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Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ 2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] ( P <0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance ( P =0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95% CI : 4.3-5.7) and 4.0 (95% CI : 1.6-6.4) months, respectively, with no statistical significance ( P =0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95% CI : 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95% CI : 1.8-2.2) months] ( P <0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95% CI : 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95% CI : 0.6-3.4) months] ( P =0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

With the advent of the precision cancer therapy era, neoadjuvant therapy has become the standard therapy for certain types of breast cancer. Neoadjuvant therapy is a fundamental treatment plan implemented at the time of disease diagnosis, and its efficacy can guide the formulation of subsequent adjuvant therapy strategies. Building on the efficacy of neoadjuvant therapy and medication regimens, in conjunction with evidence-based medicine and healthcare policy, developing adjuvant therapy strategies for breast cancer following neoadjuvant therapy has the benefit of providing more precise treatment options for patients.

Endocrine therapy is the primary systemic therapy for hormone receptor-positive breast cancer, which runs through the whole process of treatment for early and metastatic breast cancer. The development of new endocrine agents and targeted drugs such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors has improved outcome of patients with hormone receptor-positive breast cancer and changed the treatment landscape. The update of clinical research data provides more treatment options, calling for treatment optimization. Experts had a deep discussion around the hot topics on endocrine therapy of breast cancer, and formulated the'Expert consensus on endocrine therapy of breast cancer (2023 edition)'.This consensus is based on research data worldwide and clinical practice experience, with the aims of standardizing clinical diagnosis and optimizing treatment in neoadjuvant, adjuvant and metastatic setting of hormone receptor-positive breast cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies., Competing Interests: Disclosure MLTAT declares consulting fees and honoraria from MSD, Roche, Novartis, Eli Lilly and AstraZeneca. HKA declares consulting fees from Daiichi Sankyo, Amgen, Yuhan and Novartis, and honoraria from Roche, BMS, MSD, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Menarini, Eisai, Pfizer, Boryung Pharmaceutical Company, Celtrion, Pharmobio Korea Inc. and Yuhan. GC has served as consultant or advisor for Roche, Eli Lilly and BMS; served on a speaker’s bureau for Roche, Pfizer and Eli Lilly; received travel funding from Pfizer and Roche; and received honoraria from Roche, Pfizer, Eli Lilly, Novartis, AstraZeneca and SeaGen, all outside the submitted work. THF declares honoraria from AstraZeneca Oncology Indonesia, Takeda Indonesia, Eisai Indonesia, Roche Oncology Indonesia, J & J Indonesia and Zueling Pharma Indonesia and role as head of division of Area Development for West Java, Indonesia for the Indonesian Society of Hematology and Medical Oncology. AG declares honoraria for advisory boards from AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Novartis, Pfizer and Roche; honoraria for lectures from Eisai and Eli Lilly and honoraria for expert testimony from Gentili. SG declares honoraria from Lupin, Roche, Novartis, Eli Lilly, Eisai, Cipla, CADILA, Intas and AstraZeneca; honoraria for being on committees of the Indian Council of Medical Research (Government of India), Council of Scientific and Industrial Research (Government of India), Department of Biotechnology (Government of India), India Alliance and institutional; honoraria from Novartis and AstraZeneca for participation in steering committees; leadership roles include President of Indian Society of Medical and Paediatric Oncology and General Secretary of Women’s Cancer Initiative - Tata Memorial Hospital, both roles unpaid. NH reports honoraria for lectures, advisory boards and/or personal fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz and SeaGen, and minority ownership interest in the West German Study Group. RAH declares honoraria from Roche, Novartis, MSD, Pfizer and Mylan, and support for attending meetings from Roche, MSD and Kalbe Pharma. SAI declares an institutional grant from AstraZeneca, Boryung Pharm, Daewoong Pharm, Eisai, Roche and Pfizer, and honoraria from AstraZeneca, Novartis, MSD, Roche, Pfizer; advisory role for AstraZeneca, Bertis, Daiichi Sankyo, Eisai, Hanmi, Lilly, MSD, Novartis, Roche and Pfizer. JHK declares an institutional grant from Ono Pharma Ltd., and honoraria from Novartis, MSD, Roche Pharma, Roche diagnostics, Pfizer, AstraZeneca, Eisai, Lilly, and Sanofi; fees for participation in data monitoring or advisory boards from Bixink, Eisai, Yuhan, Novartis, Daiichi Sankyo, Pfizer, Roche Pharma and Everest Medicines; institutional gifts from Eisai and Ono Pharma Ltd. SBK declares institutional funding from Novartis, Sanofi-Aventis and Dongkook Pharm Co.; consulting fees from Novartis, AstraZeneca, Lilly, DaeHwa Pharmaceutical Co Ltd., ISU Abxis, Beigene, OBI Pharma and Daiichi Sankyo; honoraria from Novartis, Pfizer, Lilly, OBI Pharma and Legochem Bioscience; participation on data safety monitoring or advisory boards for Novartis, AstraZeneca, MSD, Lilly and Daiichi Sankyo, and purchased stock in Genopeaks and Neogene TC. KHL declares honoraria from Pfizer, Novartis and Eli Lilly. SCL declares grants from Pfizer, Eisai, Taiho, ACT Genomics, MSD, Adagene and Epizyme; honoraria from Pfizer, Novartis, AstraZeneca, ACT Genomics, Eli Lilly, MSD and Roche and participation in data monitoring or advisory boards for Pfizer, Novartis, Eisai, Sanofi, Daiichi Sankyo, MSD and Roche. MYM declares institutional grants from MSD, Astella, Pfizer, Novartis, AstraZeneca, ARCUS, Amgen and honoraria from MSD, Amgen, Pfizer, Roche, Novartis, Zuelling Pharma, Specialised therapeutics, Eisai, GSK, Mundi Pharma, Eli Lilly and AstraZeneca. YN declares institutional grants from the Ministry of Health, Labour and Welfare, Abbvie, Ono, Daiichi Sankyo, Taiho, Pfizer, Boehringer Ingelheim, Eli Lilly, Eisai, AstraZeneca, Chugai, Bayer and honoraria from AstraZeneca, Eisai, Ono, Gardant, Takeda, Eli Lilly, Novartis, Pfizer, Chugai, Fuji Film Toyama Chemistry, Taiho, Mundi, Bristol, Shionogi. NP declares honoraria from AstraZeneca, Eisai, Roche, Eli Lilly, Novartis, Pfizer and MSD. YHP declares grants from AstraZeneca, Pfizer, Novartis, Roche and Gencurix, consulting fees from AstraZeneca, Pfizer, Novartis, Roche, Eisai, Daiichi Sankyo, MSD and Lilly, honoraria from Pfizer, MSD, Novartis and Roche, and participation on data monitoring boards and advisory boards for Roche, Eisai, Daiichi Sankyo, AstraZeneca, MSD and Novartis. SP declares fees for consultancy/advisory roles from Abbvie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Bio Invent, Biocartis, Blueprint Medicines, Boehringer Ingelheim, BMS, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-star, Foundation Medicine, Genzyme, Gilhead, GSK, Illumina, Incyte, IQIVIA, iTHeos, Janssen, Medscape, MSD, Merck Serono, Mirati, Novartis, Novocure, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, SeaGen, Takeda, Vaccibody, speaker roles for AstraZeneca, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Fishawack, Illumina, Imedex, Medscape, Mirati MSD, Novartis, OncologyEducation, PER, Pfizer, PRIME, RMEI, Roche/Genentech, RTP, Sanofi, Takeda and steering committee and trial chair roles as follows: AstraZeneca, coordinating PI, institutional, no financial interest, MERMAID-1; AstraZeneca, steering committee member, institutional, no financial interest, MERMAID-2, POSEIDON, MYSTIC; Beigene, steering committee member, institutional, no financial interest, BGB-A317-A1217-301/AdvanTIG-301; BMS, steering committee member, institutional, no financial interest, clinical trial steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451; BMS, steering committee member, institutional, no financial interest, RELATIVITY 095; GSK, trial chair, institutional, no financial interest, clinical trial chair ZEAL-1; iTeos, steering committee member, institutional, no financial interest, Phase 2 Inupadenant with chemo; Mirati, steering committee member, institutional, no financial interest, clinical trial steering committee SAPPHIRE; MSD, steering committee member, institutional, no financial interest, clinical trial steering committee PEARLS, MK-7684A; Pharma Mar, steering committee member, institutional, no financial interest, LAGOON; Phosplatin Therapeutics, steering committee member, institutional, no financial interest, phase 1/2 trials; Roche/Genentech, trial chair, institutional, no financial interest, clinical trial chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte. Also role as ESMO president, ETOP/EORTC/SAKK PI, involved in academic trials, ETOP/IBCSG partners officer. Council member and scientific chair, SAKK, vice-President Lung Group, SAMO, Vice President. BKS declares honoraria from Novartis and Eli Lilly. MS declares honoraria from AstraZeneca, MSD, Accord Health and Novartis, support for attending meetings from the Malaysia Urology Association and roles as an ex-committee member of the Malaysian Oncological Society and chairman of the Annual Scientific congress of the Malaysian Oncological Society. KT declares grants from Pfizer, Daiichi Sankyo, Eli Lilly, AstraZeneca, Eisai; honoraria from Daiichi Sankyo, Eli Lilly, Chugai, MSD; and data monitoring or advisory board fees from Daiichi Sankyo. SSW declares a grant from Pfizer and honoraria from Pfizer, Roche, AstraZeneca, Novartis, Daiichi Sankyo, Eli Lilly, MSD and Henrui. TY declares institutional grants from Amgen, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Genomedia, MSD, Ono, Pfizer, Sanofi, Sysmex and Taiho, and honoraria Bayer, Chugai, Merck biopharma, MSD and Ono. All other authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since trastuzumab was listed and approved for breast cancer in 2002, China has entered a new epoch of targeted therapy. Over the past 20 years, anti-human epidermal growth factor receptor 2 (HER2) targeted therapy for breast cancer in China has experienced the era of single-target, tyrosine kinase inhibitors, double-target and anti-HER2 plus antibody-drug conjugate. Advancement in the anti-HER2 targeted therapy is continuously changing the treatment mode of patients with HER2 positive status and even HER2 low expression, significantly improved their prognosis. In the past 20 years, Chinese scholars have participated in international clinical researches, completed a series of registration studies of imported drugs, developed new drugs with proprietary intellectual property rights, enriched the evidence of clinical research on HER2-targeted therapy, and formed a treatment system with both international standards and Chinese characteristics. In particular, the formulation of the Chinese Society of Clinical Oncology Breast Cancer Guidelines and the Chinese expert consensus on anti-HER2 targeted treatment in breast cancer are the concentrated embodiments of Chinese wisdom.

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P <0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.

With the development of new strategies like target therapy and immunotherapy, early breast cancer treatment has become more standardized, and the interval of disease free survival has been extended. Although guidelines and expert consensus have provided supports for clinical decision making, there are still some controversial issues in clinical practice, attributing to different treatment concepts, product indications and accessibility. These controversial issues would eventually affect the treatment of early breast cancer. This year in 2021, the approval of new indications of drugs like abemaciclib and the popularity of dual anti-human epidermal growth factor receptor 2 targeted drugs have promoted the change of treatment modalities for different types of early breast cancer. To this end, ten hot topics of early breast cancer are summarized according to their different molecular typing and treatment stages for discussion.

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression-free survival of first-line and second-line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease-free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45-2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38-0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival., (© 2020 Union for International Cancer Control.)

Human epidermal growth factor receptor-2 (HER-2) tyrosine kinase inhibitors (TKI) is the targeted drug of HER-2-positive breast cancer. Lapatinib, pyrotinib and neratinib, as ErbB family TKIs, have been approved by National Medical Products Administration and applied in the treatment of HER-2 positive breast cancer in China. The most common adverse effects (AEs) of TKI agents include diarrhea, drug-induced liver injury (DILI), nausea, vomiting, skin toxicity, cardiotoxicity and oral mucositis. The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence and characteristics of AEs of TKI, evaluated the manifestations and severity of AEs, and formulated the consensus of the management of common AEs based on the clinical experiences and updated advances from domestic and abroad studies. This consensus aims to provide the practical strategy for clinicians in the management of ErbB-family TKI-related AEs in China, and eventually enhance the patients' compliance and improve the therapeutic efficacy.

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.

Objective: To evaluate the clinical efficacy and safety of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer. Methods: Patients were randomized 2∶1 to test group and control group. Patients in test group received Cipterbin (4 mg/kg loading dose and 2 mg/kg maintenance dose each week, IV) combined with vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV). Patients in control group received vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV).The primary end point was progression free survival (PFS). Results: A total of 315 patients were enrolled from Jan 2009 to Jan 2013 (212 in test group and 103 in control group). The median PFS of test group was significantly longer than that of control group, 39.1 weeks vs 14.0 weeks ( HR =0.24; 95 %CI , 0.16-0.36; P< 0.000 1). The objective response rate (ORR) and disease control rate (DCR) in test group were significantly higher than those in control group, ORR was 46.7% vs 18.45% ( P< 0.000 1) and DCR was 79.72% vs 45.63% ( P< 0.000 1). The incidence of neutropenia, leucopenia and erythrocytopenia were higher in both groups, but there was no significant difference between two groups.The most common adverse events associated with Cipterbin were infusion reactions. Left ventricular ejection fraction reduced to less than 50% in 5 patients, which were recovered. No serious cardiotoxicity. Conclusion: The recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine has significant efficacy and good safety. It is the optimized therapy regime for patients with taxane-pretreated HER2 positive metastatic breast cancer, which provides more targeted therapy opportunities for HER2 positive breast cancer patients in China.

In the past two decades, with the introduction of NCCN guidelines, the establishment of a standardized diagnosis and treatment system for breast cancer had begun. The Chinese version of the NCCN guidelines, which combines international standards and Chinese characteristics, was then developed to guide clinical practice. Since 2011, Chinese experts have entered St. Gallen International Expert Consensus Group, and to introduce the latest therapy concepts. On this basis, the Chinese Society of Clinical Oncology has developed guidelines for diagnosis and treatment in line with product accessibility and expert opinions to help clinicians choose the best treatment option. The latest Chinese Society of Clinical Oncology Breast Cancer Guideline will further contribute to the establishment of a standardized diagnosis and treatment system for breast cancer.

Real-world study is increasingly becoming an important source of evidence for changing clinical practice, especially for clinical problems that can't be randomized. In recent years, real-world research in the field of breast cancer has gradually became a boom. Existing research results have begun to assist in the epidemiological analysis of breast cancer, promote the approval of rare diseases diagnosis and indication, and promote the analysis of real-world treatment status and evaluation of curative effects. Chinese scholars have also established databases and carried out relevant real-world research, providing real-world evidence for clinical practice in China. But domestic research is still in its infancy. The number of real-world research literature published by domestic scholars is relatively small, and there is a lack of pragmatic randomized clinical trial and real-world research for decision-making. In the future, we need to take advantage of the abundant diagnosis and treatment resources, further improve the database, and carry out real-world study on drug development based on population data in China.

Background: The usefulness of 3D deep learning-based classification of breast cancer and malignancy localization from MRI has been reported. This work can potentially be very useful in the clinical domain and aid radiologists in breast cancer diagnosis., Purpose: To evaluate the efficacy of 3D deep convolutional neural network (CNN) for diagnosing breast cancer and localizing the lesions at dynamic contrast enhanced (DCE) MRI data in a weakly supervised manner., Study Type: Retrospective study., Subjects: A total of 1537 female study cases (mean age 47.5 years ±11.8) were collected from March 2013 to December 2016. All the cases had labels of the pathology results as well as BI-RADS categories assessed by radiologists., Field Strength/sequence: 1.5 T dynamic contrast-enhanced MRI., Assessment: Deep 3D densely connected networks were trained under image-level supervision to automatically classify the images and localize the lesions. The dataset was randomly divided into training (1073), validation (157), and testing (307) subsets., Statistical Tests: Accuracy, sensitivity, specificity, area under receiver operating characteristic curve (ROC), and the McNemar test for breast cancer classification. Dice similarity for breast cancer localization., Results: The final algorithm performance for breast cancer diagnosis showed 83.7% (257 out of 307) accuracy (95% confidence interval [CI]: 79.1%, 87.4%), 90.8% (187 out of 206) sensitivity (95% CI: 80.6%, 94.1%), 69.3% (70 out of 101) specificity (95% CI: 59.7%, 77.5%), with the area under the curve ROC of 0.859. The weakly supervised cancer detection showed an overall Dice distance of 0.501 ± 0.274., Data Conclusion: 3D CNNs demonstrated high accuracy for diagnosing breast cancer. The weakly supervised learning method showed promise for localizing lesions in volumetric radiology images with only image-level labels., Level of Evidence: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1144-1151., (© 2019 International Society for Magnetic Resonance in Medicine.)

Objective: To compare the bioequiavailability of paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane in the patients with metastatic breast cancer, and to investigate the safety and efficacy in the extension treatments of PAB. Methods: This study was random, two cycles, self-crossover control study in the bioequiavailability stage. PAB was the investigational drug T and Abraxane was the reference drug R. Patients were randomly assigned to two cycles therapy of either R→T or T→R(260 mg/m(2)/21d). Non-PD patients entered in the extension treatments of the investigational drug PAB(260 mg/m(2)/21d) until the disease progression or the intolerance toxicity. Results: From Mar 1, 2016 to May 24, 2016, we enrolled 40 patients. The blood concentration-time curve and the parameters of pharmacokinetics indicated the two drugs were the bioequivalent drug products in the initial two cycles crossover-therapy.The incidence of adverse drug reactions were 89.7% vs 97.4% in investigational drug vs reference drug and grade 3/4 toxicities were 20.5% vs 21.1%( P =1.000). Patients received a median of 7 treatment cycles(range 1-23) and a median of 260mg/m(2) actual drug dose (range 220-260 mg/m(2)). Seven patients (17.5%) had dose reductions because of toxicities (260 mg/m(2) reduce to 220 mg/m(2)). Twenty-two patients (55%) discontinued treatment prematurely because of toxicity.Overall response rates (ORR) were 40% (95% CI , 24.8%-55.2%). For patients who received PAB as first-line vs non-first-line therapy, the ORR were 43.8% vs 25%. For patients who taxane-naïve vs taxane-pretreated, the ORR were 45.5% vs 37.9%. Median PFS was 49 weeks(95% CI , 30weeks-NA). Conclusion: The paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane are the bioequivalent drug products.The toxicity and efficacy of the PAB are similar with abraxane.The more therapy chances for Chinese patients will come by the research and development of domestic drugs.

The rigorous randomized clinical trials and qualified real world evidence have improved the domestic standardized diagnosis and therapy. Meanwhile, the recent consensus and guideline integrated with Chinese realities have also promoted the breast cancer therapy. To expound our views and to provide suggestions for the revision of breast cancer guideline of Chinese Society of Clinical Oncology, we select ten hot issues to discuss with our experience.

Background: The metastasis of axillary lymph node (ALNs) is a critical step in the initial cancer staging of newly diagnosed breast cancer (BC) patients. Various imaging modalities can enhance the sensitivity of clinical examination in assessing the ALN status., Patients and Methods: We enrolled 135 patients with BC, confirmed via histopathology, including 4 bilateral BC cases. A total of 139 ipsilateral ALNs adjacent to the breast lesion were examined via physical examination, ultrasonography (US), and magnetic resonance imaging (MRI); of these, 100 were nonpalpable ALNs, as determined by experienced breast surgeons and physicians. The relative size parameters on MRI and US images were recorded. Receiver operating characteristic (ROC) analyses were conducted, and the area under the ROC curve (AUC) was compared., Results: Of 139 ALNs, 67 (48%) were malignant and 72 (52%) were benign on pathological examination. In all of the ALNs, the US short diameter appeared to be the most discriminative quantitative measurement for detecting positive findings (AUC, 0.854). In nonpalpable ALNs as well, the US short diameter exhibited the greatest discriminability (AUC, 0.746). However, the 2-dimensional and 3-dimensional parameters on MRI did not exhibit any significant differences between the enrolled and nonpalpable ALNs (P > .05)., Conclusion: The shortest diameter on US exhibited better discriminative ability than MRI for predicting positive ALNs in nonpalpable axillae. Moreover, the 2-dimensional and 3-dimensional parameters on MRI did not differ in terms of discriminability., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to explore the response to neoadjuvant chemotherapy (NAC) in nonconcentric shrinkage pattern of breast cancer (BC) patients using H-magnetic resonance spectroscopy., Methods: Twenty-five BC patients were the study cohort. All patients received AT-based regimen as first-line treatment. Tumor response to chemotherapy was evaluated after the second and fourth cycles using magnetic resonance imaging and magnetic resonance spectroscopy. Final histopathology following surgery after 4 to 8 cycles of NAC served as a reference. Changes in total choline integral* (tCho) and tumor size in response versus nonresponse groups were compared using the 2-way Mann-Whitney nonparametric test. Receiver operating characteristic (ROC) analyses were undertaken, and the area under the ROC curve compared among them., Results: H-magnetic resonance spectroscopy revealed a negative tCho integral* in 6 cases at the first follow-up and 14 cases at the second follow-up. Based on pathology (Miller-Payne system), there were 16 cases of response, and 9 cases of nonresponse. The tCho integral* was significantly different between the response and nonresponse groups at the second follow-up (P = 0.027). The tumor size changes were not significantly different in the response and nonresponse groups at the second follow-up study (P > 0.05). The comparison of ROC curves among the change in tCho integral* and tumor size at baseline and both follow-ups revealed the maximum area under the ROC curve of the change in tCho integral* to be 0.747 at the second follow-up, sensitivity to be 93.75%, and positive predictive value to be 78.9%., Conclusions: In nonconcentric shrinkage pattern after NAC of BC, when tumor size is difficult to reflect the response, tCho integral* reduction may be a predictive marker.

Obiective: To explorethe correlation between Neo-Bioscore and disease-free survival (DFS) after neoadjuvant therapy in patients with breast cancer in China. Methods: The clinical and pathological data of 429 patients with early or locally advanced breast cancer who received neoadjuvant therapy at the No.307 Hospital of PLA from January 1, 2005 to December 31, 2015 were analyzed and we followed up their DFS. Results: Neo-Bioscore were closely related to DFS (χ(2)=47.662, P <0.001). When the groups were divided by Neo-Bioscore 3, they weremore relevantto DFS ( HR =5.093 vs HR =2.044), equivalent tothe role of traditional recurrence risk grouping in guiding the choice of adjuvantendocrine regimen for hormone receptor (HR) positive patients who were premenopausalafter neoadjuvant chemotherapy, andmore relevantto DFS than whetherthe pathologic complete response (pCR)grouping in the same molecular pathology subgroup of HR positive/human epidermal growth factor receptor 2 (HER-2)negative ( P <0.001 vs P =0.166), HER-2 positive ( P <0.001 vs P =0.166), HRnegative/HER-2 negative ( P <0.001 vs P =0.166). Conclusions: Neo-Bioscore could be used as an early indicator of predicting DFS for breast cancer patients after neoadjuvant therapy.When the groups were divided by Neo-Bioscore 3, they were more relevant to DFS, equivalent to the role of traditional recurrence risk grouping in guiding the choice of adjuvantendocrine regimen for premenopausal HR positive patients, andmore relevantto DFS than whetherthe pCRgrouping in the same molecular pathology subgroup.

Objective: Circulating tumor cells (CTC) have become an important part of liquid biopsy, which have underwent a process from simple counting to molecular typing and genotyping. To this end, we used Cellcollector to verify the effectiveness and safety of CTC detection in patients with breast tumor, and to conduct the following analysis. Methods: One hundred and ninety patients who received treatment in six leading Chinese cancer centers were involved from April to August in 2016. Among which, 127 patients were diagnosed as metastatic breast cancer, and the other 63 patients as benign breast tumors. Results: In metastatic breast cancer group, 74.8%(95/127) were CTC positive. While in benign tumor group, they were all CTC negative patients. The area under the Receiver Operating Characteristic curve were 0.832(95% CI : 0.784-0.879). The sensitivity of Cellcollector was 74.8%, specificity was 100% (Youden index 0.748). A total of 117 patients in MBC groups received a second detection of Cellcollector after 3-4 weeks, among which 44.4% (52/117) were CTC positive patients. The incidence of adverse events and severe adverse events in MBC was 66.9%(85/127) and 39.8% (53/127). Furthermore, we used Cellcollector to perform the HER2 testing and gene sequencing. Conclusions: In vivo isolation of CTCs overcomes blood volume limitations compared to other approaches. The further application of molecular typing and gene typing might help to implement CTC-based "liquid biopsies" into clinical decision making.

Background: The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA)., Methods: From March 6, 2014 to December 10, 2014, 24 plasma samples from 20 patients with HER2-positive metastatic breast cancer who received systemic therapy were eligible. We used a panel for detection of hot-spot mutations from 50 oncogenes and tumor suppressor genes, and then used targeted next-generation sequencing (NGS) to identify somatic mutation of these samples in those 50 genes. Samples taken before their first trastuzumab administration and subsequently proven with clinical benefit were grouped into sensitive group. The others were collected after disease progression of the trastuzumab-based therapy and were grouped into the resistant group., Results: A total of 486 single-nucleotide variants from 46 genes were detected. Of these 46 genes, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), proto-oncogene c-Kit (KIT), and tumor protein p53 (TP53) were the most common mutated genes. Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred m utations in the resistant group were associated with the resistance of targeted therapy. In addition, we detected a HER2 S855I mutation in two patients who had persistent benefits from anti-HER2 therapy., Conclusion: Targeted NGS of cfDNA has potential clinical utility to detect biomarkers from HER2-targeted therapies.

In the past two years, researchers have been exploring the precision medicine. Thanks to the development of sequence industry and clinical study, the big data about the precision medicine have been more and more sufficient. However, how to deal with the precision data is still a question for clinicians. We focus on the hot issues that disturb clinicians most, wanting to help them to make suitable decisions between the traditional and precision medicine of breast cancer. We believe the precision medicine is on the way.

Objective: This retrospective study investigated the association between hormone receptor (HR) conversion and survival in breast cancer patients., Methods: Estrogen receptor (ER) and progesterone receptor (PR) status (positive or negative) of primary tumors and of paired metastatic sites in 627 breast cancer patients were analyzed by McNemar's test for rates of receptor conversion. A survival analysis was performed using the Kaplan-Meier method, and prognostic factors were assessed using Cox's proportional hazards regression model., Results: Conversion of ER occurred in 165 (26.31%) patients, and conversion of PR in 213 (33.97%; P < 0.001, both). For 82 patients whose ER and PR were reassessed 2-4 times during metastatic progression, ER and PR re-conversion occurred in 22 (26.83%) and 29 (35.36%), respectively. The change of ER or PR from positive to negative was associated with worse overall survival and post-recurrent survival (log-rank; P < 0.001, both). A subgroup analysis of HR-positive patients (i.e., positive ER, PR, or both) in primary tumor and HR-negative in metastatic sites showed that patients who accepted both salvage endocrine therapy and chemotherapy had better post-recurrent survival than did those who accepted salvage chemotherapy only (log-rank; P = 0.003)., Conclusion: ER and PR status may change several times during metastatic tumor progression. A change of HR from positive to negative was associated with worse survival compared with consistent positivity. Repeated evaluations of HR status are necessary in metastatic breast cancer. Salvage hormonal therapy is still worth trying for patients whose HR status changes from positive to negative.

Objective: To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes. Methods: Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of Military Medical Science Academy of the PLA were enrolled.The clinical and pathological characteristics of patients were collected. The primary endpoint was pCR rate and the secondary endpoint was disease free survival (DFS). We analyzed the predict values of pCR rate for patient outcome, and the predict factors for DFS by univariate and multivariate Analysis. Results: A total of 416 BC patients confirmed by pathology were enrolled and received treatment and assessment in this study. The overall pCR rate was 23.1% (96/416). The pCR rate was 6.9% (14/204) in patients of HR+ /HER2- Subtype, 41.5% (27/65) in HR-/HER2+ Subtype, 30.9% (17/55) in HR+ /HER2+ Subtype, and 41.1% (37/91) in HR-/HER2- Subtype. The correlation of the pathological status and the patient outcome was analyzed in all patients. Compared with no pCR group, pCR group had significant higher DFS rates. In HER2+ Subtype and HR-/HER2- Subtype, DFS rates of patients who achieved pCR was higher than that of who didn't achieved pCR. In HR+ /HER2- Subtype, DFS rates of patients who achieved pCR was higher than that of who didn't achievced pCR, but without statistics difference. The Cox proportional hazards regression analysis revealed that ER status, T stage, pCR affected the patient outcome of BC. Conclusion: So far, pCR was an established prognostic factor: reaching a pCR could predicte improved survival in HER2-enriched BC and triple-negative breast cancer (TNBC) subgroup, while data remain controversial for the luminal subtypes. Our results do not support the use of pCR as a surrogate end point of treatment efficacy in unselected patients with BC submitted to neoadjuvant systemic therapy.

Aim: To describe the clinical manifestations and radiological features contributing to the early diagnosis of radiation-induced sarcoma (RIS) after radiotherapy for breast cancer., Materials and Methods: This retrospective analysis included four typical cases of RIS diagnosed at Affiliated Hospital of Academy of Military Medical Sciences between 1980 and 2013. Patient and imaging characteristics, treatment modalities, and outcomes were extracted from patients' medical records. Two pathologists reviewed all histological slides., Results: All four cases were misdiagnosed and treated for several months as cases of breast cancer relapse. CT using the bone-window setting and three-dimensional reconstructions clearly displayed bone tumours of RIS in three cases. Skin alterations were observed in all cases. At the time of RIS diagnosis, three patients were free of breast cancer. In one patient with bilateral breast cancer and lung metastasis, chemotherapy resulted in complete remission of the metastasis, but RIS progression. No RIS in this series responded to chemotherapy or endocrine therapy., Conclusions: Abnormalities appearing in the radiation field long after RT should alert clinicians to the potential development of RIS. Careful physical examination and follow-up imaging studies are necessary. The presence of skin alterations, bone tumours at CT or radiography, and poor response to anti-cancer drugs may contribute to the early detection of RIS. Biopsy should be performed immediately when RIS is suspected., (Copyright © 2014. Published by Elsevier Ltd.)

Prognostic factor analysis has been conducted to determine whether the parameters of clinical data and biomarkers would predict differential progression-free survival (PFS) or overall survival (OS) from lapatinib-based therapy in patients with primary or acquired resistance to trastuzumab. Treatment with lapatinib plus capecitabine for HER2-positive metastatic breast cancer (MBC) with primary or acquired resistance to trastuzumab was analyzed retrospectively. Tumor biomarkers, which came from the biopsies before the starting of lapatinib therapy, were evaluated by immunohistochemistry (IHC). Prognostic factors related to PFS or OS of the lapatinib therapy were assessed by univariate and multivariate analysis. Ki-67 index and liver metastases were the significant prognostic factors for predicting PFS of subsequent lapatinib therapy in the univariate analysis and the multivariate analysis. The risk for disease progression in patients who had a Ki-67 index<40% was 59% less than that in patients had Ki-67 ≥ 40 (HR = 0.41, 95% CI, 0.23-0.74, P = 0.003). TTP of prior trastuzumab therapy, liver metastases, and the number of metastatic sites were three independent prognostic factors of subsequent lapatinib therapy. Ki-67 index was the significant prognostic factors for predicting PFS of the subsequent second line targeted therapy in patients with trastuzumab resistance.

Objective: To observe the preliminary efficacies and adverse events of sunitinib in the treatment of metastatic breast cancer ulcer., Methods: From December 2008 to May 2010, patients with advanced breast cancer ulcer took a single sunitinib. The dosage was adjusted on the basis of adverse events. And clinical response was evaluated., Results: Nine patients with advanced breast cancer ulcer finished the treatment. The objective response and the clinical benefit time to progression of sunitinib were 3 and 7 patients with metastatic breast cancer ulcer, and the median time to progression (TTP) was 2.0 months. The most common adverse events included fatigue, hand-foot syndrome, neutropenia, thrombocytopenia and hypertension., Conclusion: Single-agent sunitinib treatment of refractory advanced breast cancer ulcer has marked efficacies. However, neutropenia, thrombocytopenia and hypertension are the major dose-limited toxicities.

Objective: To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients., Methods: A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed., Results: Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences., Conclusions: The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

Objective: To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer (MBC) developing successive resistance to multi-line targeting therapies., Methods: The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department. All patients were treated with trastuzumab, lapatinib and retreated with trastuzumab sequentially. Twenty-one patients progressed during the initial trastuzumab therapy. All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently. A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis., Results: The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy. The time-to-progression (TTP) of prior lapatinib therapy was an influencing factor of median progression-free survival (PFS) (P < 0.0001) and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival (OS) (P = 0.008) of trastuzumab retreatment in our univariate analysis. The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy > 12 weeks (hazard ratio (HR) = 0.02, P = 0.003) or whose duration of double trastuzumab treatment ≤ 1 year (HR = 0.26, P = 0.03) was significantly prolonged in multivariate analysis. Meanwhile, the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment ≤ 4 weeks decreased 89% as compared with trastuzumab retreatment (HR = 0.11, P = 0.004)., Conclusion: TTP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment. And the duration from discontinuation of lapatinib to trastuzumab retreatment is an important independent prognostic factor for trastuzumab retreatment. The patients with HER2 positive MBC should be treated continually with anti-HER2 targeted therapy.

Objective: To evaluate the correlation of clinical effects and reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer., Methods: We reviewed retrospectively the clinical records of patients with metastatic breast cancer treated with docetaxel and statistically analyzed the correlation between clinical effects and reasonable doses of docetaxel., Results: The objective response rate and clinical benefit rate of docetaxol in patients with metastatic breast cancer were 27.0% and 35.0%, respectively, and the median progression free survival (PFS) was 5.0 (3.8 - 6.3) months. In the analysis at a single dose level, the clinical benefit rate and PFS of the ≥ 90.0 mg/m(2) docetaxel group were superior to that of the < 90.0 mg/m(2) group (P = 0.008, P = 0.045). Multi-dose level group stratified analysis showed that the docetaxel < 75.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) PFS group (P = 0.018), and the ≥ 95.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) group (P = 0.048). In patients who received >third line treatment or previously received paclitaxel adjuvant therapy, the PFS of the ≥ 94.9 mg/m(2) docetaxel group was 6.0 months, better than the 3.0 months of the 75.0 ∼ 84.9 mg/m(2) group (P = 0.031; P = 0.021)., Conclusion: There is a clear correlation between clinical effects and reasonable doses of docetaxel salvage therapy in patients with metastatic breast cancer.

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients' beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients' persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8% for the standard treatment group and the standard treatment plus patient support program group, respectively (P=0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P=0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P=0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio=3.9; 95% CI, 1.1-13.7; P=0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients' persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.

Background: Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy., Methods: In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients., Results: Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature., Conclusions: We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.

Objective: To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer., Methods: Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles., Results: Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01)., Conclusions: The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.

To investigate a quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay different from 21-gene assay which can be used to prognosticate the risk of recurrence in patients with estrogen receptor (ER) positive, lymph node (LN) negative breast cancer. To accurately determine the relationship between the Recurrence Score (RS) derived from our assay and the risk of distant recurrence in Chinese patients with LN negative and positive breast cancer through the analysis of paraffin tissues. We obtained archival paraffin-embedded tissues from patients with invasive breast cancer and varying axillary lymph node involvement. QRT-PCR reaction was performed by using the method of SYBR Green I dye with primers. Expression of the 21-genes was converted to RS by a prespecified algorithm. We then assessed the probability of the test to accurately predict distant recurrence-free survival in this retrospective cohort. Ninety-three patients were eligible based on gene expression profiles. In our population, most breast cancer patients were premenopausal (82.6%), at early stage (93.6%) and ER positive (91.4%). Median follow-up was 65.9 months. The 5-year recurrence-free survival rate for the group was 58.8%. The concordance between the reverse transcription-PCR and immunohistochemical (IHC) measurement for ER, progesterone receptor (PgR), and HER-2 determinations was high and comparable. High RS was predictive of an elevated risk of relapse (p < 0.001). In subgroups of patients, RS had significantly predictive performance both in node-negative (p = 0.009) and node-positive patients (p = 0.038). Multivariable analysis showed that nodal status, adjuvant hormonal therapy and RS were significantly related to prognosis. RS category is a better predictor than the other risk assessment criteria or clinicopatholic features, with which we can determine more accurately the risks for recurrence of various patients. We have established an easy and economical QRT-PCR assay and validated in concordance with IHC measurements for ER, PgR, and HER-2. RS was associated with distant recurrence among Chinese patients with hormone receptor (HR) positive breast cancer. This study may promote the use of RS estimated from the expression of the 21-gene set for prognostication and routine clinical diagnostic application in Chinese populations., (© 2011 Wiley Periodicals, Inc.)

Urokinase plasminogen activator (uPA) correlates closely with breast cancer metastasis via triggering the degradation of divergent matrix proteins. Here, uPA was selectively knocked down in breast carcinoma MDA-MB-231 cells by siRNAs. The in vitro migration of MDA-MB-231 cells was effectively suppressed accompanied by a decrease in extracellular MMP-9 activities. The colony formation ability of MDA-MB-231 cells was inhibited following uPA knockdown, while the proliferation was not affected. The uPA knockdown in MDA-MB-231 cells caused significantly suppressed tumor metastasis in nude mice. Thus, siRNAs targeted to uPA have implications in the development of novel approaches to preventing breast cancer metastasis.

Objective: To evaluate the efficacy and safety of weekly or 3-week docetaxel in combination with capecitabine., Methods: 83 Patients with at least one measurable lesion were randomized to receive the treatment arms: docetaxel 37.5 mg/m(2) on days 1 and 8, oral capecitabine 950 mg/m(2) twice daily on days 1-14 (Group A); docetaxel 75 mg/m(2) on days 1, oral capecitabine 950 mg/m(2) twice daily on days 1-14 (Group B). Each cycle was repeated every 3 weeks., Results: Eighty-three patients were enrolled, 78 eligible for tumor assessment. The overall clinical response rate of all groups was 61.4% (51/83). There was no progressive disease (PD) after two cycles. Efficacy outcomes were similar in the two groups. The response rate of group A and B were 61.8% (21/34) and 61.2% (30/49) respectively. There were no drug-related deaths observed. Neutropenia was the most common toxicity. In all, the frequency of Grade 3/4 neutropenia were 45.8% (38/83), but Grade 3/4 neutropenia of Group B 55.1% (27/49) was higher than Group A 32.4% (11/34), P = 0.04., Conclusion: The study confirmed the superior activity of docetaxe-capecitabine combination therapy in anthracycline resistant MBC, and comparing with 3-week schedule, weekly docetaxel plus capecitabine has same high efficacy with a favourable safety profile.

Objective: To compare the efficiency of response evaluation by clinical examination, ultrasonograghy and mammography in neoadjuvant chemotherapy (NAC) for breast cancer., Methods: A retrospective cohort study was conducted to analyze the data of 141 patients treated with neoadjuvant chemotherapy. Response evaluation was performed by clinical palpation, ultrasound and mammography., Results: Only 12 (8.5%) among the 141 patients presented with a stage I tumor. The tumor size determined by palpation was often larger than that by ultrasound before therapy (P < 0.01). Among patients with suspicions axillary nodes checked by ultrasound, 88.3% (53/60) of them had positive nodes by pathology before NAC, and 34.5% (10/29) of patients with negative nodes determined by ultrasound had positive nodes by pathology. In all the 141 patients, 21(14.9%) showed pathological complete remission in both the primary tumor and lymph node. For response evaluation, the false complete remission rate judged by clinical examination was 46.8% (22/47), and the false tumor residual rate by ultrasound was 84.0% (21/25). In 53.5% (23/43) of patients the response could not be assessed by mammography due to that the tumors were undistinguishable in size. The range of microcalcification was not reduced in 5 patients with a partial response of the tumor. 25 patients experienced needle puncture during therapy. Among them, in the 9 pathologically negative patients, only 3 achieved pCR, and the other 16 positive patients didn't achieve pCR., Conclusion: Using the puncture or sentinel lymph node biopsy, clinicians should pay enough emphasis on the pathological determination of the node status before chemotherapy. Clinicians will make a quite of false judgment of the tumor by clinical examination, ultrasound or mammography. They may use needle puncture during therapy to evaluate the response of neoadjuvant chemotherapy, and the result should be analyzed synthetically.

Objective: To investigate the predictive value of HER-2 and ER expression for chemosensitivity of taxane in the treatment of advanced breast cancer., Methods: Of 268 advanced breast cancer patients treated: 71 were by paclitaxel alone, 32 by docetaxel alone, 110 by paclitaxel combined with anthracylines or gemcitabine or platins and 55 by docetaxel-based combinations. HER-2 and ER expression of all patients treated by taxane underwent immunohistochemical (IHC) assay., Results: Univariate analysis showed: the response rate (RR) in HER-2 overexpression group was 56.7%, and in HER-2 weak expression group 33.3% (P = 0.003). The response rate in ER positive group and ER negative group was 33.3% and 48.9%, respectively, with a significant difference (P = 0.015). The RR was 67.6% in ER negative but HER-2 overexpression group. However, in ER positive but HER-2 weak expression group and the other groups, the RR were around 35% (P < 0. 01). Multivariate analysis showed that overexpression of HER-2 was the only significant factor to predict the chemosensitivity of taxane (P = 0. 007), but the ER, Karnofsky performance score (KPS), anthracylines, metastatic sites were not the statistically significant chemo-sensitivity predictive factors for taxane., Conclusion: ER negative and/or HER-2 overexpression, especially latter, may be associated with good response in advanced breast cancers treated by taxane.

Objective: To investigate the expression of oncoprotein c-erbB2 in primary breast cancer and to analyze its relation to its prognosis., Methods: Immunohistochemical staining for c-erbB2 was performed on paraffin-embedded specimens of primary breast cancer from 284 patients, and the relation to its prognosis was statistically analyzed., Results: Positive expression rate of c-erbB2 was 26.8% (76/284) in 284 primary breast cancer patients. Expression of c-erbB2 was positively correlated with the status of lymph node metastasis (P = 0.003). Univariate analysis indicated that c-erbB2 expression is a significant prognostic factor for the disease-free survival (DFS) (P = 0.024) and overall survival (OS) (P = 0.002), while multivariate analysis demonstrated that c-erbB2 is an independent prognostic factor for OS (P = 0.023). Moreover, tumors with c-erbB2 positive expression are more tend to metastasis to other viscera than those with c-erbB2 negative. c-erbB2 expression has different prognostic values for patients with different status of estrogen receptor (ER) and lymph node metastasis., Conclusion: c-erbB2 expression is an independent prognostic factor for total survival time in primary breast cancer patients, and its prognostic values are different according to the different ER status and lymph node metastasis.