Postmenopausal Japanese Women Research Articles

Predictors of discontinuation of osteoporosis treatment: sub-analysis of the Japanese osteoporosis intervention trial-05 (JOINT-05).

To identify predictors of discontinuing treatment with teriparatide (TPTD) and alendronate (ALN), data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high risk of fracture were re-analyzed. Participants received sequential therapy with once-weekly TPTD for 72weeks followed by ALN for 48weeks (TPTD-ALN group) or monotherapy with ALN for 120weeks (ALN group). Background data including comorbidities, fracture prevalence, cognitive function, quality of life, activities of daily living, bone metabolism parameters, and nutrient intake were collected. The endpoints were 3 types of discontinuations by the reason: a poor compliance, adverse events (AEs), or any reason including those unrelated to AEs or poor compliance. Odds ratios (ORs) of baseline predictors of discontinuation were evaluated by single or multiple regression analysis. A total of 234 (49.0%) patients in the TPTD-ALN group and 167 (34.2%) patients in the ALN group discontinued. In the TPTD-ALN group, a lower serum calcium level was a significant predictor of compliance-related discontinuation. Serum 25-hydroxyvitamin D levels were lower in patients with lower serum calcium levels than with higher serum calcium levels. In the ALN group, poor cognitive function was significantly associated with compliance-related discontinuation, and higher body mass index and alcohol intake were predictors of AE-related discontinuation. Predictors of discontinuation were drug-specific. Lower serum calcium levels and poor cognitive function were predictors of discontinuing once-weekly TPTD and ALN, respectively. When starting TPTD and ALN treatment, careful attention to patients with lower serum calcium levels and poor cognitive function, respectively, may be needed for better treatment continuity.

Muscle Performance as a Predictor of Bone Health: Among Community-Dwelling Postmenopausal Japanese Women from Setagaya-Aoba Study.

Osteoporosis is a significant health concern for postmenopausal women, necessitating efficient screening methods for bone health. This study explores the potential of muscle function, assessed through the 30-s chair stand test (CS-30), as an indicator for low bone stiffness in this demographic, aiming to establish a practical threshold for large-scale fitness surveillance without the need for specialized tools. We analyzed data from 1055 community-dwelling postmenopausal Japanese women, aged 41-89years, collected between 2016 and 2019. Participants underwent CS-30 to evaluate muscle function alongside quantitative ultrasound (QUS) measurements to assess bone stiffness. The cohort was divided into two groups for the development and validation of a cutoff point for low bone stiffness, defined as a QUS speed of sound less than 1487.3m/s. The CS-30 cutoff was determined using receiver operating characteristic (ROC) curve analysis and validated through logistic regression, accounting for age, body mass index, and smoking status. Among 577 postmenopausal women, 16.0% exhibited low bone stiffness. In the development group (n = 382), ROC analysis identified a CS-30 cutoff of 25 repetitions for detecting low bone stiffness, with an area under the curve of 0.744 (P < 0.001). In the validation group (n = 195), participants performing ≥ 25 repetitions had a higher risk of low bone stiffness compared to those performing ≤ 24 repetitions. The CS-30 test is an effective preliminary screening tool for identifying postmenopausal women at risk of low bone stiffness, with a threshold of 25 repetitions. This method could facilitate early detection of individuals at higher osteoporosis risk, promoting timely intervention.

Impact of Bone Mineral Density and Bone Structural Properties on Postmenopausal Women With Rheumatoid Arthritis in Japan: A Cross-Sectional Study.

Introduction There has been no study on bone structural properties in postmenopausal women with rheumatoid arthritis (RA) in Japan. This study investigated bone mineral density (BMD) and bone structural properties in Japanese postmenopausal women with RA. Methods The study had a cross-sectional design and included 119 postmenopausal women aged 50-80 years with RA symptoms for more than five years. BMD, trabecular bone score (TBS), and results of hip structure analysis (HSA) were measured on dual-energy X-ray absorptiometry scans. The control group consisted of 288 women aged 50-80 years without RA. The RA group and control group using bisphosphonates were compared after propensity score matching for age, body mass index, and fracture history. Women in the RA group were also compared according to the use of glucocorticoids (GCs). Results After the propensity matching score, there were no other significant differences in BMD, TBS, and HSA parameters between the RA group and the control group. In the RA group, the TBS was lower in patients on GCs than those not on GCs (1.272 vs 1.313, p=0.008). There were no other significant differences in BMD and HSA parameters between patients in the RA group according to the use of GCs. Conclusion Although there were no differences in BMD, the TBS was lower in patients on GCs than those not on GCs in the RA group. It is thus important for physicians who administer GCs to treat patients with RA to be aware of not only BMD but also TBS.

Association Between Osteoporosis Self-Assessment Tool for Asians and Airflow Limitation in Japanese Post-Menopausal Women.

This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.

Abstract PO1-05-05: Overall survival (OS) and subsequent therapy patterns in Japanese patients with HR+/HER2− advanced breast cancer (ABC) treated with palbociclib (PAL) plus letrozole (LET) in first-line setting (1L)

Abstract Background: PAL is a first-in-class cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) for the treatment of HR+/HER2− ABC. In PALOMA-2 study, PAL plus LET demonstrated a numerically, not statistically significant, prolonged OS versus placebo plus LET (53.9 vs 51.2 months; HR, 0.956; 95% CI, 0.777–1.177) in patients with HR+/HER2− ABC in 1L. Subgroup analyses showed a similar trend in Asia/Pacific region (73.4 vs 55.1 months; HR, 0.744), however, data specific to Japanese subgroup have not been reported. An open-label, single-arm, multicenter Japanese phase 2 study (J-Ph2) investigated the efficacy and safety of PAL plus LET in postmenopausal Japanese women with HR+/HER2− ABC in 1L and showed a median progression-free survival (PFS) of 35.7 months (95% CI, 21.7–46.7) in the final analysis of PFS. However, OS data were immature at the data cutoff. Here, we report the findings from a follow-up study of J-Ph2 (NCT04735367) evaluating OS and subsequent therapy in these Japanese patients. Methods: Patients (N=42) who participated in J-Ph2 were enrolled in this follow-up study. The primary endpoint was OS, defined as the time from the first dose of PAL plus LET in J-Ph2 to date of death due to any cause. Secondary endpoints included chemotherapy-free survival (CFS) and type and duration of subsequent therapy. Median OS, CFS, duration of subsequent therapy and associated 95% CIs were estimated using the Kaplan–Meier method. Outcomes were also assessed for baseline demographic and disease characteristic subgroups including visceral or nonvisceral metastatic disease, disease-free interval (DFI; ≤12 months, &amp;gt;12 months, de novo metastatic), and duration of 1L PAL use (≤24 months or &amp;gt;24 months). Results: Patients had a median age of 62.5 years; 48% had visceral metastases; 33% had de novo disease; 48% had a TFI &amp;gt;12 months; 93% had an ECOG performance status (PS) of 0. At a median follow up of 89.7 months, the median OS was 85.4 months (95% CI, 64.3–not estimable [NE]). Median OS was longer in patients with nonvisceral versus visceral metastases (not reached [NR] vs 67.3 months), with TFI &amp;gt;12 months versus ≤12 months (85.4 vs 45.4 months), or with duration of 1L PAL use &amp;gt;24 months versus ≤24 months (NR vs 47.5 months). Median CFS was 69.1 months (95% CI, 24.2–85.4), and that was longer in patients with nonvisceral versus visceral metastases (77.5 vs 37.5 months). At the data cutoff, 3 patients (7.1%) were still receiving PAL plus LET (90.9–93.2 months). Subsequent therapy after disease progression was administered to 34 of 42 patients (81%). Of these patients, 28 (82%) received endocrine-based therapy, while 3 (9%) patients each received chemotherapy and other therapy, respectively. The median duration of the first subsequent therapy was 8.3 months (95% CI, 3.9–12.2), and that was similar among patients with nonvisceral versus visceral metastases (7.8 vs 8.3 months). Conclusion: This interim analysis showed a median OS of &amp;gt;7 years with 1L PAL plus LET. Patient demographics (geographic, racial factors), disease characteristics (ECOG PS, visceral metastases), and subsequent therapy decisions may have contributed to the extended median OS observed in this study. Further, this report provides insight into real-world subsequent treatment patterns following PAL plus ET. Table Citation Format: Masato Takahashi, Tomofumi Osako, Hiroyuki Yasojima, Kenichi Inoue, Masahiro Kawashima, Hideki Maeda, Mitsuya Ito, Yasuaki Sagara, Kan Yonemori, Masaya Hattori, Naohito Yamamoto, Eriko Tokunaga, Shozo Ohsumi, Yutaka Yamamoto, Akemi Ichikawa, Yasuaki Muramatsu, Norikazu Masuda. Overall survival (OS) and subsequent therapy patterns in Japanese patients with HR+/HER2− advanced breast cancer (ABC) treated with palbociclib (PAL) plus letrozole (LET) in first-line setting (1L) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-05.

Achieving osteoporosis treat-to-target goals with teriparatide or alendronate: sub-analysis of Japanese Osteoporosis Intervention Trial-05 (JOINT-05)

IntroductionThe purpose of this study was to evaluate whether bone mineral density (BMD) ≥ −2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk.Materials and methodsParticipants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ −2.5 SD, and the endpoint was the proportion of participants with baseline BMD < −2.5 SD in three measurement sites achieving BMD ≥ −2.5 SD.ResultsA total of 559 participants were selected. BMD ≥ −2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD.ConclusionDuring the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ −2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.

Consideration of the process of lymph node metastasis in invasive breast cancer with squamous cell differentiation

Abstract Background Breast cancer with squamous differentiation is a relatively rare condition. Clinically, lymph node metastasis is uncommon in metaplastic carcinoma We treated a patient with lymph node metastasis of the ductal carcinoma component of invasive ductal carcinoma with squamous cell differentiation. Case Report An 84-year-old postmenopausal Japanese woman had a left-breast mass with an enlarged lymph node in the left axilla. A biopsy revealed an invasive ductal carcinoma with squamous cell differentiation. A left mastectomy with axillary lymph node dissection was performed. The Histological evaluation revealed invasive ductal carcinoma with squamous cell differentiation. One lymph node was positive for metastasis consisting of ductal carcinoma without squamous cell differentiation. Conclusion This case suggests that lymph node metastasis in ductal carcinoma with squamous differentiation may first involve the ductal carcinoma component and then differentiation may occur in the in volved lymph nodes. This is an interesting case highlighting the process of the progression of lymph node metastasis in cases with breast cancer with squamous cell differentiation.

Spinal osteoarthritis is a risk of vertebral fractures in postmenopausal women

Recent studies have revealed that despite high bone mineral density (BMD), osteoarthritis (OA) is a risk factor for osteoporotic fractures. However, the relationship between spinal OA and vertebral fractures has not yet been fully investigated. This longitudinal analysis used a subset of ongoing cohort study consist with Japanese postmenopausal women. The prevalence of spinal OA was determined using Kellgren–Lawrence grading method. The incidence of vertebral fractures were determined by semiquantitative analysis of spinal X-ray films. The relationship between the presence of spinal OA and incidence of vertebral fractures was evaluated using the Cox regression analysis. In total, 1480 women were followed up for 8.1 ± 6.4 years. Among them, 923 were diagnosed with spinal OA, and incident vertebral fractures were observed in 473 participants. After adjusting for confounding variables, the spinal OA (≥ grade 2) was a significant predictor of incident vertebral fractures (hazard ratio, 1.52; 95% confidence interval: 1.19–1.93, p = 0.001). Using ROC analysis, the thresholds of lumbar BMD for incident vertebral fractures were 0.952 g/cm2 for patients with spinal OA and 0.753 g/cm2 for patients without spinal OA. The presence of spinal OA is a risk factor for incident vertebral fractures despite high lumbar BMD.

Association between physical performance and bone mass in community-dwelling postmenopausal Japanese women: The Unzen study.

Low bone mass is an independent risk factor for osteoporotic fractures. We examined the association between physical performance and bone mass using quantitative ultrasound in community-dwelling postmenopausal Japanese women. We conducted a cross-sectional study on 524 community-dwelling postmenopausal Japanese women who were not being administered osteoporosis medications. Physical performance was assessed on the basis of grip strength, chair stand time, and functional reach. The stiffness index was measured as a quantitative ultrasound parameter for heel bone mass. Physical performance, assessed by grip strength, chair stand time, and functional reach, and the stiffness index significantly decreased with age (both p<0.001). The multiple linear regression analysis showed that grip strength (p = 0.001), chair stand time (p = 0.004), and functional reach (p = 0.048) were significantly associated with the stiffness index after adjusting for age, body mass index, smoking, drinking, and exercise. Physical performance was significantly associated with heel bone mass in community-dwelling postmenopausal Japanese women.

Clinical and phototrichogrammatic evaluation of estradiol replacement therapy on hair growth in postmenopausal Japanese women with female pattern hair loss: a pilot study.

Female pattern hair loss (FPHL) is known to present with characteristic pathological conditions, including reduced overall hair density. Female hormones affect hair condition; however, the detailed mechanism is unknown. Furthermore, research on the topic is complicated by the fact that senescent alopecia often occurs concurrently with FPHL. Therefore, we investigated the effect of estradiol, a female hormone, on hair growth by eliminating aging factors and objectively evaluating hair changes caused by female hormone replacement therapy (HRT). This study was conducted to elucidate the mechanism through which female hormones exert their effects on hair. The study included 11 female patients undergoing HRT who were evaluated before initiating HRT, 3 months after initiating HRT, and 6 months after initiating HRT. The thinning hair score, hair density, telogen hair rate, telogen plucking strength, hair growth rate, and hair thickness were measured and evaluated. Furthermore, hematological tests were performed to assess the general physical condition of the participants. HRT increased the telogen hair rate (P = .010, paired t test) at 3 months, improved frontal hairline thinning score (P = .008, Wilcoxon test), and increased the plucking strength (P = .013, paired t test) at 6 months. The limitation of this study included the relatively small sample size, inability to conduct further long-term tests because of participant burden, and lack of a control group. The results suggested that HRT improved the appearance of the frontal hairline. As few studies have analyzed the effects of female hormones on human hair, a novel finding of this study was the effects of estradiol on the plucking strength after excluding age as a factor. We believe that these findings will contribute to understanding FPHL and developing female hormone-related treatments.

Overall survival in Japanese patients with ER+/HER2− advanced breast cancer treated with first-line palbociclib plus letrozole

BackgroundAn open-label, single-arm, Japanese phase 2 study (J-Ph2) investigated the efficacy and safety of first-line (1L) palbociclib (PAL) + letrozole (LET) in postmenopausal Japanese women with ER+/HER2− advanced breast cancer (ABC). In the final analysis, median progression-free survival was 35.7 months (95% CI 21.7–46.7); but overall survival (OS) data were immature. Here, we report the findings from a follow-up study of J-Ph2 (NCT04735367) evaluating OS and subsequent therapy in these Japanese women.MethodsPatients (N = 42) who participated in J-Ph2 were enrolled in the OS follow-up study. The primary endpoint was OS and secondary endpoints included type and duration of subsequent therapy.ResultsPatients were a median age of 62.5 years; 48% had visceral metastases. At a median follow-up of 89.7 months, the median OS was 85.4 months (95% CI 64.3–not estimable). Median OS was longer in patients with nonvisceral versus visceral metastases (not reached vs 67.3 months), or with treatment-free interval > 12 months versus ≤ 12 months (85.4 vs 45.4 months), or with treatment duration ≥ 24 months versus < 24 months (not reached vs 47.5 months). Of patients who received a first subsequent therapy (81%), most (67%) continued endocrine-based therapy, while 7% received chemotherapy. The median duration of the first subsequent therapy was 8.3 months (95% CI 3.9–12.2), and the median chemotherapy-free survival was 69.1 months (95% CI 24.2–85.4).ConclusionsIn this population of Japanese women with ER+/HER2− ABC, median OS was over 7 years with 1L PAL + LET, supporting the use of 1L PAL + endocrine therapy.Trial numberNCT04735367.

Increased Risk of Tooth Loss in Postmenopausal Women With Prevalent Vertebral Fractures: An Observational Study.

The association between prevalent fractures and tooth loss in postmenopausal women remains unclear. Herein, we investigated the association between prevalent vertebral and nonvertebral fractures, the number of teeth present at baseline, and the number of teeth lost during follow-up in postmenopausal Japanese women. This cross-sectional study enrolled 843 participants (mean age 68.3 years). The number of teeth at follow-up was evaluated in 655 women in this longitudinal study. The participants were divided into four groups according to their prevalent fracture status: no fractures, vertebral fractures alone, nonvertebral fractures alone, and both fracture types. After adjusting for covariates, Poisson regression analyses were performed to investigate differences in the number of teeth at baseline and that lost during the follow-up period among the four groups. Participants with prevalent vertebral fractures alone had significantly fewer teeth at baseline than those in participants without fractures or nonvertebral fractures alone (p < 0.001 for both). Furthermore, they lost more teeth during the follow-up period than did those with no fractures (p = 0.021) and tended to lose more teeth than did those with nonvertebral fractures alone or both prevalent fracture types. We observed no significant difference in the number of teeth lost between the participants with nonvertebral fractures alone and those with no fractures. Postmenopausal women with prevalent vertebral fractures may be at a higher risk of tooth loss. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Walking Steps Prevents Loss Of Bone Mineral Density At The Femoral Neck In Postmenopausal Japanese Women

Walking Steps Prevents Loss Of Bone Mineral Density At The Femoral Neck In Postmenopausal Japanese Women

Serum cholesterol levels and the risk of brain natriuretic peptide-diagnosed heart failure in postmenopausal women: a population-based prospective cohort study.

Hormonal changes during menopause can disturb serum cholesterol which is closely associated with cardiovascular disease. This study investigated the prospective association between serum cholesterol and heart failure (HF) risk in postmenopausal women. We analyzed data from 1,307 Japanese women, aged 55 to 94 years. All women had no history of HF, and their baseline brain natriuretic peptide (BNP) levels were less than 100 pg/mL. During the follow-ups conducted every 2 years, HF was diagnosed among women who developed BNP of 100 pg/mL or greater. Cox proportional hazard models were applied to calculate hazard ratios and 95% CI of HF for women per their baseline total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels. The Cox regression models were adjusted for age, body mass index, smoking, alcohol drinking, hypertension, diabetes, cardiac murmurs, arrhythmia, stroke or ischemic heart disease, chronic kidney disease, and lipid-lowering agent use. Within an 8-year median follow-up, 153 participants developed HF. In the multivariable-adjusted model, women with total cholesterol of 240 mg/dL or greater (compared with 160-199 mg/dL) and HDL-C of 100 mg/dL or greater (compared with 50-59 mg/dL) showed an increased risk of HF: hazard ratios (95% CI) = 1.70 (1.04-2.77) and 2.70 (1.10-6.64), respectively. The results remained significant after further adjusting for baseline BNP. No associations were observed with low-density lipoprotein cholesterol. Total cholesterol of 240 mg/dL or greater and HDL-C of 100 mg/dL or greater were positively associated with the risk of HF in postmenopausal Japanese women.

Phase 1 study of oral selective estrogen receptor degrader (SERD) amcenestrant (SAR439859), in Japanese women with ER-positive and HER2-negative advanced breast cancer (AMEERA-2)

BackgroundThis AMEERA-2 study evaluated the pharmacokinetics, efficacy, and safety of the oral selective estrogen receptor degrader amcenestrant as a monotherapy with dose escalation in Japanese postmenopausal women with advanced estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer.MethodsIn this open-label, nonrandomized, phase I study, patients received amcenestrant 400 mg once daily (QD) (n = 7) and 300 mg twice daily (BID) (n = 3). The incidence of dose-limiting toxicities (DLT), recommended dose, maximum tolerated dose (MTD), pharmacokinetics, efficacy, and safety were assessed.ResultsNo DLTs were observed and MTD was not reached in the 400 mg QD group. One DLT (grade 3 maculopapular rash) was reported in a patient treated with 300 mg BID. After repeated oral administration of either dosing regimen, steady state reached before day 8, without accumulation. Four out of 5 response-evaluable patients from 400 mg QD group achieved clinical benefit and showed tumor shrinkage. No clinical benefit was reported in the 300 mg BID group. Overall, most patients (8/10) experienced a treatment-related adverse event (TRAE), with skin and subcutaneous tissue disorders most commonly reported (4/10 patients). No ≥ grade 3 TRAE in 400 mg QD group and 1 grade 3 TRAE in 300 mg BID group were reported.ConclusionsAmcenestrant 400 mg QD has a favorable safety profile and has been selected as the recommended Phase II dose for monotherapy for evaluating the safety and efficacy of amcenestrant in a larger, global, randomized clinical trial of patients with metastatic breast cancer.Trial registrationClinical trial registration NCT03816839.

Association between Dairy Product intake and Risk of Osteoporotic Fractures in Postmenopausal Japanese Women: Secondary Analysis of 15-Year Follow-Up data from the Japanese Population-Based Osteoporosis (JPOS) Cohort Study.

Few prospective cohort studies have evaluated the relationship between dairy product intake frequency and risk of osteoporotic fractures in Asians. This study aimed to investigate the association between habitual dairy product intake and risk of osteoporotic fractures. Secondary analysis of prospective cohort study. Five municipalities of Japan. This study included 1,429 postmenopausal Japanese women (age ≥45 years at baseline). Baseline milk-intake frequency was obtained using nurse-administered questionnaires. Intakes of yogurt and cheese, and estimated calcium intake, were assessed using a validated food frequency questionnaire. Osteoporotic fracture was defined as a clinical fracture diagnosed using radiography. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Over a median follow-up period of 15.1 years (interquartile range [IQR], 10.1-15.4 years; total, 18,118 person-years), 172 women sustained at least one osteoporotic fracture. The proportions of participants with milk intakes <1, 1, and ≥2 cups/d were 34.4%, 48.0%, and 17.6%, respectively. After adjustment for age, frequency of yogurt intake, frequency of cheese intake, body mass index, history of osteoporotic fractures, and frequency of natto intake, the HRs compared with that for milk intake <1 cup/d were 0.71 (95% CI: 0.51-0.98) and 0.57 (95% CI: 0.35-0.92) for 1 cup/d and ≥2 cups/d, respectively. After adjustment for bone mineral density, HR significance for milk intakes ≥2 cups/d remained significant. Yogurt and cheese intakes were not related to the risk of osteoporotic fractures. High habitual milk intake, but not a habitual yogurt or cheese intake is associated with a decreased risk of osteoporotic fractures, independent of bone mineral density, in postmenopausal Japanese women.

Serum 25-Hydroxyvitamin D Levels and 5-Year Changes in Physical Performance in Postmenopausal Japanese Women

Serum 25-Hydroxyvitamin D Levels and 5-Year Changes in Physical Performance in Postmenopausal Japanese Women

Body weight and body fat are negatively associated with severe dyspareunia in postmenopausal women.

This cross-sectional study aimed to investigate the factors associated with dyspareunia in pre-, peri-, and postmenopausal Japanese women participating in the health and nutrition education program at a menopause clinic. First-visit records of 1702 pre-, peri-, and postmenopausal Japanese women (aged 40-79 years) were analyzed. The relationship between severe dyspareunia and background characteristics was examined by multivariate logistic regression analysis. The average age of the participants was 53.0 ± 6.3 years. The percentage of women who suffered from severe dyspareunia in the pre-, peri-, postmenopausal, and the hormone therapy receiving groups were 7.1%, 10.5%, 14.6%, and 7.8%, respectively. In the postmenopausal group, the percentage of women affected by severe dyspareunia was the highest between 2 and 5 years after menopause (18.8%), presumably owing to the gradual postmenopausal decline in the number of sexually active women. In sexually active postmenopausal women, body weight, body mass index (BMI), and body fat percentage (BF%) differed significantly among those who had severe dyspareunia (N=119) and those who did not (N=334). BMI and BF% were negatively associated with severe dyspareunia, even after adjustment for age and years since menopause (adjusted odds ratio [95% confidence interval]: BMI, 0.894 [0.825-0.964], p=0.003; BF%, 0.947 [0.909-0.985], p=0.006). BMI and BF% were negatively associated with dyspareunia in sexually active postmenopausal women. In addition to aging, the loss of body weight and fat could negatively impact intercourse in sexually active postmenopausal women.

Expression of Concern on "A Radiographic Study on the Associations of Age and Prevalence of Vertebral Fractures with Abdominal Aortic Calcification in Japanese Postmenopausal Women and Men".

Expression of Concern on "A Radiographic Study on the Associations of Age and Prevalence of Vertebral Fractures with Abdominal Aortic Calcification in Japanese Postmenopausal Women and Men".

Abstract CT517: Amcenestrant, an oral selective estrogen receptor (ER) degrader (SERD), in ER+/HER2- advanced breast cancer (aBC): combined biomarker analyses from a Phase 1/2 study in postmenopausal women and a Phase 1 study in postmenopausal Japanese women

Abstract Background: Amcenestrant is an optimized oral SERD that has shown safety and clinical benefit in patients (pts) with wild-type (WT) and mutated ESR1 aBC. Here we provide a pooled analysis of biomarkers from two studies in heavily-pretreated, postmenopausal women with ER+/HER2- aBC. Methods: Pooled analysis included study data from AMEERA-1 (NCT03284957), in which pts received single-agent amcenestrant in dose escalation (20-600 mg QD or 300 mg BID) and dose expansion (400 mg QD), and from AMEERA-2 (NCT03816839), in which Japanese pts received single-agent amcenestrant at 400 mg QD or 300 mg BID. Mutational profiling of plasma circulating cell-free DNA was conducted by droplet digital polymerase chain reaction (ddPCR) for 12 pathogenic ESR1 mutations at baseline (BL) and on treatment (OT; Cycle 2, Day 28), and by next-generation sequencing (NGS; 77-gene panel) at BL and end of treatment (EOT). Clinical benefit (CB; complete response + partial response [PR] + stable disease ≥ 24 weeks) was assessed in pooled pts who received amcenestrant≥ 150 mg QD or BID. In tumor tissue, ER, progesterone receptor (PgR), Ki67 and Bcl-2 expression levels over time were assessed by immunohistochemistry; functional ER pathway activity was assessed by gene set variation analysis with RNA-seq data (ER activity score). Results: Among pts with data for ESR1 mutation status at BL (N = 80; ddPCR), 41 pts were WT and 39 pts had at least one ESR1 mutation, with D538G and Y537S the most prevalent. CB was observed in pts with both WT (13 pts) and mutated ESR1 (12 pts) at BL. The most frequent pathogenic mutations detected in pts (N = 79; NGS) at BL were ESR1 (49%), followed by PI3KCA (46%)and TP53 (33%). In response-evaluable pts with ESR1 mutational profiling at BL and OT (N = 40; ddPCR), 17 of 19 pts with ESR1 mutation at BL showed a decrease in ESR1 mutation allele frequency, independently of clinical benefit. Eight pts showed an increase (7/25 no CB and 1/15 CB). Among 17 pts with biopsies, pts with ER or PgR -/low (H-score: 0-3) at BL did not derive benefit from treatment. In the remaining patients with ER high (H-score ≥ 140), no difference between pts with and without CB was observed in ER, Bcl-2 or ER activity score, while pts with CB had a tendency for lower Ki67. ER and PgR decreased upon treatment independently of CB, while ER activity score and Ki67 mostly decreased in pts with CB and mostly increased in pts without CB. Conclusions: In postmenopausal women with ER+/HER2- aBC treated with single-agent amcenestrant, low Ki67 at BL and the pharmacodynamic decrease of Ki67 and ER activation score by amcenestrant trended toward an association with CB, whereas increase in ESR1 mutation allele frequency on treatment trended toward an association with lack of CB. Clinical benefit was observed in both pts with WT and mutated ESR1 at BL. Citation Format: Hiroji Iwata, Aditya Bardia, Simon Lord, Hannah M. Linden, Mario Campone, Kenji Tamura, Kan Yonemori, Toru Mukohara, Cécile Combeau, Nils Ternes, Dimitri Carene, Jeff Ming, Joon Sang Lee, Marina Celanovic, Anne-Laure Bauchet, Monsif Bouaboula, Tomoyuki Tanaka, Yumiko Kawabata, Sarat Chandarlapaty. Amcenestrant, an oral selective estrogen receptor (ER) degrader (SERD), in ER+/HER2- advanced breast cancer (aBC): combined biomarker analyses from a Phase 1/2 study in postmenopausal women and a Phase 1 study in postmenopausal Japanese women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT517.