI, 0.98-1.02). Raising adiponectin levels might be an attractive target for postmenopausal BC prevention.

Associations between body mass index and hormonal receptor, HER2/neu receptor, as well as other clinical characteristics of breast cancer

Background. Obesity is a growing problem in the world. Correlations have been found between increasing body mass index (BMI) and breast cancer (BC). BC has multiple predictive and prognostic factors like hormonal receptors, human epidermal growth factor 2 receptor, stage of the disease and grade. Obesity may be differentially related to the risk of different subtypes given the various potential mechanisms underlying its association with breast cancer. The study aims to analyze the association between BMI, BC histopathologic, ER, PR and HER2/neu receptors expression, tumor size axillary nodes involvement, metastasis and nuclear grade. Methods. A cross sectional study was conducted involving 256 cases with breast cancer. Oncology teaching hospital based BC cases had been interviewed and data collected regarding weight and height, estrogen and progesterone receptors status, human epidermal growth factor 2 receptor, stage of the disease, grade of tumor at time of diagnosis, and categorize the cases to pre and postmenopausal state and then subdivided according to body mass index (normal, overweight, obese) and compared between three groups. Results. Overweight/obese people showed a significant statistical effect with estrogen and progesterone receptors, positive p value = 0.026, 0.007 respectively, larger tumor size, p value =0.035, and more lymph node involvement, p-value=0.031 in post-menopausal women, while premenopausal cases did not show significant statistical effect regarding the above-mentioned variables. Body mass index difference did not show a significant statistical effect on human epidermal growth factor 2 receptor, metastasis at diagnosis, tumor grade in both pre and postmenopausal cases. Conclusion. Body mass index difference affects postmenopausal BC cases rather than premenopausal as overweight/obese cases presented with more estrogen and progesterone receptors positive, larger tumor size and more lymph node involvement.

Mammary adipocytes promote breast tumor cell invasion and angiogenesis in the context of menopause and obesity

The mechanism(s) underlying obesity-related postmenopausal (PM) breast cancer (BC) are not clearly understood. We hypothesized that the increased local presence of ‘obese’ mammary adipocytes within the BC microenvironment promotes the acquisition of an invasive and angiogenic BC cell phenotype and accelerates tumor proliferation and progression. BC cells, treated with primary mammary adipocyte secretome from premenopausal (Pre-M) and PM obese women (ObAdCM; obese adipocyte conditioned-media) upregulated the expression of several pro-tumorigenic factors including VEGF, lipocalin-2 and IL-6. Both Pre-M and PM ObAdCM stimulated endothelial cell recruitment and proliferation and significantly stimulated BC cell proliferation, migration and invasion. IL-6 and LCN2 induced STAT3/Akt signaling in BC cells and STAT3 inhibition abrogated the ObAdCM-stimulated BC cell proliferation and migration. Expression of proangiogenic regulators including VEGF, NRP1, NRP2, IL8RB, TGFβ2, and TSP-1 were found to be differentially regulated in mammary adipocytes from obese PM women. Comparative RNAseq indicated an upregulation of PI3K/Akt signaling, ECM-receptor interactions and lipid/fatty acid metabolism in PM versus Pre-M mammary adipocytes. Our results demonstrate that irrespective of menopausal status, cross-talk between obese mammary adipocytes and BC cells promotes tumor aggressiveness and suggest that targeting the LCN2/IL-6/STAT3 signaling axis may be a useful strategy in obesity-driven breast tumorigenesis.

Half of most frequently mutated genes in breast cancer are expressed differentially between premenopausal and postmenopausal breast cancer patients

Breast cancer has distinct causes and molecular characteristics at premenopausal and postmenopausal ages. The age-standardized incidence rate for postmenopausal breast cancer is more than 10 times higher than in premenopausal breast cancer. Here, we showed that the expression of 10 out of 20 most frequently mutated genes in breast cancer (namely, PIK3CA, CDH1, MUC16, PTEN, FAT3, FAT1, SPEN, ARID1A, LRP1B and RUNX1) is higher in premenopausal women with breast cancer than in postmenopausal women with breast cancer. The most significant differences in the expression in terms of menopause status were observed for RUNX1 and FAT1. Furthermore, we found that the majority of these 10 genes also show ER (estrogen receptor) or PR (progesterone receptor) status-dependent expression in both premenopausal and postmenopausal breast cancer patients. Unlike what we observed in the case of ER or PR status, the expression of most of these genes does not change depending on HER2 (human epidermal growth factor receptor 2) status in both premenopausal and postmenopausal breast cancer patients. Combined, our analysis suggests that menopause status might influence the expression of most frequently mutated genes in breast cancer, and that the most of these genes whose expression differ between pre- and post-menopausal women with breast cancer also show ER or PR status-dependent expression in women with breast cancer.

Association of germline HSD3B1 (c.1100) genotype with tumoral and clinical outcomes in breast and endometrial cancers.

10587 Background: A germline single-nucleotide polymorphism in HSD3B1 results in adrenal-permissive (c.1100 C) and adrenal-restrictive (c.1100 A) phenotypes with respect to androgen synthesis. In pre- and post-menopausal patients with breast cancer (n=3548 and 7871) and endometrial cancer (n=1588 and 8439), we annotated samples as adrenal permissive (CC/AC) or restrictive (AA) based on HSD3B1 variant status and then examined tumoral characteristics and clinical outcomes. Methods: We utilized tumors from the Caris Life Sciences Precision Oncology Alliance database and inferred germline HSD3B1 c.1100 genotype using variant allele frequencies (VAFs): c.1100 C VAF of 0% defined the AA genotype, VAF of 40-60% defined the AC genotype, and VAF of 100% defined the CC genotype. We explored associations of each HSD3B1genotypes with other genomic (WES) and transcriptomic (RNA-seq) features, as well as with survival outcomes. To performed consider menopausal status we used the patient’s age at the time of biopsy (&gt;55 indicating post-menopausal). Results: In breast cancer (BC) and endometrial cancer (EC), the permissive HSD3B1genotype had greater mRNA expression of the estrogen receptor ( ESR1) and co-alterations of the TP53 (p&lt;0.0001). In post-menopausal ECs, the permissive genotype was associated with increased alterations in the PI-3-kinase pathway ( PTEN, PIK3CA, PIK3R1, p&lt;0.0001). In pre-menopausal HER2+ BCs, the restrictive genotype was associated with worse survival (HR=1.40, 95% CI = 1.05-1.85, p=0.027) and exhibited increases in hallmark GSEA signatures including epithelial-to-mesenchymal transition. Post-menopausal basal BCs with the permissive genotype had numerically higher PD-L1 protein expression (50% vs 13%) and less PI-3-kinase alterations ( PTEN, PIK3R1, p&lt;0.01). Post-menopausal clear cell ECs with the restrictive genotype exhibited worse survival (HR=1.60, 95% CI=1.07-2.38, p=0.03) and were 3-fold more likely to be TMB-high or MSI-high (p&lt;0.05). Distinctly, post-menopausal endometrioid ECs of the restrictive genotype were less likely to be TMB- or MSI-high (p&lt;0.05). Conclusions: Breast and endometrial cancers can be classified as adrenal-permissive or -restrictive based on HSD3B1 c.1100 genotype. This classification distinguishes clinical outcomes and tumoral features, particularly when stratifying by menopausal status. Importantly, these genotypes are differentially associated with druggable pathways (PI-3-kinase) and markers of immune sensitivity (PD-L1, TMB, MSI). [Table: see text]

Gender disparities in incidence of psychological disorder among patients with breast cancer: A national cohort study.

e23285 Background: Male breast cancer (MBC) is rare. The features of MBC shares similar characteristics with female breast cancer, often resembling postmenopausal breast cancer. However, there are notable differences between male and female breast cancer, especially regarding gender and age, which can have distinct psychological impacts on male patients. In this study, we investigated whether the psychological distress experienced upon a diagnosis of breast cancer differs according to gender. Methods: Data were obtained from the National Health Insurance claims database of the Health Insurance Review and Assessment Service in South Korea. This study focused on the three most common psychological disorders: sleep disorders, anxiety disorders, and depression. Diagnosis confirmation relied on diagnostic codes based on the International Code of Disease, 10th revision, alongside breast cancer diagnoses. Propensity score matching was used in a 1:5 ratio, and adjustment variables included age, endocrine therapy, chemotherapy, HER2-targeted treatment, and Charlson Comorbidity Index score. Results: After excluding patients with previous psychological disorder, there were a total of 75,936 patients, and 281 (0.4%) male patients. Male patients were diagnosed at an older age, had a higher prevalence of hormone receptor-positive status, higher comorbidities, and lower rates of anxiety disorders, while sleep disorders and depressive disorders showed similar incidences. The Cox proportional hazard regression model exhibited that being female was a risk factor for anxiety disorder (after matching, multivariable, HR 1.498, 95% CI 1.057-2.123, p = 0.023). However, gender did not significantly influence the development of sleep or depressive disorders, despite these conditions typically having a higher incidence in females. During the acute phase shortly after diagnosis, women tend to have more distress, as seen on the cumulative incidence curves. Conclusions: MBC patients experienced similar levels of psychological distress related to sleep and depression disorders as female patients. These results suggested that both genders require an equal support system and psychological care to maintain mental well-being after a breast cancer diagnosis.

A phase II randomized double-blind placebo-controlled study of fisetin to improve physical function in frail older breast cancer survivors (TROFFi).

TPS1645 Background: Among postmenopausal breast cancer survivors treated with chemotherapy, one-third experience a persistent decline in physical function even 12 months after completing treatment. This decline has been associated with loss of independence, disability, and death. One mechanism that is thought to drive chemotherapy-related decline in physical function is cellular senescence, a state of terminal growth arrest. Chemotherapy increases the burden of senescent cells (Sncs), which develop a senescence-associated secretory phenotype (SASP) that over time leads to functional decline. Preclinical mouse studies have demonstrated that eliminating chemotherapy-induced Sncs in mice led to reductions in SASP and improved physical activity. In patients with stage I-III breast cancer treated with chemotherapy, expression of p16INK4a (p16), a known Snc marker, rapidly increased after chemotherapy and persisted over time. Higher levels of pretreatment p16 have also been associated with increased frailty in older breast cancer survivors. Novel senolytic agents have been developed to eliminate Sncs. Among existing senolytics, fisetin is a natural dietary supplement with a favorable safety profile and preclinical efficacy to reduce Snc burden and alleviate frailty in mice. There are multiple ongoing studies of this plant flavonoid in humans, but few are studying the effects of fisetin on chemotherapy-related functional decline in breast cancer survivors. Therefore, we hypothesize that targeting Sncs with fisetin after chemotherapy will improve physical function in frail older breast cancer survivors by reducing systemic Snc burden. Methods: This phase II randomized, placebo-controlled study will enroll 88 postmenopausal women with stage I-III breast cancer who experience physical functional decline after completing neo/adjuvant chemotherapy. Key eligibility criteria include being postmenopausal and within 12 months of completing neo/adjuvant chemotherapy at the time of enrollment. All participants must have evidence of physical functional decline, as measured by a 6-minute walk distance (6MWD) &lt;400 meters, prior to enrollment. Participants will be randomized 1:1 to either placebo or oral fisetin (20mg/kg) on days 1-3 of 14-day cycles for a total of 4 cycles. The primary objective is to determine the effect of fisetin on physical function, as assessed by the change in 6MWD from baseline to end of treatment. Secondary objectives include studying the effect of fisetin on quality of life and additional measures of function including fatigue, cognition, and neuropathy. We will also determine the effect of fisetin on biomarkers of aging, including circulating markers of senescence, as well as the safety of and adherence to fisetin. Enrolment on this study began March 2023 and is currently ongoing. Clinical trial information: NCT05595499 .

Assessment of sexual function in postmenopausal breast cancer survivors.

Breast cancer (BC) is considered a risk factor for sexual dysfunction, which may be associated with the diagnosis itself or with oncological treatments. However, sexual dysfunction often remains underdiagnosed and unaddressed among BC survivors. The study sought to evaluate the sexual function of postmenopausal BC survivors compared with postmenopausal women without BC. This case-control study included 178 postmenopausal BC survivors (stages I-III), 45 to 70years of age, with amenorrhea for ≥12months and sexually active. They were compared with 178 women without BC, matched (±2years) for age and time since menopause in a 1:1 ratio. Sexual function was evaluated using the Female Sexual Function Index (FSFI), which consists of 6 domains (desire, arousal, lubrication, orgasm, satisfaction, and pain), with a total score ≤26.5 indicating risk of sexual dysfunction. Statistical analysis included Student's t test, chi-square test, and logistic regression (odds ratio [OR]). Evaluation of sexual function in postmenopausal women treated for BC. Postmenopausal BC survivors showed poorer sexual function in the desire domain (P = .002). No significant differences were observed between groups in the other FSFI domains and total score (P >.05). Postmenopausal BC survivors had a higher prevalence of risk of sexual dysfunction (64.6% with a total score ≤26.5) compared with the control group (51.6%) (P = .010). Adjusted risk analysis for age and time since menopause revealed a higher risk of sexual dysfunction in BC survivors compared with women without cancer (OR, 1.98; 95% confidence interval, 1.29-2.96; P = .007). Among BC survivors, the use of hormone therapy was associated with a higher risk of sexual dysfunction (OR, 3.46; 95% confidence interval, 1.59-7.51; P = .002). Postmenopausal BC survivors should be regularly assessed before and throughout treatment to enable the early detection and diagnosis of sexual dysfunction. The main strength is that this study might contribute to a better understanding of sexual function in postmenopausal BC survivors compared with women without BC. The main limitation is that while the FSFI is a valid and reliable tool for the evaluation of female sexual function, it does not allow a comprehensive diagnosis of sexual dysfunction, as it is not applicable to partners. Compared with postmenopausal women without BC, postmenopausal BC survivors face a higher risk of sexual dysfunction, especially when treated with adjuvant hormone therapy.

A randomized trial of the impact of symptom monitoring using an electronic patient-reported outcome app on health-related quality of life in postmenopausal breast cancer patients receiving adjuvant endocrine therapy.

Electronic patient-reported outcomes (ePRO) monitoring is a useful communication tool for cancer patients and healthcare providers. In this study, we examined the impact of symptom monitoring using an ePRO app on quality of life (QoL) in postmenopausal breast cancer patients receiving adjuvant endocrine therapy. The free app "Welby My Carte ONC" was used in the study. Patients with breast cancer starting adjuvant endocrine therapy were randomly assigned in a 1:1 ratio to ePRO monitoring (ONC) and control groups. The ONC group reported five symptoms extracted from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE) (insomnia, joint pain, headache, anxiety, and hot flashes) weekly for 3months through the app. Reported symptoms were shared with medical personnel. When serious symptoms were reported, these personnel ascertained the patient's health status and provided advice over the phone. The primary endpoint was QoL measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 3months from enrollment. Differences between groups were tested using analysis of covariance. The study included 125 subjects with mean age of 64years in the ONC group (n = 61) and 63years in the control group (n = 64). In the ONC group, the response rate to PRO-CTCAE was about 70% or higher until week 10. The item missing rate was 0. The ONC group reported more symptoms related to joint pain and insomnia. The difference in FACT-B total score between the groups was -1.55 (95% confidence interval: -5.91, 2.81), indicating no significant difference. Symptom monitoring using ePRO early after initiation of adjuvant endocrine therapy after surgery did not improve QoL of breast cancer patients.

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care – The PreFace Study

AbstractAdjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy.From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed.3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88–90%) and five-year OS rates were 95% (95% CI: 94–96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients).The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies.

Lignans: Advances in Biosynthesis, Bioavailability, and Pharmacological Activity.

Lignans, a group of naturally occurring compounds abundant in various plant-based foods, are becoming increasingly popular due to their potential health benefits. The literature suggests that these bioactive substances can reduce the risk of certain types of cancer, such as postmenopausal colon and breast cancer. Moreover, the significance of lignans for improving cardiovascular health has been recognized, as studies have revealed a potential correlation between the intake of lignans and a decreased risk of cardiovascular disease. These complex molecules possess diverse bioactive capabilities, rendering them potential alternatives for preventing chronic diseases. Further research is needed to examine the mechanisms responsible for their beneficial outcomes. Recent research has emphasized the pharmacological properties of lignans as effective substances for human health. Incorporating foods rich in lignans into the diet may be a practical approach to enhancing protection against life-threatening ailments, such as cardiovascular diseases and malignancies.

Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p=.03), 53% more deaths after breast cancer (p<.001), and 44% higher breast cancer mortality (p=.03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p<.001), more total breast cancers (p<.001), and more deaths after breast cancer (p<.001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p<.001). MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

HEALTH-RELATED QUALITY OF LIFE IN POSTMENOPAUSAL WOMEN WITH ADVANCED BREAST CANCER RECEIVING ADJUVANT HORMONE THERAPY (RIBOCICLIB AND LETROZOLE)

Breast cancer is a type of cancer that affects many women in Indonesia. Adjuvant hormone therapies, such as letrozole and ribociclib, have succeeded in improving the patient's quality of life. This study aimed to assess the quality of life of postmenopausal women with advanced breast cancer who received adjuvant hormone therapy with ribociclib and letrozole. A cross-sectional study was conducted using retrospective data from postmenopausal female breast cancer patients at Dharmais Cancer Hospital between 2020 and 2023 who met the inclusion criteria. To determine the impact of sociodemographics on patient quality of life, data were examined using the quality of life score (EQ5D5L) and Spearman test. There were 29 patients, with a mean age of 54.9 years (SD = 8.65); the highest education level was high school (34.5%); The majority of occupations are housewives (69%), and the majority are stage IV (34.5%). The mean utility and VAS values of Ribociclib were 0.885 and 81.66, respectively, whereas those for letrozole were 0.725 and 78.46, respectively. Analysis of the relationship between quality of life and patient characteristics showed that the quality of life of patients with breast cancer treated with adjuvant ribociclib and letrozole therapy was influenced by the stage of breast cancer (p = 0.008). These findings indicate that patients receiving ribociclib and letrozole therapy have a good quality of life, which quality of life quality of life is influenced by the stage of malignancy. Keywords: breast cancer, quality of life, letrozole, ribociclib, post menopause