Hormone Therapy In Postmenopausal Women Research Articles

Health-related quality of life outcomes between non-steroid and steroid aromatase inhibitors and switching hormone therapy in postmenopausal women with ER+ breast cancer

Adjuvant hormone therapy can affect the quality of life of postmenopausal breast cancer patients with the estrogen receptor (ER+). This study aimed to measure the outcomes of health-related quality of life (HRQoL) in postmenopausal women with ER+ breast cancer receiving non-steroidal aromatase inhibitors (NSAI), steroidal aromatase inhibitors (SAI), and hormone change therapy (Switch). This cross-sectional study was conducted by interviewing women with postmenopausal ER+ breast cancer. The EQ-5D-5L instrument was used to measure and compare utility scores among patients who received NSAI, SAI, and switch therapy. As a result, the average utility score EQ-5D-5L for NSAI is 0.864 (SD = 0.117), significantly different (p = 0.025) from SAI 0.777 (SD = 0.211) and switch 0.776 (SD = 0.071). The conclusion is that NSAI, SAI, and Switch significantly affected HRQoL in postmenopausal breast cancer patients with ER+. NSAI has a better quality of life compared to SAI and Switch.

Navigating Hormone Therapy in Postmenopausal Women: Balancing Symptom Relief With Cancer Risk.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Hormone Therapy and Biological Aging in Postmenopausal Women

Menopause is associated with biological aging, and hormone therapy (HT) is associated with health outcomes in postmenopausal women. To evaluate the association between HT use and discrepancies between chronological and biological age in postmenopausal women as well as the potential modifying role of socioeconomic status (SES). This population-based, retrospective cohort study included postmenopausal women registered in the UK Biobank. A baseline survey on HT use and biological aging biomarkers was conducted from March 2006 to October 2010. Data analyses were conducted in December 2023. Information regarding HT use, the age at starting HT, and HT duration was collected via a touchscreen questionnaire. SES was evaluated by education, family income, occupation, and the Townsend Deprivation Index. Biological aging discrepancy was evaluated using validated phenotypic age, which was calculated using chronological age and 9 biomarkers measured at baseline. All-cause and cause-specific mortality were also assessed. Among the 117 763 postmenopausal women (mean [SD] age, 60.2 [5.4] years), 47 461 (40.3%) ever used HT. The mean phenotypic age was 52.1 (7.9) years. Ever use of HT was associated with a smaller biological aging discrepancy than never use of HT (β, -0.17 years; 95% CI, -0.23 to -0.10 years). This smaller aging discrepancy was more evident in those who started HT at age 55 years or older (β, -0.32 years; 95% CI, -0.48 to -0.15 years) and in those who used HT for 4 to 8 years (β, -0.25 years; 95% CI, -0.35 to -0.15 years). The association between HT and a smaller aging discrepancy was more evident in women with low SES, with a significant interaction observed for education (higher education: β, -0.08 years [95% CI, -0.17 to 0.01]; other education: β, -0.23 [95% CI, -0.32 to -0.14] years; P for interaction = .02). Phenotypic aging discrepancy mediated 12.7% (95% CI, 6.3% to 23.9%) of the association between HT and all-cause mortality and cause-specific mortality. In this study, postmenopausal women with historical HT use were biologically younger than those not receiving HT, with a more evident association observed in those with low SES. The biological aging discrepancy mediated the association between HT and decreased mortality. Promoting HT in postmenopausal women could be important for healthy aging.

Effect of Postmenopausal Hormone Therapy on Glucose Regulation in Women With Type 1 or Type 2 Diabetes: A Systematic Review and Meta-analysis.

Blood glucose regulation in women with diabetes may change during and after menopause, which could be attributed, in part, to decreased estrogen levels. To determine the effect of postmenopausal hormone therapy (HT) on HbA1c, fasting glucose, postprandial glucose, and use of glucose-lowering drugs in women with type 1 and women with type 2 diabetes. We conducted a systematic search of MEDLINE, Embase, Scopus, the Cochrane Library, and the ClinicalTrials.gov registry to identify randomized controlled trials (RCTs). We selected RCTs on the effect of HT containing estrogen therapy in postmenopausal women (≥12 months since final menstrual period) with type 1 or type 2 diabetes. Data were extracted for the following outcomes: HbA1c, fasting glucose, postprandial glucose, and use of glucose-lowering medication. Nineteen RCTs were included (12 parallel-group trials and 7 crossover trials), with a total of 1,412 participants, of whom 4.0% had type 1 diabetes. HT reduced HbA1c (mean difference -0.56% [95% CI -0.80, -0.31], -6.08 mmol/mol [95% CI -8.80, -3.36]) and fasting glucose (mean difference -1.15 mmol/L [95% CI -1.78, -0.51]). Of included studies, 50% were at high risk of bias. When postmenopausal HT is considered for menopausal symptoms in women with type 2 diabetes, HT is expected to have a neutral-to-beneficial impact on glucose regulation. Evidence for the effect of postmenopausal HT in women with type 1 diabetes was limited.

Cost-effectiveness of the addition of CDK4/6 inhibitors to standard endocrine therapy in first-line treatment of women with advanced HR+/HER2- breast cancer in Mexico.

To estimate the cost-effectiveness of adding a CDK4/6 inhibitor to standard endocrine therapy in the first-line setting for advanced HR+/HER2- breast cancer in postmenopausal and premenopausal women, from the perspective of the Mexican public healthcare system. We used a partitioned survival model to simulate relevant health outcomes in a synthetic cohort of patients with breast cancer derived from the PALOMA-2, MONALEESA-2, MONARCH-3 trials for postmenopausal patients, and from the MONALEESA-7 study for premenopausal patients. Effectiveness was measured in life years gained. Cost-effectiveness is reported through incremental cost-effectiveness ratios (ICER). In postmenopausal patients, palbociclib led to an increase of 1.51 life years, ribociclib of 1.58years, and abemaciclib of 1.75years, compared to letrozole alone. The ICER was 36,648 USD, 32,422 USD, and 26,888 USD, respectively. In premenopausal patients, ribociclib led to an increase of 1.82 life years when added to goserelin and endocrine therapy, with an ICER of 44,579 USD. In the cost minimization analysis, for postmenopausal patients, ribociclib was the treatment with the highest costs due to follow-up requirements. Palbociclib, ribociclib, and abemaciclib demonstrated a significant increase in effectiveness in postmenopausal patients, and ribociclib in premenopausal patients, when added to standard endocrine therapy for patients with advanced HR+/HER2- breast cancer. At the national stablished willingness to pay, only the addition of abemaciclib to standard endocrine therapy in postmenopausal women would be considered cost-effective. However, differences on results between therapies for postmenopausal patients were not statistically significant.

Adjuvant hormone therapy in early-stage estrogen-positive breast cancer: a systematic review and network meta-analysis

Relevance. Adjuvant hormonal therapy in postmenopausal women at an early-stage of estrogen-positive breast cancer (BC) includes anastrozole, letrozole, tamoxifen, toremifene, and exemestane, but the most effective drug is not known, and in this situation, the role of adjuvant hormonal therapy becomes especially debatable.The purpose of the study. Conducting an indirect comparison of oestrogen antagonists and aromatase inhibitors used in postmenopausal women with early-stage estrogen-positive breast cancer through a systematic search and selection of transitive data from randomized controlled trials (RCTs), and their subsequent quantitative synthesis in a network meta-analysis.Methods. We conducted a systematic review in two databases: MEDLINE and The Cochrane Central Register of Controlled Trials. Full-text versions of articles from RCTs were reviewed to evaluate the comparative efficacy of adjuvant hormonal monotherapy with toremifene, tamoxifen, anastrozole, letrozole, and exemestane in women with early-stage estrogen-positive postmenopausal breast cancer who had not previously received hormone therapy. Efficacy was assessed by overall survival (OS). A network meta-analysis was carried out using the NetMetaXL programme.Results. As a result of a systematic search, we selected 8 RCTs involving 25167 patients. When performing a synthesis of the obtained data using a network meta-analysis, no statistically significant differences in 5-year OS were obtained between the comparators.Conclusions. There are no clinically significant differences in 5-year OS between the compared drugs of adjuvant hormonal monotherapy in early-stage breast cancer.

Open-label phase II study of everolimus plus endocrine therapy in postmenopausal women with ER+, HER2- metastatic breast cancer (Chloe trial).

e13052 Background: In the treatment of ER-positive metastatic breast cancer (MBC), the addition of molecularly targeted drugs overcoming resistance to aromatase inhibitors (AI) improves outcomes. It is not clear, however, whether this drug is necessary in the first line treatment for all cases. Whether it should be administered before acquiring resistance, especially for MBCs with sensitivity to AI, is debatable. In this study, we prospectively investigated whether early additional administration of mTOR inhibitor to an AI-sensitive MBC regimen can delay the acquisition of resistance and extend the duration of AI efficacy. Methods: This was a multicenter, open-label, randomized, phase II study comparing patients with ER-positive postmenopausal MBC responsive to first-line treatment with AI for six months, and randomized to either continue to receive AI (standard group; SG) or add the 10 mg/day of mTOR inhibitor (experimental group; EG). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival, response rate (RR), disease control rate (DCR), adverse events (AE), and time to treatment failure (TTF). The planned number of registrations was 130 (65 cases in each group) with a registration period of 2 years. Results: The total enrollment was 44, with 21 in the SG and 22 in the EG (one patient did not receive treatment). As to patient backgrounds, 9.5% (2 patients) in SG and 22.7% in EG (5 patients) were PgR negative. Late recurrence (DFS＞5 years after surgery) was observed in 10 (47.6%) SG patients and 12 (54.5%) EG patients. Three SG patients (14.3%) and two EG patients (9.1%) had a history of chemotherapy after recurrence. Treatment was discontinued in 14 (66.7%) SG patients and 12 EG (54.5%) patients during follow-up. Progressive disease was observed in 12 (57.1%) and 4 (18.2%) patients, respectively, while in the EG we noted discontinuation due to AE (4 patients (18.2%)) and discontinuation at the patient's request (4 patients (18.2%)). There was no significant difference in PFS between the two groups. There was no significant difference in the DCR in patients with target lesions (62.5% in SG and 78.6% in EG). The frequency of AE greater than G2 was low in SG: only 3 with hyperglycemia and 1 with leukopenia. In contrast, numerous toxicities were observed in multiple patients in EG (68.2%). Conclusions: Early addition of an mTOR inhibitor for AI-sensitive MBC did not achieve significant PFS prolongation. Although the addition of mTOR inhibitors may have suppressed the deterioration of patient status, several cases required discontinuation due to AE associated with the drug. Further study with a larger sample size may be required to determine a significant difference between the two groups. Clinical trial information: jRCTs061180075 .

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the randomised phase 3 DATA trial

The DATA study evaluated the use of two different durations of anastrozole in patients with hormone receptor-positive breast cancer who were disease-free after 2-3 years of tamoxifen. We hereby present the follow-up analysis, which was performed after all patients reached a minimum follow-up of 10 years beyond treatment divergence. The open-label, randomised, phase 3 DATA study was performed in 79 hospitals in the Netherlands (ClinicalTrials.gov, number NCT00301457). Postmenopausal women with hormone receptor-positive breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen treatment were assigned to either 3 or 6 years of anastrozole (1mg orally once a day). Randomisation (1:1) was stratified by hormone receptor status, nodal status, HER2 status, and prior tamoxifen duration. The primary outcome was adapted disease-free survival, defined as disease-free survival from 3 years after randomisation onwards. Adapted overall survival was assessed as a secondary outcome. Analyses were performed according to the intention-to-treat design. Between June 28, 2006, and August 10, 2009, 1912 patients were randomly assigned to 3 years (n=955) or 6 years (n=957) of anastrozole. Of these, 1660 patients were eligible and disease-free at 3 years after randomisation. The 10-year adapted disease-free survival was 69.2% (95% CI 55.8-72.3) in the 6-year group (n=827) and 66.0% (95% CI 62.5-69.2) in the 3-year group (n=833) (hazard ratio (HR) 0.86; 95% CI 0.72-1.01; p=0.073). The 10-year adapted overall survival was 80.9% (95% CI 77.9-83.5) in the 6-year group and 79.2% (95% CI 76.2-81.9) in the 3-year group (HR 0.93; 95% CI 0.75-1.16; p=0.53). Extended aromatase inhibition beyond 5 years of sequential endocrine therapy did not improve the adapted disease-free survival and adapted overall survival of postmenopausal women with hormone receptor-positive breast cancer. AstraZeneca.

Clinical observation of menopause hormone therapy in postmenopausal women with euthyroid and mild subclinical hypothyroidism

BackgroundTo evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT).MethodsA retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25–75th percentile) age was 52 (49–54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6–18 month cycles, serum endocrine hormone and metabolic indices were reassessed.ResultsCompared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment.ConclusionMHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.

Hormone therapy in postmenopausal women living with HIV: a view towards prevention of multiple metabolic conditions and improvement of quality of life.

aModena HIV Metabolic Clinic bDepartment of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia cDepartment of Infectious Diseases, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy. Correspondence to Giovanni Guaraldi, MD, Associate Professor, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41124 Modena, Italy. Tel: +39 059 422 5318; Mob: +39 335 33 34 34; e-mail: [email protected] Received 8 June, 2022 Accepted 15 June, 2022

Ribociclib in the Treatment of Hormone-Receptor Positive/HER2-Negative Advanced and Early Breast Cancer: Overview of Clinical Data and Patients Selection.

Among pre- and postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC), combinations of an aromatase inhibitor (AI) or fulvestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) have demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard single-agent hormone therapy alone as first-line therapy for de novo metastatic disease or relapse during or after adjuvant therapy and no previous therapies in an advanced setting. We here reviewed clinical data about ribociclib in advanced and early BC. Also, we shed light on patient selection and special settings in which medical oncologists urgently await an advance in treatment. Ribociclib was FDA-approved in combination with letrozole based on a Phase III study in which 668 postmenopausal women with HR+, HER2-negative recurrent or metastatic BC were treated with first-line letrozole with or without ribociclib. For patients with metastatic disease at presentation or after a course of AIs, the results of the MONALEESA-3 trial suggest ribociclib’s efficacy in combination with fulvestrant, and this combination is FDA-approved for initial- and subsequent-line endocrine therapy for postmenopausal women with metastatic hormone receptor-positive, HER2-negative BC. In adjuvant and neoadjuvant settings, the use of CDK 4/6 inhibitors may be useful to boost outcomes in high-risk patients with HR+ BC, but data contrast with those of a phase III study, which produced positive results. New combinations are being explored in upfront disease (neoadjuvant) or in association with other targeted agents in metastatic disease. Compared to other CDK 4/6 available, ribociclib has a higher incidence of liver function test abnormalities than the other agents and can cause QTc prolongation, and therefore may be prudently avoided in patients with cardiac morbidities or other risk factors for QTc prolongation (drugs, interactions). In these cases, different agents (palbociclib or abemaciclib) may be used. In conclusion, ribociclib with letrozole or with fulvestrant is effective for the entire spectrum of patients with HR+ BC in the advanced setting. Ribociclib has all the characteristics of an innovative drug able to change the clinical practice and most BC patients’ prognoses.

Menopause and the Risk of Developing Age-Related Macular Degeneration in Korean Women.

Previous studies have shown that menopausal hormone therapy in postmenopausal women results in a higher prevalence of age-related macular degeneration. This study aimed to evaluate the effects of menopause and patient factors on the development of age-related macular degeneration in Korean women. Data between 2011 and 2014 were collected from the Korean National Health Insurance database. In this retrospective cohort study, 97,651 participants were premenopausal and 33,598 were menopausal. Participants were divided into menopausal and premenopausal groups to analyze the risk factors associated with the development of age-related macular degeneration. The prevalence of age-related macular degeneration was compared between the two groups. Other patient factors were also analyzed. Using a 1:1 propensity score matching method and adjusting for variables, the incidence of age-related macular degeneration was not significantly different between the two groups. Age and diabetes mellitus were associated with an increased risk of developing age-related macular degeneration, regardless of menopause. Menopause was not a risk factor for age-related macular degeneration. These findings may help physicians identify women with diabetes who are at a greater risk of developing age-related macular degeneration.

A0441 - The bladder or the kidney: Who is affected the most by hormonal therapy in postmenopausal women with and without nocturnal polyuria?

A0441 - The bladder or the kidney: Who is affected the most by hormonal therapy in postmenopausal women with and without nocturnal polyuria?

Differential biological effects of aromatase inhibitors: Apoptosis, autophagy, senescence and modulation of the hormonal status in breast cancer cells

Estrogen receptor-positive (ER+) breast carcinomas are the most common subtype, corresponding to 60% of the cases in premenopausal and 75% in postmenopausal women. The third-generation of aromatase inhibitors (AIs), the non-steroidal Anastrozole (Ana) and Letrozole (Let) and the steroidal Exemestane (Exe), are considered a first-line endocrine therapy for postmenopausal women. Despite their clinical success, the development of resistance is the major setback in clinical practice. Nevertheless, the lack of cross-resistance between AIs hints that these drugs may act through distinct mechanisms. Therefore, this work studied the different effects induced by AIs on biological processes, such as cell proliferation, death, autophagy and senescence. Moreover, their effects on the regulation of the hormonal environment were also explored. The non-steroidal AIs induce senescence, through increased YPEL3 expression, on aromatase-overexpressing breast cancer cells (MCF-7aro), whereas Exe promotes a cytoprotective autophagy, thus blocking senescence induction. In addition, in a hormone-enriched environment, the non-steroidal AIs prevent estrogen signaling, despite up-regulating the estrogen receptor alpha (ERα), while Exe down-regulates ERα and maintains its activation. In these conditions, all AIs up-regulate the androgen receptor (AR) which blocks EGR3 transcription in Exe-treated cells. On the other hand, in hormone-depleted conditions, a crosstalk between AR and ERα occurs, enhancing the estrogenic effects of Exe. This indicates that Exe modulates both ERα and AR, while Ana and Let act as pure AIs. Thus, this study highlights the potential clinical benefit of combining AR antagonists with Exe and discourages the sequential use of Exe as second-line therapy in postmenopausal breast cancer.

Art of prevention: The importance of dermatologic care when using aromatase inhibitors.

As of January 2021, there are more than 3.8 million women in the United States with a history of breast cancer. The current standard of care for breast cancer involves surgical resection, radiation therapy, adjuvant endocrine therapy, and/or adjuvant chemotherapy. Aromatase inhibitors (AIs) are the gold standard for endocrine therapy in postmenopausal women. Dermatologic adverse events (dAEs) associated with AIs are rare but have been reported in the literature. Commonly reported dAEs include unspecified rash, pruritus, alopecia, vulvovaginal atrophy, vasculitis, and autoimmune/connective tissue disorders. Appropriate preventative strategies and careful management considerations have the potential to optimize the comprehensive care of patients with cancer and improve quality of life. Furthermore, prevention of dAEs can lead to a reduction in cancer treatment interruptions and discontinuations. Herein, we characterize dAEs of AIs and discuss preventative management to reduce the incidence of AI therapy interruption.

Delayed hypersensitivity reactions to multiple aromatase inhibitors followed by successful desensitization to letrozole

Aromatase inhibitors (AIs) are a class of medications that can suppress plasma estrogen levels by inhibiting or inactivating aromatase—the enzyme responsible for converting androgens to estrogens.1 They are the preferred adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer.2 Anastrozole, letrozole, and exemestane are the most often used third-generation AIs with similar efficacy and tolerability.1,2 If patients develop intolerable adverse effects with one AI, they can switch to a different one.

From Theory to Practice: Bone Health in Women with Early Breast Cancer Treated with Aromatase Inhibitors.

Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor-positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. This work aimed to assess bone loss, fracture incidence, and risk factors associated with these events, as well as the prognostic influence of fractures. We have conducted a retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. Four-hundred-and-fifty-one eligible women were reviewed (median age 68 years). Median time under AI was 40 months. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in older women (mean 74 vs. 68 years, p = 0.006). Age (OR 1.01, 95% CI 1.01–1.07, p = 0.024) and time under AI (OR 1.02, 95% CI 1.00–1.04, p = 0.037) were independent predictors of fracture, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups, disfavoring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6–92.4 vs. 95.6%, 95% CI, 91.2–97.8, p = 0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted HR of 3.17, 95% CI 1.10–9.11; p = 0.032). Bone health is often forgotten, despite its great impact in survivorship. Our results validate the pathophysiologic link between EBC and bone metabolism, which translates into EBC recurrence. Further research in this area may help refine these findings. Moreover, early identification of women at higher risk for fractures is warranted.

Abstract PS12-27: From theory to practice: Impact of aromatase inhibitors in the bone health of women with early breast cancer

Abstract Background: Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. They decrease bone mineral density, accelerate osteoporosis and lead to increased risk of fractures, thus impairing quality of life. Identification of patients at higher risk would be helpful for best treatment decisions. Recommendations have been published for bone health preservation but real-world data regarding implementation and adherence to these recommendations is scarce. This work aimed to assess bone loss, fracture incidence and risk factors associated with these events, as well as the prognostic influence of fractures in women undertaking adjuvant AI. Materials and Methods: In this retrospective cohort study, we have evaluated women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. A minimum of 3 months under AI and 3 years of follow-up after AI start were necessary for inclusion. Statistical analysis of collected data was performed using R 3.5.2, R-Studio 1.1.456 and Stata 15.1 software. Results: 451 eligible women were reviewed (median age 68 years, 30-98 min-max). Median time under AI was 40 months (3-114). Baseline bone densitometry, carried out in only 69% patients, showed abnormal results in 75%, but only 69% and 16% started calcium/vitD supplementation and bisphosphonates therapy, respectively. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in women with higher age (p=0.006). This group also showed lower T-scores at lumbar spine and femoral neck (p=0.067). On multivariate analysis, age (OR 1.04, 95% CI 1.01-1.07, p=0.016) and time under AI (OR 1.02, 95% CI 1.00-1.03, p=0.045) were independent predictors of fracture events, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups disfavouring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6-92.4 vs. 95.6%, 95% CI, 91.2-97.8, p=0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted-HR of 3.17, 95% CI 1.10-9.11; p=0.032). Conclusion: Bone health is often forgotten, despite its great impact in survivorship. Our results suggest a pathophysiologic link between EBC and bone metabolism, potentially estrogen-mediated, which translates into EBC recurrence. Further research in this area may help refining these findings. Moreover, early identification of women at higher risk with individualized treatment plans comprising shorter duration of AI is warranted. Poor adherence to existing guidelines is a crucial barrier to effective approaches to bone health. Citation Format: Leonor Vasconcelos Matos, Maria Teresa Neves, Fatima Alves, Mafalda Baleiras, André Ferreira, Pedro Cotovio, Tiago Dias Domingues, Mariana Malheiro, Joana Graça, Leonor Fernandes, Ana Plácido, Helena Miranda, Ana Martins. From theory to practice: Impact of aromatase inhibitors in the bone health of women with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-27.

Meta-analyses of phase 3 randomised controlled trials of third generation aromatase inhibitors versus tamoxifen as first-line endocrine therapy in postmenopausal women with hormone receptor-positive advanced breast cancer.

Four randomised controlled trials (RCTs) in postmenopausal women with advanced breast cancer (ABC) comparing aromatase inhibitors (AIs) versus the selective estrogen receptor modulator tamoxifen, each individually reported significantly longer progression-free survival (PFS) but none showed a significant difference in overall survival (OS). In these trials between 6.8% and 55% of tumours were hormone receptor (HR) status unknown or negative. This meta-analysis restricted the comparison to HR-positive (HR+) tumours. Anonymised individual patient data were obtained from three RCTs, EORTC (exemestane versus tamoxifen), Study 0027 and Study 0030 (both anastrozole versus tamoxifen). For the remaining RCT (Femara Study PO25; letrozole versus tamoxifen), odds ratio (OR) or hazard ratio (HzR), with confidence intervals were obtained from the clinical study report, for patients with HR+ tumours, in addition to published data. In total, data were obtained from 2296 patients; 1560 (68%) had HR+ ABC. The OR for clinical benefit rate was 1.56, in favour of AIs (p<0.001). The duration of clinical benefit was not significantly increased by AIs (HzR0·88; p=0.08). For PFS the HzR (0.82) was in favour of AIs (p=0·007). However, for OS the HzR (1.05) was not significantly different between AIs and tamoxifen (p=0.42). Although third generation AIs put significantly more patients into 'clinical benefit', their tumours were not controlled for significantly longer. Overall, while this resulted in a significantly greater PFS in favour of the AIs, this did not translate into improvement in OS.

Hormone therapy for postmenopausal women

Hormone therapy is recommended for relief from hot flashes or night sweats in women younger than age 60 years or those who entered menopause within 10 years of seeking treatment. Hormone therapy also can reduce bone loss and the risk of fractures; offer a potential cardioprotective benefit; and alleviate the genitourinary symptoms of menopause, including dysfunction of the bladder and irritation of the vagina and vulva.For women with early menopause without contraindications, hormone therapy is recommended until at least the average age of natural menopause. Observational studies suggest that the risk of thromboembolism and stroke is lower with transdermal therapy than with oral hormone therapy. Compounded bioidentical hormone therapies that have not been approved by the Food and Drug Administration are not recommended owing to safety concerns. Hormone therapy is not recommended for primary or secondary prevention of coronary heart disease or dementia. Nonhormone therapies that have been shown to reduce hot flashes include low-dose selective serotonin-reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors, gabapentinoids, weight loss, hypnosis, and cognitive behavioral therapy. For women with only genitourinary symptoms, local vaginal hormone therapies are recommended.The treatment is not without its risks, including concerns about cognitive decline and breast cancer. More research is warranted, to determine the long-term benefits and risks of menopausal hormone therapy, to gauge the effects of prolonged use in women initiating therapy close to menopause, to inform the timing of and approach to hormone therapy discontinuation, and to answer additional unknowns. As scientists work to address these questions, technology can help identify women likely to benefit from hormone therapy. The MenoPro mobile app, backed by the North American Menopause Society, provides a free algorithm to flag the strongest candidates.