Effects of Lasofoxifene Versus Fulvestrant on Vaginal and Vulvar Symptoms in Patients With ESR1-Mutated, ER+/HER2-, Metastatic Breast Cancer From the ELAINE 1 Study.

Background: Lasofoxifene, a novel endocrine therapy (ET), showed antitumor activity versus fulvestrant in women with ESR1-mutated, metastatic breast cancer (mBC) that progressed on prior ET (phase 2, ELAINE 1 study). We investigated changes in genitourinary syndrome of menopause (GSM) vulvar-vaginal symptoms with lasofoxifene and how patient/disease characteristics affect baseline vulvar-vaginal symptoms in ELAINE 1.

Methods: Women were randomized to oral lasofoxifene 5 mg/day or IM fulvestrant 500 mg (days 1, 15, and 29, then every 28 days) until disease progression/severe toxicity.

Overcoming challenges in conducting early phase breast cancer prevention trials: Bazedoxifene and conjugated estrogens vs waitlist control.

Background: The combination of bazedoxifene 20 mg (BZA) and conjugated estrogens 0.45 mg (CE) marketed as Duavee® is approved for vasomotor symptom relief and osteoporosis prevention. Our pilot study suggested it had potential breast cancer risk reduction, and we proposed a multisite Phase IIB primary prevention trial assessing change in breast imaging and tissue risk biomarkers.

Lasofoxifene as a potential treatment for aromatase inhibitor-resistant ER-positive breast cancer.

Background: Breast cancers treated with aromatase inhibitors (AIs) can develop AI resistance, which is often driven by estrogen receptor-alpha (ERα/ESR1) activating mutations, as well as by ER-independent signaling pathways. The breast ER antagonist lasofoxifene, alone or combined with palbociclib, elicited antitumor activities in a xenograft model of ER + metastatic breast cancer (mBC) harboring ESR1 mutations. The current study investigated the activity of LAS in a letrozole-resistant breast tumor model that does not have ESR1 mutations.

Oral lasofoxifene's effects on moderate to severe vaginal atrophy in postmenopausal women: two phase 3, randomized, controlled trials.

Objective: The aim of this study was to demonstrate whether lasofoxifene improves vaginal signs/symptoms of genitourinary syndrome of menopause.

Methods: Two identical, phase 3 trials randomized postmenopausal women with moderate to severe vaginal symptoms to oral lasofoxifene 0.25 or 0.

Epigenetic and transcriptome responsiveness to ER modulation by tissue selective estrogen complexes in breast epithelial and breast cancer cells.

Selective estrogen receptor modulators (SERMs), including the SERM/SERD bazedoxifene (BZA), are used to treat postmenopausal osteoporosis and may reduce breast cancer (BCa) risk. One of the most persistent unresolved questions regarding menopausal hormone therapy is compromised control of proliferation and phenotype because of short- or long-term administration of mixed-function estrogen receptor (ER) ligands. To gain insight into epigenetic effectors of the transcriptomes of hormone and BZA-treated BCa cells, we evaluated a panel of histone modifications.

Spinal alignment shift between supine and prone CT imaging occurs frequently and regardless of the anatomic region, risk factors, or pathology.

Computer-assisted spine surgery based on preoperative CT imaging may be hampered by sagittal alignment shifts due to an intraoperative switch from supine to prone. In the present study, we systematically analyzed the occurrence and pattern of sagittal spinal alignment shift between corresponding preoperative (supine) and intraoperative (prone) CT imaging in patients that underwent navigated posterior instrumentation between 2014 and 2017. Sagittal alignment across the levels of instrumentation was determined according to the C2 fracture gap (C2-F) and C2 translation (C2-T) in odontoid type 2 fractures, next to the modified Cobb angle (CA), plumbline (PL), and translation (T) in subaxial pathologies.

Evaluation of endometrial progesterone receptor expression after 12 weeks of exposure to a low-dose vaginal estradiol insert.

Objective: To evaluate endometrial progesterone receptor (PGR) expression in menopausal women who used vaginal 4-μg and 10-μg estradiol (E2) inserts or placebo.

Methods: REJOICE was a randomized, placebo-controlled trial investigating vaginal E2 inserts in women with moderate to severe dyspareunia due to menopause. In this post hoc analysis, 25 eligible women with endometrial biopsies were randomly selected from each treatment group (4-μg and 10-μg E2 vaginal inserts and placebo).

Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer.

Background: Endocrine therapy remains the mainstay of treatment for estrogen receptor-positive (ER+) breast cancer. Constitutively active mutations in the ligand binding domain of ERα render tumors resistant to endocrine agents. Breast cancers with the two most common ERα mutations, Y537S and D538G, have low sensitivity to fulvestrant inhibition, a typical second-line endocrine therapy.

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings.

Initial investigation into the optimal dose ratio of conjugated estrogens and bazedoxifene: a double-blind, randomized, placebo-controlled phase 2 dose-finding study.

Objective: The aim of the study was to explore dose-related endometrial effects of conjugated estrogens/bazedoxifene (CE/BZA).

Methods: In this randomized, double-blind, phase 2 study, 408 nonhysterectomized, symptomatic (with hot flushes [HFs]) postmenopausal women received ≥1 dose of CE 0.3 or 0.

Efficacy and safety of bazedoxifene in postmenopausal Latino women with osteoporosis.

Objective: Bazedoxifene (BZA) reduces fractures and bone turnover in postmenopausal women with osteoporosis. This report evaluates safety and efficacy of BZA in Latin American women in the global trial.

Methods: In the 3-year, phase 3, randomized, double-blind trial, postmenopausal women with osteoporosis (N = 7,492) received BZA 20 or 40 mg/d, raloxifene 60 mg/d, or placebo.

Hot flush frequency and severity at baseline as predictors of time to transient and stable treatment success: pooled analysis of two CE/BZA studies.

Objective: To evaluate the impact of baseline hot flush frequency and severity on time to symptom improvement during treatment with conjugated estrogens/bazedoxifene (CE/BZA).

Methods: Data were pooled through week 12 from two randomized placebo-controlled trials (SMART-1 and SMART-2) of nonhysterectomized postmenopausal women with hot flushes treated with CE 0.45 mg/BZA 20 mg or CE 0.

Time to first occurrence of breast pain and vaginal bleeding in phase 3 trials of CE/BZA.

Objective: In studies of the menopausal therapy, conjugated estrogens/bazedoxifene, breast pain and vaginal bleeding rates were comparable to placebo and lower than conjugated estrogens/medroxyprogesterone acetate (MPA). This post hoc analysis determined median time to occurrence of these events.

Methods: Participants in phase 3 conjugated estrogens/bazedoxifene trials recorded breast pain and vaginal bleeding in daily diaries.

Relationship between changes in vulvar-vaginal atrophy and changes in sexual functioning.

Objective: Conjugated estrogens/bazedoxifene (CE/BZA) has demonstrated benefit in vulvar-vaginal atrophy (VVA, part of genitourinary syndrome of menopause) and the sexual function domain of the Menopause-specific Quality of Life (MENQOL) questionnaire. The study's objective was to determine the relationship of VVA symptoms and clinical parameters with MENQOL sexual functioning in postmenopausal women receiving VVA treatment.

Study Design: Post hoc analysis data were derived from the 12-week SMART-3 trial, which evaluated CE/BZA's effect on VVA in nonhysterectomized postmenopausal women (aged 40-65 years) experiencing one or more moderate to severe VVA symptoms (dryness, itching/irritation, pain with intercourse) and vaginal pH>5.

Time to transient and stable reductions in hot flush frequency in postmenopausal women using conjugated estrogens/bazedoxifene.

Objective: This post hoc analysis estimates time to transient and stable reductions in hot flush frequency in postmenopausal women using conjugated estrogens/bazedoxifene.

Methods: In the 12-week Selective estrogens, Menopause, And Response to Therapy (SMART)-2 trial of conjugated estrogens/bazedoxifene 0.45 mg/20 mg and 0.

Direct and indirect effects of conjugated estrogens/bazedoxifene treatment on quality of life in postmenopausal women.

Objective: Determine the direct and indirect effects of conjugated estrogens/bazedoxifene (CE/BZA) treatment on menopause-specific quality of life in a post-hoc analysis of 2 phase 3 Selective estrogens, Menopause, And Response to Therapy (SMART-1, SMART-2) trials.

Study Design: Data from participants in SMART-1 and SMART-2 who received CE 0.45mg/BZA 20mg, CE 0.

Timing and persistence of effect of conjugated estrogens/bazedoxifene in postmenopausal women.

Objective: The aim of the study was to determine the time course of effect with conjugated estrogens/bazedoxifene (CE/BZA) in nonhysterectomized postmenopausal women in five phase 3 trials.

Methods: This post hoc analysis identified when CE 0.45 mg/BZA 20 mg and CE 0.

Pooled Analysis of the Effects of Conjugated Estrogens/Bazedoxifene on Vasomotor Symptoms in the Selective Estrogens, Menopause, and Response to Therapy Trials.

Objectives: Conjugated estrogens/bazedoxifene (CE/BZA) reduced menopause-related hot flashes (HFs) in the Selective estrogens, Menopause, And Response to Therapy (SMART) trials. This post hoc pooled analysis of SMART-1 and -2 further characterized effects of CE/BZA on HFs in the overall population and patient subgroups.

Methods: Data from two randomized, double-blind, placebo- and active-controlled, phase 3 studies were pooled for nonhysterectomized postmenopausal women with moderate/severe HFs given CE 0.

CE/BZA effects on bone and quality of life in European postmenopausal women: a pooled analysis.

Objectives: To evaluate the efficacy of conjugated estrogens/bazedoxifene (CE/BZA) on bone mineral density (BMD), bone turnover markers (BTM), and menopause-specific quality of life (MENQOL) in European women.

Methods: Data through 12 months were pooled from two double-blind, randomized, controlled trials in non-hysterectomized postmenopausal women who received CE/BZA or placebo. Women from European study sites with evaluable BMD (n = 60), BTM (n = 56), and MENQOL questionnaire (n = 236) data were included and compared with 1523 women from US study sites (n = 730 with evaluable data for bone outcomes).

Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials.

Objective: Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials.

Methods: Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women.

Relationship between changes in vasomotor symptoms and changes in menopause-specific quality of life and sleep parameters.

Objective: This study characterizes and quantifies the relationship of vasomotor symptoms (VMS) of menopause with menopause-specific quality of life (MSQOL) and sleep parameters to help predict treatment outcomes and inform treatment decision-making.

Methods: Data were derived from a 12-week randomized, double-blind, placebo-controlled phase 3 trial that evaluated effects of two doses of conjugated estrogens/bazedoxifene on VMS in nonhysterectomized postmenopausal women (N = 318, mean age = 53.39) experiencing at least seven moderate to severe hot flushes (HFs) per day or at least 50 per week.

Most bothersome symptom in women with genitourinary syndrome of menopause as a moderator of treatment effects.

Objective: Conjugated estrogens/bazedoxifene (CE/BZA) is indicated to treat moderate/severe menopausal vasomotor symptoms and prevent postmenopausal osteoporosis. This analysis examines the impact of the most bothersome vaginal symptom at baseline on effects of CE/BZA.

Methods: This post hoc analysis used data from a 12-week clinical trial of nonhysterectomized postmenopausal women (n = 664) randomly assigned to double-blind treatment with CE/BZA (0.

Conjugated estrogens and bazedoxifene in minority populations: pooled analysis of four phase 3 trials.

Objective: The aim of the study was to compare efficacy of conjugated estrogens (CE)/bazedoxifene (BZA) for treatment of menopausal symptoms and prevention of postmenopausal osteoporosis in minorities (black/Hispanic) versus whites.

Methods: In a post hoc analysis, data were pooled from 3,424 white or minority nonhysterectomized postmenopausal women randomized to CE 0.45 or 0.

Efficacy and tolerability of bazedoxifene in Mexican women with osteoporosis: a subgroup analysis of a randomized phase 3 trial.

Objective: Bazedoxifene (BZA) is a selective estrogen receptor modulator that reduces fracture risk and bone turnover in postmenopausal women with osteoporosis. This analysis evaluated BZA's effects on bone mineral density (BMD) and bone turnover in Mexican women with osteoporosis from the global pivotal trial (Study Evaluating Bazedoxifene Acetate in Osteoporosis in Postmenopausal Women).

Methods: In this 3-year, phase 3, randomized, double-blind trial, healthy postmenopausal women with osteoporosis (N = 7,492) received BZA 20 or 40 mg/d, raloxifene 60 mg/d, or placebo.

Patient considerations in the management of menopausal symptoms: role of conjugated estrogens with bazedoxifene.

Menopausal symptoms (eg, hot flushes and vaginal symptoms) are common, often bothersome, and can adversely impact women's sexual functioning, relationships, and quality of life. Estrogen-progestin therapy was previously considered the standard care for hormone therapy (HT) for managing these symptoms in nonhysterectomized women, but has a number of safety and tolerability concerns (eg, breast cancer, stroke, pulmonary embolism, breast pain/tenderness, and vaginal bleeding) and its use has declined dramatically in the past decade since the release of the Women's Health Initiative trial results. Conjugated estrogens paired with bazedoxifene (CE/BZA) represent a newer progestin-free alternative to traditional HT for nonhysterectomized women.