Breast cancer is a severe problem for women worldwide.Among them,estrogen receptor(ER)positive breast cancer accounted for 70%of total breast cancer cases,which is the most common subtype.Currently,the main therapy th...Breast cancer is a severe problem for women worldwide.Among them,estrogen receptor(ER)positive breast cancer accounted for 70%of total breast cancer cases,which is the most common subtype.Currently,the main therapy that targeted ER positive breast cancer is endocrine therapy.Herein,we summarized the latest research advances in combination therapies for ER positive breast cancer,focusing on ER as the main therapeutic target.The therapeutic approaches,therapeutic mechanism and resistance will be reviewed and discussed.The combinatorial targets and synergistic effects such as cell cycle-dependent kinase 4/6,phosphatidylinositol-3 kinase,histone deacetylase,bromodomain and extraterminal domain were summarized.In addition,the chemical structures of the inhibitors were also illustrated,along with a brief structure-activity relationship study.Finally,perspective and future directions on breast cancer were proposed and discussed.展开更多
The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9%between the experimental and control groups.That is to say,in the intermediate-risk hormone receptor pos...The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9%between the experimental and control groups.That is to say,in the intermediate-risk hormone receptor positive/human epidermal growth factor receptor-2 negative subgroup,there are also some patients with primary resistance to ribociclib.These patients benefit less from ribociclib,and they are unable to gain significant benefit even with the intensive adjuvant therapy of ribociclib.Considering the drug toxicity and health economic benefits,a 3-year course of ribociclib may not be appropriate for all intermediate-risk populations.Therefore,how to screen out the prime population for intensive adjuvant therapy of ribociclib needs to worth explored.In this paper,we discussed that the adaptive neoadjuvant endocrine therapy can screen out the prime population for intensive adjuvant therapy of ribociclib.展开更多
Objective：To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy-associated hot flashes symptom in breast cancer patients.Methods：Sixty-six patients with breast cancer receiving adj...Objective：To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy-associated hot flashes symptom in breast cancer patients.Methods：Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups,the control group received endocrine therapy alone,the other group is administered with Chinese herbs decoction Shu-Gan-Liang-Xue besides the endocrine therapy：Shu-Gan-Liang-Xue decoction was administered above 6 months per year for more than 2 years.Frequency of hot flashes per day was recorded,and the effect of Shu-Gan-Liang-Xue decoction on hot flashes symptom being assessed with Kupperman Scoring Index.Results：Sixty cases were analyzed,32 cases in endocrine therapy combining Chinese herbs decoction group,28 cases in mere endocrine therapy group.For hot flashes symptom,in Chinese herbs decoction administration group,7 cases（21.9%） reported symptom disappeared,22 cases（68.7%） reported symptom alleviated,3 cases（9.4%） reported symptom not changed;in endocrine therapy alone group,5 cases（17.9%） reported symptom disappeared,13 cases（46.4%） reported symptom alleviated,10 cases（10/28,35.7%） reported symptom not changed.The difference between two groups was statistically significant（P=0.013）.For sleeping disorder,in Chinese herbs decoction administration group,27 cases（84.4%） reported symptom improved,5 cases（15.6%） reported no change;in endocrine therapy alone group,16 cases（57.1%） symptom improved,12 cases（42.9%） reported no change in sleeping disorder（P=0.019）,the difference was also of significance statistically.Conclusion：Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy,meanwhile without definite toxicity and influence on the risk of recurrence of tumor.展开更多
Objective： To determine the predictive ability of biomarkers for responses to neoadjuvant endocrine therapy （NET） in postmenopausal breast cancer. Methods： Consecutive 160 postmenopausal women with T 1-3 N 0-1 M 0...Objective： To determine the predictive ability of biomarkers for responses to neoadjuvant endocrine therapy （NET） in postmenopausal breast cancer. Methods： Consecutive 160 postmenopausal women with T 1-3 N 0-1 M 0 hormone receptor （HR）-positive invasive breast cancer were treated with anastrozole for 16 weeks before surgery. New slides of tumor specimens taken before and after treatment were conducted centrally for biomarker analysis and classified using the Applied Imaging Ariol MB-8 system. The pathological response was evaluated using the Miller ＆ Payne classification. The cell cycle response was classified according to the change in the Ki67 index after treatment. Multivariable logistic regression analysis was used to calculate the combined index of the biomarkers. Receiver operating characteristic （ROC） curves were used to determine whether parameters may predict response. Results： The correlation between the pathological and cell cycle responses was low （Spearman correlation coefficient =0.241, P〈0.001; Kappa value =0.119, P=0.032）. The cell cycle response was significantly associated with pre-treatment estrogen receptor （ER） status （P=0.001）, progesterone receptor （PgR） status （P〈0.001）, human epidermal growth factor receptor 2 （Her-2） status （P=0.050） and the Ki67 index （P〈0.001）, but the pathological response was not correlated with these factors. Pre-treatment ER levels [area under the curve （AUC） =0.634, 95% confidence interval （95% CI）, 0.534-0.735, P=0.008] and combined index of pre-treatment ER and PgR levels （AUC =0.684, 95% CI, 0.591-0.776, P〈0.001） could not predict the cell cycle response, but combined index including per-treatment ER/PR/Her-2/Ki67 expression levels could （AUC =0.830, 95% CI, 0.759-0.902, P〈0.001）. Conclusions： The combined use of pre-treatment ER/PgR/Her-2/Ki67 expression levels, instead of HR expression levels, may predict the cell cycle response to NET.展开更多
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 a...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.展开更多
Approximately 50%of breast cancer patients under hormone therapy experience osteoarticular pain,which increases the risk of treatment discontinuation and relapse.The aim of the study was to assess the feasibility of y...Approximately 50%of breast cancer patients under hormone therapy experience osteoarticular pain,which increases the risk of treatment discontinuation and relapse.The aim of the study was to assess the feasibility of yoga practice associated with patient education(PE)for at-home practice in breast cancer patients under hormone therapy.We also evaluated osteoarticular pain,flexibility and patients’satisfaction.In this study,intervention was split into two 6-week periods(P):P1 consisting of a supervised yoga-PE session of 90 minutes/week and 15-minutes of daily at-home yoga,and P2,involving daily autonomous athome yoga sessions.Feasibility was evaluated by patient adherence defined as completion of at least 4 out of the 6 supervised yoga-PE sessions and 70%or more of the at-home yoga sessions.Evaluations(at inclusion and at the end of each period)consisted in assessment of osteoarticular pain,forward flexibility and patient satisfaction.Twenty-four women with a median age of 53 years[36–72]were included.Feasibility was validated with a successful adherence rate reaching 83%,combined with a mean satisfaction score of 10/10[8–10].In addition,58%of patients reported reduced osteoarticular pain,with a 2-point reduction on the numerical rating scale.The forward flexibility also improved,with a median gain of 8 cm.Combined physiotherapy-yoga-PE intervention is a feasible strategy,increasing at-home yoga practice with potential benefit on pain,flexibility,and patient satisfaction.Evaluation of this innovative program is ongoing in a larger randomized multicenter trial.展开更多
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 ...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.展开更多
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...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.展开更多
Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine ther...Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.展开更多
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...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.展开更多
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 thera...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.展开更多
Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy(BCP), focusing on biology, diagnosis and staging, local ...Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy(BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.展开更多
The transforming growth factor β1（TGF-β1） and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two fa...The transforming growth factor β1（TGF-β1） and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130（stageⅠ–Ⅲ） invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival（DDFS）（HR=8.416, 95% CI=1.636–43.292, P=0.011） in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival（OS） than their counterparts with CD8-positive cell infiltration into tumor nests（Log-Rank, P=0.003）. But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy（Log-Rank, P=0.013） and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor（t-TGF-β1-pre）-positive patients than in the negative patients in patients without recieiving chemotherapy（P=0.053）, OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy（P=0.035） and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS（HR=0.392 95% CI=0.157–0.978, P=0.045） in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.展开更多
Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in...Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in breast cancer and its relationship to clinicopathologic findings. Methods: DNAs of tumor tissues and blood lymphocytes were collected from 40 cases of primary breast cancer patients and LOH were detected using the microsatellite repeat assay and combined with other ER immunohistochemical assays. Results: ER-positive staining was observed in 65% of breast cancer. Heterogeneity of ER expression was found. Seven of the patients (17.5%) showed LOH. In three of the seven cases, there was total loss, and there was a marked reduction in the intensity of signal in the other four cases. LOH was associated with histologic grade, occurring more frequently in ER-negative and lymph node metastasis group, but not with tumor size and patient ages. Conclusion: This result implied that LOH of the ER gene may have an important role in the progression of breast cancer. It was postulated that the lack of ER function induced by LOH may contributed to endocrine therapy resistance of breast cancer since the tumor clone would escape from the ER regulation, obtain growth predisposition and finally lost response to therapy.展开更多
BACKGROUND Globally,prostate cancer has become a major threat to men's health,with an increasing incidence and causes serious effects on the quality and length of life of patients.Despite the rapid development of ...BACKGROUND Globally,prostate cancer has become a major threat to men's health,with an increasing incidence and causes serious effects on the quality and length of life of patients.Despite the rapid development of medical technology,which provides treatments,including surgery,radiotherapy,and endocrine therapy,the treatment of patients with prostate cancer,especially with endocrine therapy,has become a major challenge in clinical treatment owing to the lengthy course of treatment,side effects of drugs,and impact of the disease on the psychological and physiological functioning of the patient,producing poor treatment adherence and a decline in quality of life.After the nursing intervention,the anxiety and depression scores of the observation group were significantly lower than those of the control group(P<0.05).The quality of life score,sexual function,and hormone function were significantly higher than those in the control group(P<0.05).CONCLUSION Case management guidance based on patient safety effectively reduced anxiety and depression in patients undergoing endocrine therapy for prostate cancer and improved their quality of life,treatment compliance,and satisfaction.展开更多
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 rela...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.展开更多
Background:Bireociclib(XZP-3287)is a novel selective cyclin-dependent kinase 4 and 6(CDK4/6)inhibitor,with a favorable safety profile demonstrated in preclinical and phase I studies.BRIGHT-1 aimed to further explore t...Background:Bireociclib(XZP-3287)is a novel selective cyclin-dependent kinase 4 and 6(CDK4/6)inhibitor,with a favorable safety profile demonstrated in preclinical and phase I studies.BRIGHT-1 aimed to further explore the efficacy and safety of bireociclib monotherapy in patients with locally advanced,recurrent or metastatic,hormone receptor-positive and human epidermal growth factor receptor 2-negative(HR+/HER2−)breast cancer who had progressed on or after prior chemotherapy and endocrine therapy in advanced settings,without previous exposure to CDK4/6 inhibitors.Methods:In this open-label phase II trial,eligible patients received bireociclib 480 mg twice daily(BID)until disease progression or intolerable toxicities.The primary endpoint was the confirmed objective response rate(ORR)assessed by an independent review committee(IRC).The secondary endpoints included progression-free survival(PFS),investigator-assessed ORR,disease control rate(DCR),clinical benefit rate(CBR),duration of response(DoR),overall survival(OS),safety and the pharmacokinetic properties of bireociclib.Results:A total of 131 patients were enrolled.At data cutoff(July 31,2023),the IRC-assessed ORR was 29.8%(95%confidence interval[CI],22.1%to 38.4%),with a DCR of 73.3%(95%CI,64.8%to 80.6%),CBR of 42.0%(95%CI,33.4%to 50.9%)and a median DoR of 15.2 months(95%CI,9.5 months to not reached).The median PFS was 11.0 months(95%CI,7.3 months to 12.9 months)assessed by the IRC,and the median OS was 29.0 months(95%CI,24.9 months to not reached).The most frequently reported treatment-emergent adverse events(TEAEs)of any grade were diarrhea(93.1%),neutrophil count decreased(87.0%),white blood cell decreased(86.3%),vomiting(78.6%),anemia(72.5%),and platelet count decreased(72.5%).The grade≥3 TEAEs occurred in 109(83.2%)patients.The most common grade≥3 TEAEs were neutrophil count decreased(43.5%),white blood cell decreased(32.8%),hypokalemia(20.6%),and diarrhea(19.1%).Conclusions:Bireociclib monotherapy at 480 mg BID exhibited promising and sustained clinical activity,with no unexpected and acceptable toxicity in patients with recurrent or metastatic HR+/HER2−breast cancer who had progressed on or after previous therapy.Trial registration:Clinicaltrials.gov ID,NCT04539496.展开更多
According to the latest WHO data in 2020, the number of new cases of breast cancer reached 2.26 million and that of lung cancer was 2.2 million. Breast cancer officially replaced lung cancer as the world's largest...According to the latest WHO data in 2020, the number of new cases of breast cancer reached 2.26 million and that of lung cancer was 2.2 million. Breast cancer officially replaced lung cancer as the world's largest cancer. With the continuous development of cancer research technology and the improvement of anti-tumor technology, the prognosis of breast cancer is also improving. In this study, the development and advantages of endocrine therapy for breast cancer patients were analyzed by analyzing the occurrence factors of breast cancer, common treatment methods, and the drug action mechanism of fulvestrant in the treatment of breast cancer patients. It has certain reference value for researching the anti-tumor value of the fulvestrant drugs.展开更多
Breast cancer(BC)is the most prevalent and destructive tumor in developing countries.The implementation of mammography screening programs has enabled access to appropriate therapeutic interventions,including adjuvant ...Breast cancer(BC)is the most prevalent and destructive tumor in developing countries.The implementation of mammography screening programs has enabled access to appropriate therapeutic interventions,including adjuvant endocrine therapy and breast-conserving surgery;earlier diagnosis translates into a wider survival-rate range,making hypofractionated radiotherapy(HFRT)the preferred option.This review examines the current literature comparing the two radiation therapies,HFRT and conventional radiotherapy(CR),with reconstructed breasts,focusing on efficacy,toxicity,cosmetic outcomes,quality of life(QOL),and cost-effectiveness.A comprehensive literature search was conducted using major scientific databases,including PubMed,Scopus,Web of Science,and Google Scholar.The search focused on articles published primarily in English,from 2010 to 2024,and the period is about 15 years.The following search terms and Boolean operators were used:“hypofractionated radiotherapy”OR“hypofractionation”AND“breast cancer”AND“toxicity”OR“complications”OR“reconstruction”OR“quality of life”OR“HFRT versus CFRT”OR“intensitymodulated radiation therapy”OR“proton therapy”.CR can be safely replaced with HFRT in terms of overall survival and local recurrence rates.HFRT is associated with lesser risks of both acute and chronic side effects,breast complications,increased patient satisfaction,and reduced breast problems.In addition,new radiotherapy modalities,such as intensitymodulated radiation therapy,have shown great potential in targeting tumors.In treating BC,HFRT is gradually becoming standard,especially for patients who undergo reconstruction after surgery.Its low toxicity and equal effectiveness make it a key element in improving the QOL of BC survivors.It is recommended that future studies focus on long-term outcomes to provide better care to patients.展开更多
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 ...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.展开更多
基金the financial supports of the National Natural Science Foundation of China(No.82204181)Nanjing University of Chinese Medicine National Natural Science Foundation of China Counterpart Funding(No.XPT82204181)+3 种基金Jiangsu Provincial Health Commission(No.Z2021057)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine)High level key discipline construction project of the National Administration of Traditional Chinese Medicine-Resource Chemistry of Chinese Medicinal Materials(No.zyyzdxk-2023083)the Key R&D Program of Jiangsu Province(No.BE2023840)。
文摘Breast cancer is a severe problem for women worldwide.Among them,estrogen receptor(ER)positive breast cancer accounted for 70%of total breast cancer cases,which is the most common subtype.Currently,the main therapy that targeted ER positive breast cancer is endocrine therapy.Herein,we summarized the latest research advances in combination therapies for ER positive breast cancer,focusing on ER as the main therapeutic target.The therapeutic approaches,therapeutic mechanism and resistance will be reviewed and discussed.The combinatorial targets and synergistic effects such as cell cycle-dependent kinase 4/6,phosphatidylinositol-3 kinase,histone deacetylase,bromodomain and extraterminal domain were summarized.In addition,the chemical structures of the inhibitors were also illustrated,along with a brief structure-activity relationship study.Finally,perspective and future directions on breast cancer were proposed and discussed.
基金supported by China Postdoctoral Science Foundation(No.2022M721987)Natural Science Foundation of Shandong Province(No.ZR2024QH058).
文摘The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9%between the experimental and control groups.That is to say,in the intermediate-risk hormone receptor positive/human epidermal growth factor receptor-2 negative subgroup,there are also some patients with primary resistance to ribociclib.These patients benefit less from ribociclib,and they are unable to gain significant benefit even with the intensive adjuvant therapy of ribociclib.Considering the drug toxicity and health economic benefits,a 3-year course of ribociclib may not be appropriate for all intermediate-risk populations.Therefore,how to screen out the prime population for intensive adjuvant therapy of ribociclib needs to worth explored.In this paper,we discussed that the adaptive neoadjuvant endocrine therapy can screen out the prime population for intensive adjuvant therapy of ribociclib.
文摘Objective：To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy-associated hot flashes symptom in breast cancer patients.Methods：Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups,the control group received endocrine therapy alone,the other group is administered with Chinese herbs decoction Shu-Gan-Liang-Xue besides the endocrine therapy：Shu-Gan-Liang-Xue decoction was administered above 6 months per year for more than 2 years.Frequency of hot flashes per day was recorded,and the effect of Shu-Gan-Liang-Xue decoction on hot flashes symptom being assessed with Kupperman Scoring Index.Results：Sixty cases were analyzed,32 cases in endocrine therapy combining Chinese herbs decoction group,28 cases in mere endocrine therapy group.For hot flashes symptom,in Chinese herbs decoction administration group,7 cases（21.9%） reported symptom disappeared,22 cases（68.7%） reported symptom alleviated,3 cases（9.4%） reported symptom not changed;in endocrine therapy alone group,5 cases（17.9%） reported symptom disappeared,13 cases（46.4%） reported symptom alleviated,10 cases（10/28,35.7%） reported symptom not changed.The difference between two groups was statistically significant（P=0.013）.For sleeping disorder,in Chinese herbs decoction administration group,27 cases（84.4%） reported symptom improved,5 cases（15.6%） reported no change;in endocrine therapy alone group,16 cases（57.1%） symptom improved,12 cases（42.9%） reported no change in sleeping disorder（P=0.019）,the difference was also of significance statistically.Conclusion：Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy,meanwhile without definite toxicity and influence on the risk of recurrence of tumor.
文摘Objective： To determine the predictive ability of biomarkers for responses to neoadjuvant endocrine therapy （NET） in postmenopausal breast cancer. Methods： Consecutive 160 postmenopausal women with T 1-3 N 0-1 M 0 hormone receptor （HR）-positive invasive breast cancer were treated with anastrozole for 16 weeks before surgery. New slides of tumor specimens taken before and after treatment were conducted centrally for biomarker analysis and classified using the Applied Imaging Ariol MB-8 system. The pathological response was evaluated using the Miller ＆ Payne classification. The cell cycle response was classified according to the change in the Ki67 index after treatment. Multivariable logistic regression analysis was used to calculate the combined index of the biomarkers. Receiver operating characteristic （ROC） curves were used to determine whether parameters may predict response. Results： The correlation between the pathological and cell cycle responses was low （Spearman correlation coefficient =0.241, P〈0.001; Kappa value =0.119, P=0.032）. The cell cycle response was significantly associated with pre-treatment estrogen receptor （ER） status （P=0.001）, progesterone receptor （PgR） status （P〈0.001）, human epidermal growth factor receptor 2 （Her-2） status （P=0.050） and the Ki67 index （P〈0.001）, but the pathological response was not correlated with these factors. Pre-treatment ER levels [area under the curve （AUC） =0.634, 95% confidence interval （95% CI）, 0.534-0.735, P=0.008] and combined index of pre-treatment ER and PgR levels （AUC =0.684, 95% CI, 0.591-0.776, P〈0.001） could not predict the cell cycle response, but combined index including per-treatment ER/PR/Her-2/Ki67 expression levels could （AUC =0.830, 95% CI, 0.759-0.902, P〈0.001）. Conclusions： The combined use of pre-treatment ER/PgR/Her-2/Ki67 expression levels, instead of HR expression levels, may predict the cell cycle response to NET.
基金supported by grant from the CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2021I2M-1-014)。
文摘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.
文摘Approximately 50%of breast cancer patients under hormone therapy experience osteoarticular pain,which increases the risk of treatment discontinuation and relapse.The aim of the study was to assess the feasibility of yoga practice associated with patient education(PE)for at-home practice in breast cancer patients under hormone therapy.We also evaluated osteoarticular pain,flexibility and patients’satisfaction.In this study,intervention was split into two 6-week periods(P):P1 consisting of a supervised yoga-PE session of 90 minutes/week and 15-minutes of daily at-home yoga,and P2,involving daily autonomous athome yoga sessions.Feasibility was evaluated by patient adherence defined as completion of at least 4 out of the 6 supervised yoga-PE sessions and 70%or more of the at-home yoga sessions.Evaluations(at inclusion and at the end of each period)consisted in assessment of osteoarticular pain,forward flexibility and patient satisfaction.Twenty-four women with a median age of 53 years[36–72]were included.Feasibility was validated with a successful adherence rate reaching 83%,combined with a mean satisfaction score of 10/10[8–10].In addition,58%of patients reported reduced osteoarticular pain,with a 2-point reduction on the numerical rating scale.The forward flexibility also improved,with a median gain of 8 cm.Combined physiotherapy-yoga-PE intervention is a feasible strategy,increasing at-home yoga practice with potential benefit on pain,flexibility,and patient satisfaction.Evaluation of this innovative program is ongoing in a larger randomized multicenter trial.
基金This work was partially funded by NIH T32 CA009515(PM and NED),P30CA015704(NED)Breast Cancer Research Foundation.
文摘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.
文摘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.
基金supported by the Program of Introducing Talents of Discipline to Universities(111 Project)-TCM Prevention and Treatment of Major Chronic Diseases(Tumor-B21028).
文摘Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.
基金State Administration of Traditional Chinese Medicine(No.ZyzB-2022-798)National Natural Science Foundation of China(No.82205222)Special Research Project of Beijing Municipal Health Commission on Capital Health Development(No.First edition 2022-4-2234)。
文摘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.
基金Science and Technology Foundation of Liaoning Provincegrant number:20170540995+5 种基金Science and Technology Foundation of Shenyang Citygrant number:RC170545the National Science Foundation of Chinagrant number:81302313Talent Project of Shengjing Hospital of China Medical Universitygrant number:345
文摘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.
文摘Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy(BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.
基金supported by the Wu Jieping Medical Foun-dation(No.320.6752.1230)
文摘The transforming growth factor β1（TGF-β1） and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130（stageⅠ–Ⅲ） invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival（DDFS）（HR=8.416, 95% CI=1.636–43.292, P=0.011） in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival（OS） than their counterparts with CD8-positive cell infiltration into tumor nests（Log-Rank, P=0.003）. But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy（Log-Rank, P=0.013） and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor（t-TGF-β1-pre）-positive patients than in the negative patients in patients without recieiving chemotherapy（P=0.053）, OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy（P=0.035） and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS（HR=0.392 95% CI=0.157–0.978, P=0.045） in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.
基金This work was supported by the National Natural Science Foundation of China (No.39870753).
文摘Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in breast cancer and its relationship to clinicopathologic findings. Methods: DNAs of tumor tissues and blood lymphocytes were collected from 40 cases of primary breast cancer patients and LOH were detected using the microsatellite repeat assay and combined with other ER immunohistochemical assays. Results: ER-positive staining was observed in 65% of breast cancer. Heterogeneity of ER expression was found. Seven of the patients (17.5%) showed LOH. In three of the seven cases, there was total loss, and there was a marked reduction in the intensity of signal in the other four cases. LOH was associated with histologic grade, occurring more frequently in ER-negative and lymph node metastasis group, but not with tumor size and patient ages. Conclusion: This result implied that LOH of the ER gene may have an important role in the progression of breast cancer. It was postulated that the lack of ER function induced by LOH may contributed to endocrine therapy resistance of breast cancer since the tumor clone would escape from the ER regulation, obtain growth predisposition and finally lost response to therapy.
文摘BACKGROUND Globally,prostate cancer has become a major threat to men's health,with an increasing incidence and causes serious effects on the quality and length of life of patients.Despite the rapid development of medical technology,which provides treatments,including surgery,radiotherapy,and endocrine therapy,the treatment of patients with prostate cancer,especially with endocrine therapy,has become a major challenge in clinical treatment owing to the lengthy course of treatment,side effects of drugs,and impact of the disease on the psychological and physiological functioning of the patient,producing poor treatment adherence and a decline in quality of life.After the nursing intervention,the anxiety and depression scores of the observation group were significantly lower than those of the control group(P<0.05).The quality of life score,sexual function,and hormone function were significantly higher than those in the control group(P<0.05).CONCLUSION Case management guidance based on patient safety effectively reduced anxiety and depression in patients undergoing endocrine therapy for prostate cancer and improved their quality of life,treatment compliance,and satisfaction.
文摘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.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09711002-011-027)the Chinese Academy of Medical Sciences(CAMS)Inno-vation Fund for Medical Sciences(CIFMS,2021-I2M-1-014 and 2023-12M-2-004).
文摘Background:Bireociclib(XZP-3287)is a novel selective cyclin-dependent kinase 4 and 6(CDK4/6)inhibitor,with a favorable safety profile demonstrated in preclinical and phase I studies.BRIGHT-1 aimed to further explore the efficacy and safety of bireociclib monotherapy in patients with locally advanced,recurrent or metastatic,hormone receptor-positive and human epidermal growth factor receptor 2-negative(HR+/HER2−)breast cancer who had progressed on or after prior chemotherapy and endocrine therapy in advanced settings,without previous exposure to CDK4/6 inhibitors.Methods:In this open-label phase II trial,eligible patients received bireociclib 480 mg twice daily(BID)until disease progression or intolerable toxicities.The primary endpoint was the confirmed objective response rate(ORR)assessed by an independent review committee(IRC).The secondary endpoints included progression-free survival(PFS),investigator-assessed ORR,disease control rate(DCR),clinical benefit rate(CBR),duration of response(DoR),overall survival(OS),safety and the pharmacokinetic properties of bireociclib.Results:A total of 131 patients were enrolled.At data cutoff(July 31,2023),the IRC-assessed ORR was 29.8%(95%confidence interval[CI],22.1%to 38.4%),with a DCR of 73.3%(95%CI,64.8%to 80.6%),CBR of 42.0%(95%CI,33.4%to 50.9%)and a median DoR of 15.2 months(95%CI,9.5 months to not reached).The median PFS was 11.0 months(95%CI,7.3 months to 12.9 months)assessed by the IRC,and the median OS was 29.0 months(95%CI,24.9 months to not reached).The most frequently reported treatment-emergent adverse events(TEAEs)of any grade were diarrhea(93.1%),neutrophil count decreased(87.0%),white blood cell decreased(86.3%),vomiting(78.6%),anemia(72.5%),and platelet count decreased(72.5%).The grade≥3 TEAEs occurred in 109(83.2%)patients.The most common grade≥3 TEAEs were neutrophil count decreased(43.5%),white blood cell decreased(32.8%),hypokalemia(20.6%),and diarrhea(19.1%).Conclusions:Bireociclib monotherapy at 480 mg BID exhibited promising and sustained clinical activity,with no unexpected and acceptable toxicity in patients with recurrent or metastatic HR+/HER2−breast cancer who had progressed on or after previous therapy.Trial registration:Clinicaltrials.gov ID,NCT04539496.
文摘According to the latest WHO data in 2020, the number of new cases of breast cancer reached 2.26 million and that of lung cancer was 2.2 million. Breast cancer officially replaced lung cancer as the world's largest cancer. With the continuous development of cancer research technology and the improvement of anti-tumor technology, the prognosis of breast cancer is also improving. In this study, the development and advantages of endocrine therapy for breast cancer patients were analyzed by analyzing the occurrence factors of breast cancer, common treatment methods, and the drug action mechanism of fulvestrant in the treatment of breast cancer patients. It has certain reference value for researching the anti-tumor value of the fulvestrant drugs.
文摘Breast cancer(BC)is the most prevalent and destructive tumor in developing countries.The implementation of mammography screening programs has enabled access to appropriate therapeutic interventions,including adjuvant endocrine therapy and breast-conserving surgery;earlier diagnosis translates into a wider survival-rate range,making hypofractionated radiotherapy(HFRT)the preferred option.This review examines the current literature comparing the two radiation therapies,HFRT and conventional radiotherapy(CR),with reconstructed breasts,focusing on efficacy,toxicity,cosmetic outcomes,quality of life(QOL),and cost-effectiveness.A comprehensive literature search was conducted using major scientific databases,including PubMed,Scopus,Web of Science,and Google Scholar.The search focused on articles published primarily in English,from 2010 to 2024,and the period is about 15 years.The following search terms and Boolean operators were used:“hypofractionated radiotherapy”OR“hypofractionation”AND“breast cancer”AND“toxicity”OR“complications”OR“reconstruction”OR“quality of life”OR“HFRT versus CFRT”OR“intensitymodulated radiation therapy”OR“proton therapy”.CR can be safely replaced with HFRT in terms of overall survival and local recurrence rates.HFRT is associated with lesser risks of both acute and chronic side effects,breast complications,increased patient satisfaction,and reduced breast problems.In addition,new radiotherapy modalities,such as intensitymodulated radiation therapy,have shown great potential in targeting tumors.In treating BC,HFRT is gradually becoming standard,especially for patients who undergo reconstruction after surgery.Its low toxicity and equal effectiveness make it a key element in improving the QOL of BC survivors.It is recommended that future studies focus on long-term outcomes to provide better care to patients.
文摘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.
