Endocrine Therapy For Breast Cancer Research Articles

Tamoxifen induced ovarian hyperstimulation during hormonal therapy for breast cancer

Background: Adjuvant endocrine therapy is an integral component of care for endocrine-dependent breast cancer. Tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenone were not clarified.

Primary hormonal therapy for breast cancer in patients aged over 80 years: single unit outcomes

Background. Patients with oestrogen receptor (ER)-positive breast cancer who wish to avoid surgery or those who are considered unsuitable for surgery may be treated with primary hormonal therapy. Elderly patients are more likely to present with more advanced cancers but are less likely to undergo an operation, 39% vs. 90% of those under 50. Recent studies advocate surgery for all patients with operable tumours except those with significant medical co-morbidities. We retrospectively assessed the number of patients treated with this method to determine their outcomes.

Living longer and living better: breast cancer endocrine therapy

It was with great enthusiasm that we have seen the results published by Francis et al concerning the adjuvant hormone therapy. In the SOFT study (Suppression of Ovarian Function With...

Predicting resistance to endocrine therapy in breast cancer: It's time for epigenetic biomarkers (Review)

Notwithstanding the marked progress in breast cancer (BC) management, it still constitutes the most common malignancy in women and a major cause of morbidity and mortality, thus remaining a major health issue worldwide. Most BC cases are hormone receptor (HR) positive (luminal A or B molecular subtypes) and endocrine treatment (ET) is an important therapeutic modality at all disease stages. Nevertheless, despite substantial improvements in BC patient outcome, effectiveness of ET is limited, as up to 40% of patients eventually relapse or progress and endocrine resistant BC has a less favorable prognosis and constitutes a therapeutic challenge. The biological mechanisms underlying endocrine resistance are, however, still poorly understood. In this review, we focused on data regarding the main epigenetic mechanisms associated with the development of endocrine treated‑resistant BC described so far, including alterations in DNA methylation, non‑coding RNAs, chromatin remodeling, post‑translational histone modifications and histone variants. Notably, specific epigenetic alterations have been characterized in this subset of breast tumors and may be of clinical value for individualized patient management in the future.

Adherence to adjuvant endocrine therapy in postmenopausal breast cancer patients: A 5-year prospective study

PurposeAdjuvant endocrine therapy (ET) in breast cancer reduces recurrence risk and increases overall survival. The aim of the study was to quantify non-adherence and discontinuation to ET in postmenopausal women with breast cancer, and identify possible clinical or social risk factors. MethodsWomen with hormone-receptor positive breast cancer (N = 138), mean age 58 (SD 9.3) years, filled in 4 questionnaires within 1–12, 24, 36 and 48–60 months after surgery; Subjective Health Complaints Inventory (SHC), Functional Assessment of Cancer Therapy-Social Support Subscale (FACT-ES), and Quality of Patient Information Questionnaire (QPI). Adherence to Tamoxifen (Tam) or Aromatase Inhibitors (AI) was examined using the self-reported Morisky Medication Adherence Scale (MMAS-8) and data from the Norwegian Prescription Database (NorPD). Kaplan-Meier curves and Cox proportional hazards regression models estimated adherence to ET. ResultsThe estimate of discontinued ET within 60 months was 38%. Self-reported discontinuation was 7% compared with 25% from the NorPD. Being overweight or obese were significantly time dependent factors predictive for discontinuing ET, p = 0.025. ConclusionCloser follow-ups, tailor-made information about the proven benefits of ET, and keeping a normal body mass index (BMI) may improve adherence to ET in postmenopausal women with breast cancer.

Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting.

Background:The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT).Methods:Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered.Results:The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature (p = 0.011). In models of Ki-67 reduction, ‘luminal B’ subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant (p < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival (p = 0.027) and overall survival (p = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades (p < 0.05 for both).Conclusions:We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms.

The potential influence of breast cancer estrogen receptors' distribution on active DNA demethylation.

Alterations in DNA methylation may cause disturbances in regulation of gene expression, including drug metabolism and distribution. Moreover, many cancers, including breast cancer, are characterized by DNA hypomethylation and a decreased 5-hydroxymethylcytosine level. The abnormal cell growth found in breast carcinoma might be the result of impaired up-regulation of breast cancer receptors. Receptors’ expression in breast cancer determines clinical outcome, and it is possible that they lead to different DNA methylation patterns. Excessive steroid exposure can affect DNA methylation by promoting demethylation of CpG islands in promoter regions of genes, and hence may have an impact on promotion and progression of breast cancer cells. Tamoxifen, as a leading drug in breast cancer hormone therapy, has an ability to act like estrogen or antiestrogen depending on the type and localization of the breast cancer receptor. Further studies are needed to determine whether tamoxifen, similarly to steroids, may evoke changes in methylation pattern.

The impact of state parity laws on copayments for and adherence to oral endocrine therapy for breast cancer.

Adherence to endocrine therapy for breast cancer is often inadequate, in part because of out-of-pocket costs for medication. Numerous states have enacted parity laws to limit patient cost-sharing for oral anticancer drugs. The objective of this study was to estimate the impact of these laws on patient copayments for and adherence to oral endocrine therapy for breast cancer. Administrative health insurance claims data from 2007 to 2014 derived from a US health care database were used to identify female patients aged 18 to 64 years with invasive cancer or ductal carcinoma in situ of the breast who initiated endocrine therapy and were enrolled in fully insured health plans in states that either enacted parity legislation between 2008 and 2013 or had not yet enacted such legislation by 2015. Differences-in-differences analysis was used to compare copayments for and adherence to endocrine therapy during the 1-year period before and after each year of legislation enactment. In total, 6900 individuals who received 7778 unique drug therapy courses were identified. Parity legislation was associated with significant decreases in the 25th percentile of copayments for anastrozole of $4.39 (95% confidence interval [CI], -$4.52 to -$4.26; P < .001) and for exemestane of $3.08 (95% CI, -$4.80 to -$1.35; P < .001). The median copayment for exemestane decreased by $10.25 (95% CI, -$12.61 to -$7.89; P < .001). A higher median monthly copayment was significantly associated with a greater risk of medication nonadherence (adjusted risk ratio, 1.006 per dollar increase; P < .001). Parity laws had a modest effect on lowering the cost of anastrozole and exemestane, but more focused efforts to limit out-of-pocket costs for endocrine therapy may have a greater impact on medication adherence.

Higher symptom burden is associated with lower function in women taking adjuvant endocrine therapy for breast cancer.

To explore the impact of symptoms on physical function in women on adjuvant endocrine therapy for breast cancer. Eligible women were postmenopausal, had hormone receptor positive, stage I-IIIA breast cancer, completed surgery, chemotherapy, radiation, and on adjuvant endocrine therapy. At a routine follow-up visit, women (N = 107) completed standardized symptom measures: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy Neurotoxicity scales. Two performance measures assessed function: grip strength (Jamar dynamometer; n = 71) and timed get-up-and-go (TUG; n = 103). Analyses were performed with an overall symptom composite score. Correlations and multiple linear regression analyses were performed to test adverse effects on physical function. The mean age was 64 years (range 45-84), 81% white, 84% on an aromatase inhibitor, and on endocrine therapy for mean 35 months (range 1-130 months). Dominant hand grip strength was inversely correlated with symptom composite scores (r = -0.29, p = .02). Slower TUG was positively correlated with higher Charlson comorbidity level (r = 0.36, p < .001) and higher symptom composite scores (r = 0.24, p = .01). In multivariate analyses, weaker dominant and non-dominant hand grip strength were significantly associated with greater symptom composite scores (β = -0.27, t = 2.43, p = .02 and β = -0.36, t = 3.15, p = .003, respectively) and slower TUG was associated with higher symptom composite scores (β = 0.18, t = 1.97, p = .05). Higher symptom burden is associated with worse physical function, as measured by hand grip strength and TUG. Further study to determine the impact of endocrine therapy and its side effects on function is warranted.

Tamoxifen Sensitizes Gallbladder Cancer to Cisplatin Resistance by Impaired Glucose Metabolism via Activation of AMPK Signaling

Purpose: Gallbladder cancer (GBC) is the leading malignancy of biliary system showing refractory chemoresistance to current first-line drugs. Growing epidemiological evidences have established that the incidence of GBC exhibits significant gender predominance with females 2-3 fold higher than males, suggesting estrogen/estrogen receptors (ERs) signaling might be a critical driver of tumorigenesis in gallbladder. This study aims to evaluate the antitumor activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model. Experimental Design: The antitumor activity of TAM alone or with cisplatin was examined using cell viability, apoptosis and in vivo models. Results: Increased ERɑ expression was found in GBC tissues and predicted poor clinical outcomes. TAM was showed effective against a variety of GBC cell lines. Mechanical investigations revealed that TAM enabled potent reactive oxygen species (ROS) production by reduced nuclear factor (erythroid-derived 2)-like 2(Nrf2) expression and its target genes, leading to the activation of Adenosine Monophosphate Activated Protein Kinase (AMPK), which subsequently induced impaired glycolysis and survival advantages. Moreover, the inhibitory effect of TAM for GBC cells was remarkably attenuated by N-acetyl-L-cysteine (NAC) and AMPK inhibitor, suggesting ROS/AMPK axis was required for TAM tumor-suppressive function. Notably, TAM was demonstrated to sensitize GBC cells to cisplatin (CDDP) both in vitro and in vivo. In agreement with these findings, elimination of estrogens by ovariectomy in nude mice prevented CDDP resistance. Conclusions: These results provide basis for TAM-mediated chemosensitivity for GBC and shed novel light on the potential application of endocrine therapy for patients with GBC. Funding Statement: This work was supported by National Science Foundation of China (81472240，81272748 and 81072011)，Science and Technology Commission of Shanghai Municipality (16411952700, 10411955400, and 09411960800), Program for Outstanding Academic Leader of Shanghai (2016, JW) Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The collection and analysis of patient samples were approved by the Ethical Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine, and written informed consent was obtained from all patients. All methods and experiments were carried out in accordance with the approved guidelines and regulations. Animal maintenance and experimental procedures were strictly performed following the guidelines of the Animal Care and Use Committee of Shanghai Jiao Tong University and approved by IACUC committee of Shanghai Jiao Tong University

Tamoxifen mechanically reprograms the tumor microenvironment via HIF‐1A and reduces cancer cell survival

The tumor microenvironment is fundamental to cancer progression, and the influence of its mechanical properties is increasingly being appreciated. Tamoxifen has been used for many years to treat estrogen‐positive breast cancer. Here we report that tamoxifen regulates the level and activity of collagen cross‐linking and degradative enzymes, and hence the organization of the extracellular matrix, via a mechanism involving both the G protein‐coupled estrogen receptor (GPER) and hypoxia‐inducible factor‐1 alpha (HIF‐1A). We show that tamoxifen reduces HIF‐1A levels by suppressing myosin‐dependent contractility and matrix stiffness mechanosensing. Tamoxifen also downregulates hypoxia‐regulated genes and increases vascularization in PDAC tissues. Our findings implicate the GPER/HIF‐1A axis as a master regulator of peri‐tumoral stromal remodeling and the fibrovascular tumor microenvironment and offer a paradigm shift for tamoxifen from a well‐established drug in breast cancer hormonal therapy to an alternative candidate for stromal targeting strategies in PDAC and possibly other cancers.

Sphingosine kinase 1 activation by estrogen receptor α36 contributes to tamoxifen resistance in breast cancer

In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, nongenomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors, leading to important breast cancer signaling. However, the E2 receptor responsible for SphK1 activation has not yet been identified. Here, we demonstrate in triple-negative breast cancer cells, which lack the canonical ERα66 but express the novel splice variant ERα36, that ERα36 is the receptor responsible for E2-induced activation of SphK1 and formation and secretion of S1P and dihydro-S1P, the ligands for S1PRs. Tamoxifen, the first-line endocrine therapy for breast cancer, is an antagonist of ERα66, but an agonist of ERα36, and, like E2, activates SphK1 and markedly increases secretion of S1P. A major problem with tamoxifen therapy is development of acquired resistance. We found that tamoxifen resistance correlated with increased SphK1 and ERα36 expression in tamoxifen-resistant breast cancer cells, in patient-derived xenografts, and in endocrine-resistant breast cancer patients. Our data also indicate that targeting this ERα36 and SphK1 axis may be a therapeutic option to circumvent endocrine resistance and improve patient outcome.

Switching endocrine therapy in breast cancer as a strategy for musculoskeletal symptoms, tolerance, and adherence.

192 Background: Adverse effects of endocrine therapy (ET), especially musculoskeletal symptoms (MSS), represent the major cause of treatment discontinuation in breast cancer (BC) patients, resulting in increased risk of recurrence. Aromatase inhibitors (AI), the mainstay of ET, are associated with a high incidence of MSS such as arthralgia and myalgia. The hypothesis of whether switching ET subclass improves adherence and symptoms was tested. Methods: We conducted a retrospective single site chart review of female patients with nonmetastatic BC, who were seen at Cancer Clinic from January to June of 2017. All patients received AI as a first choice of adjuvant ET; those with disease recurrence while on ET were excluded. We collected data on baseline health, adherence and discontinuation rate, as well as whether switching to a different ET agent (another AI or tamoxifen) was attempted. The subsequent compliance and symptomatology after switching were assessed. Results: 483 eligible patients were identified and divided into 4 groups based upon adherence: 354 (73.3%) were found to be compliant with AI without interruption, 109 (22.5%) switched to a different ET and remained compliant (≥ 1 switch), 16 (3.3%) eventually discontinued ET despite attempting ≥ 1 switch, and 5 patients (1.0%) stopped treatment without a switch. On comparison of the different groups, patients who permanently discontinued ET were more likely to be elderly and have preexisting musculoskeletal condition. MSS was found to be the single most common cause for AI intolerance (105 patients, 81.4%). The median time to switch was 6.3 months (0.3-63.9). Among the compliant switchers, most needed only 1 switch (79) but there were patients who required 2 or 3 switches (23 and 6, respectively). Majority of patients switched from anastrozole to exemestane (84, 51.8%). Significant improvement in symptoms after the switch was reported by 73.3% of patients. Conclusions: Switching between different ET subclasses is an effective treatment strategy to alleviate side effects and enhance adherence to ET. A higher compliance rate of 95.8% was observed in our study compared to a national average estimated at &lt; 80%.

Impact of preexisting mental illness on breast cancer endocrine therapy adherence.

Patients with estrogen receptor positive (ER+) breast cancer are often non-adherent to endocrine therapies, despite clear survival benefits. We utilized a nationally representative cancer cohort to examine the role of specific mental illnesses on endocrine therapy adherence. Using the SEER-Medicare database, we included 21,894 women aged 68+ at their first surgically treated stage I-IV ER+ breast cancer during 2007-2013. All had continuous fee-for-service Medicare Parts A and B for 36+ months before, 18+ months after diagnosis, and continuous PartD for 4+ months before, 18+ after diagnosis. Mental illness was defined as occurring in the 36 months prior to cancer onset. We analyzed endocrine therapy adherence, initiation, and discontinuation using longitudinal linear and Cox regression models. Unipolar depression (11.0%), anxiety (9.5%), non-schizophrenia psychosis (4.6%), and dementias (4.6%) were the most prevalent diagnoses. Endocrine therapies were initiated by 80.0% of women. Among those with at least one year of use, 28.0% were non-adherent (< 0.80 adherence, mean = 0.84) and 25.7% discontinued. Patients with dementia or bipolar depression/psychotic/schizophrenia disorders had lower adjusted initiation probabilities by year one of follow-up, versus those without these diagnoses [0.74 95% CI (0.73-0.74) and 0.73 (0.72-0.73), respectively, reference 0.76 (0.76-0.77)]. Patients with substance use or anxiety disorders less frequently continued endocrine therapy for at least one year, after adjustment, [0.85 95% CI (0.85-0.86) and 0.88 (0.87-0.88), respectively, reference 0.90 (0.89-0.90)]. Patients with substance use disorders had 2.3% lower adherence rates (p < 0.001). Nearly one-quarter of female Medicare beneficiaries have diagnosed mental illness preceding invasive breast cancer. Those with certain mental illnesses have modestly reduced rates of initiation, adherence, and discontinuation and this may help define patients at higher risk of treatment abandonment. Overall, endocrine therapy adherence remains suboptimal, unnecessarily worsening recurrence and mortality risk.

18F-FLUOROESTRADIOL PET/CT IN DIFFERENTIAL DIAGNOSIS OF LUNG LESIONS IN BREAST CANCER PATIENTS: CASE REPORTS

Background. Breast cancer is the second most common cancer worldwide. Despite significant advances in breast cancer treatment, more than 50 % of patients develop recurrence following completion of treatment. If there is a suspicion of disease progression, the differential diagnosis of metastatic tumor and non-metastatic lesion using the standard imaging methods can be difficult. A modern approach to the detection and assessment of the extension of recurrent disease is individual evaluation of the biological characteristics of the tumor, including determination of the status of estrogen receptors with the goal of adequate treatment. PET/CT with 18F-fluoroestradiol in patients with hormone-dependent breast cancer can be used to determine the expression of estrogen receptors (RE) in tumor tissue and assess the presence of receptor-positive metastases throughout the body in a single study. Case description. We report the cases of 55-year-old and 57-year-old women with hormone-dependent breast cancer after standard treatment (surgery, radiation therapy and hormone therapy). During hormone therapy, lung lesions were detected in both patients. To assess the activity of these lesions, 18F-fluoroestradiol PET/CT was used. In the first case, a low uptake of 18F-FDG was observed. In the other case, no18F-FDG uptake was found. Given that both patients had hormone-dependent breast cancer, it was decided to perform PET/CT with 18F-fluoroestradiol (18F-FES) to evaluate the expression of ER. In the first case, the 18F-FES uptake was detected in all lesions that indicated the evidence of metastases. Histological examination confirmed the evidence of metastatic tumor. In the second case, no uptake of 18FFES was detected in the foci and the patient was followed-up for 6 months. Computed tomography showed decrease in the size of lesions.Conclusion. The use of 18F-FES PET/CT can be an important diagnostic tool for detection of disease progression in patients with hormone-dependent breast cancer. In case of detection of positive foci on 18F-FES PET/CT scans, hormone therapy for breast cancer can be administered without invasive procedures for verifying the diagnosis.

Topical Estrogen Prescription Fill Rates for Women With a History of Breast Cancer Who Are Taking Hormone Therapy

To evaluate how often women with a history of breast cancer who are taking hormone therapy (HT) filled prescriptions for topical estrogens and whether this frequency varied over time and by type of HT used. We performed a retrospective cohort study using medical and outpatient drug claims from a large commercial claims database for the years 2010-2015. Women younger than age 65 years taking HT for breast cancer were classified as users of 1) tamoxifen only, 2) aromatase inhibitor(s) only, or 3) any other or multiple HTs. Our outcome variable was filling a prescription for topical estrogen in a given year. We used multivariable logistic regression models estimated with generalized estimating equations to determine whether the fill rate varied over time and by HT category adjusting for age, receipt of surgical or radiation treatment, types of outpatient health care provider visits, and comorbidities. We identified 352,118 records from 176,012 unique patients (mean age 54.3 years, range 18-64 years) who met eligibility criteria. Aromatase inhibitors were used more commonly (56.0% of patient-years) than tamoxifen (38.8%). Overall, 3.0% (range 2.9-3.1%) of women filled any topical estrogen prescription in a given calendar year. More than half of filled topical estrogen prescriptions were for tablets (57.0%) with the remainder for creams (25.8%) and rings (17.3%). In adjusted analyses, the fill rate for women taking tamoxifen was significantly less (2.4%; 95% CI 2.3-2.5%) than for women taking aromatase inhibitors (3.3%; 95% CI 3.2-3.4%). There was a small but statistically significant increase in fill rates across years (odds ratio 1.03, 95% CI 1.02-1.04). A small proportion of women with a history of breast cancer who were taking HT filled a topical estrogen prescription, with significant differences by type of HT. More evidence is needed to inform national guidelines regarding safety and appropriate use of topical estrogens in this patient population.

Cancer information needs according to cancer type: A content analysis of data from Japan's largest cancer information website.

The provision of information about cancer is an important aspect of cancer care. Cancer information provided online is expected to meet the needs of information seekers. Whether information needs vary according to tumor site is largely unknown. We aimed to examine similarities and differences in informational needs by cancer type. Data were collected using a questionnaire administered on Japan's largest cancer information website, “Ganjoho service”. A total of 2782 free descriptive responses in the period from April 2012 to December 2017 were analyzed using text-mining software. We identified the top 10 informational need contents, in order of appearance frequency, for eight tumor sites: gastric, colorectal, esophageal, lung, pancreatic, breast, cervical, and prostate cancer. Frequent information needs common to all tumor sites included symptoms, disease stages, treatments, chance of cure, recovery, metastasis, and recurrence. A need for information about diet, pain, side effects of treatments, complementary and alternative medicine was frequent for some tumor sites. Tumor site-specific information should include the following, according to cancer type: information of scirrhous carcinoma for gastric cancer; unusual feces for colorectal cancer; lung X-ray images for lung cancer; early detection for pancreatic cancer; adenocarcinoma, sexual activity, pregnancy, and childbirth for cervical cancer; breast conservation or reconstruction and triple negative cancer for breast cancer; test values and diagnosis and urinary problems for prostate cancer; and hormone therapy for breast and prostate cancer. Cancer information provided online should meet these frequent informational needs, considering similarities and differences of the information required according to tumor site.

31. Neoadjuvant Endocrine Therapy in Breast Cancer Up-Regulates the Cytotoxic Drug Pump ABCG2/BCRP, and May Lead to Resistance to Subsequent Chemotherapy

Background: Neoadjuvant endocrine therapy (NAET) for breast cancer is utilised to down-stage tumours, thereby increasing rates of breast conserving surgery. However, little is known about how NAET impacts on response to subsequent adjuvant therapies. Here, we investigate the relevance of expression of the xenobiotic transporter ABCG2/BCRP, a gene/protein associated with chemoresistance, in the context of NAET and particularly with reference to subsequent chemotherapy treatment after NAET.

1601. Neoadjuvant Endocrine Therapy in Breast Cancer Up-Regulates the Cytotoxic Drug Pump ABCG2/BCRP, and May Lead to Resistance to Subsequent Chemotherapy

1601. Neoadjuvant Endocrine Therapy in Breast Cancer Up-Regulates the Cytotoxic Drug Pump ABCG2/BCRP, and May Lead to Resistance to Subsequent Chemotherapy

Breast cancer in young patients. Peculiarities of prognosis and adjuvant hormone therapy (a literature review)

Breast cancer (BC) keeps being the most predominant malignant disease in women. In recent years, a trend towards “rejuvenescence” of the disease has been observed that affects its features. Despite modern methods of diagnosis and complex treatment used in young patients, survival in this age group are inferior that’s associated with biological and morphological peculiarities of BC in young age. Gradually are being collected data according to what age might be an independent factor exacerbating prognosis. For BC patients younger 40 years, various aspectsof hormone therapy remain ambiguous: prolonged tamoxifen use, aromatase inhibitors prescription, ovarian function suppression, a role of chemotherapy-induced amenorrhea on prognosis. The issue of appropriate, personalized adjuvant hormone therapy of BC is complex and heterogenous that requires a necessity to further conduct international randomized trials.