Systematic review and meta-analysis of endometrial thickening during endocrine therapy combined with Chinese herbal medicine intervention after breast cancer surgery

Objective:To systematically evaluate the endometrial thickening and Chinese herbal medicine intervention effects during endocrine therapy following breast cancer surgery.Methods:Computerized searches were performed on CNKI,CBM,Wanfang,VIP,Pub Med,Embase,and Cochrane to gather randomized controlled trials(RCTs)of endometrial thickening combined with Chinese herbal medicine intervention during endocrine therapy after breast cancer surgery.The meta analysis is done using Rev Man 5.4,and the retrieval range is from the database's creation to January 2023.Results:There were 710 patients enrolled in a total of 12 RCTs.The results of Meta-analysis were as follows:combined with Chinese herbal medicine treatment for 3 months of endometrial thickness(MD=-1.12,95%CI[-1.47,0.77],P<0.00001);6 months endometrial thickness(MD=-1.90,95%CI[-2.38,-1.42],P<0.00001);endometrial thickness at 12 months(MD=-2.24,95%CI[-2.96,-1.52],P<0.00001);modified Kupperman score(MD=-10.45,95%CI[-19.10,-1.80],P=0.02);TCM syndrome score(SMD=-1.53,95%CI[-1.84,-1.22],P<0.00001);KPS score(MD=3.75,95%CI[2.81,4.68],P<0.00001);there was no significant difference in CA153,CEA,FSH and E2 between the two groups.Conclusion:After breast cancer surgery,endocrine therapy combined with Chinese herbal medicine can significantly lessen endometrial thickening and enhance patient quality of life.

Clinical value of next-generation sequencing in guiding decisions regarding endocrine therapy for advanced HR-positive/HER-2-negative breast cancer

Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2(HER-2)-negative metastatic breast cancer patients.Methods: In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy;2) estrogen receptor 1(ESR1) mutation preferred fulvestrant;3) HER-2 mutations preferred pyrotinib;and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival(PFS), and the secondary outcome measure was overall survival(OS).Results: In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio(HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group(P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group(P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 mutation.Conclusions: The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing(NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.

Updates in endocrine therapy for metastatic breast cancer

Endocrine therapy(ET)remains the mainstay of treatment for steroid hormone receptor-positive,human epidermal growth factor 2(HER2)-negative metastatic breast cancer(MBC).Tumor resistance to hormone therapy has led to the development of novel endocrine drug combinations,transforming the landscape of MBC management.The options for ET are expanding,with promising agents in the pipeline.Although MBC remains incurable,many patients can enjoy years of survival with good quality of life by cycling through the many available agents.With the plethora of available agents and rapid approvals,clinicians look to evidencebased guidelines to assist in treatment selection to maximize patient well-being.In this review,we provide a contemporary review of the advances in ET and a suggested algorithm to guide clinicians in daily management of patients with hormone receptor-positive,HER2-negative MBC.We will discuss landmark trials and highlight their impact in reshaping treatment approaches.Finally,we will provide a glimpse into advances on the horizon and the promise they bring to improve outcomes in patients with advanced breast cancer.

Evaluation of endocrine therapy combined with intensity modulated radiation therapy in patients with advanced prostate cancer

Objective The aim of this study was to study the effect of endocrine therapy combined with intensity-modulated radiation therapy in patients with advanced prostate cancer.Methods The clinical data of 231 patients with advanced prostate cancer treated with radiotherapy in our hospital from May 2010 to March 2018 were collected.A total of 135 patients were treated with endocrine therapy combined with intensity-modulated radiotherapy,and 96 patients were treated with intensity-modulated radiotherapy only because of drug allergy,serious adverse reactions,and economic reasons.Two months after the end of the treatment,the short-term curative effect was evaluated using imaging reexamination.The total prostate-specific antigen(TPSA)and free prostate-specific antigen(FPSA)were detected before and 2 months after the end of the treatment.All patients were followed up for at least 3 years,and the metastasis-free survival rate and cumulative survival rate of the two groups were calculated.Results The remission rates(RRs)of the observation and control groups were 64.45%and 46.87%,respectively;the difference was not statistically significant(P>0.05);however,the efficacy distribution of the endocrine therapy combined with intensity-modulated radiotherapy group was significantly better than that of the intensity-modulated radiotherapy group(P<0.05).There was no significant difference in clinical efficacy between the two groups in different TNM stages and Gleason grades.After treatment,the levels of TPSA and FPSA were significantly decreased compared with those before treatment;however,the decrease in the endocrine therapy combined with the intensity-modulated radiation therapy(IMRT)group was significantly higher than that in the IMRT group(P<0.05).Although there were no significant differences in the 1-year and 3-year cumulative survival rates between the two groups,the 1-year and 3-year metastasis-free survival rates of the endocrine therapy combined with the IMRT group were 60%and 38.17%,respectively,which were significantly higher than those of the IMRT group(37.5%and 20.83%,P<0.05).Conclusion Endocrine therapy combined with IMRT significantly improved the clinical efficacy of advanced prostate cancer,reduced PSA(prostate specific antigen)levels,and improved the metastasis-free survival rates.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer

Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

Endocrine therapy combined with targeted therapy in hormone receptor-positive metastatic breast cancer

Increasing numbers of targeted drugs are used in hormone receptor(HR)-positive metastatic breast cancer(MBC)to overcome or delay resistance to endocrine therapy.This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC.From the“AI(aromatase inhibitor)era”represented by aromatase inhibitors,we have gradually entered the“post-AI era”represented by fulvestrant.Under the guidance of research on the molecular mechanism of endocrine therapy resistance,the“combination of endocrine therapy and targeted therapy”era is approaching.The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors,histone deacetylase inhibitors,and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)pathway,providing new strategies for HR-positive MBC.Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.

A Promising Predictor of the Efficacy of Endocrine Therapy for Breast Cancer: 14-3-3-zeta

Objective 14-3-3-zeta protein has been found to be associated with survival signaling in cancer.However,prognostic value and the predictive effect of its gene expression for determining the efficacy of endocrine therapy in breast cancer are unclear.Methods The differential 14-3-3-zeta gene expression between cancer and normal tissue was assayed using ONCOMINE database analysis.The correlation between 14-3-3-zeta gene and proliferative/metastasis-associated genes was analyzed using Breast Cancer Gene-Expression Miner v4.1(bc-Gen Ex Miner v4.1).The prognostic value of its expression in breast cancer was analyzed using bc-Gen Ex Miner v4.1 and Kaplan-Meier Plotter.Results The 14-3-3-zeta gene expression was elevated in breast cancer tissue compared with normal breast tissue,which was higher in invasive ductal breast cancer than in ductal breast cancer in situ.It was also positively correlated with the degree of malignancy and the clinical stage of breast cancer and with some proliferative genes.A high level of 14-3-3-zeta expression was predictive of shorter relapse-free survival(RFS)in ER-positive but not ER-negative breast cancer.Further analysis showed the association of high 14-3-3-zeta expression and a shorter RFS in endocrine therapy or tamoxifen-only-treated population,regardless of whether chemotherapy had been used.Conclusion 14-3-3-zeta gene expression is upregulated and associated with a relatively high degree of malignancy and late clinical stage in breast cancer.It is a promising prognostic factor for ER-positive breast cancer and a predictor of the efficacy of endocrine therapy.

Advances in endocrine and targeted therapy for hormone-receptorpositive,human epidermal growth factor receptor 2-negative advanced breast cancer

Nearly 70%of breast cancer(BC)is hormone-receptor(HR)-positive,human epidermal growth factor receptor 2(HER2)-negative,and endocrine therapy is the mainstay of treatment for this subtype.However,intrinsic or acquired endocrine resistance can occur during the endocrine treatment.Based on insights of endocrine resistance mechanisms,a number of targeted therapies have been and continue to be developed.With regard to HR-positive,HER2-negative advanced BC,aromatase inhibitor(AI)is superior to tamoxifen,and fulvestrant is a better option for patients previously exposed to endocrine therapy.Targeted drugs,such as cyclindependent kinases(CDK)4/6 inhibitors,mammalian target of rapamycin(mTOR)inhibitors,phosphoinositide-3-kinase(PI3K)inhibitors,and histone deacetylase(HDAC)inhibitors,play a significant role in the present and show a promising future.With the application of CDK4/6 inhibitors becoming common,mechanisms of acquired resistance to them should also be taken into consideration.

Can cyclin-dependent kinase 4/6 inhibitors convert inoperable breast cancer relapse to operability? A case report

BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.

Insights into breast cancer phenotying through molecular omics approaches and therapy response

Breast cancer is the most common cancer in the world.Despite advances in early detection and understanding of the molecular bases of breast cancer biology,approximately 30%of all patients with early-stage breast cancer have metastatic disease.Breast cancers are comprised of molecularly distinct subtypes that respond differently to pathway-targeted therapies and neoadjuvant systemic therapy.However,no tumor response is observed in some cases and development of resistance is most commonly seen in patients with heterogeneous breast cancer subtype.To offer better treatment with increased efficacy and low toxicity of selecting therapies,new technologies that incorporate clinical and molecular characteristics of intratumoral heterogeneity have been investigated.This short review provides some examples of integrative omics approaches(genome,epigenome,transcriptome,immune profiling)and mathematical/computational analyses that provide mechanistic and clinically relevant insights into underlying differences in breast cancer subtypes and patients’responses to specific therapies.

Metabolic reprogramming as an emerging mechanism of resistance to endocrine therapies in prostate cancer

Prostate cancer(PCa)is the second leading cause of cancer-related death in the US.Androgen receptor(AR)signaling is the driver of both PCa development and progression and,thus,the major target of current in-use therapies.However,despite the survival benefit of second-generation inhibitors of AR signaling in the metastatic setting,resistance mechanisms inevitably occur.Thus,novel strategies are required to circumvent resistance occurrence and thereby to improve PCa survival.Among the key cellular processes that are regulated by androgens,metabolic reprogramming stands out because of its intricate links with cancer cell biology.In this review,we discuss how cancer metabolism and lipid metabolism in particular are regulated by androgens and contribute to the acquisition of resistance to endocrine therapy.We describe the interplay between genetic alterations,metabolic vulnerabilities and castration resistance.Since PCa cells adapt their metabolism to excess nutrient supply to promote cancer progression,we review our current knowledge on the association between diet/obesity and resistance to anti-androgen therapies.We briefly describe the metabolic symbiosis between PCa cells and tumor microenvironment and how this crosstalk might contribute to PCa progression.We discuss how tackling PCa metabolic vulnerabilities represents a potential approach of synthetic lethality to endocrine therapies.Finally,we describe how the continuous advances in analytical technologies and metabolic imaging have led to the identification of potential new prognostic and predictive biomarkers,and non-invasive approaches to monitor therapy response.

Advances in medical treatment of breast cancer in 2022

Breast cancer has replaced lung cancer as the most common malignancy worldwide.The 5‐year survival rate of breast cancer has reached 90%.Systemic treatment of breast cancer has developed into a mature system including chemotherapy,targeted therapy,endocrine therapy and immunotherapy.This article summarizes the annual progress of breast cancer chemotherapy,targeted therapy,endocrine therapy and immunotherapy in 2022,providing valuable information for future research to better guide individualized treatment of breast cancer,thereby improving the prognosis and quality of life of breast cancer patients.

Estrogen receptor-low breast cancer:Biology chaos and treatment paradox

Hormone receptor testing mainly serves the purpose of guiding treatment choices for breast cancer patients.Patients with estrogen receptor(ER)-positive breast cancers show significant response to endocrine therapy.However,the methods to define ER status and eligibility for treatment remain controversial.Despite recent guidelines considering staining≥1% of tumor nuclei by immunohistology as ER-positive,it has raised concerns on the benefit of endocrine therapy for tumors with ER 1%-10% expression,termed“ER-low positive”.This subgroup accounts for 3% to 9% of all patients and is likely to have unique molecular features,and therefore distinct therapeutic response to endocrine therapy compared with ER-high positive tumors.The latest guidelines did not provide detailed descriptions for those patients,resulting in inconsistent treatment strategies.Consequently,we aimed to resolve this dilemma comprehensively.This review discusses molecular traits and recent ER-low positive breast cancer innovations,highlighting molecular-targeted treatment rather than traditional unified endocrine therapy for future basic and clinical research.

ESR1 alterations and metastasis in estrogen receptor positive breast cancer

Endocrine therapy is essential for the treatment of patients with estrogen receptor positive (ER+) breast cancer, however, resistance and the development of metastatic disease is common. Understanding how ER+ breast cancer metastasizes is critical since the major cause of death in breast cancer is metastasis to distant organs. Results from many studies suggest dysregulation of the estrogen receptor alpha gene (ESR1) contributes to therapeutic resistance and metastatic biology. This review covers both pre-clinical and clinical evidence on the spectrum ofESR1 alterations including amplification, point mutations, and genomic rearrangement events driving treatment resistance and metastatic potential of ER+ breast cancer. Importantly, we describe how these ESR1 alterations may provide therapeutic opportunities to improve outcomes in patients with lethal, metastatic breast cancer.