Hormone Therapy Research Articles

Anti-cancer potential of casein and its derivatives: novel strategies for cancer treatment.

Cancer is one of the leading causes of death worldwide, with over 10million fatalities annually. While tumors can be surgically removed and treated with chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or combined therapies, current treatments often result in toxic side effects in normal tissue. Therefore, researchers are actively seeking ways to selectively eliminate cancerous cells, minimizing the toxic side effects in normal tissue. Caseins and its derivatives have shown promising anti-cancer potential, demonstrating antitumor and cytotoxic effects on cells from various tumor types without causing harm to normal cells. Collectively, these data reveals advancements in the study of caseins and their derivative peptides, particularly providing a comprehensive understanding of the molecular mechanism of action in cancer therapy. These mechanisms occur through various signaling pathways, including (i) the increase of interferon-associated STAT1 signaling, (ii) the suppression of stemness-related markers such as CD44, (iii) the attenuation of the STAT3/HIF1-α signaling, (iv) the down-expression of uPAR and PAI-1, (v) the loss of mitochondrial membrane potential and reduced intracellular ATP production, (vi) the increase of caspase-3 activity, and (vii) the suppression of TLR4/NF-кB signaling. Therefore, we conclude that casein could be an effective adjuvant for cancer treatment.

Adipose Tissue Sex Steroids in Postmenopausal Women with and without Menopausal Hormone Therapy.

The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized. We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women. Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n=50) and without (n=13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction. HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to non-users. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to non-users of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users. Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT, and these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity.

Effect of Postmenopausal Hormone Therapy on Metabolic Syndrome and its Components

Effect of Postmenopausal Hormone Therapy on Metabolic Syndrome and its Components

Barriers to quality healthcare among transgender and gender nonconforming adults.

To determine the barriers transgender and gender nonconforming (TGNC) adults face when accessing or receiving healthcare in the United States. Primary data were collected between September 2022 and March 2023 from a purposive sample of TGNC adults (N = 116 participants) using an online survey with a series of open-ended and closed-ended questions. Thematic analysis was employed to extract and analyze participants' responses to an open-ended question about challenges they experienced when accessing or receiving healthcare. Two members of the research team conducted qualitative data analyses using Dedoose. The quality of each analysis was subsequently reviewed by a third research team member. Data were collected from responses to one open-ended question that asked about participants' healthcare barriers as a TGNC individual. Five main themes surrounding healthcare barriers emerged from the content analysis: (1) acceptability, (2) accommodation, (3) affordability, (4) availability, and (5) accessibility. First, participants who noted acceptability issues reported explicit discriminatory treatment from providers, providers not using their chosen names and pronouns (e.g., misgendering), and provider refusal to provide gender-affirming care. Second, participants who experienced accommodation challenges identified provider medical training gaps on TGNC patient needs and administrative barriers to care. Third, participants explained affordability issues due to a lack of adequate health insurance coverage. Fourth, participants described availability challenges with accessing hormone therapy prescriptions. Finally, participants noted accessibility issues with obtaining TGNC-specific care at LGBTQ+-affirming clinics. There is a growing interest in the needs of TGNC adults within healthcare settings. This requires that health policies are enacted to ensure that TGNC adults have access to healthcare that is accommodating and accepting/affirming. Study findings may provide insight into the potential impact of current legislation on transgender access and availability.

Healthcare professionals’ perspectives towards the digitalisation of paediatric growth hormone therapies: expert panels in Italy and Korea

Healthcare professionals’ perspectives towards the digitalisation of paediatric growth hormone therapies: expert panels in Italy and Korea

Reduced protein carbonylation on hormone therapy is associated with improved fibrinolysis in postmenopausal women: the impact of PAI-1 and TAFI activity.

Hormone therapy (HT) has been reported to reduce protein carbonylation (PC) in postmenopausal women, in whom fibrinolysis is impaired. We investigated whether PC affects fibrinolysis and if HT modulates this effect. We enrolled 150 women aged 55.5 ± 4.7years in a randomized interventional open-label study, including 50 on standard oral HT, 50 on ultra-low-dose HT, and 50 controls. PC, along with global fibrinolysis (clot lysis time, CLT), fibrinolysis proteins, and prothrombotic markers were determined at baseline and at 24weeks. Patients with the baseline top quartile PC (> 2.07nM/mg protein) had 10.3% longer CLT, higher activity (but not antigen) of TAFI (+ 19.9%) and PAI-1 (+ 68.1%) compared to the remainder. No differences were observed in thrombin generation, factor VIII, plasminogen or α2-antiplasmin. On-treatment PC decreased by 16.4% (p < 0.0001), without differences related to the type of HT, compared to baseline and by 30% compared to controls, in whom PC and fibrinolysis markers remained unchanged. Patients with PC > 2.07nM/mg had shortened CLT during HT compared to baseline, along with lower PAI-1 (-69%) and TAFI (-26%) activity. In this subgroup CLT was 5.8% shorter compared to controls with the highest PC. In postmenopausal women with increased PC, HT was accompanied by PC reduction and faster clot lysis together with decreased PAI-1 and TAFI activity.

Recurrent catamenial hemoptysis: diagnostic challenges and management strategies—a case report

Catamenial hemoptysis (CH) is a rare, known disease for which diagnosis is crucial and treatment is indefinite. In this case report, CH was identified 2 years ago while taking medical history of the patient. It has disclosed hemoptysis at night with breathlessness that was concurrent with her menses every month for the past 6 months. A series of radiological tests followed by a bronchoscopic examination during menses confirmed the diagnosis. A complex fluid-filled cystic lesion with few air foci in the right lower lobe superior segment with ground glass opacity was seen by a CT scan test. Subsequent bronchoscopy examination showed an active bleeding site at the right lower lobe superior segment. The bronchial wash tests were negative for microbial infections as well as for malignancies. Bronchial artery embolization (BAE) was done and it ceased the hemoptysis. However, it recurred after 2 years of the BAE procedure. The symptoms and amount of hemoptysis were milder; hence, repeated BAE was not required. Earlier, the patient refused hormonal therapy (HT) owing to its side effects, but this time, she accepted HT. After 2 months of HT, hemoptysis gradually ceased. If complications arise in the future, then surgical treatment along with HT (combination therapy) would be the course of treatment. The diagnosis of CH is challenging, and treatment procedures vary from patient to patient; hence, they are customised. Hormones regulate the CH recurrence even though the symptoms have ceased after treatment. Therefore, regular follow-up and close vigilance are crucial requirements.

Are clinics not affiliated with a Menopause Society Certified Practitioner more likely to offer guideline-nonconcordant treatment compared to clinics affiliated with a Menopause Society Certified Practitioner?

To identify clinics in Ohio, Michigan, and Pennsylvania that advertise menopause treatment on their website and evaluate whether clinics not affiliated with a Menopause Society Certified Practitioner (MSCP) are more likely to offer guideline-nonconcordant treatment compared to clinics affiliated with an MSCP. We performed an Internet search to identify clinics advertising on their website menopause treatment in Ohio, Michigan, and Pennsylvania. We checked clinic personnel against The Menopause Society directory of practitioners to determine if the clinic was affiliated with an MSCP. We identified 174 clinics (41% in OH, 28% in PA, and 31% in MI). Thirteen percent of clinics were affiliated with an MSCP. Clinics with an MSCP are significantly less likely to advertise hormone testing (primary outcome; odds ratio [OR], 0.11; 95% confidence interval, 0.02-0.39), compounded hormone therapy (OR, 0.06; 95% confidence interval, 0.001-0.41), and bioidentical hormone therapy (OR, 0.07; 95% confidence interval, 0.001-0.26), compared to clinics without an MSCP-affiliated clinics that are also less likely to advertise that hormone therapy will help maintain youth or help with weight loss. Our pilot study has shown that in the states of Ohio, Michigan, and Pennsylvania, clinics with an MSCP were more likely to advertise on their website an adherence to The Menopause Society's guidelines and not advertise for compounded or bioidentical hormones, recommend hormone testing, or advertise hormones for a youthful appearance or weight loss.

EMBER creates a unified space for independent breast cancer transcriptomic datasets enabling precision oncology

Transcriptomics has revolutionized biomedical research and refined breast cancer subtyping and diagnostics. However, wider use in clinical practice is hampered for a number of reasons including the application of transcriptomic signatures as single sample predictors. Here, we present an embedding approach called EMBER that creates a unified space of 11,000 breast cancer transcriptomes and predicts phenotypes of transcriptomic profiles on a single sample basis. EMBER accurately captures the five molecular subtypes. Key biological pathways, such as estrogen receptor signaling, cell proliferation, DNA repair, and epithelial-mesenchymal transition determine sample position in the space. We validate EMBER in four independent patient cohorts and show with samples from the window trial, POETIC, that it captures clinical responses to endocrine therapy and identifies increased androgen receptor signaling and decreased TGFβ signaling as potential mechanisms underlying intrinsic therapy resistance. Of direct clinical importance, we show that the EMBER-based estrogen receptor (ER) signaling score is superior to the immunohistochemistry (IHC) based ER index used in current clinical practice to select patients for endocrine therapy. As such, EMBER provides a calibration and reference tool that paves the way for using RNA-seq as a standard diagnostic and predictive tool for ER+ breast cancer.

Retrospective text and qualitative analyses of patient experience and management of vasomotor symptoms due to menopause: voices from the PatientsLikeMe community.

Vasomotor symptoms (VMS) due to menopause cause substantial burden and distress. Some women join online communities to share experiences and treatment outcomes through peer-to-peer interactions. This study describes women's experiences with VMS and symptom management on the PatientsLikeMe online support group. Mixed-methods research included women aged 40 to 65 years in the PatientsLikeMe community who were recruited using convenience sampling. Text from online posts by members was analyzed retrospectively using natural language processing. Relevant data, including numbers and percentages of women and frequencies of mentions, were summarized descriptively. Qualitative semistructured interviews were conducted; data, notes, and recordings were transcribed and deidentified and thematic analyses were performed. Demographic information was available from 1,614 accounts included in retrospective text analyses. Women had a mean age of 56.7 years; most were White (87.8%) and not Hispanic/Latino (90.2%). Hot flashes and night sweats were most commonly mentioned symptoms (n = 146). Of 16 women who were interviewed, 14 met the inclusion criteria, and their responses were included in the analysis. VMS impacted life quality in terms of physical (43%) and mental well-being (36%), social activities (21%), and productivity (14%). Symptom management included temperature regulation (43%), lifestyle changes (36%), over-the-counter Estroven (29%), hormone therapy (21%), and contraceptives (21%). Half of the women were surprised by symptom intensity and duration; many felt unheard by their healthcare providers. VMS have a substantial negative impact on multiple aspects of women's life. Management strategies for these symptoms vary widely, and many women feel unprepared for navigating the complex challenges of menopause.

Effects of Resistance Training, Estrogen Therapy, and Calcium Chitosan Supplement Containing Vitamin D on Bone Turnover in Ovariectomized Rats: An Experimental-Comparative Study

Background: Hormone therapy is a highly effective method for treating menopausal disorders. However, its side effects may include an increased risk of cancer, heart disease, and pulmonary embolism. Previous research has demonstrated that both exercise and nutrition separately have positive effects on menopausal symptoms. Therefore, we suggest that combining exercise and nutrition interventions may provide a synergistic effect, yielding results at least similar to those of estrogen (Est) therapy. Objectives: This study aims to compare the independent and combined effects of resistance training (RT), Est therapy, and vitamin D calcium chitosan (Vit D + Ca++ + Chit) supplementation on markers of bone turnover in ovariectomized (OVX) rats. Methods: Forty-two female Wistar rats were randomly divided into seven groups (n = 6 per group): (1) healthy-control (He-Co), (2) OVX-Vit D + Ca++ + Chit + RT, (3) OVX-saline (Sal) + Est + RT, (4) Sal + RT, (5) OVX-Vit D + Ca++ +Chit, (6) OVX-Sal + Est, and (7) OVX-Control (OVX-Co). Bone samples were extracted 48 hours after the final session. Two-way ANOVAs were used to determine differences in intervention effects between groups. The alpha level was set to 0.05. Results: Ovariectomy (OVX) decreased bone tissue expression of alkaline phosphatase (ALP) and osterix (OSX) while increasing peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression. Ovariectomy also decreased the number of osteocytes and osteoblasts while increasing the number of osteoclasts. Resistance training (RT) and Vit D + Ca++ + Chit intake increased bone tissue expression of ALP, OSX, and PPAR-γ gene expression. Additionally, RT and Vit D + Ca++ + Chit supplementation increased the number of osteocytes and osteoblasts and decreased the number of osteoclasts. Conclusions: The combined interventions had synergistic effects compared to each intervention separately on ALP, osteocyte, osteoblast, and osteoclast observations. Therefore, combining RT with Vit D + Ca++ + Chit could be a non-pharmacological approach to address bone turnover alterations caused by OVX.

Evaluation of Sexual Function of Transgender Individuals.

The current study sought to evaluate the sexual function of transgender men and women and to identify associated factors. Trans individuals who were outpatients at our gender incongruence (GI) center for follow-up of gender-affirming hormone therapy with age ranging 27 to 50 years were invited to participate in this cross-sectional study. Clinical data were collected from the medical records. Two scales, the Female Sexual Function Index (FSFI) and the Male Sexual Function Index (MSFI), were administered to all females (n = 50) and all males (n = 58). Each participant also responded to a semi-structured questionnaire that assessed feelings regarding being transgender and satisfaction with sexual life. Relative to trans women, trans men had a higher total FSFI score, and higher scores in the FSFI domains of arousal, lubrication, orgasm, and satisfaction (all p < 0.01), and in the total MSFI score, and higher scores in the MFSI domains of arousal, erection, orgasm, and satisfaction (all p < 0.01). A separate semi-structured evaluation indicated that more than half of the trans men and almost half of the trans women were satisfied or very satisfied with their sexual life. The total scores from the FSFI and MSFI indicated a high risk of sexual dysfunction in trans men and especially, in trans women. However, the semi-structured evaluation showed that more than half of the trans men and almost half of the trans women were satisfied with their sexual life.

Metformin Prevents Tumor Cell Growth and Invasion of Human Hormone Receptor-Positive Breast Cancer (HR+ BC) Cells via FOXA1 Inhibition

Women with type 2 diabetes (T2D) have a higher risk of being diagnosed with breast cancer and have worse survival than non-diabetic women if they do develop breast cancer. However, more research is needed to elucidate the biological underpinnings of these relationships. Here, we found that forkhead box A1 (FOXA1), a forkhead family transcription factor, and metformin (1,1-dimethylbiguanide hydrochloride), a medication used to treat T2D, may impact hormone-receptor-positive (HR+) breast cancer (BC) tumor cell growth and metastasis. Indeed, fourteen diabetes-associated genes are highly expressed in only three HR+ breast cancer cell lines but not the other subtypes utilizing a 53,805 gene database obtained from NCBI GEO. Among the diabetes-related genes, FOXA1, MTA3, PAK4, FGFR3, and KIF22 were highly expressed in HR+ breast cancer from 4032 breast cancer patient tissue samples using the Breast Cancer Gene Expression Omnibus. Notably, elevated FOXA1 expression correlated with poorer overall survival in patients with estrogen-receptor-positive/progesterone-receptor-positive (ER+/PR+) breast cancer. Furthermore, experiments demonstrated that loss of the FOXA1 gene inhibited tumor proliferation and invasion in vitro using MCF-7 and T47D HR+ breast cancer cell lines. Metformin, an anti-diabetic medication, significantly suppressed tumor cell growth in MCF-7 cells. Additionally, either metformin treatment or FOXA1 gene deletion enhanced tamoxifen-induced tumor growth inhibition in HR+ breast cancer cell lines within an ex vivo three-dimensional (3D) organoid model. Therefore, the diabetes-related medicine metformin and FOXA1 gene inhibition might be a new treatment for patients with HR+ breast cancer when combined with tamoxifen, an endocrine therapy.

The cardiovascular and metabolic effects of ovarian suppression in combination with tamoxifen or an aromatase inhibitor as adjuvant therapy for early estrogen receptor-positive breast cancer: a systematic review

Adjuvant endocrine therapy is a key treatment in oestrogen receptor positive early breast cancer (BC). For premenopausal women ovarian function suppression (OFS) in combination either tamoxifen or aromatase inhibitor (AI) is utilised in high-risk cases. The resultant suppression of circulating oestradiol from OFS could have adverse cardiovascular and metabolic effects, subsequently increasing the risk of cardiovascular disease. Our study highlights the potential cardio-metabolic impact endocrine therapy and OFS have on premenopausal women with BC. It also highlights the pressing need for standardisation of routine collection and recording of cardiometabolic history and risk factors as part of baseline assessment and adverse event reporting to better understand the cardiometabolic impact these treatment has on our patients. Further studies, with particular focus on baseline and subsequent development of cardiovascular risk factors are needed to explore the impact of these drugs on the cardiovascular health of these young women with BC

Fibroblast growth factor receptor signaling in estrogen receptor-positive breast cancer: mechanisms and role in endocrine resistance

Fibroblast Growth Factor Receptors (FGFRs) play a significant role in Estrogen Receptor-positive (ER+) breast cancer by contributing to tumorigenesis and endocrine resistance. This review explores the structure, signaling pathways, and implications of FGFRs, particularly FGFR1, FGFR2, FGFR3, and FGFR4, in ER+ breast cancer. FGFR1 is frequently amplified, especially in aggressive Luminal B-like tumors, and its amplification is associated with poor prognosis and treatment resistance. The co-amplification of FGFR1 with oncogenes like EIF4EBP1 and NSD3 complicates its role as a standalone oncogenic driver. FGFR2 amplification, though less common, is critical in hormone receptor regulation, driving proliferation and treatment resistance. FGFR3 and FGFR4 also contribute to endocrine resistance through various mechanisms, including the activation of alternate signaling pathways like PI3K/AKT/mTOR and RAS/RAF/MEK/ERK. Endocrine resistance remains a major clinical challenge, with around 70% of breast cancers initially hormone receptor positive. Despite the success of CDK 4/6 inhibitors in combination with endocrine therapy (ET), resistance often develops, necessitating new treatment strategies. FGFR inhibitors have shown potential in preclinical studies, but clinical trials have yielded limited success due to off-target toxicities and lack of predictive biomarkers. Current clinical trials, including those evaluating FGFR inhibitors like erdafitinib, lucitanib, and dovitinib, have demonstrated mixed outcomes, underscoring the complexity of FGFR signaling in breast cancer. The interplay between FGFR and other signaling pathways highlights the need for comprehensive molecular profiling and personalized treatment approaches. Future research should focus on identifying robust biomarkers and developing combination therapies to enhance the efficacy of FGFR-targeted treatments. In conclusion, targeting FGFR signaling in ER+ breast cancer presents both challenges and opportunities. A deeper understanding of the molecular mechanisms and resistance pathways is crucial for the successful integration of FGFR inhibitors into clinical practice, aiming to improve outcomes for patients with endocrine-resistant breast cancer.

Corrigendum: Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations

Corrigendum: Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations

A review of endocrine therapy for hormone-dependent breast cancer

Purpose of the study: to provide current data on pharmacotherapy of hormone-dependent breast cancer (hdBC) and to consider the feasibility of introducing new hormone therapy drugs for breast cancer into clinical practice. Material and Methods. We analyzed 80 publications available Pubmed, Springer, Cochrane Library, etc. concerning the study of pharmacological characteristics of various groups of drugs for the treatment of hdBC, of which 49 were included in this review. Results. Currently, there are several approaches to the treatment of hdBC. Selective estrogen receptor modulators and aromatase inhibitors are the most studied and frequently used drugs. The cyclin-dependent kinase 4/6 inhibitors can be present in both the first- and second-line therapy. Currently, close attention is paid to the development of new drugs based on genomic profiling of the tumor, which is the standard of treatment for hdBC, and contributes to the personalization of therapy. Conclusion. Further development of drugs holds great promise for increasing overall survival and more accurate prognosis, response to conventional systemic therapy, and individualization of pharmacotherapy for hdBC. However, further research and development of new drugs is required. In this regard, the introduction of oral selective estrogen receptor degraders into practice and the development of new drugs that block estrogen-dependent and independent signaling to estrogen receptors are the most promising trends.

Methods of Determining Energy Expenditure in Individuals with Prader-Willi Syndrome: A Systematic Literature Review

Prader-Willi syndrome (PWS) is a rare disorder characterised by varying nutritional phases that occur throughout the lifespan, ranging from failure to thrive to hyperphagia. If uncontrolled, the imbalance between energy intake and expenditure results in obesity development and increased morbidity and mortality risk. Although measures of energy requirements for accurate nutrition assessment are vital, the evidence appears sparse and heterogeneous; hence, the aim of this review was to examine the available literature on energy expenditure predicted or measured using various methods in individuals with PWS. Studies were sought that presented methods and results on resting energy expenditure or basal metabolic rate. A narrative synthesis was completed to present the study characteristics and results. Methods of determining energy requirements included predictive equations and indirect calorimetry. Differences amongst ages, growth hormone therapy, fasting status, and measures in which results were presented were limitations to appropriately summarising and identifying trends in energy expenditure. Indirect calorimetry was identified as the most accurate method; however, it is not widely available in all settings. Further research is encouraged to support the development of valid and reliable predictive equations that will better inform and improve the efficiency of clinical practice in supporting people with PWS.

Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up.

Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.

Pathological Changes Following Neoadjuvant Endocrine Therapy (NAET): A Multicentre Study of 391 Breast Cancers

Oestrogen receptor (ER)-positive breast cancer (BC) is generally well responsive to endocrine therapy. Neoadjuvant endocrine therapy (NAET) is increasingly being used for downstaging ER-positive tumours. This study aims to analyse the effect of NAET on a well-characterised cohort of ER-positive BC with particular emphasis on receptor expression. This is a retrospective United Kingdom (UK) multicentre study of 391 patients who received NAET between October 2012 and October 2020. Detailed analyses of the paired pre- and post-NAET morphological changes and hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression were performed. The median duration of NAET was 86 days, with median survival and overall survival rates of 380 days and 93.4%, respectively. A total of 90.3% of cases achieved a pathological partial response, with a significantly higher rate of response in the HER2-low cancers. Following NAET, BC displayed some pathological changes involving the tumour stroma including central scarring and an increase in tumour infiltrating lymphocytes (TILs) and tumour cell morphology. Significant changes associated with the duration of NAET were observed in tumour grade (30.6% of cases), with downgrading identified in 19.3% of tumours (p &lt; 0.001). The conversion of ER status from positive to low or negative was insignificant. The conversion of progesterone receptor (PR) and HER2 status to negative status was observed in 31.3% and 38.1% of cases, respectively (p &lt; 0.001). HER2-low breast cancer decreased from 63% to 37% following NAET in the paired samples. Significant morphological and biomarker changes involving PR and HER2 expression occurred following NAET. The findings support biomarker testing on pre-treatment core biopsies and post-treatment residual carcinoma.