晚期三阴性乳腺癌药物治疗进展

目前,晚期三阴性乳腺癌(triple negative breast carcinoma,TNBC)的药物治疗已取得了一些进展,相应的临床研究即有阳性的结果,也有阴性的结果,都为我们的临床实践带来帮助。其中,靶向治疗尚没有突破,化疗方案的优化方兴未艾,免疫治疗则初现端倪。作者就晚期TNBC的药物治疗进展进行了综述。

紫杉醇联合表阿霉素治疗晚期乳腺癌28例临床观察

目的:观察紫杉醇联合表阿霉素治疗晚期乳腺癌的近期疗效及其毒副作用。方法:28例晚期乳腺癌患者进入研究组,全组患者既往均行CMF/CAF方案化疗。治疗方法:紫杉醇135mg/m2静脉滴注3小时,第1天,表阿霉素50mg/m2静脉推注第1天,3周重复,所有患者至少接受2周期治疗。结果:经过2周期化疗,完全缓解4例(14.3%),部分缓解11例(39.3%),总有效率53.6%,9例患者无变化(32.1%),恶心、呕吐、骨髓抑制为主要不良反应,毒性相对较弱。结论:紫杉醇和表阿霉素治疗晚期乳腺癌缓解率高,毒性相对低。

国产长春瑞滨联合顺铂治疗晚期乳腺癌的临床观察

目的：观察国产长春瑞滨（盖诺）联合顺铂治疗晚期乳腺癌的临床疗效及不良反应。方法：盖诺25mg／m^2静滴，第1、8天，顺铂DDP40mg静滴，第1天-3天，共治疗晚期乳腺癌25例。结果：25例晚期乳腺癌患者近期疗效显示CR3例，PR13例，NC5例，PD4例，总有效率64．0％，主要毒副反应为骨髓抑制，胃肠道反应和静脉炎。恶心、呕吐的发生率为96％，静脉炎的发生率为24．0％。结论：盖诺联合顺铂治疗晚期复治性乳腺癌有效率高，不良反应可耐受。

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.

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.

Docetaxel and cisplatin combination chemotherapy in anthracyclines-resistant advanced breast cancer

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.

Central venous port placement in advanced breast cancer patients:comparison of the anatomic- landmark and ultrasound-guided techniques

Objective： The aim of this study was to compare the anatomic-landmark and ultrasound-guided techniques in the placement of an internal jugular vein port in patients with advanced breast cancer. Methods： Between March 2010 and October 2010, 60 patients with advanced breast cancer underwent central venous port placement for the delivery of chemotherapy, preferably through the internal jugular vein. Patients were randomly assigned to either the anatomic-landmark or the ultrasound-guided group. Failure on first attempt, number of attempts until successful catheterization, time to successful placement, the accordance of the two placement approaches, and the demographics of each patient were recorded. Results： The consistency of the direction of two lines drawn using the anatomic-landmark and ultrasound-guided techniques or of the diameter of the internal jugular vein as determined by the two approaches was 85% （51/60）. The rate of successful place- ment at first attempt was higher in the ultrasound group than in the anatomic-landmark group （P 〈 0.05）. A greater number of attempts and longer time to successful port placement were needed in the latter （P 〈 0.05）. Conclusion： The findings of this study indicate that, in the placement of an internal jugular vein port, the ultrasound （US）-guJded technique has several advantages over the anatomic-landmark technique.

Neoadjuvant Combination Chemotherapy with Pegylated Liposomal Doxorubicin and Vinorelbine for Locally Advanced Breast Cancer

OBJECTIVE In China, vinorelbine plus an anthracycline is a common neoadjuvant regimen for locally-advanced breast cancer （LABC）. Pegylated liposomal doxorubicin （PLD） is an alternate anthracycline formulation with a more favorable safety profile compared with conventional anthracyclines. METHODS In this open-label trial, 61 women with LABC received up to 6 cycles of PLD 30 mg/m2 on Day 1 and vinorelbine 25 mg/m2 on Days 1 and 8 every 21 days. Hormone receptor and/or HER2 status was not routinely available. RESULTS The overall clinical response rate （primary efficacy endpoint） was 80% （95% CI： 68%-89%）. Two patients achieved a pathological complete response （3%）, with 75% having their tumor down-staged, and 89% proceeding to tumor resection. The most frequent nonhematologic adverse events were stomatitis, fever, rash, and palmar-plantar erythrodysesthesia, with none considered serious. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 10% and 2% of patients, respectively. CONCLUSION PLD plus vinorelbine demonstrated comparable efficacy to conventional anthracyclines plus vinorelbine in the neoadjuvant treatment of LABC, but may offer safety advantages.

The clinical observation of neoadjuvant chemotherapy in locally advanced breast cancer with DX regimen

The recent clinical curative effect and adverse events of docetaxel and capecitabine （DX） of neo- adjuvant chemotherapy in patients with locally advanced breast cancer was discussed. Methods： The data of 72 cases of neoadjuvant chemotherapy （DX） in locally advanced breast cancer after 4 cycles were retrospectively analyzed. Docetaxel 75 mg/m^2 by infusion 1 h on dl, capecitabine 2000 mg/m^2 by oral for twice daily on d1-14, 21 days was a cycle. Results： All 72 patients were assessed for efficacy and adverse events. The total effective rate was 80.5% （58/72）, including pathological complete response （pCR） was 7 （9.7%）, clinical complete remission （cCR） was 15（20.8%）, clinical partial response （PR） was 43 （59.7%）, stable disease （SD） was 8 （11.1%） and progressive disease （PD） was 6 （8.3%）. The main adverse events were gastrointestinal reactions and bone marrow suppression. The 3 to 4 degrees of adverse reactions including granulocytopenia in 7 patients （20.6%）, hand-foot syndrome in 6 patients （15.2%）. Conclusion： The DX regimen provide a favorable efficacy and safety profile in patients with locally advanced breast cancer for neoadjuvant chemotherapy.

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.

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.

Pharmacokinetics Evaluation of Nimotuzumab in Combination with Doxorubicin and Cyclophosphamide in Patients with Advanced Breast Cancer

EGFr （Epidermal growth factor receptor） overexpression has been detected in many tumors of epithelial origin, specifically in breast cancer and it is often associated with tumor growth advantages and poor prognosis. The nimotuzumab is a genetically engineered humanized MAb （monoclonal antibody） that recognizes an epitope located in the extracellular domain of human EGFr. The aim of this study was to assess the pharmacokinetics of nimotuzumab in patients with locally advanced breast cancer who are receiving neoadyuvant therapy combined with the AC chemotherapy regimen （i.e., 60 mg/m2 of Doxorubicin and 600 mg/m2 of Cyclophosphamide in 4 cycles every 21 days）. A single center, non-controlled, open Phase I clinical trial, with histopathological diagnosis of locally advanced stage III breast cancer, was conducted in 12 female patients. Three patients were enrolled at each of the following fixed dose levels： 50, 100, 200 and 400 mg/week. Multiple intermittent short-term intravenous infusions of nimotuzumab were administered weekly, except on weeks 1 and 10, when blood samples were drawn for pharmacokinetic assessments. Nimotuzumab showed dose-dependent kinetics. No anti-idiotypic response against nimotuzumab was detected in blood samples of participants. There was not interaction between the administration of nimotuzumab and chemotherapy at the dose levels studied. The optimal biological doses ranging were estimated to be 200 mg/weekly to 400 mg/weekly.

Clinical observation on docetaxel plus S1 in the treatment of advanced metastatic breast cancer

Objective: The aim of our study was to observe the efficacy and adverse reactions of docetaxel plus S1 in patients with advanced metastatic breast cancer. Methods: Twenty-seven patients with advanced metastatic breast cancer receiving docetaxel plus S1 in our hospital were analyzed. The efficacy and safety were evaluated according to RECIST and NCI CTC 3.0. Results: The clinical efficacy and toxicity were evaluated in all the 27 patients, including 1 case of CR, 12 of PR, 6 of SD, and 8 of PD (ORR = 48.1%, CBR = 70.3%). The median time to tumor progression (mTTP) was 7.3 months. No IV degree of adverse reaction was observed in the observation group. Most adverse reactions were degrees I and II, the most common reactions were neutropenia (59.3%), abnormal liver function (33.3%), gastrointestinal adverse events (29.6 %) and stomatitis (7.4%). Conclusion: With good efficacy and low toxicity, docetaxel plus S1 could be administered in the treatment of advanced metastatic breast cancer.

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.