[Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer].

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 χ2 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.

[Adjuvant therapy strategies for breast cancer based on the efficacy of neoadjuvant therapy].

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.

[A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer].

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.

[Rediscussion on hot issues of endocrine therapy for breast cancer].

In the past decade, generated data of large-scale clinical research of endocrine therapy and the update of guidelines have changed clinical practice of breast cancer treatment. However, there are unresolved issues on endocrine therapy. Based on new evidences and clinical experience, we expounded our points on neoadjuvant endocrine therapy, CDK4/6 inhibitoradjuvant therapy, concepts of endocrine sensitivity and endocrine resistance, first-line treatment for metastatic breast cancer, treatment options after progression on CDK4/6 inhibitor and treatment ofvisceral crisis.

[Expert consensus on endocrine therapy of breast cancer (2023 edition)].

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.

[Development in the last 20 years of anti-HER2 targeted therapy for breast cancer].

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.

[Expert consensus on the management of adverse events of CDK4/6 inhibitors in 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.

[Cold thinking on ten hot issues in the treatment of early breast cancer].

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.

[Chinese Society of Clinical Oncology Breast Cancer Guideline version 2021: updates and interpretations].

Objective: Since the first publication in 2017, the Chinese society of clinical oncology breast cancer guidelines have been updated in four editions, and nearly 300 000 volumes have been published, which has been widely recognized by scholars at home and abroad. The important updates from pathological diagnosis to therapies in the newest guideline has been updated in accordance with evidence, drug accessibility and expert opinions. Meanwhile, more chapters, like drug adverse reaction management, real-world research, biosimilar drugs, have been added, making a comprehensive guideline in guiding breast cancer standardized diagnosis and treatment.

[Opportunity and challenge of neoadjuvant treatment in triple negative breast cancer].

Triple negative breast cancer (TNBC) is a special type of breast cancer. At present, the major treatment for TNBC is chemotherapy. Neoadjuvant therapy and obtained pathology completed response could bring the TNBC patients better prognosis. The most used TNBC chemotherapy protocols are established on the basis of anthracycline and taxane. Through the thorough knowledge of molecular mechanism of TNBC, neoadjuvant therapy protocols have optimized, including the use of platinum, immune checkpoint inhibitors and poly-ADP-ribose polymerase inhibitors, and assumed positive outcome for TNBC patients.

[Expert consensus on the management of adverse events of ErbB family tyrosine kinase inhibitors in breast cancer].

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.

[Phase â ¢ randomized controlled, multicenter, prospective study of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer: the HOPES Study].

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.

[Development of guidelines and clinical practice for breast cancer].

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.

[The present situation and future of real world research in diagnosis and treatment of 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.

[Cold thinking in the boom of artificial intelligence].

Artificial intelligence clinical decision-support system is an important direction of artificial intelligence in the medical field. Both international and domestic researchers are exploring the application value of intelligent decision-making system in the field of cancer. But at the same time of the craze, there are still some problems in the intelligent decision-making system. Combining the work of the research groups in this field, this paper explores the current confusions and solutions, and hopes to help clinicians better understand intelligent decision-making. It is believed that with the deepening of the concept and the advancement of technology, intelligent decision-making will become a good help for doctors in the future.

[Study of bioequiavailability of paclitaxel for Injection (Albumin Bound) and abraxane and the efficacy of extension treatments in patients with metastatic breast cancer].

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.

[A multicenter, randomized, controlled, phase â £ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

[Ten hot issues of breast cancer in diagnosis and therapy in 2018].

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.

[Circulating tumor cells in patients with breast tumors were detected by a novel device: a multicenter, clinical trial in China].

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.

[A study on the correlation between Neo-Bioscoresystem and disease-free survival of breast cancer patients with neoadjuvant chemotherapy].

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.