Endocrine Therapy For Breast Cancer Research Articles

Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review.

Simple SummaryMany persons diagnosed with breast cancer are treated with endocrine therapy and will experience the side effects of endocrine therapy. Cognitive adverse effects of endocrine therapy are increasingly being recognised, and can significantly affect quality of life, adherence and treatment outcome. This review aims to discuss the nature of cognitive dysfunction associated with endocrine therapy, the mechanisms underpinning its development, and evidence-based management strategies.Endocrine therapy forms the backbone of systemic therapy for the majority of persons with early and late-stage breast cancer. However, the side effects can negatively affect quality of life, and impact treatment adherence and overall oncological outcomes. Adverse effects on cognition are common, underreported and challenging to manage. We aim to describe the nature, incidence, risk factors and underlying mechanisms of endocrine therapy-induced cognitive dysfunction. We conducted a comprehensive literature review of the studies reporting on cognitive dysfunction associated with endocrine therapies for breast cancer. We also summarise prevention and treatment strategies, and ongoing research. Given that patients are taking endocrine therapies for longer durations than ever before, it is essential that these side effects are managed pro-actively within a multi-disciplinary team in order to promote adherence to endocrine therapy and improve patients’ quality of life.

The Oncology Care Model and Adherence to Oral Cancer Drugs: A Difference-in-Differences Analysis.

Adherence to oral cancer drugs is suboptimal. The Oncology Care Model (OCM) offers oncology practices financial incentives to improve the value of cancer care. We assessed the impact of OCM on adherence to oral cancer therapy for chronic myelogenous leukemia (CML), prostate cancer, and breast cancer. Using 2014-2019 Medicare data, we studied chemotherapy episodes for Medicare fee-for-service beneficiaries prescribed tyrosine kinase inhibitors (TKIs) for CML, antiandrogens (ie, enzalutamide, abiraterone) for prostate cancer, or hormonal therapies for breast cancer in OCM-participating and propensity-matched comparison practices. We measured adherence as the proportion of days covered and used difference-in-difference (DID) models to detect changes in adherence over time, adjusting for patient, practice, and market-level characteristics. There was no overall impact of OCM on improved adherence to TKIs for CML (DID = -0.3%, 90% confidence interval [CI] = -1.2% to 0.6%), antiandrogens for prostate cancer (DID = 0.4%, 90% CI = -0.3% to 1.2%), or hormonal therapy for breast cancer (DID = 0.0%, 90% CI = -0.2% to 0.2%). Among episodes for Black beneficiaries in OCM practices, for whom adherence was lower than for White beneficiaries at baseline, we observed small improvements in adherence to high cost TKIs (DID = 3.0%, 90% CI = 0.2% to 5.8%) and antiandrogens (DID = 2.2%, 90% CI = 0.2% to 4.3%). OCM did not impact adherence to oral cancer therapies for Medicare beneficiaries with CML, prostate cancer, or breast cancer overall but modestly improved adherence to high-cost TKIs and antiandrogens for Black beneficiaries, who had somewhat lower adherence than White beneficiaries at baseline. Patient navigation and financial counseling are potential mechanisms for improvement among Black beneficiaries.

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

Factors influencing five-year adherence to adjuvant endocrine therapy in breast cancer patients: A systematic review.

PurposeThis systematic review aimed to determine the rate and identify correlates of adherence and persistence over five years of treatment with adjuvant endocrine therapy in female breast cancer patients.MethodsRelevant articles were identified from Medline, Embase, AMED, PsycINFO, International Pharmaceutical s, and APA PsycArticles. Studies that measured patient adherence in the implementation or persistence phase for a period of at least five years using objective or multiple measures of adherence and investigated correlates of adherence were included. The titles, abstracts and full articles were screened and reviewed by two authors and any discrepancies were discussed with a third author.ResultsTwenty-six studies were included. Mean rate of adherence at five-year for implementation phase was 66.2% (SD = 17.3%), and mean persistence was 66.8% (SD = 14.5%). On average, adherence decreased by 25.5% (SD = 9.3%) from the first to fifth year. Higher rate of adherence was observed through self-report in comparison to database or medical record. Older age, younger age, higher comorbidity index, depression and adverse effects were associated with lower adherence. Treatment with aromatase inhibitors, received chemotherapy, and prior medication use were associated with improved adherence.ConclusionAdherence to adjuvant endocrine therapy decreased from the first to fifth year of treatment. On average, one-third of patients were not adherent to treatment by the fifth year. Nineteen recurring factors were found to be significantly associated with long-term adherence in multiple studies. Further research using objective or multiple measures of adherence are needed to improve validity of results.

Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes.

Breast cancer(BC) is considered a heterogeneous disease composed of distinct subtypes with diverse clinical outcomes. Luminal subtype tumors have the best prognosis, and patients benefit from endocrine therapy. However, resistance to endocrine therapies in BC is an obstacle to successful treatment, and novel biomarkers are needed to understand and overcome this mechanism. The RET, BCAR1, and BCAR3 genes may be associated with BC progression and endocrine resistance. Aiming to evaluate the expression profile and prognostic value of RET, BCAR1, and BCAR3, we performed immunohistochemistry on tissue microarrays(TMAs) containing a cohort of 361 Luminal subtype BC. Low expression levels of these three proteins were predominantly observed. BCAR1 expression was correlated with nuclear grade (p = 0.057), and BCAR3 expression was correlated with lymph node status (p = 0.011) and response to hormonal therapy (p = 0.021). Further, low expression of either BCAR1 or BCAR3 was significantly associated with poor prognosis (p = 0.005; p = 0.042). Pairwise analysis showed that patients with tumors with low BCAR1/low BCAR3 expression had a poorer overall survival (p = 0.013), and the low BCAR3 expression had the worst prognosis with RET high expression stratifying these patients into two different groups. Regarding the response to hormonal therapy, non-responder patients presented lower expression of RET in comparison to the responder group (p = 0.035). Additionally, the low BCAR1 expression patients had poorer outcomes than BCAR1 high (p = 0.015). Our findings suggest RET, BCAR1, and BCAR3 as potential candidate markers for endocrine therapy resistance in Luminal BC.

Comparison of adverse drug reactions between tamoxifen and toremifene in breast cancer patients with different CYP2D6 genotypes: A propensity-score matched cohort study.

CYP2D6 gene polymorphism has a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancer. However, it had never been reported whether the adverse drug reactions vary by CYP2D6 metabolic status for patients treated with tamoxifen or toremifene. We conducted a retrospective study in breast cancer patients to investigate the impact of CYP2D6 metabolic status on liver dysfunction events, gynecological events and dyslipidemia events. According to CYP2D6*10 (100C → T) genotype, the enrolled patients were further categorized into four cohorts (extensive metabolizers taking tamoxifen [EM + TAM], extensive metabolizers taking toremifene [EM + TOR], intermediate metabolizers taking tamoxifen [IM + TAM], and intermediate metabolizers taking toremifene [IM + TOR]). A total of 192 patients were included in the study, with a median follow-up time of 26.2months. In EM + TAM cohort, the risks of liver dysfunction events (P=.004) and gynecological events (P=.004) were significantly higher compared to EM + TOR cohort. In IM + TAM cohort, the risks of liver dysfunction events (P=.14) and gynecological events (P=.99) were not significantly different from IM + TOR cohort. A significant decrease of total cholesterol was observed in EM + TAM cohort around 1year after taking tamoxifen (P < .001). Significant interactions between CYP2D6 metabolic status and endocrine agents were observed in terms of liver dysfunction events (P-interaction=.007) and gynecological events (P-interaction=.026). These findings suggested that CYP2D6 gene polymorphism played a significant role in predicting liver dysfunction, gynecological diseases and lipid metabolism changes among patients taking tamoxifen or toremifene.

Sexuality in breast cancer survivors: sexual experiences, emotions, and cognitions in a group of women under hormonal therapy.

Earlier diagnosis and improved treatments have led to better outcomes in breast cancer, making quality of life a key issue. Sexuality represents a pillar of quality of life, although it is often neglected by both healthcare providers and patients when it comes to cancer. This study aims to explore the differences in sexual functioning, distress, psychopathology, emotions, and cognitions between breast cancer patients under hormonal treatment and controls. Seventy-nine women (age range between 24 and 69years) in hormonal therapy for breast cancer completed a self-reported protocol. A matched control group of 103 women was randomly extracted from an Italian general population database. Eight self-report questionnaires exploring biopsychosocial factors were administered. The current study showed an impaired sexuality in breast cancer patients compared to controls. Breast cancer women under hormonal treatment were characterized by diminished or absent sexual activity (chi2 = 36.16; p < 0.001), lower level of sexual functioning in all areas except for pain (F(1,180) = 8.1; p < 0.01), higher sexual (F(1,180) = 10.08; p < 0.001) and psychological distress (F(1,180) = 6.23; p < 0.05), higher scores in Difficulties in Identifying Feelings (F(1,180) = 7.31; p < 0.01) and Externally Oriented Thinking (F(1,180) = 6.64; p < 0.05), higher level of negative emotions related to sexuality (F(1,180) = 11.13; p < 0.001), and more rigid cognition towards peculiar aspects of sexuality, such as Failure Disengagement Thoughts (F(1,180) = 22.01; p < 0.001) and Age related Beliefs (F(1,180) = 5.7; p < 0.05). Health care providers do not usually assess those issues in their routine practice, so that sexuality remains an unmet need with remarkable effects on general health and quality of life.

Hormone Therapy and Risk of Breast Cancer: Where Are We Now?

Several studies have examined the clinical benefits of hormone replacement therapy (HRT). However, because long-term use of HRT has been implicated as a risk factor for the development of breast cancer, some women remain skeptical when considering this therapy to address their vasomotor symptoms. Hence, physicians and nurses should actively engage in constructive discourse with their patients regarding HRT while specifically reviewing the potential risks of its extended use as well as provide the available medical alternatives the patients could potentially use.

Ocular Side Effects of Aromatase Inhibitor Endocrine Therapy in Breast Cancer - A Review.

Aromatase inhibitor therapy is currently the preferred choice in postmenopausal women with estrogen receptor positive breast cancer. This article reviews the ocular side effects of treatment with aromatase inhibitors (AIs) in patients with breast cancer. A comprehensive search was performed on PubMed, Web of Science and Google scholar. After duplication removal, 14 clinical studies and 5 case reports, published between 2008 and 2021, were identified. Most frequently, AI treatment resulted in minor to moderate dry eye symptoms. "De novo" onset of Sjogren syndrome during AI therapy was also reported. Retinal and optic nerve side effects varied from mild, subclinical anatomic and functional impairment to severe decreased vision, secondary to hemi-central retinal artery occlusion, bilateral optic neuritis or uveitis with bilateral macular edema. Visual disturbances encountered during AI treatment may be underestimated. Ophthalmic screening is important for early detection and appropriate treatment.

Simulation modeling of breast cancer endocrine therapy duration by patient and tumor characteristics

BackgroundExtending endocrine therapy from 5 to 10 years is recommended for women with invasive estrogen receptor (ER)‐positive breast cancers. We evaluated the benefits and harms of the five additional years of therapy.MethodsAn established Cancer Intervention and Surveillance Network (CISNET) model used a lifetime horizon with national and clinical trial data on treatment efficacy and adverse events and other‐cause mortality among multiple birth cohorts of U.S. women ages 25–79 newly diagnosed with ER+, non‐metastatic breast cancer. We assumed 100% use of therapy. Outcomes included life years (LYs), quality‐adjusted life years (QALYs), and breast cancer mortality. Results were discounted at 3%. Sensitivity analyses tested a 15‐year time horizon and alternative assumptions.ResultsExtending tamoxifen therapy duration among women ages 25–49 reduced the lifetime probability of breast cancer death from 11.9% to 9.3% (absolute difference 2.6%). This translates to a gain of 0.77 LYs (281 days)/woman (undiscounted). Adverse events reduce this gain to 0.44 QALYs and after discounting, gains are 0.20 QALYs (73 days)/woman. Extended aromatase inhibitor therapy in women 50–79 had small absolute benefits and gains were offset by adverse events (loss of 0.06 discounted QALYs). There were greater gains with extended endocrine therapy for women with node‐positive versus negative cancers, but only women ages 25–49 and 50–59 had a net QALY gain. All gains were reduced with less than 100% treatment completion.ConclusionThe extension of endocrine therapy from 5 to 10 years modestly improved lifetime breast cancer outcomes, but in some women, treatment‐related adverse events may outweigh benefits.

Impact of Medicaid expansion and state-level racial diversity on breast cancer endocrine therapy prescriptions: A quasi-experimental, comparative interrupted time series study

AimsTo determine whether Medicaid expansion impacted racially more diverse states similarly as racially less diverse states in endocrine therapy (ET) prescriptions. MethodsA quasi-experimental, comparative interrupted time series study of Medicaid-financed ET prescriptions from 2011 to 2018 Medicaid State Drug Utilization Database. The exposures were state’s Medicaid expansion and racial diversity status. The outcome was state’s quarterly number ET prescriptions per 100,000 non-elderly adult females (NAFs). ResultsDuring the year of expansion, ET prescriptions increased sharply in expansion states but remained flat in nonexpansion states (slope: 11.96 vs. 0.43 prescriptions per 100,000 NAFs per quarter, p < 0.001). After that, the slopes were similar between expansion and nonexpansion states (1.75 vs. 0.24, p = 0.057) but the level of prescriptions in expansion states maintained at a higher level. When stratified by state’s racial diversity status, the slope of increase in the first year was sharper for raciallymore diverse expansion states (16.49, p = 0.008) than racially less diverse expansion states (8.46, p < 0.001), resulting in significant differences in ET prescriptions between racially more diverse expansion and nonexpansion states but largely nonsignificant differences between racially less diverse expansion and nonexpansion states. ConclusionsAlthough Medicaid expansion significantly increased ET prescriptions in expansion vs. nonexpansion states, this difference was only observed among raciallymore diverse states. Racially more diverse nonexpansion states had the lowest rates of ET prescriptions and the gaps from racially more diverse expansion states significantly widened after expansion. Policy summaryOur study shows that, before expansion, racially more diverse nonexpansion states had the lowest rates of ET prescriptions. After expansion, the gaps between these states and racially more diverse expansion states significantly widened. These results highlighted the importance of continuing to examine the health impacts of states not expanding Medicaid, including the health equity impacts for low income racial/ethnic minority populations with cancer and other life-threatening diseases.

Overall survival and progression-free survival with cyclin-dependent kinase 4/6 inhibitors plus endocrine therapy in breast cancer: an updated meta-analysis of randomized controlled trials.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been recommended as standard therapeutic strategies for hormone receptor-positive (HR+), human epidermal growth factor receptor type 2-negative (Her2-) advanced breast cancer (ABC). While the benefits to progression-free survival (PFS) rates have been confirmed, whether the combination of CDK4/6i and ET leads to overall survival (OS) rate improvements remains controversial. This study aimed to assess the long-term efficacy and safety of CDK4/6i in HR+, Her2- ABC patients and identify a population suitable for treatment with CDK4/6i by subgroup analysis. Electronic literature databases (MEDLINE, EMBASE and the Cochrane Library) were searched for relevant randomized controlled trials (rcts) published from Jan 2014 to Jan 2020. In addition, abstracts and presentations from all major conference proceedings were reviewed. All rcts that compared the efficacy and safety of CDK4/6i plus ET with ET alone in HR+, Her2- ABC patients were selected. The pooled analyses of hazard ratios (hrs) for PFS and OS, and risk ratios (rrs) for the objective response rate (ORR) and adverse events (aes) were obtained with the random-effects model. A total of 6 rcts and 3421 HR+, Her2- ABC patients were enrolled for OS outcome analysis, while all 8 trials and 4580 patients were included for PFS outcome analysis. The pooled hrs for the OS and PFS were 0.76 (95% CI: 0.67-0.84) and 0.55 (95% CI: 0.50-0.59), respectively, and were consistent in the subgroup analysis. Moreover, CDK4/6i meaningfully improved the ORR in both the intention-to-treat population (RR=1.47; 95% CI: 1.29-1.67) and patients with measurable disease (RR=1.47; 95% CI: 1.30-1.67); however, CDK4/6i increased the incidence of grade 3/4 aes (RR=2.69; 95% CI: 2.43-2.97). The combination of CDK4/6i and ET was superior to ET alone in terms of OS and PFS regardless of the drugs administered, the treatment line, age distribution, race, PR status, menopausal status, metastasis site and endocrine resistance status.

Anti-hyperplastic effects of the Dacryodes edulis (Burseraceae) leaves aqueous extract on tamoxifen-induced endometrium hyperplasia on Wistar rat.

Combining tamoxifen, the most common breast cancer hormonal therapy, with natural antitumor substances may prevent its hyperplastic effects on the uterine endometrium. Dacryodes edulis (DE) is traditionally recommended for the treatment of cancerous diseases. To investigate its antiproliferative properties, the present study was designed to assess the ability of the combined administration of tamoxifen with the aqueous extract of DE leaves to inhibit the trophic effect of this hormone therapy on rat uterine endometrium without compromising its non-proliferative effect on breast tissue. Ovariectomized (OVX) female Wistar rats were simultaneously treated with tamoxifen (10mg/kg) intraperitoneally and DE leaves (at doses of 25, 50 and 100mg/kgBW) by gavage. Control groups received either distilled water or tamoxifen alone. Treatments lasted 37days. The 38th day, animals were sacrificed under anesthesia (diazepam: 10mg/kgBW and ketamine: 50mg/kgBW). The relative uterine weight was determined and the histological analysis of the uterus and mammary gland was performed. The oxidative status of the uterus was assessed and the levels of cholesterol and estradiol were evaluated in serum and uterus. Tamoxifen increased uterine weight and induced endometrial hyperplasia. This effect was associated with increased uterine levels of cholesterol (164.22%; p<0.001), estradiol (927.5%; p<0.001) and malondiadehyde (86%; p<0.05), but unchanged antioxidant enzymes activities. The administration of DE leaves unchanged tamoxifen-increased uterine weight but reduced uterine epithelium hypertrophy (56.4%; p<0.01). DE also increased uterine levels of malondiadehyde and antioxidant enzymes. The levels of estradiol and cholesterol in the uterus decreased while no changes were observed in the mammary gland of animals treated with tamoxifen alone or in co-administration with DE. D.edulis has antiproliferative properties and could complement endocrine therapy of estrogen-dependent breast cancer.

The Role of Ki67 in Evaluating Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer.

Ki67 is a proliferation marker. It has been proposed as a useful clinical marker for breast cancer subtype classification, prognosis, and prediction of therapeutic response. But the questionable analytical validity of Ki67 prevents its widespread adoption of these measures for treatment decisions in breast cancer. Currently, Ki67 has been tested as a predictive marker for chemotherapy using clinical and pathological response as endpoints in neoadjuvant endocrine therapy. Ki67 can be used as a predictor to evaluate the recurrence-free survival rate of patients, or its change can be used to predict the preoperative “window of opportunity” in neoadjuvant endocrine therapy. In this review, we will elaborate on the role of Ki67 in neoadjuvant endocrine therapy in breast cancer.

Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis.

Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo(HR 1.46, 95% CI 1.12-1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80-1.77, p = 0.390). Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

IHC-based Ki67 as response biomarker to tamoxifen in breast cancer window trials enrolling premenopausal women

Window studies are gaining traction to assess (molecular) changes in short timeframes. Decreased tumor cell positivity for the proliferation marker Ki67 is often used as a proxy for treatment response. Immunohistochemistry (IHC)-based Ki67 on tissue from neo-adjuvant trials was previously reported to be predictive for long-term response to endocrine therapy for breast cancer in postmenopausal women, but none of these trials enrolled premenopausal women. Nonetheless, the marker is being used on this subpopulation. We compared pathologist assessed IHC-based Ki67 in samples from pre- and postmenopausal women in a neo-adjuvant, endocrine therapy focused trial (NCT00738777), randomized between tamoxifen, anastrozole, or fulvestrant. These results were compared with (1) IHC-based Ki67 scoring by AI, (2) mitotic figures, (3) mRNA-based Ki67, (4) five independent gene expression signatures capturing proliferation, and (5) blood levels for tamoxifen and its metabolites as well as estradiol. Upon tamoxifen, IHC-based Ki67 levels were decreased in both pre- and postmenopausal breast cancer patients, which was confirmed using mRNA-based cell proliferation markers. The magnitude of decrease of Ki67 IHC was smaller in pre- versus postmenopausal women. We found a direct relationship between post-treatment estradiol levels and the magnitude of the Ki67 decrease in tumors. These data suggest IHC-based Ki67 may be an appropriate biomarker for tamoxifen response in premenopausal breast cancer patients, but anti-proliferative effect size depends on estradiol levels.

Влияние эндокринотерапии рака молочной железы на липидный профиль сыворотки крови женщин в постменопаузе

Актуальность. Рак молочной железы (РМЖ) занимает первое место в мире среди всех злокачественных новообразований у женщин. Удельный вес гормончувствительного РМЖ в структуре заболеваемости составляет более 60 %. Адъювантная эндокринотерапия является неотъемлемой частью послеоперационного лечения больных гормончувствительным раком молочной железы. Современные публикации свидетельствуют, что эндокринотерапия РМЖ имеет определенное влияние на уровень липидов сыворотки крови. Однако количество исследований, которые фокусируются исключительно на этой проблеме, является незначительным, а вопрос о характере влияния различных препаратов для эндокринотерапии РМЖ на липидный профиль сыворотки крови остается спорным. Значительную часть пациентов с гормончувствительным раком молочной железы составляют женщины в естественной или искусственной постменопаузе. В возрастной группе пациенток 60 лет и старше заболевания сердечно-сосудистой системы занимают первое место в структуре смертности. Благодаря современным подходам к лечению РМЖ общая выживаемость значительно увеличилась, и приобрел актуальность комплексный подход к лечению пациенток с учетом возрастной сопутствующей патологии, не менее важной с точки зрения продолжительности и качества жизни. В данной статье рассмотрено влияние наиболее распространенных средств эндокринотерапии на липидный профиль сыворотки крови, что является чрезвычайно актуальным для профилактики заболеваемости и смертности от сердечно-сосудистых событий у женщин в постменопаузе. Материалы и методы. Данная статья основана на результатах 13 клинических исследований, полученных в поисковом ресурсе PubMed по ключевым словам: «гормончувствительный рак молочной железы», «дислипидемия», «липидный профиль сыворотки», «адъювантная эндокринотерапия рака молочной железы», «селективные модуляторы эстрогеновых рецепторов» (SERM), «ингибиторы ароматазы»; клинических рекомендациях NCCN; клинических рекомендациях Европейского общества кардиологов и Европейского общества атеросклероза (ESC/EAS) по лечению дислипидемий. Результаты. SERM оказывают положительное влияние на липидный профиль сыворотки крови с некоторыми отличиями торемифена от тамоксифена (не вызывает повышения уровня триглицеридов). Ингибиторы ароматазы, по данным исследований, оказывают скорее нейтральное влияние; среди распространенных ингибиторов ароматазы летрозол оказывает наиболее выраженное негативное влияние на липидный профиль женщин в постменопаузе с гормончувствительным РМЖ. Выводы. Селективные модуляторы эстрогеновых рецепторов могут быть препаратами выбора для пациентов с высоким риском дислипидемии, кроме пациентов с изолированной гипертриглицеридемией. Использование ингибиторов ароматазы должно сопровождаться более пристальным контролем показателей липидного обмена и может потребовать дополнительного назначения гиполипидемических препаратов (статины, фибраты, секвестранты желчных кислот и т.п.). Проблема требует дальнейшего исследования с учетом внимания, уделяемого коррекции дислипидемии как средства профилактики развития заболеваний сердечно-сосудистой системы, которые являются ведущей причиной смерти в исследуемой возрастной категории.

Optimal adjuvant endocrine therapy for breast cancer.

Adjuvant endocrine therapy is the principal systemic treatment for non-metastatic hormone receptor-positive breast cancer. Incorporation of an aromatase inhibitor is superior to tamoxifen alone for postmenopausal women.1 Guidelines recommend aromatase inhibitor either upfront or as part of an early switch strategy after 2–3 years of tamoxifen.2 Recommendations on extended adjuvant endocrine therapy after 5 years are evolving. A randomised trial3 of extended adjuvant tamoxifen showed a survival benefit, but results from trials2,4,5 evaluating extended aromatase inhibitor therapy have been mixed and the optimal duration or type of endocrine therapy remains uncertain.

Real-world benefit of combination palbociclib and endocrine therapy for metastatic breast cancer and correlation with neutropenia.

BackgroundCombination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression‐free survival (PFS) in patients with hormone receptor (HR)‐positive, HER2‐negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real‐world benefit of first‐line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors.MethodsThis study included HR‐positive, HER2‐negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression‐free survival (PFS) was determined using Kaplan–Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil‐to‐lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time‐dependent variable.ResultsIn total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93–NR). Median PFS for patients with bone‐only metastases (n = 54) was not reached (95% CI 18.21–NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33–33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71–0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97–1.18, p = 0.203).ConclusionThe effectiveness of palbociclib and endocrine therapy in the treatment of HR‐positive, HER2‐negative mBC in the real‐world setting is similar to the efficacy reported in the PALOMA‐2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.

Longitudinal Trends in Illness Perception and Depression during Adjuvant Breast Cancer Endocrine Therapy: A Prospective Observational Study.

This study aimed to identify the changes in the illness perceptions and depression of women with breast cancer, undergoing AET, at three time points (i.e., before initiating AET, 3 months follow-up, and 12 months follow-up). We investigated the interaction effects of their demographic and clinical characteristics on illness perception changes over time. Furthermore, factors including the patient’s characteristics and illness perceptions associated with depressive symptoms 1 year after starting AET were explored. Illness perception and depressive symptoms were assessed with the brief illness perception questionnaire and the Center for Epidemiologic Studies Depression Scale, in a prospective study of 150 women. The changes in illness perceptions and depression between the three time points were analyzed using repeated measures ANOVA. The factors associated with depressive symptoms were identified using regression analysis. Illness perception improved overall over the 12 months. However, more patients perceived their illness as chronic, experienced more symptoms, and developed negative beliefs that treatment could not control their disease. Patients’ depressive symptoms decreased significantly. Depression at the baseline, cancer stage, and the perception of personal control were highly associated with depression after 12 months. These findings suggest that healthcare providers should offer appropriate interventions to patients, for managing symptoms, having a positive belief that treatment can control their disease, and preventing long-term depressive symptoms.