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Background: Although there are a growing number of studies investigating the benefits of music therapy interventions with patients diagnosed with cancer, few studies have taken an approach that specifically examines indices of perceived well-being in women with breast cancer. Overcoming these challenges can be an important step in the recovery process. Purpose: The purpose of our study was to know the positive influence of responsive music therapy through gong sounds, emitted live, on different areas of well-being of women with breast cancer. Methods: Four individual sessions of responsive music therapy with live gong sounds were conducted in which three women (M = 54; SD = 5.57) participated both in the music therapy program and in the completion of the Functional Assessment of Cancer Therapy – Breast (FACT-B) and a semi-structured interview with ad hoc designed questions about perception of qualitative aspects. Results: The results showed that the music therapy sessions significantly improved, p =.043 < 0.05, various domains of perceived well-being in women with breast cancer. Discussion: This article highlights several key benefits associated with music therapy and various indices of well-being in women with breast cancer, identifies the limitations of the study, and discusses the findings. It is considered necessary to replicate this practice in future studies that include a larger sample and age range over longer follow-up periods. Translation for Health Education Practice: The text highlights the importance of considering music therapy as a complementary intervention in comprehensive cancer care programs, which may be relevant to health educators when considering intervention and support approaches for cancer patients. Health education interventions targeting the enhancement of cancer patients' well-being should incorporate music therapy techniques. [ABSTRACT FROM AUTHOR]

Breast cancer survivorship is increasing, due to earlier diagnosis of the disease and more effective therapies. Long-term endocrine sequelae, including early menopause, bone health, fertility implications and menopausal symptoms, are important survivorship issues. Ovarian failure is common with chemotherapy and options for preserving fertility in young women include ovarian suppression during chemotherapy and oocyte or embryo cryopreservation before chemotherapy. Tamoxifen as adjunct therapy in premenopausal women leads to ovarian stimulation, sometimes ovulation and occasionally pregnancy with important teratogenic implications. Aromatase inhibitor therapy with or without gonadotrophin releasing hormone (GnRH) agonist leads to profound bone loss and anti-resorptive therapy is advised to prevent fracture. Tamoxifen acts to preserve bone in postmenopausal women but not premenopausal women. Pregnancy is not discouraged in young women with early breast cancer, even to the point of pausing adjunct therapy in order to conceive. However, menopausal hormone therapy is discouraged even years later. Non-hormonal therapy for menopausal symptoms in breast cancer survivors is available but, in some cases, estrogen-containing therapy may be worthy of consideration for quality of life in the informed patient. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage. [ABSTRACT FROM AUTHOR]

We assessed the real-world effectiveness of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors as first-line treatments in postmenopausal patients with HR+/HER2− advanced breast cancer, focusing on younger (<45 years) and older (>78 years) populations not considered in clinical trials. We analyzed nationwide claims data from the Health Insurance Review and Assessment Service between November 2016 and February 2021. In this retrospective cohort study, patients using CDK4/6 inhibitors and aromatase inhibitors were selected and grouped by age as follows: 45–78 years (trial-enrolled), <45 years (younger), and >78 years (older). We estimated the median real-world progression-free survival (rwPFS) and overall survival (OS) using the Kaplan-Meier method. We conducted Cox regression analysis using a sub-distribution hazard model to evaluate risk factors (age, history of prior systemic treatment, presence of metastasis, comorbidity index, and type of provider) and estimated hazard ratios (HR). Among the 2,830 patients who received CDK4/6 inhibitors as first-line therapy, we identified 358 (12.65%) younger and 148 (5.23%) older underrepresented patients. The younger patient group (50.84%) had the highest rate of prior systemic therapy, followed by the trial-enrolled (25.39%) and older patient groups (8.11%). The median rwPFS was shorter in the older group (19.30 months) than those in the younger and the trial-enrolled age groups (30.33 and 34.53 months, respectively; p =.002). The HR of older age for death was 1.59 (95% confidence interval (CI) = 1.24–2.03). For rwPFS, the HR of prior systemic therapy was 1.19 (95% CI = 1.04–1.37). The younger age group, which was underrepresented in the trial, did not show a significant difference in risk compared with the enrolled age group. However, the older age group, which was also underrepresented in the trial, faces a risk of mortality but not progression. Patients who fall outside the specified age groups for the clinical trial can still expect the same level of effectiveness in terms of progression. [ABSTRACT FROM AUTHOR]

Cancer-related pain is primarily treated with opioids which while effective can add significant patient burden due to side effects, associated stigma, and timely access. The purpose of this perspective discussion is to argue for a precision approach to pain in cancer based on a biopsychosocial and spiritual model which we argue can offer a higher quality of life while limiting opioid use. Pain in cancer represents a heterogenous process with multiple contributing and modulating factors. Specific characterization of pain as either nociceptive, neuropathic, nociplastic, or mixed can allow for targeted treatments. Additional assessment of biopsychosocial and spiritual issues can elucidate further points of targeted intervention which can lead to overall greater pain control. Precision Pain Management in Cancer Pain in cancer is complex and heterogeneous with multiple contributing etiologies. A comprehensive assessment addressing the biopsychosocial and spiritual aspects of pain may lead to better control. Utilizing multiple targeted treatment strategies may help to curb opioid use. [ABSTRACT FROM AUTHOR]

Treatment with aromatase inhibitors (AIs) in patients with breast cancer can lead to dry eye disease (DED). The purpose of the study is to determine the prevalence and risk factors of DED in patients treated with AIs for breast cancer. Participants in this cross-sectional study were patients with breast cancer treated with AIs. Demographic and clinical data, including age, sex, type of cancer, stage, grade, duration of treatment and adjuvant chemotherapy and/or radiotherapy were collected. All patients underwent a detailed ophthalmic examination, as well as Tear Break up Time (TBUT) and Schirmer test, while Ocular Surface Disease Index (OSDI) questionnaires were administered. Based on the clinical findings, a diagnosis of DED was made, and prevalence was calculated. Univariate analysis of the association of different variables with DED was performed. A logistic regression analysis was done to identify risk factors for DED among study population. A total of 102 participants were included in the study. The mean age of patients was 62.4 ± 10.8 years. A total of 77 out of 102 patients (75.5%) had ductal, 16 (15.7%) lobular and 9 (8.8%) other types of breast cancer. A total of 83 patients (81.4%) received chemotherapy and 70 patients (68.6%) received radiotherapy. The mean duration of treatment was 24.4 ± 18.9 months. The prevalence of DED in the study sample was 69.6%. Patients who received radiotherapy (OR = 3.31, 95%CI = 1.30–7.82, p = 0.01) or were under treatment with AIs for more than 24 months (OR = 3.53, 95%CI = 1.47–9.21, p = 0.002) were found to have an increased risk of DED. There was a high prevalence of DED among the study population. Radiotherapy and duration of treatment with AIs were independently associated with DED. [ABSTRACT FROM AUTHOR]

Hormone therapy with aromatase inhibitors (AIs) for estrogen receptor-dependent breast cancer may expose patients to an increased osteoporosis risk. This study was performed to estimate fracture risk in women with breast cancer to whom AIs were prescribed in Japan. This retrospective study used data from the Japanese Medical Data Vision database. Women with breast cancer prescribed AIs over a 12-month period were identified and matched to women not prescribed AIs using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared using a cause-specific Cox hazard model. The proportion of women undergoing bone density tests was retrieved. For all fractures sites combined, cumulative fracture incidence at 10 years was 0.19 [95%CI: 0.16–0.22] in women prescribed AIs and 0.18 [95%CI: 0.15–0.21] without AIs. AI prescription was not associated with any changes in risk (adjusted hazard ratio: 1.08 [95%CI: 0.99–1.17] p = 0.08). Women prescribed AI more frequently underwent bone density testing (31.9% [95% CI: 31.2%; 32.6%] versus 2.2% [95% CI: 2.0%; 2.4%]). The anticipated association between AI exposure and osteoporotic fracture risk in Japanese women with breast cancer was not seen clearly. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign chronic inflammatory disease responsible for debilitating pain and decreased quality of life. The traditional treatment is based on estroprogestins, progestins, GnRH analogs, and surgery. Recently, aromatase inhibitors (AIs) demonstrated good efficacy in controlling symptoms and size of endometriotic implants, mostly because they suppress extraovarian estrogen synthesis, which can enhance the hypoestrogenic state ameliorating symptoms of endometriosis. Phase I, II, III and IV trials, on the use of AIs used for the treatment of endometriosis, have been retrieved. The pharmacokinetics and pharmacodynamics of third-generation non-steroidal AIs have also been investigated. A MEDLINE search has been performed using the following MeSH keywords: 'endometriosis,' aromatase inhibitors,' 'therapy,' and 'treatment'. The timeframe was from 2010 up to November 2022 including reviews, systematic reviews, reports, case series, and retrospective or prospective trials. AIs have shown good clinical efficacy in combination with hormonal therapy in disease control, and they represent a promising second-line therapy in selected patients, yet more research is needed on alternative drug delivery systems and better control of adverse effects. In postmenopausal women in which surgery is contraindicated, AIs represent an excellent treatment option. Their application in routine clinical practice remains limited by adverse effects. [ABSTRACT FROM AUTHOR]

Pathology-supported genetic testing (PSGT) enables transitioning of risk stratification from the study population to the individual. We provide an overview of the translational research performed in postmenopausal breast cancer patients at increased risk of osteoporosis due to aromatase inhibitor therapy, as the indication for referral. Both tumor histopathology and blood biochemistry levels were assessed to identify actionable disease pathways using whole exome sequencing (WES). The causes and consequences of inadequate vitamin D levels as a modifiable risk factor for bone loss were highlighted in 116 patients with hormone receptor-positive breast cancer. Comparison of lifestyle factors and WES data between cases with vitamin D levels at extreme upper and lower ranges identified obesity as a major discriminating factor, with the lowest levels recorded during winter. Functional polymorphisms in the vitamin D receptor gene contributed independently to therapy-related osteoporosis risk. In a patient with invasive lobular carcinoma, genetic counseling facilitated investigation of the potential modifying effect of a rare CDH1 variant co-occurring with BRCA1 c.66dup (p.Glu23ArgfsTer18). Validation of PSGT as a three-pronged pharmacodiagnostics tool for generation of adaptive reports and data reinterpretation during follow-up represents a new paradigm in personalized medicine, exposing significant limitations to overcome. [ABSTRACT FROM AUTHOR]

To evaluate the effects of 24 weeks of Mat Pilates in breast cancer survivors (BCS) undergoing hormone therapy on lower and upper body muscle strength parameters and flexibility. Forty-three BCS (≥40 years) with confirmed breast cancer stage 0–III undergoing hormone therapy were included. Participants were randomized into Mat Pilates (three times/week, 60 min session) or control group (relaxation activities every two weeks). The difficulty and number of exercise repetitions were increased over the weeks. Assessments were performed at three times points (baseline, 12 weeks, and 24 weeks). The generalized estimating equations (GEE) model was used to compare each outcome measure during the analysis of intention to treat (ITT) and "Per protocol analysis" (PPA). The Pilates group presented significantly increased (p < 0.05) isometric flexor–extensor PT, and concentric and eccentric flexor PT and mechanical work (MW) after the intervention. Most of the upper body strength parameters, time to achieve maximal force (TFmax), maximal force (Fmax), and rapid force index (RFI) and right-left upper and lower body flexibility (p < 0.05) also improved. From our findings, we conclude that 24 and 12-weeks of Mat Pilates induced strength and flexibility gains for lower and upper body, respectively. Mat Pilates can be adapted to the fitness level of breast cancer survivors, with a great variety of exercises that can be performed using a mat only or a few pieces of equipment. Patients can practice at home to gain different health benefits (i.e., increasing strength, flexibility, and functional capacity level), which could positively impact on quality of life. Mat Pilates performed three times per week with systematized increments in exercise level, load, and volume throughout the intervention was effective to improve hip extensor–flexor muscles peak torque and mechanical work at different muscle contractions, as well as upper and lower body flexibility. Mat Pilates was also able to improve right-left shoulder abductor and trunk extensor muscles strength parameters after 12 weeks of intervention, as well as both surgery and non-surgery sides of the upper body. [ABSTRACT FROM AUTHOR]

While endocrine therapy is the standard-of-care adjuvant treatment for hormone receptor-positive (HR+) breast cancers, there is also extensive evidence for the role of pre-operative (or neoadjuvant) endocrine therapy (NET) in HR+ postmenopausal women. We conducted a thorough review of the published literature, to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET. We describe the importance of on-treatment assessment of response, the different predictors available (including Ki67, PEPI score, and molecular signatures) and the research opportunities the pre-operative setting offers. We also summarize recent combination trials and discuss how the COVID-19 pandemic led to increases in NET use for safe management of cases with deferred surgery and adjuvant treatments. NET represents a safe and effective tool for the management of postmenopausal women with HR+/HER2- breast cancer, enabling disease downstaging and a wider range of surgical options. Aromatase inhibitors are the preferred NET, with evidence suggesting that longer regimens might yield optimal results. However, NET remains currently underutilised in many territories and institutions. Further validation of predictors for treatment response and benefit is needed to help standardise and fully exploit the potential of NET in the clinic. [ABSTRACT FROM AUTHOR]

Antineoplastic treatments can negatively affect body composition, leading to metabolic derangements and worse clinical outcomes in breast cancer patients. This scoping review assesses body adiposity changes during breast cancer therapy. We included clinical and observational studies, published until the last search date in any language, with women aged >18 years, after breast cancer diagnosis, at any clinical stage and with any history of breast cancer treatment, who had body adiposity quantified by imaging tools at least twice during follow-up. In total, 17 studies were included (n = 1,009 individuals), six of which found a significant increase in body adiposity during treatment, two found a significant decrease, one presented divergent findings according to the imaging method and the analyzed body adiposity depots, and eight studies found no significant change in the outcome. Selective estrogen receptor modulators were associated with increased body adiposity, whereas aromatase inhibitors were associated with its decrease (n = 3). Chemotherapy was associated with increased body adiposity (n = 1), and monoclonal antibody with reduced brown adipose tissue activity (n = 1). Breast cancer treatment may have different effects on body adiposity, according to its mechanisms and protocols. Further studies are necessary to better elucidate this scenario. [ABSTRACT FROM AUTHOR]

Due to safety concerns on estrogen-based treatments for genitourinary syndrome of menopause (GSM) in breast cancer survivors (BCS), new options are appearing, such as androgen-based treatments, which according to proprieties would not be transformed systemically to estrogens in patients receiving aromatase inhibitors (AIs). The aim of this pilot study is to assess the security and efficacy of vaginal prasterone (dehydroepiandrostenedione [DHEA]) in BCS treated with AIs. This open, prospective, pilot study included 10 BCS treated with AIs. All participants complained of severe GSM. DHEA was administrated as a vaginal ovule. Participants were instructed to use one ovule every night during the first month, and one ovule every two nights for the entire five remaining months. The patients were requested to attend seriated visits after the beginning of the prasterone treatment to evaluate symptoms, physical improvement and serum estradiol. Mean serum estradiol remained low from 3.4 pg/ml to 4.3 pg/ml (p = 0.9136) after 6 months of follow-up. The visual analog scale of dyspareunia improved from 8.5 to mean values after treatment of 0.4 (p = 0.0178). The Vaginal Health Index (VHI) scale and Female Sexual Function Index improved from 9.75 to 15.8 (p = 0.0277) and from an initial score of 11.2 to 20.6 (p = 0.0277), respectively. Vaginal pH changed from basal 8.1 to final 6.5 (p = 0.0330). Symptoms and physical examination regarding sexuality and vaginal health improved significantly, while serum estradiol remained at low levels. Prasterone seems a safe and effective option to treat GSM in BCS receiving AIs. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common disorders among women of reproductive age and can be diagnosed when at least two of the following criteria are present: chronic ovulatory disorder, clinical and/or biochemical hyperandrogenism, and polycystic ovaries. Diet and lifestyle modifications are the main therapeutic intervention and they can fully restore ovary function and avoid PCOS consequences in a certain number of patients. However, prescription of medications or dietary supplements is often needed. The literature has confirmed the significant role of inositol therapy in PCOS, with particular reference to Myo-inositol and D-chiro-Inositol. The aim of this review is to clarify the use of inositols for the treatment of PCOS and the recent scientific theories about D-Chiro-Inositol properties as an ovarian aromatase inhibitor. [ABSTRACT FROM AUTHOR]

We report and review the clinical effectiveness of aromatase inhibitors in a patient with refractory, recurrent and infiltrating endometriosis. We demonstrate excellent clinical, radiological and endoscopic responses after failure of multiple other modalities. Our case and the literature show that single-agent letrozole is capable to treat deep infiltrative endometriosis involving the rectum and the urinary tract. The use of aromatase inhibitor treatment of endometriosis in postmenopausal women makes sense, is safe and is well tolerated. Difficult cases of deep infiltrative endometriosis might require use of combined surgical and medical treatment modalities. Multidisciplinary involvement of the gynecologist, bowel surgeon, urologist and invasive radiologist might be needed. Aromatase inhibitors should be considered to be an integral part of the armamentarium in the management of women with endometriosis, especially in refractory cases that have failed conventional therapeutic modalities. [ABSTRACT FROM AUTHOR]

The Journal of Obstetrics & Gynaecology has retracted an article titled "Clomiphene citrate or aromatase inhibitors combined with gonadotropins for superovulation in women undergoing intrauterine insemination: a prospective randomised trial." The retraction was made due to concerns about the integrity of the data and reported results in the article. The authors did not respond to questions about the concerns raised and did not provide sufficient supporting information. The retracted article will remain online but will be digitally watermarked as "Retracted." [Extracted from the article]

Anastrozole (ANA), is an inhibitor of non-steroidal aromatase, widely employed for the treatment of breast cancer. However, ANA-associated liver injury cases have been documented in the application of the drug. The major purposes of the present study were to identify the structure of reactive metabolites derived from ANA and to study related metabolic pathways of ANA. We found ANA itself is an electrophilic species reactive to GSH. ANA can be metabolised to ANA-N+-glucuronide (1) catalysed by UGT1A4. An ANA GSH conjugate (2) was detected in bile and livers of rats treated with ANA. UGT1A4 participated in the phase II metabolic pathway. This work allowed us to better understand the mechanisms of the hepatotoxicity of ANA and provided new avenue to define the possible role of metabolic activation in hepatotoxicity. [ABSTRACT FROM AUTHOR]

Bioactivity-guided fractionation was performed between March and June 2019 to identify the phytoconstituents in extracts of Withania somnifera and Chlorophytum borivilianum that were responsible for androgenic efficacy by inducing maleness in Nile tilapia. Fish hatchlings were fed diets containing water, methanol, and ethanol extracts at 0.5, 0.75, and 0.9 gm/kg feed concentrations. For W. somnifera, the highest male percentage (89.63 ± 0.9) was obtained with methanol extract at 0.75 gm/kg feed concentration. For C. borivilianum, the highest male percentage (93.64 ± 0.9) was obtained with ethanol extract at 0.75 gm/kg feed concentration. Three fractions of methanol extract of Withania somnifera roots (W1 to W3) and six fractions of ethanol extract of Chlorophytum borivilianum roots (S1 to S6) were obtained through column chromatography followed by TLC. During dietary treatment (0.75 gm/kg feed) with those fractions, W1 and S4 showed higher male percentage than others. Gas chromatography-mass spectrometry analysis of W1 and S4 revealed the presence of various unsaturated fatty acids with antiaromatase activity that might be responsible for the androgenic effect of the extracts. [ABSTRACT FROM AUTHOR]

Nonsteroidal aromatase inhibitors (NSAIs) are well-established drugs for the therapy of breast cancer. However, they display some serious side effects, and their efficacy can be compromised by the development of chemoresistance. Previously, we have reported different indazole-based carbamates and piperidine-sulphonamides as potent aromatase inhibitors. Starting from the most promising compounds, here we have synthesised new indazole and triazole derivatives and evaluated their biological activity as potential dual agents, targeting both the aromatase and the inducible nitric oxide synthase, being this last dysregulated in breast cancer. Furthermore, selected compounds were evaluated as antiproliferative and cytotoxic agents in the MCF-7 cell line. Moreover, considering the therapeutic diversity of azole-based compounds, all the synthesized compounds were also evaluated as antifungals on different Candida strains. A docking study, as well as molecular dynamics simulation, were carried out to shed light on the binding mode of the most interesting compound into the different target enzymes catalytic sites. [ABSTRACT FROM AUTHOR]

Adjuvant treatment for post-menopausal women with early breast cancer (BC) includes aromatase inhibitors (AI), known to decrease bone mineral density (BMD). In this study, we investigate whether denosumab is a valid second option for patients unable to receive standard adjuvant i.v. zoledronic acid (ZA). In total, 212 patients have been evaluated after they did not receive ZA. Of those 194 were included. After evaluation by an endocrinologist, all patients were offered ZA as their first choice and 15% accepted (N = 29). The remaining 85% were offered denosumab (N = 165). All patients were followed prospectively with blood tests up to 24 months. DXA scans were performed at baseline and 24 months. No difference was observed between the two treatment groups at baseline, with regard to anthropometry and standard biochemistry. Markers of bone turnover (p-PINP, p-CTX, p-bone-specific alkaline phosphatase and p-osteocalcin) all showed significant suppression compared to baseline and remained suppressed throughout the 2 years. BMD showed small and significant increases at the spine (0.024 g/cm2) and total hip (0.019 g/cm2) in the denosumab group but no change at the femoral neck(–0.011g/cm2). In the ZA group, we observed no significant change at the spine (0.015 g/cm2) and total hip (–0.001g/cm2) and a small significant decrease at the femoral neck (–0.037 g/cm2). However, when we compared BMD change between the treatment groups, we found no significant difference. Conclusions: Our data indicate that for BC patients in AI treatment who refused or were not able to receive ZA treatment, denosumab might be recommended as a second choice. Regarding markers of bone turnover and BMD denosumab is equal to ZA. Summary: Women with early breast cancer receiving anti-estrogen treatment are at risk of developing osteoporosis. We followed 194 women receiving zoledronic acid (ZA) or denosumab for up to 2 years. We find that with regard to bone protection, denosumab is a viable alternative to ZA and might be recommended as a second choice [ABSTRACT FROM AUTHOR]

Radiation-induced pulmonary fibrosis (RIPF) is a known complication in cancer patients after getting thoracic radiotherapy. Aromatase inhibitors (AIs) as anastrozole have been used instead of tamoxifen for adjuvant endocrine treatment of postmenopausal women with hormone sensitive breast cancer. This study is to evaluate the concurrent treatment of anastrozole and RIPF in rats. Twenty four female Wistar rats were distributed into 4 groups: Control (C), Radiation group (R) (total dose 30 Gy in 10 fractions, 5 fractions/week), anastrozole group (A) (0.003 mg/200 g body weight) orally for 14 consecutive days, and Radiation + anastrozole group (R + A). Radiation exposure resulted in a significant increase (p < 0.05) in pulmonary Transforming growth factor-beta 1 (TGF-β), SMAD family member 3 (Smad3), Platelet-derived growth factor (PDGF), malondialdehyde (MDA), Total nitrate/nitrite (NO), interleukin 1β (IL-1β) and interleukin 6 (IL-6) compared to the control group. While, significant decreases (p < 0.05) in superoxide dismutase (SOD) activity, reduced glutathione (GSH) and connective tissue growth factor (CTGF) were observed in lung tissue. These alterations were minimized by anastrozole intervention. Also, anastrozole markedly hindered the lung histopathological changes observed after radiation. Concomitant use of anastrozole with radiation seems to attenuate radiation-induced pulmonary toxicity via TGF-β/Smad 3 and TGF-β/PDGF pathways in rats. [ABSTRACT FROM AUTHOR]

Purpose/Aim of the study: The role of estrogen (E) in the regulation of bone turnover in women is well established, though the contributions of E versus testosterone (T) in the control of bone turnover in men are poorly understood. The aim of this study was to examine the association between chronic treatment with letrozole, a nonsteroidal inhibitor blocking the aromatase activity and thus the conversion of androgens into estrogens, and cortical bone morphology in the femur and humerus of male adult rats. Materials and Methods: Adult male rats were treated with letrozole for 6 months and the body and femur weight, morphology, collagen structure, blood serum, and bone tissue concentrations of calcium and magnesium were examined. Results: Long-term aromatase inhibition resulted in a decrease in femur mass, a wavelike arrangement of bone and lamellae with an altered organization of collagen in compact bone, a increased concentration of calcium in blood serum, and no change in calcium bone tissue concentration, magnesium serum, or bone tissue concentration. MicroCT study of the humerus revealed significant decreases of whole bone tissue volume, cortical bone thickness, cortical bone volume, and external cortical bone thickness with letrozole treatment. Conclusion: Chronic treatment with letrozole affected cortical bone structure and produced histomorphological changes in male rat bone similar to that observed in the aging processes. [ABSTRACT FROM AUTHOR]

This retrospective observational study described baseline characteristics, real-world treatment patterns, and outcomes among patients with metastatic breast cancer treated with abemaciclib in the United States. De-identified electronic health record-derived data were used to describe patients who began abemaciclib treatment on or after 30 June 2016 and ≥4 months before data cutoff (31 December 2018). Real-world response (rwR) and real-world progression assessments were abstracted from clinical documentation. Descriptive statistics were used to calculate the real-world best response. The Kaplan–Meier method estimated real-world time to first response (rwTTFR) and real-world progression-free survival (rwPFS). The median age of 118 female patients at abemaciclib initiation was 66.5 years (interquartile range, 57.0, 73.0). The breakdown of patients who received abemaciclib in first, second, third, or later lines was 28.8%, 21.2%, 20.3%, and 29.7%, respectively. Patients received abemaciclib as monotherapy (12.7%) or in combination with endocrine therapy: fulvestrant (59.3%); aromatase inhibitor (22.9%); aromatase inhibitor and fulvestrant (5.1%). There were 68 patients (57.6%) with ≥1 rwR assessment: 41.2% with a real-world complete response or real-world partial response. Median rwTTFR was 3.6 months (95% confidence interval, 3.5, 5.2). Twelve-month rwPFS probability was 61.7%. This study represents utilization and outcomes associated with abemaciclib approximately 1 year following FDA approval. Treatment patterns demonstrated heterogeneity and, as in clinical trials, patients appeared to benefit from abemaciclib treatment in the real world. More research investigating outcomes associated with abemaciclib treatment is needed, with larger samples and longer follow-up to enable closer evaluation by subgroup, regimen, and line of therapy. [ABSTRACT FROM AUTHOR]

To determine the role of estrogens in myofiber cross-sectional area (CSA) of the pubococcyegeus (Pcm) and iliococcygeus muscles (Icm). In Experiment 1, we excised the Pcm and Icm during the metestrus and proestrus stages of the estrous cycle to measure the myofiber CSA. In Experiment 2, we allocated other rats into the following groups: sham (Sh), ovariectomized (OVX), OVX plus 1,4,6-androstatriene-3,17-dione (ATD; OVX + ATD), an aromatase inhibitor, and OVX plus estradiol benzoate (OVX + EB). We carried out appropriate statistical tests to determine significant differences (p ≤ 0.05) in variables measured for both Experiments. The Pcm myofiber CSA at proestrus was higher than at metestrus, while the Icm myofiber CSA did not change. Ovariectomy increased the Pcm myofiber CSA, which was exacerbated with the ATD administration. The EB supplementation successfully reversed the ovariectomy-induced enlargement of the CSA. No significant changes were detected for the Icm myofiber CSA. Fluctuating ovarian steroid levels at the estrus cycle significantly influence the CSA myofiber of the Pcm but not that of the Icm. Estrogen actions, having a gonadal or extragonadal origin, influence importantly the CSA of the Pcm. [ABSTRACT FROM AUTHOR]

The medications used in assisted reproduction are given before and during early pregnancy, and hence, they may potentially result in adverse fetal effects. In this review we present an updated account of their fetal safety and discuss methodological challenges in interpretation of existing data. The fetal safety/risks of clomiphene citrate, aromatase inhibitors, metformin, gonadotropins and progestins are discussed. We searched PubMed, EMBASE, Cochrane, Google, and Google Scholar from inception to 30 April 2020 for publications pertinent to our topic. There are several major challenges in studying fetal safety of medications used in assisted reproduction. The fact is that the rates of congenital malformations among infertile women giving birth spontaneously is higher than the rates among healthy women conceiving spontaneously. In most clinical studies of assisted reproduction, the primary endpoint is the success in inducing pregnancy, neglecting to report pregnancy outcome and adverse neonatal event. As an example for this reality, it has been estimated that between 1977 and 2005 around 10 million pregnancies were treated with dydrogesterone (DYD), yet till 2019 only very few studies, with a total sample size of less than 600 were reported with regards to fetal safety. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the effects of a new protocol with letrozole on the outcomes of in vitro fertilization (IVF) cycles in women with endometriosis. This retrospective cohort study was conducted for women diagnosed with endometriosis undergoing IVF from an infertility clinic. A new protocol, combination therapy with letrozole and gonadotropin, was used from August 2016 to January 2018 ('protocol 1', n = 38). From March 2014 to July 2016, conventional IVF with gonadotropin was administered ('protocol 2', n = 26). Age and ovarian reserve were comparable between the two groups. The patients who received protocol 1 resulted in a significantly lower peak estradiol level in IVF compared with those received protocol 2 (722 ± 1076 pg/mL versus 2168 ± 1521 pg/mL, p <.001). The length of stimulation, the total dose of gonadotropin, number of oocytes retrieved, fertilization rates, and number of embryos obtained were similar between the two groups. The mean percentage of mature oocytes was lower (69.9 ± 23.7% versus 80.2 ± 21.0%, p =.029) in patients with protocol 1. While maintaining low estrogen levels, the combination therapy with letrozole and gonadotropin produce similar oocyte and embryo yield to the conventional IVF protocol in women with endometriosis. [ABSTRACT FROM AUTHOR]

Intravaginal rings (IVRs) are an option for continuous administration of drugs in women. As an attractive approach for the treatment of endometriosis-associated pelvic pain, IVRs delivering a combination of the aromatase inhibitor anastrozole (ATZ) and the progestin levonorgestrel (LNG) have been developed. This article describes the developmental pharmacokinetic (PK) aspects covering the characterization of in vitro release, preclinical IVR PK investigations in monkeys, and clinical PK considerations. An IVR for ATZ has been developed and investigated in healthy menstruating female cynomolgus monkeys showing effective in vivo release. PK data from the size-adapted IVR used in these animals can be translated into a human context as confirmed in human studies where predefined exposure levels of ATZ were reached. As ATZ may cause harm to the fetus, use of effective contraception has to be assured in women of childbearing potential. Therefore, the IVR delivers a low dose of LNG as a contraceptive. Although the daily dose differed strongly between both drugs (20 µg LNG/d to >1 mg ATZ/d), simultaneous delivery of ATZ and LNG in vitro and in vivo was observed with a high correlation between the in vitro release and PK profiles. The PK characteristics successfully guided the design of clinical studies investigating the drug–drug interaction (DDI) potential. No relevant DDI between both the investigated or other vaginally administered drugs were identified. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore whether postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy differ from healthy postmenopausal women in their response to the same aerobic + resistance training. Methods: The participants were separated into two groups: postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy for an average of 20 months (18 women) and healthy postmenopausal women (24 women). We assessed aerobic capacity (predicted maximum oxygen uptake (VO2max) and maximum running velocity test (Vmax)) through a walking test, upper and lower body muscle strength using an estimated one-repetition maximum test, and body composition by dual-energy X-ray absorptiometry at baseline and at three, six, and nine months, respectively. The exercise program was performed three times/week over nine months and consisted of 40 min of machine-based strength training (seated cable row, bench press, leg extension, leg press, and leg curl, as well as bridge, abdominal, and standard plank exercises) followed by 30 min of treadmill walking. Analysis of variance (ANOVA) with repeated measures was used to compare the groups over time. Results: Postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy postmenopausal women presented similar improvements in estimated lower body strength, predicted VO2max and Vmax, and body fat mass. For maximal upper body strength, there was a significant group x time interaction after six months of training (p = 0.01). The healthy postmenopausal women presented a significant increase in upper body strength after six months, while postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy demonstrated an improvement only at nine months of training. The breast cancer survivors undergoing aromatase inhibitor therapy presented increased lean mass while healthy postmenopausal women maintained values over time (Breast cancer: 33.7 ± 3.9(Pre) vs. 34.1 ± 3.4 kg (Post) and healthy women: 36.4 ± 5.1 (Pre) vs. 36.4 ± 5.0 kg (Post), p = 0.004). Conclusion: Our findings suggest that postmenopausal women undergoing aromatase inhibitor therapy for breast cancer demonstrated adaptations and similar trainability to the same regimen of resistance + aerobic training as healthy postmenopausal women. Combined exercise program (aerobic plus resistance) is an important non-pharmacological strategies to improve strength, aerobic capacity, and body composition in breast cancer survivors undergoing aromatase inhibitor therapy. Furthermore, it is important to highlight that the time of intervention seems to influence the upper body strength response in this population. This study showed that trainers and other specialists do not need to modify the prescription of exercise related to healthy women, since the combined exercise program induced similar benefits in strength, aerobic capacity, and body composition in postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and healthy postmenopausal women. [ABSTRACT FROM AUTHOR]

Endometriosis is common among those with infertility, although many cases go undiagnosed. This study was performed to determine whether empiric treatment with two months of depo-leuprolide 3.75 mg monthly (dep-GnRH-ag) and letrozole 5 mg daily improves pregnancy outcomes in patients with at least two unexplained failed embryo transfers (ETs) but without a previous diagnosis of endometriosis. A retrospective cohort study was performed with subjects who failed at least two good quality ET. The study excluded women with a known history of endometriosis or ovarian cysts (possible endometriomas). Subjects (N = 38) were treated with dep-GnRH-ag and letrozole pre-cycle. Matched women (N = 37) who did not receive either pretreatment served as a control group. Data were compared by non-paired T-tests and multivariate logistic regression to control for confounding effects. Demographic data, hormonal profiles, and ovarian reserve parameters were similar between the two groups. The treated group had failed more embryo transfers (3.5 ± 1.7 vs. 2.0 ± 1.3, p = .01) than the controls. When adjusting for the number of MII oocytes collected, number of blastocysts developed and number of blastocysts transferred, there were more pregnancies (24/38 vs. 11/37, p = .02) and ongoing pregnancies (18/38 vs. 9/37, p = .03) in the treated group. Patients with multiple unexplained failed ET may have undiagnosed endometriosis and may benefit from pretreatment with dep-GnRH-ag and letrozole. These results would benefit from being subjected to a randomized prospective study. [ABSTRACT FROM AUTHOR]

Introduction: Recent improvements in the survival of hormone-responsive breast cancer are strongly associated with therapeutic advances, particularly with the uptake of adjuvant endocrine therapy. Nevertheless, endocrine therapy is also linked with adverse effects that impact quality of life, social function, and adherence to treatment. Areas covered: This review examines the spectrum and consequences of adverse effects of tamoxifen and aromatase inhibitors, and the pharmacological and non-pharmacological approaches to mitigate some of the most frequent and disturbing side effects of endocrine therapy (including vasomotor, musculoskeletal, and vulvovaginal symptoms). The authors performed a qualitative analysis of English papers indexed in PubMed through May 2017, including meta-analysis, randomized controlled trials, observational studies, and systematic reviews. Expert commentary: Side effects of endocrine treatments are frequent and often underestimated in the care of breast cancer survivors, leading to a poor adherence to treatments that can compromise oncological outcomes. Many of the most common adverse events can be mitigated through pharmacological and non-pharmacological approaches that should be discussed and offered to patients in a dedicated setting of care. [ABSTRACT FROM AUTHOR]

This review aims to draw a clearer clinical picture of postmenopausal endometriosis. Based on limited literature, postmenopausal endometriosis emerges as an infrequent entity but with a clinical picture significantly unlike that of premenopausal endometriosis. In contrast to the premenopausal disease, postmenopausal endometriosis occurs in a state of ovarian estrogen deficiency, appears to have a greater predisposition to malignant change, may have a greater tendency to spread to extragonadal organs and develop into constrictive and/or obstructive lesions, and is preferably treated surgically. The need to use hormone therapy for the management of menopausal symptoms that may concomitantly affect women with postmenopausal endometriosis is an unresolved therapeutic dilemma. This is mainly because the relationships of menopausal hormone therapy to recurrence of endometriosis and, more importantly, to increased risk of malignant degeneration, remain unclear. [ABSTRACT FROM AUTHOR]

Introduction: The frequency of late-onset hypogonadism (LOH) ranges between 2 and 15%. Up to 85% of LOH is due to a functional impairment of the hypothalamus-pituitary-testicular axis, mostly secondary to metabolic conditions. Areas covered: This paper provides a comprehensive review of all the available medications for treating LOH, including antiestrogens, gonadotropins and testosterone therapy (TTh). In addition, the evidence on clinical outcomes of these treatments is provided by meta-analyzing the results from the available randomized clinical trials. Expert commentary: The present data indicate that antiestrogens are able to increase testosterone levels without changing gonadotropins or even increasing them. Therefore, they may maintain, and even to stimulate spermatogenesis. However, their efficacy in treating LOH-associated symptoms has been scarcely tested and their use in LOH is off-label. In contrast, gonadotropins are indicated for hypogonadism, in particular when fertility is required. Information on the effects of gonadotropins on LOH is scanty and the impractical administration limits their use. TTh can be administered with different modalities, making it a suitable option for LOH, when fertility is not desired. The available meta-analyses show that TTh is able to improve sexual function and body composition, with more evident results obtained with transdermal and injectable preparations. [ABSTRACT FROM AUTHOR]

1. There are numerous investigations demonstrating that the cyclooxygenase-2 (COX-2) inhibitors might enhance the efficiency of anastrozole in breast cancer. Hence, this study was conducted to investigate the comparative pharmacokinetics of anastrozole after single administration and combination with celecoxib. 2. A simple protein precipitation procedure was adopted for the sample preparation with satisfactory extraction recovery for both anastrozole and the internal standard, and then anastrozole was separated and analysed on an ACQUITY BEH UPLC C18column (50 × 2.0 mm, 1.7 μm, Waters) within 2 min. The calibration curves showed good linarites (r = 0.994). Intra- and inter-day precision were within 4.93 and 13.83%, respectively. The mean extraction recoveries across QC levels were within 91.4%, and the matrix effects were within 94.5%. 3. Results showed that the method was reliable to determine anastrozole in rat plasma. Compared with rats in single administration group, no significant difference was found in the combination group. It is workable to use celecoxib combined with anastrozole in clinical therapy. [ABSTRACT FROM AUTHOR]

Post-menopause hyperandrogenism is a condition that needs careful evaluation. Aromatase inhibitors (AI), which are important in the management of positive estrogen breast cancer, and chronic kidney disease (CKD) can puzzle the evaluation of this condition. A postmenopause female with type-2 diabetes and advanced CKD was attended due to progressive virilization, which has started after the introduction of an AI for breast cancer 5 years earlier. Clinical and radiological investigation has confirmed a pure Leydig cell tumor as source of hyperandrogenism. Re-evaluation of the breast tumor immunohistochemistry has shown positive androgen receptor expression and negative expression for estrogen, progesterone and HER-2 receptors. Even though an ovarian tumor was the source of androgen excess, we discuss that AI could exert a slight contribution to patient’s virilization by reducing estradiol counterbalance. Also, although the onset of hyperandrogenic symptoms was unclear, we could not exclude that the ovarian tumor had produced enough androgens to play a role in breast tumor progression. This case report supports the literature regarding the possible association between Leydig cell tumor and androgen-receptor-positive breast cancer development. Finally, progressive hyperandrogenic symptoms in postmenopause, even under AI therapy or the presence of advanced CKD, impose a more detailed investigation. [ABSTRACT FROM PUBLISHER]

Selective estrogen receptor modulators (SERMs), anti-estrogens and aromatase inhibitors are prohibited in human sports doping. However, they also present a risk of being used illegally in animal husbandry for fattening purposes. A method was developed and validated using UHPLC-MS/MS for the determination and confirmation of SERMs, anti-estrogens and aromatase inhibiters in bovine and porcine urine. This method was used in a survey of more than 200 bovine and porcine urine samples from Dutch farms. In 18 out of 103 porcine urine samples (17%) and two out of 114 bovine samples (2%) formestane, an aromatase inhibitor, was detected. None of the other compounds was detected. From human doping control it is known that formestane can, in some cases, be of natural origin. Analyses of reference samples from untreated bovine and porcine animals demonstrated the presence of formestane in bovine animals, but not yet in porcine animals. Future research will focus on whether the detected formestane in porcine and bovine urine is from endogenous or exogenous origin, using GC-c-IRMS. [ABSTRACT FROM PUBLISHER]

Endometriosis is a hormone-dependent inflammatory disease that is usually characterized by infertility and pain symptoms. This disease mainly occurs during the reproductive years and is rarely diagnosed after menopause. We discuss the physiopathology of this condition after menopause as well as treatment options and the risk of malignant transformation. Occurrence or progression of postmenopausal endometriosis lesions could be related to extra-ovarian production of estrogen by endometriosis lesions and adipose tissue, which becomes the major estrogen-producing tissue after menopause. Postmenopausal women with symptomatic endometriosis should be managed surgically because of the risk of malignancy; medical treatments can be used in cases of pain recurrence after surgery. Aromatase inhibitors act by decreasing extra-ovarian estrogen production and by blocking the feed-forward stimulation loop between inflammation and aromatase within endometriosis lesions. The evidence is currently insufficient to support a conclusion about the optimal hormone replacement therapy for women with endometriosis. The question of malignant transformation of endometriosis in response to hormone replacement therapy in women with a history of endometriosis remains unanswered and needs a long-term follow-up study to evaluate the risk of an adverse outcome. Further studies should be performed to determine the optimal management of menopausal women with endometriosis. [ABSTRACT FROM PUBLISHER]

Introduction: Extended adjuvant (5–10 years) therapy targeted to the estrogen receptor (ER) has significantly decreased mortality from breast cancer (BC). Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops. Expert commentary:Compliance ensures optimal benefit from extended antihormone adjuvant therapy.Retarding acquired resistance using CDK4/6 or mTOR inhibitors is discussed. Preventing acquired resistance from mutations of ER could be achieved with Selective ER Downregulators (SERDs), eg fulvestrant. Fulvestrant is a depot injectable so oral SERDs are sought for extended use. In reality, a ‘super SERD’ which destroys ER but improves women’s health like a Selective ER Modulator (SERM), would aid compliance to prevent recurrence and death. Estrogen-induced apoptosis occurs in 30% of BC with antihormone resistance. The ‘one in three’ rule that dictates that one in three unselected patients respond to either hormonal or antihormonal therapy in BC occurs with estrogen or antiestrogen therapy and must be improved. The goal is to maintain patients for their natural lives by blocking cancer cell survival through precision medicine using short cycles of estrogen apoptotic salvage therapy, and further extended antihormone maintenance. [ABSTRACT FROM PUBLISHER]

Introduction: The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers. Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however, patients can also be asymptomatic. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies, such as transvaginal ultrasound and magnetic resonance imaging. The aim of this review is to discuss the medical approach to the management of adenomyosis symptoms, including pain and abnormal uterine bleeding. The standard treatment of adenomyosis is hysterectomy, but there is no medical therapy to treat the symptoms of adenomyosis while still allowing patients to conceive. Medical therapies using suppressive hormonal treatments, such as continuous use of oral contraceptive pills, high-dose progestins, selective oestrogen receptor modulators, selective progesterone receptor modulators, the levonorgestrel-releasing intrauterine device, aromatase inhibitors, danazol, and gonadotrophin receptor hormone agonists can temporarily induce regression of adenomyosis and improve the symptoms. [ABSTRACT FROM AUTHOR]

Introduction: The gynaecological toxicity profile of tamoxifen presents a significant burden to the patients and oncologist as tamoxifen-related side effects result in additional investigations, procedures and referrals. Aromatase inhibitor have been shown to result in significant reduction in gynaecological problems, possibly including endometrial cancer. Areas covered: We reviewed the main breast cancer trials, observation or cohort studies investigating tamoxifen or an aromatase inhibitor to report on endometrial adverse events and cancer. Expert commentary: Evidence for an increase in endometrial cancers with tamoxifen in breast cancer treated patients is now very clear. Aromatase inhibitors have shown to have a beneficial effect on the endometrium. There is an important need for further studies to clearly determine the influence of aromatase inhibitors on the endometrial in tamoxifen-naïve women. The effect of aromatase inhibitors on gynaecological problems may have potentially a very important impact in clinical practice. [ABSTRACT FROM PUBLISHER]

Background: A mixed treatment analysis of the comparative effectiveness of denosumab versus zoledronic acid in the prevention of fractures in early postmenopausal breast cancer patients treated with aromatase inhibitors has been conducted. Methods: Eligible studies included randomized studies evaluating adjuvant immediate denosumab or immediate zoledronic acid versus delayed treatment for patients with postmenopausal early breast cancer on adjuvant aromatase inhibitors. Results: At 12 months cutoff, the risk of fractures is not different between immediate treatment (denosumab or zoledronic acid) vs. delayed treatment [OR: 0.78 (95% CrI 0.48 – 1.38) and 0.88 (95% CrI 0.46 – 1.58); respectively]. On the other hand, at the 36 months cutoff, the risk of fractures is reduced for immediate denosumab compared to delayed treatment while it was not decreased for immediate zoledronic acid versus delayed treatment [OR: 0.50 (95% Crl 0.33–0.75) and 0.91 (95% Crl 0.56–1.44) respectively]. For immediate denosumab versus zoledronic acid, there was a significant difference when analyzed by fixed effects models but not by random effects model [OR: 0.55 (95% Crl 0.33–0.89) and 0.55 (95% Crl 0.30–1.04) respectively]. Conclusion: This analysis demonstrated that in postmenopausal patients receiving adjuvant aromatase inhibitors, immediate denosumab decreases the risk of fractures compared to delayed treatment at the cutoff of 36 months. Immediate zoledronic acid, however, does not provide the same level of fractures’ protection in this category of patients. [ABSTRACT FROM PUBLISHER]

Introduction: Progress made in breast cancer management along with treatment-related symptoms has drawn a lot of attention from both scientists and clinicians. Establishing predictive factors for treatment response facilitate tailoring of therapy to each individual patient and leads to a reduction in unnecessary treatments. Body mass index is confirmed to be a risk factor for breast cancer development as well as for disease recurrence, which additionally negatively influence the overall survival. Due to the increased level of fatty tissue in obese and overweight patients, their total level of body aromatase is elevated. This lead to the hypothesis about a worse response to aromatase inhibitors in these groups as compared to normal weight patients, due to incomplete aromatase blockage and thus higher peripheral androgen aromatization.Areas Covered: This review aims to summarize the data from clinical trials assessing the effect of BMI on response to AI-based therapy in the setting of breast cancer. Expert commentary: Our conclusion made on the data available to date does not exclude BMI from the list of potential predictive factors however further research in this area is warranted. [ABSTRACT FROM AUTHOR]

The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their “value for money” in various health care jurisdictions. [ABSTRACT FROM PUBLISHER]

Background: The present cross-sectional study has the purpose to investigate the impact of aromatase inhibitors (AIs) on retinal nerve fiber layer (RNFL) thickness, optic nerve and macular function in patients using AIs for breast cancer treatment. Methods: Participants in our study were 41 hormone-receptor-positive earlystage breast cancer patients who were treated with AIs in the adjuvant setting. Moreover, 40 age- and gender-matched control subjects, having neither ocular nor systemic disorders, were included in this study. All participants underwent a complete ophthalmological examination, including best corrected visual acuity (BCVA) assessment, RNFL thickness and central foveal thickness (CFT) measurement, visual evoked potentials (VEP) recording and multifocal-electroretinogram (mf-ERG) recording. Univariate and multiple regression analyses were performed. Results: At the multiple regression analyses, patients receiving AIs presented with lower average RNFL and inferior RNFL. Moreover, similarly to the univariate analysis, intake of AIs was associated with lower amplitude P100, lower retinal response density in ring 1 and ring 2, longer peak time P100 and longer P1 time in ring 1. Conclusion: Our study is the first in the literature investigating the potential effect of AIs on RNFL thickness, optic nerve and macular function in patients using AIs for breast cancer treatment. The principal message of our study is that patients using AIs exhibited a significant decrease in RNFL thickness (average, superior and inferior), retinal response density and visual acuity compared to healthy controls, while VEP findings (both amplitude and peak time of P100) differ significantly as well. [ABSTRACT FROM PUBLISHER]

Nearly 60% of all breast cancer premenopausal women are diagnosed with a hormone receptor positive tumor and, therefore, are candidates for adjuvant hormonal therapy. Treatment with tamoxifen for at least 5 years has been for a long time the standard of care, as it is associated with overall positive clinical outcomes. However, in the last decade, a number of studies on adjuvant endocrine therapy in premenopausal women with hormone receptor positive breast cancer have been published, adding a bulk of evidence to existing knowledge in this field. A critical appraisal of their results appears necessary in order to put the recently collected data into the current framework of treatment, and to discuss the several issues that remain open. Here, we review the most recent evidence on the following: the optimal duration of tamoxifen treatment, results of the studies comparing tamoxifen alone to tamoxifen plus ovarian function suppression (OFS), results of the studies comparing tamoxifen plus OFS to aromatase inhibitors plus OFS. [ABSTRACT FROM AUTHOR]

Many commonly prescribed medications, such as selective serotonin reuptake inhibitors, proton pump inhibitors, thiazolidinediones, aromatase inhibitors, and androgen deprivation therapy, have been associated with adverse skeletal effects. The levels of evidence in support of a causal relationship between drug use and the development of bone loss and fractures are variable. For some drugs, a causal relationship is suspected (but not proven) based on observational studies, while in others causality is firmly established with randomized, controlled clinical trials. The mechanism of action for skeletal damage is poorly understood for some drugs and well known for others. Guidelines for managing bone health in patients taking some medications with potential skeletal toxicity have been developed using the best available evidence and expert opinion. This is a review of selected medications that have been associated with bone loss and fractures, with recommendations for clinical care. [ABSTRACT FROM PUBLISHER]

Older American Indians experience high rates of depression and other psychological disorders, yet little research exist on the depression literacy of this group. Depression literacy is fundamental for individuals seeking help for depression in a timely and appropriate manner. In the present study the authors examine levels and predictors of knowledge of depression symptoms in a sample of rural older American Indians (N = 227) living in the Midwestern United States. Data from self-administered questionnaires indicate limited knowledge of depression and negative attitudes toward seeking help for mental health problems. Additional findings and implications for social work practice and policy are discussed. [ABSTRACT FROM AUTHOR]

The goal of this survey-based study was to examine whether aromatase inhibitor (AI) therapy was associated with depressive symptoms and self-rated health among Black and White breast cancer survivors (N = 761). Results showed that among Black, but not White, breast cancer survivors current AI therapy was associated with a significant increase in the odds of both depressive symptoms (OR 3.59; 95% CI 1.01, 13.00) and poorer self-rated health (OR 3.16; 95% CI 1.06, 9.46). Presence of pain was significantly associated with increased odds of both outcomes among both groups. The findings underscore the importance of addressing not only physical but mental health among breast cancer survivors on AIs, especially those of Black race. [ABSTRACT FROM PUBLISHER]