A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

Comparison of Letrozole and Aminoglutethimide in Treatment of 113 Cases of Postmenopausal Women with Advanced Breast Cancer

Objective: To compare the efficacy and tolerability of letrozole with aminoglutethimide (AG) in postmenopausal women with advanced breast cancer. Methods: The multicenter, randomized controlled clinical trial was conducted in 113 patients. They randomly received letrozole 2.5 mg once daily (letrozole group) or AG 250 mg 4 times daily (AG group) with hydrocortisone. Results: The OR in letrozole group was 23.73% (2 cases of CR and 12 cases of PR, ITT OR was 21.88%), which was higher than in AG group (the OR 11.11%, 1 CASE of CR and 5 cases of PR, ITT 10.17%), but there was no statistically significant difference (P>0.05). Adverse events (AE) and the treatment related AE (RAE) in letrozole group (n=59) was 18.54% and 13.56% respectively, significantly lower than those (42.11% and 33.33% respectively) in AG group (n=57, P=0.002). Conclusion: The OR of letrozole in the treatment of postmenopausal advanced breast cancer positive or unknown for hormonal receptor is 23.73%, showing no significant difference to that of AG. The AE of letrozole are significantly less than AG.

Efficacy and safety of trastuzumab combined with chemotherapy for first-line treatment and beyond progression of HER2-overexpressing advanced breast cancer

Objective： To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 （HER2）-overexpressing advanced breast cancer. Methods： A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31-73 years with a median of 51 years. HER2-positivity was defined as 3（＋） staining in immunochemistry or amplification of fluorescence in situ hybridization （FISH, ratio ≥2.0）. Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a second- line, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival （PFS） and overall survival （OS）. Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox＇s proportional hazards regression model, and the level of significance was P〈0.05. Results： All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 （80.00%） patients had visceral metastasis, and 43 （47.78%） patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months （range, 2-59 months）, and the median OS after metastasis or initially local advanced disease was 22 months （range, 2-1 16 months）. Conclusions： Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its efficacy is certainly less beyond this point.

Exploratory clinical study of chidamide,an oral subtype-selective histone deacetylase inhibitor,in combination with exemestane in hormone receptor-positive advanced breast cancer

Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deacetylase(HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming.The purpose of this study was to evaluate the safety,pharmacokinetics(PK),and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients.Methods: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy.Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis.In combination treatment,patients were given exemestane 25mg daily and chidamide 30mg twice a week(BIW) until progression of disease or intolerable toxicities.A treatment cycle was defined as 4 weeks.Safety,PK parameters,and preliminary efficacy were evaluated.Results: A total of 20 patients were enrolled between July and December,2015.The median number of treatments cycle was 5.2(20.8 weeks) with 2 patients still on treatment at the data cut-off date of October,2017.The treatment-related adverse events(AE) ≥ grade 3 in more than 2 patients were neutropenia(35%),thrombocytopenia(30%),and leucopenia(20%).The plasma exposure of exemestane was consistent in the presence or absence of chidamide.A slight increase in chidamide exposure was noted in the presence of exemestane,probably due to the inter-and intra-patient variations.The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors(RECIST),including 4 patients with partial response,10 patients with stable disease.The median progression-free survival(PFS) was 7.6 months.Conclusions: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients.The overall results from this study encourage further pivotal trial in this patient population.

Decrease in the Ki67 index during neoadjuvant chemotherapy predicts favorable relapse-free survival in patients with locally advanced breast cancer

Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.

Efficacy of platinum in advanced triple-negative breast cancer with germline BRCA mutation determined by next generation sequencing

Objective:To compare the efficacy of platinum-and non-platinum-based regimens as first-line treatment for advanced triple-negative breast cancer(TNBC)and analyze the relationship between their efficacy and BRCA gene status.Methods:Retrospectively analyze clinical data of 220 patients diagnosed pathologically with advanced TNBC and treated at the Department of Breast Oncology,Peking University Cancer Hospital from 2013 to 2018 and evaluate the efficacy of chemotherapy.A total of 114 patients had BRCA1/2 gene tested by next generation sequencing(NGS)using peripheral blood,and we analyzed the correlation between their efficacy and BRCA1/2 gene status.Results:Non-platinum-based chemotherapy(NPCT)was administered to 129 and platinum-based chemotherapy(PBCT)to 91 study patients.The clinical benefit rate(CBR)and median progression-free survival(PFS)were not statistically different between NPCT and PBCT groups.The median overall survival(OS)was 30.0 and 22.5 months for PBCT and NPCT group,respectively[P=0.090,hazard ratios(HR)=0.703].BRCA status was assessed in 114 patients,14 of whom had deleterious germline BRCA1/2(g BRCA)mutations(seven in each group).In PBCT group,the CBR was 85.7%and 35.1%for patients with and without deleterious g BRCA mutations,respectively(P=0.039).The median PFS were 14.9 and 5.3 months and median OS were 26.5 and 15.5 months for patients with and without deleterious g BRCA mutations,respectively(P=0.001,P=0.161,respectively).Patients in PBCT group had significantly greater rates of grade 3-4 anemia(5.5%vs.0%)and thrombocytopenia(8.8%vs.0%),whereas palmar-plantar erythrodysesthesia(12.4%vs.0%)and peripheral neuropathy(8.6%vs.1.1%)occurred more frequently in NPCT group.Conclusions:Platinum-based regimens are more effective in patients with deleterious g BRCA mutations,but no difference in patients without BRCA gene mutations,so non-platinum is an option in patients without BRCA gene mutations considering the toxicity and side effect.And we recommend that patients with advanced TNBC should have BRCA gene test.

Symptom burden in advanced breast cancer patients and its association between death anxiety and psychological distress

Objective:Recent research has documented psychological distress in advanced breast cancer(ABC)patients,but few studies have examined how death anxiety is affected by the symptom burden.Therefore,this study aims to explore the association among symptom burden,death anxiety and psychological distress(depression and anxiety)in ABC patients.Methods:This cross-sectional study used the Death and Dying Anxiety Scale(DADDS),9-item Patient Health Questionnaire(PHQ-9),General Anxiety Disorder-7(GAD-7)and MD Anderson Symptom Inventory(MDASI)to assess death anxiety,depression,anxiety,and symptom burden,respectively.Bias-corrected bootstrapping methods were used to estimate indirect effects and 95%confidence intervals.Results:Two hundred ABC patients completed the questionnaires.All of the respondents were females,with a mean age of 50±10 years.Initial correlation analyses revealed significant associations of death anxiety with depression(r=0.57,P<0.001),anxiety(r=0.60,P<0.001)and symptom burden(r=0.43,P<0.001).Moreover,depression(r=0.53,P<0.001)and anxiety(r=0.45,P<0.001)were significantly correlated with symptom burden.An analysis using Hayes’PROCESS macro revealed the partial effecting role of death anxiety in the relationship between depression and symptom burden,and between anxiety and symptom burden(contributions to the total effect of 0.247 and 0.469,respectively).Conclusions:This study provides insight into the relationship between death anxiety and symptom burden.The results suggest that interventions addressing death anxiety may be more effective for alleviating the depression and anxiety experienced by ABC patients with a symptom burden.

Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer:a randomized controlled trial

Background:Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer.However,few studies have assessed the efficacy of weekly taxane-anthracycline regimens on locally advanced breast cancer.This study was to compare the efficacy and safety of a weekly taxaneanthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breast cancer.Methods:Patients with locally advanced breast cancer were randomized to receive 4-6 cycles of neoadjuvant chemotherapy with tri-weekly 5-fluorouracil-epirubicin-cyclophosphamide(FEC) regimen or weekly paclitaxel-epirubicin(PE) regimen.The primary endpoint was the pathologic complete response(pCR) rate.Other endpoints included the clinical tumor response,breast-conserving surgery rate,and adverse events.Results:Between March 2010 and September 2013,293 patients were randomized to the FEC(n=151) and PE(n=142) arms.The overall clinical response rate was significantly higher in the PE arm than in the FEC arm(76.06%vs.59.95%,P=0.001).Consistently,the post-chemotherapy pathologic T and N stages were significantly lower in the PE arm than in the FEC arm(P<0.001).However,the pCR rate was similar in the two arms(10.61%vs.12.31%,P=0.665).Overall,36(27.27%) patients in the FEC arm and 6(35.28%) in the PE arm were qualified for breast-conserving surgery.Most adverse events were comparable in both arms,with more severe neutropenia in the PE arm than in the FEC arm(11.97%vs.5.96%,P=0.031).Conclusions:In patients with locally advanced breast cancer,weekly PE was not superior to FEC in terms of pCR.However,weekly PE has a higher response rate and superior down-staging effects.On this account,the PE regimen may be considered an alternative option for locally advanced breast cancer.Long-term follow-up data are needed to confirm the efficacy of this regimen on locally advanced breast cancer.Trial registration Chinese clinical trial registry,ChiCTR-TRC-10001043,September 21。

Combination of Aromatase Inhibitors with Metronomic Capecitabine: A New Chemoendocrine Treatment for Advanced Breast Cancer

Purpose: Endocrine therapy is one of the main treatment options for hormone receptor (HR)-positive advanced breast cancer (ABC). However, whether the combination of endocrine therapy with chemotherapy is practicable and more effective than endocrine therapy alone remains unknown. The aim of this study was to investigate the clinical efficacy of the aromatase inhibitors (AIs) combined with metronomic capecitabine to provide the clinical evidence for further research in patients with HR-positive ABC. Methods: Data from 407 patients with HR-positive ABC were retrospectively analyzed. A total of 305 patients were given AIs alone, and 102 patients were given AIs plus capecitabine as first-line treatment. Progression-free survival (PFS) was the primary endpoint. Results: The median follow-up for all patients was 47.0 months (range, 3 - 119 months). The median overall survival (OS) and PFS were 52.0 months and 24.2 months, respectively. The median PFS in the combination group was significantly longer than that in the AIs group (22.0 months vs. 14.0 months, p = 0.002). Additionally, patients in the combination group had significantly longer OS than patients in the AI group (66.0 months vs. 49.0 months, p = 0.003). Multivariate analysis showed that combination therapy was a significant favorable predictor for PFS and OS. Furthermore, young age (<40 years), low estrogen receptor (ER) expression level (<40%), presence of visceral metastasis, prior adjuvant AI use and long disease-free interval (DFI) (>24 months) improved the benefit from combination therapy. Conclusions: AIs plus metronomic capecitabine significantly improves PFS and OS in patients with HR-positive ABC. Thus, chemo-endocrine therapy should be further explored.

Skin Sparing Mastectomy in Locally Advanced Breast Cancer: A Possibility?

Breast cancer is the second most common cause of cancer death in women in India in spite of advances in the adjuvant treatment of breast cancer. Locally advanced breast cancer (LABC) still represents the major presenting picture in many urban and rural institutions in our country. Skin Sparing Mastectomy (SSM) and primary reconstruction is a popular option for patients with breast cancer. There are similar local and distant recurrences in SSM compared to the traditional non-skin sparing mastectomy. A 57-year-old lady presented with a locally advanced left breast cancer. After undergoing neoadjuvant chemotherapy and a PET-CT to accurately detect residual disease in breast and axilla, she underwent skin sparing mastectomy with nipple-areola complex preservation and primary reconstruction with silicon prosthesis implant over a latissimus dorsi myocutaneous flap for primary reconstruction. SSM in LABC has not been reported in the literature so far. This patient is disease free for the past 24 months.

Clinical observation of capecitabine monotherapy in elderly patients with advanced breast cancer

Objective The aim of the study was to evaluate the safety and efficacy of capecitabine mono-chemotherapy in elderly patients with advanced breast cancer. Methods The data from 36 cases of capecitabine monotherapy in elderly patients with advanced breast cancer were retrospectively analyzed. Oral administration of capecitabine 2000 mg/m^2 twice daily （D1-14） for 21 days constituted a cycle. The effect of the disease and main adverse reactions were evaluated every 2 cycles. Results The data from 36 elderly patients were studied. The median number of chemotherapy cycles was 4. The total effective rate was 30.6% （11/36） and the disease control rate was 72.2% （26/36）. The number of patients with clinical comptete remission was 2, clinical partial response was 9, stable disease was 15, and progressive disease was 10. Where treatment was effective, the median time to progression was 6 months and the median overall survival was 9.5 months. The main adverse events were gastrointestinal reactions, bone marrow suppression, and oral mucositis; most of the reactions were grade 1 to 2. Grade 3 to 4 adverse reactions included granulocytopenia in 2 patients （12.5%） and hand-foot syndrome in 1 patient （6.7%）. Conclusion Capecitabine monotherapy was effective in controlling disease progression, and adverse reactions were tolerated by elderly patients with advanced breast cancer.

Gemcitabine Based Combination Regimens for Treatment of Refractory Advanced Breast Cancer

Objective： Anthracycline and taxane are the standard agents in combined chemotherapy of advanced breast cancer. However, when these agents based chemotherapy is failure, the selection of salvage regimen is still of problem. Gemcitabine, an active agent in both lung cancer and pancreas cancer, is demonstrated effective in breast caner. But there have been relatively less data of gemcitabine in anthracycline and/or taxane-resistant breast cancer. Therefore we employe this study to explore the efficacy and safety of gemcitabine based combination regimen in this population. Methods： From May 2002 to March 2006, 28 patients with measurable lesion of advanced metastatic breast cancer who were resistant to prior anthracycline and taxane based chemotherapy were enrolled. Patients were treated with gemcitabine based combination chemotherapy with a median cycles of 3 （range 2-6）. Results： The overall response rate was 28.6% （8/28）, with 1 CR （Complete response 3.5%） and 7 PRs （Partial response 25%）. Stable disease was seen in 8 patients （28.6%） while disease progressed in 12 patiens （42.8%）. The median time to progression was 4.5 m （range, 2-23 m）. The main toxicity included bone marrow depression, alopecia, mucositis and peripheral neurotoxicity. The grade 3 to 4 clinical adverse effect was leukopenia in 5 cases （17.9%） and thrombocytopenia in 8 cases （30%）. Conclusion： Gemcitabine based combination regimens is feasible in anthracycline and taxane-resistant advanced breast cancer. The clinical response and TTP is acceptable with limited toxicity pattern.

Oncoplastic Breast Surgery after Neoadjuvant Chemotherapy Replacing Mastectomy in Locally Advanced Breast Cancer (LABC): Single Institute Experience

Background: Integration of neoadjuvant chemotherapy (NCT) in early 70s resulted that many LABC tumors become resectable but with total mastectomy especially those with partial response, oncoplastic techniques give better oncological outcome with better cosmetic results. Objective: We evaluate the oncological safety of oncoplastic breast surgery (OS) in LABC showing partial response to NCT. Methods: We prospectively analyzed the data of 32 out of 58 patients with LABC who showed partial response to NCT and could have conservative surgery with advanced oncoplastic techniques rather than total mastectomy. Results: Out of 58 patients with LABC, received neoadjuvant chemotherapy, complete response was observed in 8 patients (13%), partial response reported in 32 (55.1%) cases, 12 patients (20%) had stable disease and 6 patients (10%) showed progressive disease. Data of 32 cases were studied (mean age 44.84 ± 9.10 years;range 26 - 59 years). Inferior pedicle was performed in 9 cases, mini LD flap in 3 patients, 5 had Grissotti technique, 6 with superomedial pedicle, 4 had V mammoplasty and 3 with J mammoplasty and 2 had vertical mammoplasty. Margins were positive in 5 cases (15.6%) with mean margin width 9.63 ± 5.72 (range 0 - 22 mm), and the local recurrence was reported in 2 cases (6.2%). Complications were reported in 3 cases (9.3%). The follow up was 1.67 ± 1.03 (range 0 - 3.3 years). Conclusions: Integration of neoadjuvant chemotherapy together with advanced oncoplastic techniques opens a new way for management of LABC especially those showing partial response with avoidance of total mastectomy, and comparable oncological safety in addition to better aesthetic and psychological outcome.

Comparison of vinorelbine plus cisplatin with vinorelbine plus capecitabine in patients with anthracyclines- and taxanes-refractory advanced breast cancer

Objective: The aim of our study was to compare the efficacy and toxicities of vinorelbine plus cisplatin(NP) regimen with that of vinorelbine plus capecitabine(NX) regimen in the treatment of anthracycline- and taxane-refractory advanced breast cancer. Methods: Forty-six patients with anthracycline- and taxane-refractory advanced breast cancer were equally randomized into a NP group(n = 23) and a NX group(n = 23). Response rates and toxicities were evaluated after 2 cycles of chemotherapy. Results: The overall response rate were 48.0% in both groups. There were no significant differences in disease control rates(78.0% vs. 83%) or 1-year survival rates(54.6% vs. 55.9%). The main adverse events were bone marrow depression and gastrointestinal reaction, and no significant difference was found in toxicities between the groups. Conclusion: For anthracycline- and taxane-refractory advanced breast cancer, NP and NX regimens exerted similar curative effects with acceptable toxicity.

Bilateral oophorectomy combined with exemestane treating advanced refractory breast cancer

Objective： Taking tamoxifen orally is the main endocrine therapy of the premenopausal breast cancer with positive hormone receptor, but numerous patients developed to be advanced refractory breast cancer because of drug resistance. Our study investigated a role of the combination of bilateral oophorectomy and exemestane in the management of advanced refractory breast cancer. Methods： The bilateral oophorectomy was carried out in 17 patients. One week after the operation, exemestane was taken orally （25 mg/d）. The median time to progression （TTP）, the median survival time and the survival rate were calculated using Kaplan-Meier methods. Results： Seventeen patients age ranged from 26 to 44 years （median, 36 years） were treated with an overall response rate of 64.70%, TTP was 8 months and the median survival time was 31 months. The survival rate of 1-year, 3 years and 5 years was 88.24%, 64.71%, 29.41%, respectively. There have no grade Ⅲ/Ⅳ side effects appeared. Conclusion： Bilateral oophorectomy combined with exemestane is safe and effective for advanced refractory premenopausal breast cancer with positive hormone receptor and it is well-torerated.

Evaluation of dynamic contrast-enhanced MRI in monitoring early response of locally advanced breast cancer to neoadjuvant chemotherapy

Objective： The aim of our study was to assess the value of dynamic contrast-enhanced magnetic resonance imaging （DMRI） in predicting early response to neoadjuvant chemotherapy （NAC） in patients with locally advanced breast cancer （LABC） and to assess the accuracy of DMRI in evaluating residual disease after NAC. Methods： DMRI were per- formed in 43 women with LABC （44 lesions, all were invasive ductal carcinoma） before, after the first and final cycle of NAC. Tumour volume, early enhanced ratio （El）, maximum enhanced ratio （Emax）, and maximum enhanced time （Tmax）, dynamic signal intensity-time curve were obtained during treatment. Residual tumour volumes obtained using DMRI were compared with pathological findings to assess the accuracy of DMRI. Results： After 1st cycle of NAC, the mean volume of responders decreased insignificantly, P 〉 0.05, but after NAC, mean volume of residual tumor decreased significantly （P 〈 0.01）. Morphol- ogy change： 29 cases showed a concentric shrinkage pattern while 7 cases showed a dendritic shrinkage pattern. Significant differences were found in El, Emax and Tmax between responders and non-responders （P 〈 0.05）. After 1st cycle of NAC, El, Emax and Tmax of responders changed significantly （P 〈 0.001）; while there is no significant change in non-responders （P 〉 0.05）. After NAC, dynamic signal intensity-time types were changed in responders, and tended to be significantly flat- tening, while no significant change was found in non-responders. The residual tumour volume correlation coefficient between DMRI and pathology measurements was very high （r = 0.866, P = 0.000）. Conclusion： DMRI is useful to evaluate the early response to NAC in LABC. The presence and volume of residual disease in LABC patients treated with NAC could be ac- curately evaluated by DMRI.

Evaluation of the effect of neoadjuvant chemotherapy on tumor and axillary lymph nodes in locally advanced breast cancer: a study of 50 patients

Objective： The purpose of the study was to correlate between effect of pre-neoadjuvant chemotherapy （NACT） and post-NACT clinical, sonographic and pathologic features of the tumor and axillary lymph nodes （ALNs） and to raise the possibility of applying the concept of sentinel lymph node biopsy （SLNB） in patients with initially positive ALNs before NACT. Methods： A prospective study of 50 female patients with locally advanced breast cancer （LABC） with clinically palpable.and cytologically （under ultrasonographic guidance） positive ALNs. All patients received NACT and then referred for ultrasono- graphic assessment of the axilla regarding any detectable sonographic criteria of metastatic deposits in ALNs as well as the tumor size in relation to its prechemotherapy size, All patients were then subjected either to modified radical mastectomy or breast conserving surgery. The clinical, sonographic and pathological response of the tumor and the ALNs were documented, classified and correlated with each other. Results： Patients＇ mean age was 47.7±9.1 years. The mean clinical tumor size was 6.7 ± 1.4 cm; stage IliA that was presented in 32 patients （64%） and IIIB was presented in 18 patients （36%）. Chemotherapy was given for a median of 4 cycles, there was reduction of the mean clinical tumor size from 6.7 ± 1.4 cm to 4.3 ± 2.7 cm （P 〈 0.001）. Clinical response was complete in 5 （10%） tumors, complete pathological tumor response （post-neoadjuvant） was detected in 6 （16%） of patients. Complete clinical nodal response （post-neoadjuvant） in 23 （46%） axillae, on sonographic assessment of the axilla, response was complete in 17 （34%） axillae. Complete pathological nodal response occurred in 16 （32%） axillae. Out of 17 axillae that showed complete sonographic response 11 axillae showed complete pathological nodal response （P 〈 0.001）. Conclusion： Formal axillary lymph node dissection can be avoided and replaced by SLNB post NACT in patients with LABC with metastatic ALNs if there were complete clinical and sonographic criteria of nodal response as well as complete pathological tumor response.

The Therapeutic Effect of Capecitabine Single Drug Maintenance Therapy in the Advanced Breast Cancer

Objective:To analyze the efficacy of capecitabine(referred to as Cap)single-agent maintenance therapy in the advanced breast cancer.Methods:The subjects of the study were 50 patients with advanced breast cancer who were admitted to our hospital between March 2016 and March 2019.They were divided into groups A and B with 25 cases each.The subjects of these two groups were treated conventional method,respectively.And then,Capecitabine maintenance therapy was continued for group A,clinical observation for groups B.Progressionfree survival(PFS)was compared between the two groups.Results:The median PFS was 14.2 months for group A and 8.9 months for group B(P<0.05).The complication rate of group A was 24.0%compared to that of group B was 22.0%(P>0.05).Conclusion:The patients with advanced breast cancer who received Cap maintenance therapy were benefited from better curative effect and controllable complications,which has high promotion value.

Effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer

Objective:To study the effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer.Methods: 76 patients with advanced breast cancer treated in our hospital between May 2012 and November 2015 were collected and divided into the combined treatment group (n=34) who accepted Xiao Chaihu Tang combined with intravenous chemotherapy and the control group (n=42) who accepted intravenous chemotherapy alone according to different treatment, and the treatment cycle was 3 months for both groups. Before treatment and 3 months after treatment, ELISA method was used to detect serum levels of broad-spectrum tumor markers and breast cancer-specific tumor markers;flow cytometer was used to detect cellular immune function index levels, and turbidimetric immunoassay was used to detect humoral immune function index levels in peripheral blood.Results: Before treatment, differences in serum tumor marker levels as well as cellular immunity and humoral immunity index levels in peripheral blood were not statistically significant between two groups of patients (P>0.05);after 3 months of treatment, broad-spectrum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153) and carbohydrate antigen 125 (CA125) levels in serum of combined treatment group were lower than those of control group, and breast cancer-specific tumor markers insulin-like growth factor-1 (IGF-1), midkine (MK), soluble E-cadherin (sEC) and thymidine kinase 1 (TK1) levels were lower than those of control group (P<0.05);CD3+ and CD4+ T lymphocyte levels as well as CD4+/CD8+ ratio in peripheral blood of combined treatment group were higher than those of control group while CD8+ T lymphocyte level was lower than that of control group, and immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) levels in peripheral blood were higher than those of control group (P<0.05).Conclusions:Xiao Chaihu Tang combined with intravenous chemotherapy can decrease the severity of advanced breast cancer and optimize the body's immune function.

A narrative review on palbociclib for hormone receptor-positive and human epidermal growth factor receptor-2 negative advanced breast cancer

As a specific cyclin-dependent kinase 4/6 inhibitor,palbociclibimproved the prognosis in patients with hormone receptor-positive and human epidermal growth factor receptor-2 negative breast cancer.Emerging data showed that palbociclib shed a new therapeutic regimen forbreast cancers and playsan essentialmilestone in the development of anti-tumor drugs,especially for advanced breast cancer.In this minireview,we aimed to summarize the mechanism,clinical application,and side effectsof palbociclib.