Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer / 中华医学杂志(英文版)

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

Conversion of ER, PR, HER2 and Ki-67 and Prognosis in breast cancer metastases to the brain.

Objective: This study aimed to analyze the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index in the brain metastatic lesions and primary lesions in Chinese patients with breast cancer brain metastasis (BCBM) and determine the correlation between their changes and patients' survival. Methods: A retrospective analysis was performed on patients with BCBM. The clinical characteristic of these patients was collected. The differences in the expression levels of the ER, PR, HER-2, and Ki-67 index between the primary lesions and brain lesions were evaluated, and the association between the differences and survival was analyzed. Results: The conversion rate of anyone receptor (ER, PR, or HER2) between the primary lesions and brain metastatic lesions was 45.0% (18/40), of which the ER inconsistency rate was 25.0%, the PR inconsistency rate was 22.5%, and the HER-2 inconsistency rate was 15.0%, and the receptor conversion resulted in a subtype conversion of 27.5% (11/40). The patients with HER-2 expression discordance between the primary lesions and the brain metastatic lesions had significantly longer survival times (58.9 vs. 26.4 months, P = 0.04) after diagnosis of brain metastases. Conclusion: In this study, 45.0% of breast cancer patients developed biomarker-conversion between the primary lesions and brain metastatic lesions, and the differences in the expression levels of the ER, PR, and HER-2, the change in Ki-67 index between the primary lesions and brain lesions may predict patients' survival.

Two Color Single Molecule Sequencing on GenoCare 1600 Platform to Facilitate Clinical Applications

With the rapid development of precision medicine industry, DNA sequencing becomes increasingly important as a research and diagnosis tool. For clinical applications, medical professionals require a platform which is fast, easy to use, and presents clear information relevant to definitive diagnosis. We have developed a single molecule desktop sequencing platform, GenoCare 1600. Fast library preparation (without amplification) and simple instrument operation make it friendlier for clinical use. Here we presented sequencing data of E. coli sample from GenoCare 1600 with consensus accuracy reaches 99.99%. We also demonstrated sequencing of microbial mixtures and COVID-19 samples from throat swabs. Our data show accurate quantitation of microbial, sensitive identification of SARS-CoV-2 virus and detection of variants confirmed by Sanger sequencing.

The present situation and future of real world research in diagnosis and treatment of breast cancer / 中华外科杂志

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.

Development of guidelines and clinical practice for breast cancer / 中华外科杂志

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.

Effect of ethnicity on vinorelbine pharmacokinetics: a population pharmacokinetics analysis.

BACKGROUND: Pharmacokinetics of vinorelbine is mainly known from studies conducted in European patients. Interethnic differences in drug disposition may, however, induce interethnic variation in drug exposure. This paper aimed to evaluate the effect of ethnicity on the bioavailability and clearance of oral and intravenous vinorelbine. METHODS: Oral and intravenous vinorelbine pharmacokinetics data in Asian patients were pooled from two-phase II studies of patients with non-small-cell lung cancer or advanced breast cancer in China. Blood vinorelbine and its active metabolite, 4'-O-deacetylvinorelbine, were quantified using liquid chromatography-tandem mass spectrometry. Bayesian pharmacokinetic parameters were calculated and vinorelbine monotherapy results (intravenous 25 mg/m2; oral 60 mg/m2) of the Asian data set were compared to a reference European data set (intravenous 30 mg/m2; oral 80 mg/m2). Subsequently, a population pharmacokinetics analysis was conducted in a combined cohort (Asian data set + historical vinorelbine pharmacokinetics database) to investigate for a potential effect of ethnicity. RESULTS: Pharmacokinetics data from the Asian data set (oral: n = 47; intravenous: n = 34) was compared to the European reference data set (oral: n = 48; intravenous: n = 48). Mean apparent clearance of oral vinorelbine and mean absolute clearance of intravenous vinorelbine was comparable between the Asian and reference European data set. A population pharmacokinetic analysis (oral: n = 222; intravenous: n = 111) demonstrated no influence of ethnicity on oral and intravenous vinorelbine bioavailability and clearance. CONCLUSION: Vinorelbine pharmacokinetics were found to be comparable between Asian and European patients. No relevant influence of ethnicity on vinorelbine bioavailability and clearance for oral and intravenous routes of administration was observed.

Cold thinking in the boom of artificial intelligence / 中华外科杂志

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.

Ten hot issues of breast cancer in diagnosis and therapy in 2018 / 中华外科杂志

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.

Treatment with everolimus for a patient with systemic metastatic breast cancer results in severe pulmonary injury: a case report.

Everolimus has been used in patients with hormone receptor-positive breast cancer. This study reports that treatment with everolimus alone induced severe pulmonary injury in a patient with systemic metastatic breast cancer. A 58-yearold woman with systemic metastatic breast cancer was treated with everolimus alone for 4 weeks and developed severe cough and dyspnea. Computed tomography (CT) scan of the chest showed a progressive lung tumor accompanied by bilateral pulmonary homogeneous ground-glass opacity, especially in the inferior lobe of the left lung. Laboratory examinations revealed a high frequency of monocytes, higher levels of serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and C-reactive protein as well as mild hypoxemia and hypocarbia. However, she had no evidence of infection with mycoplasma pneumoniae, chlamydia, pneumocystis, tuberculosis, influenza A virus, and was negative for serum galactomannan (GM) antigen assay. She was suspected to have drug-induced interstitial pneumonia. Everolimus treatment was stopped, and treated with methylprednisolone and empiric antibiotic therapy for 7 days. She received further corticosteroid treatment and felt much better, accompanied by clearance of lung inflammation; she was discharged from hospital. Our experience suggests that treatment with everolimus alone may cause severe pulmonary injury and should be considered carefully in cases of patients with systemic metastatic breast cancer.

The progression of tumor liquid biopsy and its applications in precision medicine / 中华外科杂志

Malignant tumor is the most heterogeneous human disease, and it has been gradually reached the consensus in clinical oncology that the personalized treatment of tumor patients should be directed by molecular diagnostics. However, the ever-changing characteristic of tumor in heterogeneity and the fact that tissue samples are usually unavailable highlight the function and significant of liquid biopsy. The material that could be used in liquid biopsy are mainly the circulating tumor DNA, circulating tumor cells and extracellular vesicles, which though have their own advantages and disadvantages, but could complement to each other, thus accurately and comprehensively reflecting the characteristic of the tumor and gave the best direction for patient′s individualized therapy. This article reviewed the recent advances of liquid biopsy and explained its importance in tumor precision medicine.

Calm thinking for precision medicine of breast cancer in the boom / 中华外科杂志

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.

Clinical utility of circulating tumor DNA detection for diagnosis of breast cancer / 中国癌症杂志

With the development of the next generation sequencing technology, considerable attention has been paid to the utility of circulating tumor DNA (ctDNA) detection in breast cancer. There are many clinical trials showed the ctDNA detection is a potential biomarker for the diagnosis, management and prognosis of breast cancer. ctDNA detection can provide a more accurate diagnosis for patients to guide clinical treatment in precision medicine era.

Opportunities of precision medicine for triple-negative breast cancer / 中国肿瘤临床

Triple-negative breast cancer (TNBC) is a heterogeneous disease. Recently, the development of a gene expression profile fa-cilitated the re-classification of TNBC into six new subtypes, which show varied sensitivities to different therapies. In the era of preci-sion medicine, precision therapy may be directed at various potentially actionable molecular mutations in different subtypes of TNBC.

Some hot issues in the treatment of bone metastasis of breast cancer: interpretation of Expert Consensus on the Diagnosis and Treatment of Bone Metastasis and Skeletal Related Diseases in Breast Cancer (2014 version) / 肿瘤研究与临床

Breast cancer is the most common malignant tumor in women, bone related events (SREs), such as bone pain, pathological fracture and so on, can affect seriously the quality of life.Experts in Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) discussed the Consensus on the Diagnosis and Treatment of Bone Metastasis and Skeletal Related Diseases in Breast Cancer (2014 version), here reflections on several hot issues were explored.

The application of Lapatinib in breast cancer and its mechanism of drug resistance / 实用肿瘤学杂志

With development of molecular biology,breast cancer has entered an era of molecular classifi-cation,thus making biomarker based personalized medicine is the trend of breast cancer treatment.HER2-posi-tive breast cancer of high invasiveness and bad prognosis accounts for 20%~30%.Targeting HER2,trastuzumab is the first humanized monoclonal antibody which can improve the prognosis of HER2-positive patients and it is recommended by guidelines and expert consensus at home and abroad for anti-HER2 therapy in any stage.How-ever,the cardiotoxicity,de novo resistance and acquired resistance of trastuzumab make the clinician to explore the second line anti-HER2 therapy.Lapatinib is the first FDA approved and HER1,HER2 double-targeting tyrosine kinase inhibitor which can be a better choice after failure with trastuzumab.This article reviews the appli-cation,some clinical and mechanism of drug resistance researches of Lapatinib.

Consideration and discussion on ten hot issues of endocrine therapy for breast cancer / 中华外科杂志

Endocrine therapy is one of the main treatment for hormone receptor positive breast cancer. In recent years, some of the critical results of clinical studies have been published, triggering a heat discussion. Guidelines and expert consensus have made appropriate updates based on some results. However, the selection and duration of the endocrine therapy for premenopausal women, the judgment of the menstrual conditions, the application of ovarian function suppression and the choice of endocrine drug combining with ovarian function suppress, and monitoring the endometrial thickness and hormone levels during therapy, as well as the endocrine therapy for postmenopausal patients and metastatic cancer are still controversial. Based on the evidence from study and clinical experience, this article will focus and discuss the ten hot issues.

The clinical value of liquid tumor biomarker detection for breast cancer / 中国癌症杂志

Circulating tumor markers have been paid more attention in the application of the treatment for breast cancer, the level of which has extended from protein to gene, including traditional tumor markers, HER-2 extracellular domain, circulating tumor cells, circulating tumor DNA (ctDNA), circulating RNA (ctRNA) and so on. As “liquid detection”, the detection of circulating tumor markers with real-time dynamic, easy operation, good reproducibility and other advantages are widely used in aiding early diagnosis, determining prognosis, prospectively predicting response or resistance to speciifc therapies, surveillance after primary surgery, and monitoring therapy in patients with advanced disease, The further study of circulating tumor markers may contribute to patient’s individual treatment.

Risk of Trastuzumab-Related Cardiotoxicity in Early Breast Cancer Patients: A Prospective Observational Study / 한국유방암학회지

PURPOSE: In the present study, we investigated the incidence of cardiotoxicity within 5 years of trastuzumab treatment and evaluated potential risk factors in clinical practice. METHODS: The study cohort included 415 patients diagnosed with early breast cancer (EBC). Cardiotoxicity incidence was evaluated in patients receiving trastuzumab and those who did not. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals of potential risk factors for trastuzumab-related cardiotoxicity after appropriate adjustments. RESULTS: Incidence of cardiotoxicity in patients treated with trastuzumab was significantly higher than that in controls (23.7% vs. 10.8%, p<0.001). This result was adjusted for factors that might increase the risk of cardiotoxicity, such as history of coronary artery diseases or the use of anthracyclines for more than four cycles. CONCLUSION: Our findings indicated that treatment with trastuzumab was strongly associated with cardiotoxicity in EBC patients.

Multicenter prospective study of magnetic resonance imaging prior to breast-conserving surgery for breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This multicenter prospective study aimed to assess the utility of dynamic enhanced magnetic resonance imaging (MRI) prior to breast-conserving surgery for breast cancer.</p><p><b>METHODS</b>The research subjects were drawn from patients with primary early resectable breast cancer treated in the breast disease centers of six three-level hospitals in Beijing from 1 January 2010 to 31 December 2012. The participants were allocated to a breast-conserving surgery group (breast-conserving group) or a total mastectomy group (total mastectomy group). Enhanced MRI was used to measure breast volume, longest diameter of tumor and tumor volume. The correlations between these measurements and those derived from histopathologic findings were assessed. The relationships between the success rate of breast-conserving surgery and MRI- and pathology-based measurement results were statistically analyzed in the breast-conserving group.</p><p><b>RESULTS</b>The study included 461 cases in the total mastectomy group and 195 in the breast-conserving group. Allocation to these groups was based on clinical indications and patient preferences. The cut-off for concurrence between MRI- and pathology-based measurements of the longest diameter of tumor was set at 0.3 cm. In the total mastectomy group, the confidence interval for 95% concurrence of these measurements was 35.41%-44.63%. Correlation coefficients for MRI and histopathology-based measurements of breast volume, tumor volume and tumor volume/breast volume ratio were r = 0.861, 0.569, and 0.600, respectively (all P < 0.001). In the breast-conserving group, with 0.30 cm taken as the cut-off for concurrence, the 95% confidence interval for MRI and pathology-based measurements of the longest diameter of tumor was 29.98%-44.01%. The subjective and objective success rates for breast-conserving surgery were 100% and 88.54%, respectively.</p><p><b>CONCLUSIONS</b>There were significant correlations between dynamic enhanced MRI- and histopathology-based measurements of the longest diameter of breast lesions, breast and tumor volumes, and breast volume/tumor volume ratios. Preoperative MRI examination improves the success rate of breast-conserving surgery.</p>

Progestin as an alternative treatment option for multi-treated recurrent triple-negative breast cancer.

OBJECTIVE: Patients with recurrent triple-negative breast cancer (TNBC) currently have no established treatment option other than chemotherapy. However, long-term chemotherapy is often difficult due to adverse effects. A previous study documented a 10%-30% response rate of progestins in oestrogen receptor-negative breast cancer. The aim of this study was to investigate the effect of medroxyprogesterone/megestrol acetate (MPA/MA) in patients with recurrent TNBC. METHODS: This retrospective observational analysis included 51 patients with recurrent TNBC; 17 were treated with MPA/MA and 34 underwent chemotherapy. The two groups were matched at a 1:2 ratio according to age, metastatic sites, and salvage treatment lines. Efficacy was compared using the χ2 and rank-sum tests. Progression-free survival (PFS) was calculated using the Kaplan-Meier method, and the two groups were compared using the log-rank test. RESULTS: The two groups were well balanced in terms of age, disease-free survival, number of metastases, and salvage therapy lines. Clinical benefit rates in the MPA/MA and chemotherapy groups were 52.94% and 73.53%, respectively (χ2 test, p = 0.208), and median PFS was comparable between groups (log-rank test, p = 0.135). Median PFS of 1st-6th-line salvage treatments was shorter in the MPA/MA group than in the chemotherapy group (log-rank test, p = 0.036), but median PFS of ≥7th-line salvage treatments was comparable (log-rank test, p = 0.139). Eight patients discontinued chemotherapy due to adverse effects, and one patient withdrew from MPA treatment because of weight gain. CONCLUSIONS: Progestins (MPA/MA) are an alternative treatment option for multi-treated recurrent TNBC.