ER-positive Research Articles

New treatment strategy for early hormone receptor-positive HER2-negative breast cancer: updated results of adjuvant abemaciclib trial in operable and locally advanced breast cancer

Abemaciclib is an oral inhibitor 4 and 6 (CDK4/6). Abemaciclib differs from other drugs in this group in suppression spectrum of cyclin-dependent kinases and is proven to improve survival rates in different treatment lines of metastatic breast cancer. In randomized clinical trials 3rd phase in patients with early hormone-dependent HR+ HER2 negative breast cancer high risk of progression abemaciclib in conjunction with hormone therapy significantly improves invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS). Long- term outcome studies monarchE with 5 – year follow – up of patients showed that abemaciclib adding to ET increases 5-year IDFS from 76 to 83.6% (HR0.680; 95% CI 0.599 to 0.772; p <0.001) and 5-year DRFS from 79.2% to 86.0% (HR0.675; 95% CI 0.588 to 0.774; p <0.001). Adverse events of 3rd degree and higher are registrated in 45.5% of patients in abemaciclib group and in 12,7% in control group and mainly presented by neutropenia (18.6 and 0.7%) and diarrhea (7,6 and 0.1%). Toxicity profile was expected and controlled. The reasonable dose reduction of abemaciclib did not lead to deterioration of long-term treatment result.

Complete response and long-term survival to endocrine monotherapy in a patient with metastatic breast cancer in a low-income country: a case report

BackgroundBreast cancer is the most common cancer in women. Progression-free survival for hormone receptor-positive/human epidermal growth factor receptor-2-negative metastatic breast cancer treated with endocrine therapy in combination with cyclin4/6-dependent kinase is approximately 25 months. This case represents metastatic breast cancer treated with endocrine therapy, leading to long-term survival.Case presentationA 40-year-old Syrian woman diagnosed with hormone receptor-negative breast cancer was treated surgically with adjuvant chemotherapy and radiotherapy. She developed local and nodal recurrences that were hormone receptor-positive, followed by a recurrence of malignant pleural effusion. She was initially treated with chemotherapy and then placed on endocrine therapy with a complete response from 2014 until now. The patient also suffered from adverse events of medications, such as heart failure and osteoporosis, which were treated appropriately.ConclusionThis case demonstrates a long-lasting complete response to metastatic breast cancer with malignant pleural effusion. This shows the validity of endocrine therapy in recurrent hormone receptor-positive breast cancer, especially in countries that cannot afford targeted therapies or genetic tests. It also highlights the necessity for a better understanding of the prognostic and predictive factors.

Breast Cancer: From Etiology to Therapeutic Interventions

Breast cancer, a prevalent malignancy affecting women globally, is characterized by the uncontrolled growth of abnormal cells in the breast tissue with various risk factors such as age, genetic predisposition, hormonal influences, and lifestyle choices, early detection remains paramount for effective treatment. Diagnostic modalities, including mammography, ultrasound, and biopsy, play crucial roles in identifying the disease at its nascent stages. Therapeutic approaches for breast cancer encompass a multidisciplinary strategy, incorporating surgery, radiation therapy, chemotherapy, hormonal therapy, and targeted therapies. Surgical interventions, such as lumpectomy or mastectomy, aim to remove the tumour, while radiation therapy targets residual cancer cells. Chemotherapy utilizes cytotoxic drugs to destroy rapidly dividing cancer cells, and hormonal therapies modulate hormone receptor-positive tumours. Targeted therapies, including monoclonal antibodies and small molecule inhibitors, focus on specific molecular pathways implicated in cancer progression. Advancements in precision medicine have led to the development of personalized therapies tailored to individual patients based on genetic and molecular profiling. Immunotherapy, harnessing the body's immune system to combat cancer cells, emerges as a promising frontier in breast cancer treatment. In this review article, we have studied how breast cancer is evolved and how we can cure it together with the therapies involved in the management of breast cancer.

Survival rate and prognosis of single hormone receptor positive breast cancer.

Survival rate and prognosis of single hormone receptor positive breast cancer.

1814O Breastfeeding in women with hormone receptor-positive breast cancer who conceived after temporary interruption of endocrine therapy: Results from the POSITIVE trial

1814O Breastfeeding in women with hormone receptor-positive breast cancer who conceived after temporary interruption of endocrine therapy: Results from the POSITIVE trial

Experience With Palbociclib in Metastatic Breast Cancer Patients Managed Under a Government Health Scheme at a Cancer Care Center in Southern India.

Introduction According to Globocan 2022, breast cancer ranks number one among the cancers worldwide. South Asian women have a higher incidence comparedto Westerners. Estrogen receptor (ER) and progesterone receptor (PR) positive tumors, termed hormonal receptor-positive tumors, account for most breast cancer presentations. In India, advanced-stage presentations are more common. In metastatic hormone receptor-positive breast cancer, hormonal therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors is the standard treatment. Aim This study aimed to analyze the experience with generic palbociclib provided under the Government Health Scheme for metastatic hormone receptor-positive breast cancer at our institution. Methods This retrospective study was conducted on breast cancer patients admitted to a tertiary carecenter in South India. The data of ER and PR receptor-positive metastatic breast cancer patients who received palbociclib were identified and reviewed using medical records from 2023 to 2024. Results A total of 238 patients were analyzed, of which41 received palbociclib for hormone receptor-positive metastatic breast cancer. The median age was 49 (33-75), with 53.5% (22) of women above 50. Denovo stage IV presentation was observed in 21patients (51.2%), while progression to stage IV disease was noted in 11 patients (26.8%), and stages II and IIIwere noted in nine patients (22%). Invasive ductal carcinoma was the most common histology. All patients were ER-positive, and 38 (92.7%) were PR-positive. About 17 patients (41.5%) had visceral metastasis, and 12 (29.3%) had bone-only metastasis. Local recurrence was seen in six patients (14.6%), and bone with visceral metastasis was seen in another six patients (14.6%). Progression within one year of hormonal therapy initiation was observed in 50% (10) of patients. Among 21 patients with upfront metastasis, nine were treated with prior chemotherapy. All patients were given 125 mg of oral palbociclib. Fatigue was the most common side effect in 34.1% (14), followed by myalgia in 21.9% (9), low hemoglobin levels of less than 8 g/dl in 14.6% (6), and nausea and vomiting in only 9.8% (4) of patients. Conclusion Hormone therapy combined with CDK4/6 inhibitors is the backbone of treatment for metastatic hormone-positive breast cancer. However, in developing countries like India, where most patients come from rural areas, using innovator palbociclib may not be feasible for many. With the availability of generic palbociclib under the Government Health Scheme, patients of metastatic hormone receptor-positive breast cancer will receive the protocol-based treatment.

374P Real-world (Rw) outcomes in patients (pts) with hormone receptor-positive and human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (mBC) treated with chemotherapy (CT) in France and Germany

374P Real-world (Rw) outcomes in patients (pts) with hormone receptor-positive and human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (mBC) treated with chemotherapy (CT) in France and Germany

LBA22 Effects of trastuzumab deruxtecan (T-DXd) vs choice of chemotherapy (TPC) on patient-reported outcomes (PROs) in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer (mBC): Results from DESTINY-Breast06

LBA22 Effects of trastuzumab deruxtecan (T-DXd) vs choice of chemotherapy (TPC) on patient-reported outcomes (PROs) in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer (mBC): Results from DESTINY-Breast06

358P Everolimus or ribociclib in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and circulating tumor cells: Results from DETECT IVa

358P Everolimus or ribociclib in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and circulating tumor cells: Results from DETECT IVa

Populations of Triple Negative and Hormone Receptor Positive HER2 Negative Breast Tumors Share Immune Gene Profiles

Background: Immune therapy has revolutionized the treatment of certain cancers including melanoma and lung cancer. Breast cancer has fewer tumors with high immune infiltrate and Immune Checkpoint Inhibitor (ICI) therapy has shown the most significant responses in the Triple Negative (TN) subtype although roles are emerging in the other subtypes. The presence of Tumor Infiltrating Lymphocytes (TIL) is predictive of response to ICI therapy in metastatic TN and associated with better survival in local TN disease. Hormone Receptor (HR) positive HER2 negative (HR+HER2-) breast tumors do not show improved prognosis with increasing TIL and only a small portion of HR+HER2- tumors respond to ICI in both metastatic and local disease. We therefore sought to identify genetic differences between TN and HR+HER2- tumors to identify how these may contribute to their differences in immune infiltrate. Methods: We contrasted immune-associated gene expression between 119 TN and 475 HR+HER2- breast tumors from The Cancer Genome Atlas (TCGA) and confirmed our findings from 299 TN and 1369 HR+HER2- breast tumors in METABRIC. Results: We found that TN and HR+HER2- tumors can be grouped into immune-high or -low tumors, with both subtypes represented in the immune-high group (40% HR+HER2- tumors of both Luminal A and Luminal B type and 71% TN tumors) in the TCGA. The genes upregulated in the immune-high cluster included GZMB, CXCL9, and IDO1 (Log2FC > 2; Adj. p < 10X10-40). The largest expression difference between the immune-high TN and HR+HER2- tumors was that TN tumors had more abundant Th1 and Th2 CD4+ T cells while HR+HER2- tumors had more abundant fibroblasts (Log2FC > 0.3; Adj p < 10X10-10). Conclusions: Our data suggest that an immune-high signature is not dictated by breast cancer subtype. However, fibroblasts, particularly fibroblast subsets associated with worse outcome, are more abundant in the immune-high HR+HER2- tumors.

Comparing CD10 Expression With the Clinicopathological Features and Hormone Status of Invasive Breast Cancer.

Background Worldwide, female breast cancer is the most common cancer (11.7%), followed by lung (11.4%), colorectal, prostate, and stomach. Breast cancer is the fifth most common cause of cancer-related mortality, with lung cancer being the leading cause. In India, breast and cervical cancers are the two most common cancers among women. This study was undertaken to analyse the expression of CD10 in invasive duct cancer (IDC) and its correlation with the various clinicopathological features and hormone status. Materials and methods This study was conducted in the Department of Pathology, Saveetha Medical College and Hospital on 42 cases of invasive ductal carcinoma - no special type (IDC NST). The clinical and histopathologic parameters such as age, tumor site, tumor size, histologic type, histologic grade, lymph node metastases, lymphovascular invasion, and perineural invasion were assessed in hematoxylin and eosin-stained sections of the tumor tissue along with the hormone status of positivity for ER, PR and Her2Neu. These parameters were subsequently compared with the expression of CD10 in the corresponding slides and statsitical correlation was done using the chi square test. Results The most common age group was more than 40 years, with 41-50 years, and 51-60 years in particular. CD10 was positive in 93% of cases. There was a positive correlation between CD 10 expression and lymphovascular invasion in the study (p-0.006). There was no significant relationship between hormone status and CD10 expression. Conclusion A significant association was seen between CD10 expression and lymphovascular invasion. No relation was found between CD10 and the other parameters such as tumour grade, lymph node metastases, lymphovascular invasion, perineural invasion and hormone status. Further studies are required to explore the potential of CD10 as a prognostic marker for IDC.

304P Impact of estrogen receptor positivity for adjuvant endocrine therapy in luminal T1a/bN0M0 breast cancer: A multi-institutional retrospective observational study

304P Impact of estrogen receptor positivity for adjuvant endocrine therapy in luminal T1a/bN0M0 breast cancer: A multi-institutional retrospective observational study

CHST4 associates with high-abundance immune infiltration in hormone receptor-positive breast cancer.

Hormone receptor-positive breast cancer (HR+ BRCA) with high-risk factors such as lymph node metastasis has a relatively poor prognosis. However, the biological basis of tumor cell migration is still poorly understood, especially as some of the metastatic events occur at an early stage. Here, we identified that carbohydrate sulfotransferase 4 (CHST4), which has an important role in lymphocyte homing, was abnormally down-regulated in HR+ BRCA and associated with lymph node metastasis. By enrichment analysis and immune infiltration evaluation, we predicted the potential ability of CHST4 to enhance immune cell infiltration. Then, IHC staining further demonstrated the contribution of CHST4 to the infiltration abundance of CD8+ T cells and CD4+ T cells in HR+ BRCA. IHC staining of MECA-79 further identified the correlation between CHST4 and sulfated perpheral lymphonode vascular addressin (PNAd). Finally, we demonstrated that CHST4 was connected to increased tumor-immune cell communication by analyzing single-cell sequencing data. In summary, our study provided novel insights into the regulation of HR+ BRCA immune infiltration by CHST4.

Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.

Endocrine therapy is the standard treatment for hormone receptor-positive (HR+) breast cancer (BC). Yet, it is accompanied by treatment-related toxicities, leading to poor treatment adherence, high relapse, and low rates of survival. While pharmacogenomic variants have the potential to guide personalized treatment, their predictive value is inconsistent across published studies. To systematically assess the literature's current landscape of pharmacogenomics of endocrine therapy-related adverse drug effects, systematic searches in MEDLINE, Embase, Cochrane CENTRAL, Google Scholar and PharmGKB databases were conducted. We identified 87 articles. Substantial heterogeneity and variability in pharmacogenomic effects were evident across studies, with many using data from the same cohorts and predominantly focusing on the Caucasian population and postmenopausal women. Meta-analyses revealed Factor V Leiden mutation as a predictor of thromboembolic events in tamoxifen-treated women (p<0.0001). Meta-analyses also found that rs7984870 and rs2234693 were associated with musculoskeletal toxicities in postmenopausal women receiving aromatase inhibitors (p<0.0001 and p<0.0001, respectively). Overall, the current body of evidence regarding the potential role of pharmacogenomics in endocrine therapy-related toxicity in BC remains largely inconclusive. Key concerns include the heterogeneity in toxicity definitions, lack of consideration for genotype-treatment interactions, and the failure to account for multiple testing. The review underscores the necessity for larger and well-designed studies, particularly with the inclusion of premenopausal women and non-Caucasian populations.

Targeted Therapies, Sequencing Strategies, and Beyond in Metastatic Hormone Receptor-Positive Breast Cancer: ASCO Guideline Clinical Insights.

Targeted Therapies, Sequencing Strategies, and Beyond in Metastatic Hormone Receptor-Positive Breast Cancer: ASCO Guideline Clinical Insights.

PIK3CA mutation analysis in circulating tumor cells of patients with hormone receptor positive metastatic breast cancer

In metastatic breast cancer (MBC), blood is a source of circulating tumor cells (CTCs). CTCs may serve as a ‘‘real-time liquid biopsy” as they represent metastatic tumor genetics better than primary tumor. PIK3CA is one of the most important oncogenes in treatment-unresponsive breast cancers. The aim of this study was to detect PIK3CA mutations and hereditary cancer variants in CTCs from MBC patients. Forty-seven blood samples were obtained from 20 MBC patients from at least 1/3 consecutive time points. CTCs were quantified using the CellSearch system and isolated from 11/20 patients with ≥5/7.5 ml CTCs (14/47 blood samples) using the DEPArray system. DNA was extracted and amplified to perform Sanger sequencing on PIK3CA gene. Sequencing revealed a pathogenic PIK3CA mutation in 2/11 (18 %) cases. Subsequently, we evaluated a 26-target hereditary gene panel by Next Generation Sequencing and identified a concomitant pathogenic mutation in the TP53 gene in a patient with a PIK3CA mutation. No pathogenic germline variants were found. Our data support the conclusion that CTCs analysis may be used to identify mutations in patients to identify those more likely to metastasize.

Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer.

Anti-oestrogen-based therapies, often combined with a CDK4/6 inhibitor, are the current standard-of-care first-line therapy for patients with advanced-stage hormone receptor-positive (HR+) breast cancer. Resistance to anti-oestrogen agents inevitably occurs, mediated by oestrogen receptor (ER)-dependent or ER-independent mechanisms that drive tumour progression. Emerging endocrine therapies include, but are not limited to, next-generation oral ER degraders and proteolysis targeting chimeras, which might be particularly effective in patients with ESR1-mutant breast cancer. Furthermore, cancers harbouring driver alterations in oncogenic signalling pathways, including AKT and PI3K, might be susceptible to novel combination strategies involving targeted inhibitors. Next-generation CDK2/4 inhibitors are an area of active clinical investigation, and efforts are ongoing to evaluate the role of sequential CDK inhibition. Approved and emerging antibody-drug conjugates exploiting novel target antigens have also demonstrated promising clinical activity. These novel agents, as well as further identification and characterization of predictive biomarkers, will hopefully continue to improve clinical outcomes, reduce the incidence of toxicities, and limit the extent of overtreatment in this population. In this Review, we describe the evolving treatment paradigm for patients with metastatic HR+ breast cancer in light of the growing armamentarium of drugs and biomarkers that will helpto shape the future therapeutic landscape. These strategies are expected to involve tumour molecular profiling to enable the delivery of precision medicine.

Precision medicine in breast cancer (Review).

Precision medicine in breast cancer is a revolutionary approach that customizes diagnosis and treatment based on individual and tumor characteristics, departing from the traditional one-size-fits-all approach. Breast cancer is diverse, with various subtypes driven by distinct genetic mutations. Understanding this diversity is crucial for tailored treatment strategies that target specific vulnerabilities in each tumor. Genetic testing, particularly for mutations in breast cancer gene (BRCA) DNA repair-associated genes, helps assess hereditary risks and influences treatment decisions. Molecular subtyping guides personalized treatments, such as hormonal therapies for receptor-positive tumors and human epidermal growth factor receptor 2 (HER2)-targeted treatments. Targeted therapies, including those for HER2-positive and hormone receptor-positive breast cancers, offer more effective and precise interventions. Immunotherapy, especially checkpoint inhibitors, shows promise, particularly in certain subtypes such as triple-negative breast cancer, with ongoing research aiming to broaden its effectiveness. Integration of big data and artificial intelligence enhances personalized treatment strategies, while liquid biopsies provide real-time insights into tumor dynamics, aiding in treatment monitoring and modification. Challenges persist, including accessibility and tumor complexity, but emerging technologies and precision prevention offer hope for improved outcomes. Ultimately, precision medicine aims to optimize treatment efficacy, minimize adverse effects and enhance the quality of life for patients with breast cancer.

Breast Cancer in Young Women: Analysis of Incidence, Clinicopathological Profile and Biological Behaviour in a Tertiary Care Institute from South India

Aims and Objectives: There is an increasing incidence of breast cancer in young women and many of these patients are considered to have more aggressive disease biology. The study aimed to find out the demographic profile, clinicopathological profile, and management details in patients under the age of 40 years treated for breast cancer in a tertiary care institute. Materials and Methods: The study retrospectively analysed all the females with biopsy proven breast cancer treated at our oncology department between January 2012 and December 2018. Patients aged below 40 years were stratified from the total breast cancer patients. The data related to demographic profile, clinical staging, pathological staging, hormonal status and treatment details were collected from medical records for the patients and analysed. Results: A total of 1056 biopsy proven breast cancer patients were treated during the study period. Out of which, the breast cancer patients under the age of 40 years were 161 (15.24%). The mean age at presentation was 33 years. Maximum patients were between the age group of 35 to 40 years (45.4%). Most of the patients were presented with Stage III (44%). Infiltrating Ductal Carcinoma, Grade II was the most common histologic type and grade. ER (Oestrogen Receptor) positivity seen in 49% of patients and PR (Progesterone receptor) Positivity in 49.7% and 46% had HeR2 Positivity. Conclusion: Our study concludes that the incidence of breast cancer patients under the age of 40 years is increasing. These patients tend to have higher grade tumours, Her2 Positive and triple-negative breast cancer. Young patients presenting with breast lumps should undergo all standard screening and diagnostic investigations must be carried out for early diagnosis and proper interventions.

Profiling the Cardiovascular Toxicities of CDK4/6 Inhibitors: A Real-World Pharmacovigilance Study.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are approved for the treatment of human epidermal growth factor receptor 2 (HER-2)-negative, hormone receptor-positive breast cancer. The cardiovascular toxicity of CDK4/6 inhibitors is not well understood. This study aims to profile the cardiac events associated with CDK4/6 inhibitors. Reports from 2015Q1 to 2024Q1 were obtained from the FDA Adverse Event Reporting System (FAERS). Reports identifying palbociclib, ribociclib, and abemaciclib as the primary suspect were examined for cardiovascular toxicity, including hypertension, cardiac failure, cardiomyopathy, arrhythmia, myocardial infarction, and myocarditis. Signal detection was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). A total of 69,139 reports were analyzed. The median time to adverse events was 69 days (interquartile range [IQR], 18-260 days). Of these, 2065 reports documented cardiac adverse events. Ribociclib and QT prolongation were re-confirmed as a signal (PRR 8.43, ROR 8.65, IC025 2.86). Hypertension and cardiac failure were the most frequently reported cardiovascular toxicities. This study demonstrates that the use of CDK4/6 inhibitors is associated with cardiovascular adverse events, such as heart failure and hypertension. Further research is needed to understand the mechanisms and risk factors contributing to the cardiovascular toxicity of CDK4/6 inhibitors.