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Calcification-associated molecular traits and therapeutic strategies in hormone receptor-positive HER2-negative breast cancer

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Cancer Biology & Medicine 2024年第5期21卷 400-415页

作者： Yuwei Li Yuzheng Xu Caijin Lin Xi Jin Ding Ma Zhiming Shao Department of Breast Surgery Fudan University Shanghai Cancer Center Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University

Objective: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2-) breast cancer remain unclear.Methods: We retrospectively collected mammography records of an HR+/HER2-breast cancer cohort(n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor(ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6) inhibitors.Conclusions: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2-breast cancer.

关键词： HR+/HER2-breast cancer mammographic calcifications molecular features precision treatment endocrine therapy SENSITIVITY REPAIR

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Updates in endocrine therapy for metastatic breast cancer

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Cancer Biology & Medicine 2022年第2期19卷 202-212页

作者： Poorni M.Manohar Nancy E.Davidson University of Washington/Seattle Cancer Care Alliance Seattle 98109WAUSA Fred Hutchinson Cancer Research Center Seattle 98109WAUSA

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.

关键词： endocrine therapy metastatic breast cancer

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

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Chinese Medical Journal 2023年第12期136卷 1459-1467页

作者： Yang Yuan Shaohua Zhang Tao Wang Li Bian Min Yan Yongmei Yin Yuhua Song Yi Wen Jianbin Li Zefei Jiang Department of Oncology No.4 Ward The Fifth Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100071China Department of Oncology No.3 Ward The Fifth Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100071China Department of Breast Disease Henan Breast Cancer CenterThe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008 China Department of Breast Cancer Jiangsu Province Hospital&The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029 China Department of Breast Cancer Center The Affiliated Hospital of Qingdao UniversityQingdaoShandong 260000 China Medical Department Medpion(Beijing)Medical Technology Co.LtdBeijing 100062 China

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.

关键词： Breast neoplasms Metastatic breast cancer Hormone receptor-positive HER2-negative Chemotherapy endocrine therapy First-line treatment Maintenance therapy

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

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Chinese Journal of Cancer Research 2022年第4期34卷 343-352页

作者： Dan Lyu Binliang Liu Bo Lan Xiaoying Sun Lixi Li Jingtong Zhai Haili Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Breast Cancer Medical Oncology Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Medical Oncology Cancer Hospital of Huanxing Chaoyang DistrictBeijing 100122China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

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

关键词： ctDNA next-generation sequencing breast cancer endocrine therapy

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

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Chinese Medical Journal 2020年第19期133卷 2338-2345页

作者： Li Bian Feng-Rui Xu Ze-Fei Jiang Department of Breast Oncology The Fifth Medical Center of Chinese PLA General HospitalBeijing 100071China.

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.

关键词： endocrine therapy Hormone receptor positive Metastatic breast cancer Targeted therapy

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

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Chinese Medical Journal 2020年第9期133卷 1099-1108页

作者： Le-Sang Shen Xiao-Yan Jin Xu-Meng Wang Lai-Zhen Tou Jian Huang Department of Breast Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Tumor Microenvironment and Immune therapy of Zhejiang Province HangzhouZhejiang 310009China Department of Surgical Oncology Zhejiang Taizhou Municipal HospitalTaizhouZhejiang 318000China Department of Surgical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China

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.

关键词： endocrine therapy Advanced breast cancer endocrine resistance Targeted therapy

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Long-Term Chinese Herbs Decoction Administration for Management of Hot Flashes Associated with endocrine therapy in Breast Cancer Patients

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Chinese Journal of Cancer Research 2011年第1期23卷 74-78页

作者： Dong Xue Hong Sun Ping-ping Li Key Laboratory of Carcinogenesis and Translational Research（Ministry of Education） Department of Integrative MedicinePeking University School of OncologyBeijing Cancer Hospital ＆ InstituteBeijing 100142China

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.

关键词： Breast cancer endocrine therapy Tamoxifen Hot flashes Chinese herbs decoction

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The importance of combined radiation and endocrine therapy in locally advanced prostate cancer

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Asian Journal of Andrology 2012年第2期14卷 245-246页

作者： PhiUip J Gray William U Shipley Harvard Radiation Oncology Program BostonMA 02114USA Department of Radiation Oncology Massachusetts General HospitalBostonMA 02114USA

The management of all stages of prostate cancer has become an increasingly com-plex task as new treatment paradigms are tested and the results of large randomized studies become available. Despite these advances, prostate cancer remains the second leading cause of cancer death and the seventh overall cause of death in men in the United States.

关键词： radiation endocrine therapy cancer

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

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Oncology and Translational Medicine 2021年第5期7卷 229-234页

作者： Xiulong Ma Hongbing Ma Dongli Ruan Department of Radiotherapy The Second Affiliated HospitalXi'an Jiaotong UniversityXi'an 710004China Department of Urology Xijing HospitalAir Force Military Medical UniversityXi'an 710032China

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(Pendocrine therapy combined with the intensity-modulated radiation therapy(IMRT)group was significantly higher than that in the IMRT group(Pendocrine therapy combined with the IMRT group were 60%and 38.17%,respectively,which were significantly hi

关键词： conformal intensity-modulated radiation endocrine therapy prostate cancer metastasis-free survival rate

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A Promising Predictor of the Efficacy of endocrine therapy for Breast Cancer: 14-3-3-zeta

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Chinese Journal of Biomedical Engineering(English Edition) 2020年第4期29卷 1-10页

作者： Shunchao Yan Xin Jiao Na Li Yangfan Du Department of Oncology Shengjing Hospital of China Medical UniversityShenyang 110022China Department of Respiratory Medicine Shenyang Chest HospitalShenyang 110044China

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.

关键词： 14-3-3-zeta endocrine therapy tamoxifen breast cancer

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