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Translational Andrology and Urology Feb 2024In men with impaired semen parameters, empiric medical therapies such as clomiphene citrate, a selective estrogen receptor modulator (SERM), and anastrozole, a selective...
In men with impaired semen parameters, empiric medical therapies such as clomiphene citrate, a selective estrogen receptor modulator (SERM), and anastrozole, a selective aromatase inhibitor, are often employed. The effects of jointly administering these agents on semen parameters are not well understood. Here, we describe the findings of our multi-center, retrospective cohort study of men with idiopathic primary or secondary infertility. Twenty-one men were treated with combination therapy (anastrozole and clomiphene) and 69 men were treated with monotherapy (anastrozole). Patients with pre-treatment normozoospermia and recent or current exogenous testosterone therapy were excluded. Baseline and post-treatment semen and sex hormone parameters were compared among groups. The median follow-up duration was 91 days [interquartile range (IQR), 64-117 days]. Following treatment, 43% of men in the combination therapy group demonstrated normozoospermia, compared to 25% in the monotherapy group. Furthermore, men in the combined group demonstrated marked improvements in total motile sperm count (TMSC) [11.3 2.1 million (M), P=0.03]. There were no significant differences in hormone levels among the two groups following treatment. Combination therapy with clomiphene citrate and anastrozole was associated with modest benefits in post-treatment semen parameters, when compared to anastrozole monotherapy. These benefits may contribute to improvements in pregnancy outcomes with less invasive assisted reproductive technologies, such as intrauterine insemination (IUI). Future investigations with larger sample sizes and prospective study designs are necessary.
PubMed: 38481873
DOI: 10.21037/tau-23-454 -
Annals of Pediatric Endocrinology &... Feb 2024Familial male-limited precocious puberty (FMPP) is a rare form of gonadotropin-independent precocious puberty that is caused by an activating mutation of the LHCGR gene....
Familial male-limited precocious puberty (FMPP) is a rare form of gonadotropin-independent precocious puberty that is caused by an activating mutation of the LHCGR gene. Herein, we report a case of FMPP with a mutation of the LHCGR gene in a Korean boy with familial history of precocious puberty through 3 generations. A 16-month-old boy presented with signs of precocious puberty, including pubic hair, acne, and increased growth velocity. The patient's grandfather and father had a history of precocious puberty and profound short stature. On physical examination, the patient had prepubertal testes with pubic hair development appropriate for Tanner stage II. The stretched penile length was 7 cm (>2 standard deviation score), and observed bone age was that of a 4-year-old boy. Laboratory findings showed high serum testosterone (5.74 ng/mL [appropriate for Tanner IV-V]; normal range, <0.05 ng/mL) with suppressed luteinizing hormone (<0.07 mIU/mL) and normal serum level of follicular stimulating hormone (0.56 mIU/mL; normal range, 0.38-1.11 mIU/mL). Genetic testing revealed a pathogenic variant of LHCGR (c.1730 C>T (p.Thr577Ileu)), confirming FMPP. Bicalutamide and anastrozole were administered, and pubertal progression was sufficiently suppressed without any specific side effects. To our knowledge, this is the first case of genetically confirmed FMPP in Korea.
PubMed: 38461807
DOI: 10.6065/apem.2346042.021 -
Antibodies (Basel, Switzerland) Feb 2024This study examines the intricate relationship between protein glycosylation dynamics and therapeutic responses in Luminal A and Luminal B breast cancer subtypes,...
This study examines the intricate relationship between protein glycosylation dynamics and therapeutic responses in Luminal A and Luminal B breast cancer subtypes, focusing on anastrozole and tamoxifen impacts. The present methods inadequately monitor and forecast patient reactions to these treatments, leaving individuals vulnerable to the potential adverse effects of these medications. This research investigated glycan structural changes by following patients for up to 9 months. The protocol involved a series of automated steps including IgG isolation, protein denaturation, glycan labelling, purification, and final analysis using capillary gel electrophoresis with laser-induced fluorescence. The results suggested the significant role of glycan modifications in breast cancer progression, revealing distinctive trends in how anastrozole and tamoxifen elicit varied responses. The findings indicate anastrozole's association with reduced sialylation and increased core fucosylation, while tamoxifen correlated with increased sialylation and decreased core fucosylation. These observations suggest potential immunomodulatory effects: anastrozole possibly reducing inflammation and tamoxifen impacting immune-mediated cytotoxicity. This study strongly emphasizes the importance of considering specific glycan traits to comprehend the dynamic mechanisms driving breast cancer progression and the effects of targeted therapies. The nuanced differences observed in glycan modifications between these two treatments underscore the necessity for further comprehensive research aimed at thoroughly evaluating the long-term implications and therapeutic efficacy for breast cancer patients.
PubMed: 38390870
DOI: 10.3390/antib13010009 -
Cureus Jan 2024Breast cancer often metastasizes to the lungs, bones, liver, and brain; however, gastric and colonic metastases from breast cancer are rare. Nevertheless, here, we...
Breast cancer often metastasizes to the lungs, bones, liver, and brain; however, gastric and colonic metastases from breast cancer are rare. Nevertheless, here, we present the case of a 50-year-old woman diagnosed with recurrent breast cancer, exhibiting gastric and colonic metastases that were detected when she experienced intermittent abdominal pain. The differentiation between primary gastric cancer and metastasis from breast cancer was made through immunohistochemical staining. The patient underwent treatment with palbociclib, a cyclin-dependent kinase (CDK)4/6 inhibitor, and anastrozole, with no significant adverse effects. Subsequent upper and lower endoscopic examinations following the initiation of these treatments revealed tumor shrinkage in both gastric and colonic metastases. This case report presents the first instance in which morphological changes in gastrointestinal metastasis induced by CDK4/6 inhibitors could be evaluated.
PubMed: 38389643
DOI: 10.7759/cureus.52765 -
Preventive Medicine Reports Feb 2024Uptake to anastrozole for breast cancer prevention is low, partly due to women's concerns about side effects including gains in weight and specifically gains in body...
BACKGROUND
Uptake to anastrozole for breast cancer prevention is low, partly due to women's concerns about side effects including gains in weight and specifically gains in body fat. Previous evidence does not link anastrozole with gains in weight, but there is a lack of data on any effects on body composition i.e. changes in fat and fat free mass. Here we assess association of anastrozole with body composition changes in a prospective sub-study from the second international breast intervention trial (IBIS-II).
METHODS
Participants had DXA scans at baseline and for five years of anastrozole/placebo and beyond (between March 2004 and September 2017. Primary outcomes were changes in body weight, body fat and fat free mass at 9-18 months. A linear model was used to estimate the size of a differential effect in these outcomes by randomised treatment allocation adjusted for baseline value and time since last scan, age, 10-year breast cancer risk, smoking and HRT status.
RESULTS
203 postmenopausal women were recruited (n = 95 anastrozole, n = 108 placebo), mean age 58 years (SD = 5.4), BMI 28.0 kg/m (SD = 5.5). There was no evidence of a strong association between anastrozole or placebo and endpoints at 9-18 months; effect size (95 %CI) for anastrozole minus placebo for body weight (per/kg) -0.11 (-1.29-1.08); body fat 0.11 (-0.75-0.96) and fat free mass -0.30 (-0.79-0.19).
CONCLUSIONS
There is unlikely to be a clinically significant change to body composition with anastrozole for breast cancer prevention.
PubMed: 38375161
DOI: 10.1016/j.pmedr.2024.102620 -
Frontiers in Oncology 2024Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors...
Aromatase inhibitor-induced arthralgia ameliorated by Mediterranean diet and active lifestyle guided by continuous glucose monitoring: a case report and review of the literature.
Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors suffer from AI-induced arthralgia (AIA), also known as AI-associated musculoskeletal syndrome (AIMSS), for which there are limited evidence-based treatments. Pharmacologic management and complementary methods including supplements, exercise, physical therapy, yoga, acupuncture, and massage have all shown mixed results. Comprehensive diet and lifestyle strategies are understudied in AIA/AIMSS despite their disease-modifying effects across many chronic conditions. Here we report a case of a woman with stage 2 estrogen and progesterone receptor-positive invasive ductal carcinoma on adjuvant anastrozole whose AI-induced arthralgia was durably controlled through a Mediterranean plant-forward diet and daily physical activity guided by continuous glucose monitoring. We posit that diet and a lifestyle inclusive of daily physical activity constitute a low-cost, low-risk, and potentially high-reward strategy for controlling common AI-induced musculoskeletal symptoms and that more investigation in this arena, including well-designed randomized trials, is warranted.
PubMed: 38361780
DOI: 10.3389/fonc.2024.1189287 -
JMIR Research Protocols Feb 2024Patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer often experience a reduced quality of life after primary treatment. The disease and...
BACKGROUND
Patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer often experience a reduced quality of life after primary treatment. The disease and treatment trajectory consists of surgery followed by chemotherapy or radiation therapy. Upon this, maintenance hormone therapy with an aromatase inhibitor can result in several physical and psychosocial symptoms. Optimal symptom control during maintenance therapy is central to maintaining the patient's quality of life.
OBJECTIVE
This study aims to (1) develop an electronic symptom management tool for patients with postmenopausal early breast cancer receiving maintenance aromatase inhibitors with an endocrine aspect and (2) assess the feasibility, acceptability, and usability of the pilot version of the Bone@BC app. Furthermore, longitudinally, symptom prevalence and quality of life for patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer will be explored.
METHODS
This study follows a multistage research plan. In stage 1, a systematic literature review to establish an overview of aromatase inhibitor-related symptoms reported by postmenopausal women with nonmetastatic estrogen receptor-positive breast cancer will be completed. In stage 2, a comprehensive overview of symptoms related to aromatase inhibitors (letrozole, exemestane, and anastrozole) will be performed (eg, by reviewing medical leaflets and guidelines). In stage 3, an electronic app with a user-friendly Patient Concern Inventory list to comprise symptoms and concerns will be developed. Last, in stage 4, a convergent mixed methods feasibility study of the pilot version of the Bone@BC app will be conducted. A total of 45 patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer will use the app daily for symptom identification and respond to 6 serial patient-reported outcome measurements for 12 weeks. Finally, semistructured interviews will be performed. The primary outcome includes consent rate, attrition rate, retention rates, technical issues, and adherence, assessed using preestablished criteria on feasibility and a mixed methods approach for exploring acceptability. A patient advisory board consisting of 5 women with breast cancer is recruited to include their perspectives and experiences in the planning, organization, implementation, and dissemination of the research throughout the project.
RESULTS
At the time of submitting this paper (January 2024), a total of 23 patients have been included in the stage 2 medical audit over the recruitment period of 3 months (November 2022 to February 2023), and 19 patients have been enrolled in stage 2, the semistructured patient interviews.
CONCLUSIONS
This protocol describes a study investigating the feasibility, acceptability, and usability of the symptom management tool Bone@BC developed for patients with breast cancer with an endocrine aspect.
TRIAL REGISTRATION
ClinicalTrails.gov NCT05367830; https://clinicaltrials.gov/ct2/show/NCT05367830.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/49549.
PubMed: 38358787
DOI: 10.2196/49549 -
BMC Health Services Research Feb 2024The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole...
PURPOSE
The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole for the prevention of breast cancer in women with a high risk of breast cancer and to determine whether anastrozole for the primary prevention of breast cancer can improve the quality of life of women and save health-care resources.
METHODS
A decision-analytic model was used to assess the costs and effects of anastrozole prevention versus no prevention among women with a high risk of breast cancer. The key parameters of probability were derived from the IBIS-II trial, and the cost and health outcome data were derived from published literature. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies,One-way and probabilistic sensitivity analyses were performed.
RESULTS
In the base case, the incremental cost per QALY of anastrozole prevention was £125,705.38/QALY in the first 5 years compared with no prevention in the UK, above the threshold of WTP (£3,000/QALY),and in the 12-year period, the ICER was £8,313.45/QALY, less than WTP. For the US third-party payer, ICER was $134,232.13/QALY in the first 5 years and $8,843.30/QALY in the 12 years, both less than the WTP threshold ($150,000/QALY).
CONCLUSION
In the UK and US, anastrozole may be a cost-effective strategy for the prevention of breast cancer in high-risk postmenopausal women. Moreover, the longer the cycle of the model, the higher the acceptability. The results of this study may provide a scientific reference for decision-making for clinicians, patients, and national medical and health care government departments.
Topics: Humans; Female; Anastrozole; Breast Neoplasms; Cost-Effectiveness Analysis; Postmenopause; Quality of Life; Nitriles; Triazoles; Cost-Benefit Analysis; United Kingdom; Quality-Adjusted Life Years
PubMed: 38350960
DOI: 10.1186/s12913-024-10658-0 -
International Journal of Molecular... Jan 2024The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no...
The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no overexpression of HER-2. However, TNBC can express the androgen receptor (AR) or estrogen receptor β (ERβ). Also, TNBC secretes steroid hormones and is influenced by hormonal fluctuations, so the steroid inhibition could exert a beneficial effect in TNBC treatment. The aim of this study was to evaluate the effect of dutasteride, anastrozole and ASP9521 in in vitro processes using human TNBC cell lines. For this, immunofluorescence, sensitivity, proliferation and wound healing assays were performed, and hormone concentrations were studied. Results revealed that all TNBC cell lines expressed AR and ERβ; the ones that expressed them most intensely were more sensitive to antihormonal treatments. All treatments reduced cell viability, highlighting MDA-MB-453 and SUM-159. Indeed, a decrease in androgen levels was observed in these cell lines, which could relate to a reduction in cell viability. In addition, MCF-7 and SUM-159 increased cell migration under treatments, increasing estrogen levels, which could favor cell migration. Thus, antihormonal treatments could be beneficial for TNBC therapies. This study clarifies the importance of steroid hormones in AR and ERβ-positive cell lines of TNBC.
Topics: Humans; Androgens; Receptors, Estrogen; Triple Negative Breast Neoplasms; Estrogen Receptor beta; Cell Line, Tumor; Estrogens; Receptors, Androgen; Steroids; Estrogen Receptor alpha; Cell Proliferation
PubMed: 38338747
DOI: 10.3390/ijms25031471 -
JAMA Network Open Feb 2024Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1,...
IMPORTANCE
Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed.
OBJECTIVE
To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs.
DESIGN, SETTING, AND PARTICIPANTS
In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed.
EXPOSURES
CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention.
MAIN OUTCOMES AND MEASURES
The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated.
RESULTS
In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs.
CONCLUSIONS AND RELEVANCE
In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.
Topics: Female; Humans; Adult; Middle Aged; Breast Neoplasms; Cost-Benefit Analysis; Mastectomy; Ovarian Neoplasms; Salpingo-oophorectomy
PubMed: 38334999
DOI: 10.1001/jamanetworkopen.2023.55324