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Journal of Endocrinological... Jun 2024The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs).
PURPOSE
The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs).
METHODS
This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors.
RESULTS
A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively.
CONCLUSION
Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.
PubMed: 38856966
DOI: 10.1007/s40618-024-02401-7 -
Pharmacological management of testosterone deficiency in men current advances and future directions.Expert Review of Clinical Pharmacology Jun 2024Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most... (Review)
Review
INTRODUCTION
Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most common medical approach for subjects who are not interested in fathering.
AREAS COVERED
This review summarizes advances in TRT, including approved or non-approved pharmacological options to overcome TD. When possible, a meta-analytic approach was applied to minimize subjective and biased interpretations of the available data.
EXPERT OPINION
During the last decade, several new TRT formulations have been introduced on the market, including oral, transdermal, and parenteral formulations. Possible advantages and limitations have been discussed appropriately. Anti-estrogens, including selective estrogen modulators or aromatase inhibitors still represent further possible off-label options. However, long-term side effects on sexual function and bone parameters constitute major limitations. Glucagon-like peptide 1 analogues can be an alternative option in particular for massive obesity-associated TD. Weight loss obtained through lifestyle modifications including diet and physical exercise should be encouraged in all overweight and obese patients. A combination of TRT and lifestyle changes can be considered in those subjects in whom a reversal of the condition cannot be expected in a reasonable time frame.
PubMed: 38853775
DOI: 10.1080/17512433.2024.2366505 -
Sexual Medicine Reviews Jun 2024Sexual pain has a profound impact on individuals, regardless of their sexual orientation or gender identity, and affects women more often than men. It adversely affects...
INTRODUCTION
Sexual pain has a profound impact on individuals, regardless of their sexual orientation or gender identity, and affects women more often than men. It adversely affects both sexual function and interpersonal relationships. Despite its prevalence, sexual pain in women often remains unaddressed and untreated. Various underlying causes contribute to sexual pain, sometimes involving multiple factors. We explore treatment options and offer clinical insights into the evaluation and management of 4 common conditions which cause sexual pain in women. In this article, we use the term "women" to indicate cisgender women.
OBJECTIVES
Our aim is to highlight the most common clinical scenarios of sexual pain and provide comprehensive discussions on each, to improve patient care and outcomes in the management of sexual pain.
METHODS
We conducted a comprehensive review of literature and clinical cases to explore the various causes and management strategies for sexual pain in women. We systematically searched databases such as PubMed, Google Scholar, and relevant medical journals. We included peer-reviewed articles, case studies, and clinical trials published between 2000 and 2023. Additionally, we analyzed real-life cases from our clinical practice at our academic institution.
RESULTS
Our review identified various factors contributing to sexual pain in women, ranging from hormonal imbalances to neuroproliferative and inflammatory conditions affecting the genitourinary system. Each case should be approached individually to offer optimal management strategies accordingly.
CONCLUSION
The management of sexual pain in women requires a comprehensive approach that addresses the multifactorial nature of the condition. Patient education and counseling play a crucial role in the management of sexual pain, empowering individuals to advocate for their own health and well-being. The collaboration between healthcare providers and patients can improve our understanding and management of this complex condition.
PubMed: 38850562
DOI: 10.1093/sxmrev/qeae040 -
Breast Cancer Research : BCR Jun 2024Breast cancers treated with aromatase inhibitors (AIs) can develop AI resistance, which is often driven by estrogen receptor-alpha (ERα/ESR1) activating mutations, as...
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.
METHODS
Letrozole-resistant, MCF7 LTLT cells tagged with luciferase-GFP were injected into the mammary duct inguinal glands of NSG mice (MIND model; 6 mice/group). Mice were randomized to vehicle, lasofoxifene ± palbociclib, fulvestrant ± palbociclib, or palbociclib alone 2-3 weeks after cell injections. Tumor growth and metastases were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. The experiment was repeated with the same design and 8-9 mice in each treatment group.
RESULTS
Western blot analysis showed that the MCF7 LTLT cells had lower ERα and higher HER2 expressions compared with normal MCF7 cells. Lasofoxifene ± palbociclib, but not fulvestrant, significantly reduced primary tumor growth versus vehicle as assessed by in vivo imaging of tumors at study ends. Percent tumor area in excised mammary glands was significantly lower for lasofoxifene plus palbociclib versus vehicle. Ki67 staining showed decreased overall tumor cell proliferation with lasofoxifene ± palbociclib. The lasofoxifene + palbociclib combination was also associated with significantly fewer bone metastases compared with vehicle. Similar results were observed in the repeat experiment.
CONCLUSIONS
In a mouse model of letrozole-resistant breast cancer with no ESR1 mutations, reduced levels of ERα, and overexpression of HER2, lasofoxifene alone or combined with palbociclib inhibited primary tumor growth more effectively than fulvestrant. Lasofoxifene plus palbociclib also reduced bone metastases. These results suggest that lasofoxifene alone or combined with a CDK4/6 inhibitor may offer benefits to patients who have ER-low and HER2-positive, AI-resistant breast cancer, independent of ESR1 mutations.
Topics: Animals; Female; Humans; Mice; Aromatase Inhibitors; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Drug Resistance, Neoplasm; Estrogen Receptor alpha; Fulvestrant; Letrozole; MCF-7 Cells; Piperazines; Pyridines; Pyrrolidines; Tetrahydronaphthalenes; Xenograft Model Antitumor Assays
PubMed: 38849889
DOI: 10.1186/s13058-024-01843-4 -
Frontiers in Endocrinology 2024The term 'differences of sex development' (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, and/or... (Review)
Review
46,XX Differences of Sex Development outside congenital adrenal hyperplasia: pathogenesis, clinical aspects, puberty, sex hormone replacement therapy and fertility outcomes.
The term 'differences of sex development' (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, and/or anatomical sex. DSD in individuals with a 46,XX karyotype can occur due to fetal or postnatal exposure to elevated amount of androgens or maldevelopment of internal genitalia. Clinical phenotype could be quite variable and for this reason these conditions could be diagnosed at birth, in newborns with atypical genitalia, but also even later in life, due to progressive virilization during adolescence, or pubertal delay. Understand the physiological development and the molecular bases of gonadal and adrenal structures is crucial to determine the diagnosis and best management and treatment for these patients. The most common cause of DSD in 46,XX newborns is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, determining primary adrenal insufficiency and androgen excess. In this review we will focus on the other rare causes of 46,XX DSD, outside CAH, summarizing the most relevant data on genetic, clinical aspects, puberty and fertility outcomes of these rare diseases.
Topics: Humans; Adrenal Hyperplasia, Congenital; Puberty; Hormone Replacement Therapy; Fertility; Female; Male; Disorders of Sex Development; Sexual Development
PubMed: 38841305
DOI: 10.3389/fendo.2024.1402579 -
Annals of Oncology : Official Journal... Jun 2024
Interpretation of long-term survival data from MONARCH 3. Letter to the Editor regarding "Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3" by M. P. Goetz et al.
PubMed: 38838846
DOI: 10.1016/j.annonc.2024.05.543 -
Annals of Oncology : Official Journal... Jun 2024
To explain the unexplainable in MONARCH 3 overall survival: the restricted mean survival time. Letter to the Editor regarding 'Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: Final overall survival results of MONARCH 3' by M. P. Goetz et...
PubMed: 38838845
DOI: 10.1016/j.annonc.2024.05.544 -
ESMO Open Jun 2024The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC)... (Randomized Controlled Trial)
Randomized Controlled Trial
Palbociclib combined with endocrine treatment in hormone receptor-positive, HER2-negative breast cancer patients with high relapse risk after neoadjuvant chemotherapy: subgroup analyses of premenopausal patients in PENELOPE-B.
BACKGROUND
The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) did not improve invasive disease-free survival (iDFS) compared to placebo. Here, we report results for premenopausal women.
PATIENTS AND METHODS
Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC at high risk of relapse [defined as no pathological complete response after neoadjuvant chemotherapy and a clinical, pathological stage, estrogen receptor, grading (CPS-EG) score ≥3 or 2/ypN+] were randomized to receive 13 cycles of palbociclib or placebo + standard ET. Ovarian function (OF) was evaluated by centrally assessed estradiol, follicle-stimulating hormone and anti-Müllerian hormone serum levels.
RESULTS
Overall, 616 of 1250 randomized patients were premenopausal; of these, 30.0% were <40 years of age, 47.4% had four or more metastatic lymph nodes, and 58.2% had a CPS-EG score ≥3. 66.1% of patients were treated with tamoxifen alone, and 32.9% received ovarian function suppression (OFS) in addition to either tamoxifen or aromatase inhibitor (AI). After a median follow-up of 42.8 months (97.2% completeness) no difference in iDFS between palbociclib and placebo was observed [hazard ratio = 0.95, 95% confidence interval (CI) 0.69-1.30, P = 0.737]. The estimated 3-year iDFS rate was marginally higher in the palbociclib arm (80.6% versus 78.3%). Three year iDFS was higher in patients receiving AI than tamoxifen plus OFS or tamoxifen alone (86.0% versus 78.6% versus 78.0%). Patients receiving tamoxifen plus OFS showed a favorable iDFS with palbociclib (83.0% versus 74.1%, hazard ratio = 0.52, 95% CI 0.27-1.02, P = 0.057). Hematologic adverse events were more frequent with palbociclib (76.1% versus 1.9% grade 3-4, P < 0.001). Palbociclib seems not to negatively impact the OF throughout the treatment period.
CONCLUSIONS
In premenopausal women, who received tamoxifen plus OFS as ET, the addition of palbociclib to ET results in a favorable iDFS. The safety profile seems favorable and in contrast to chemotherapy palbociclib does not impact OF throughout the treatment period.
Topics: Humans; Female; Breast Neoplasms; Piperazines; Pyridines; Adult; Premenopause; Neoadjuvant Therapy; Receptor, ErbB-2; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Receptors, Estrogen; Disease-Free Survival
PubMed: 38838498
DOI: 10.1016/j.esmoop.2024.103466 -
Journal of the National Cancer Institute Jun 2024Despite the wide use of a three-month gonadotropin-releasing hormone agonist (3M GnRHa) for ovarian function suppression (OFS) in premenopausal breast cancer patients,...
BACKGROUND
Despite the wide use of a three-month gonadotropin-releasing hormone agonist (3M GnRHa) for ovarian function suppression (OFS) in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a one-month GnRHa regimen (1M GnRHa) when combined with selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs), especially in younger patients.
METHODS
This retrospective cohort study included 1109 premenopausal hormone receptor-positive (HR+) breast cancer patients treated with GnRHa plus SERM or AI. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1M or 3M GnRHa in cohorts and different subgroups was analyzed.
RESULTS
Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1M and 3M groups achieved >90% E2 inhibition within 24 months (94.53% vs 92.84%, 95% CI (-4.78%, 1.41%)), confirming the non-inferiority of 3M GnRHa. Both 1M and 3M GnRHa rapidly and consistently reduced E2 levels. 60 (6.3%) patients experienced incomplete ovarian function suppression (iOFS), with similar rates in the 1M and 3M groups (5.5% vs 7.2%). iOFS mainly occurred within the first 12 months, with age <40 years and no prior chemotherapy being the risk factors. Similar disease-free survival (DFS) and overall survival (OS) were found in the 1M and 3M groups, and in patients with complete and incomplete OFS (p > .05).
CONCLUSIONS
The OFS with 3M GnRHa was not inferior to that with 1M GnRHa, regardless of age or combination with a SERM or an AI.
PubMed: 38833681
DOI: 10.1093/jnci/djae115 -
Therapeutic Advances in Medical Oncology 2024The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet...
BACKGROUND
The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority.
OBJECTIVES
To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022.
DESIGN
Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database.
METHODS
There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions.
RESULTS
In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods pre-pandemic (IRR range: 0.31-0.62).
CONCLUSION
During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.
PubMed: 38832300
DOI: 10.1177/17588359241253115