不同分子亚型局部晚期乳腺癌的新辅化疗反应率的临床研究(英文)

Objective: The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry (IHC) staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods: One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined (TE) neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes: luminal A, luminal B, HER-2 and triple negative breast cancer (TNBC) according to different combination patterns of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER-2) expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results: The pathological complete response (PCR), clinical complete response (CCR), clinical partial response (CPR), and clinical stable disease (CSD) rate of whole group was 15.89% (17/107), 22.43% (24/107), 63.55% (68/107), 14.02% (15/107), respectively, and the overall response rate (ORR) was 85.98% (92/107). The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes (P = 0.019, P = 0.002, respectively). Conclusion: Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2/TNBC subtypes have a higher PCR and ORR rate than that of luminal A/B subtypes.     

三阴乳腺癌在新辅助化疗中相关预测因子的Meta分析(英文)

Objective: Neoadjuvant chemotherapy (NAC) was increasingly used as a systemic therapy for triple-negative breast cancer (TNBC). The pathological complete response (PCR) rates of neoadjuvant chemotherapy in TNBC were higher than other types of breast cancer with fluctuate data. Predictors to identify which subgroup TNBC was more likely to achieve PCR in neoadjuvant chemotherapy would give us some hints on how to improve outcomes of TNBC patients. The meta-analysis was conducted to contrast the prognostic function of some clinicopathological parameters in the PCR rates of neoadjuvant chemotherapy for TNBC. Methods: Studies were selected from the PubMed database. The relevant parameters to PCR rates in TNBC group were recorded. Review Manager and MIX were used to estimate prognostic function of some biological markers and clinicopathological parameters in PCR rates of TNBC. Results: The analysis included 6 studies with 723 patients, the aggregate PCR rate was 27.9% in TNBC group. The association of lymph nodes metastasis, Ki-67 expression, p53 expression and CK5/6 expression with PCR rate of TNBC was investigated in the analysis, and the odds ratios were 0.50, 9.87, 1.17 and 0.53 respectively. Conclusion: This meta-analysis demonstrated that Ki-67 expression and lymph nodes metastasis were predictors of PCR rate for TNBC in neoadjuvant chemotherapy, while p53 and CK5/6 expression could not be confirmed for the prognostic function.     

妊娠乳腺癌患者2例终止妊娠前或后行首程化疗的疗效分析并文献复习(英文)

Pregnancy-associated breast cancer (PABC) is defined as breast cancer occurring anytime during gestation, lactation, or within 1 year after delivery. The incidence is between 1 in 3000 and 1 in 10,000 pregnancies and comprises about 0.2% to 3.8% of all breast cancers diagnosed in women under the age of 50 years. As women tend to delay childbearing into their third and fourth decades, the incidence of PABC is expected to increase. Here we reported two PABC patients with similar clinic and pathologic characters received chemotherapy before or after termination of pregnancy respectively, and found that the former got pathologic complete response. Based on the phenomena and the fact that endocrine hormones may have chemosensitization role in cancer chemotherapy, which is called hormonosensitizing chemotherapy (HSCT), endocrinosensitizing chemotherapy (ESCT) or neoendocrinochemotherapy (NECT), suggestion is proposed that chemotherapy should be taken before or immediately after termination for PABC, especially for the patients who prefer to artificial abortion, which may possibly acquire improved chemotherapeutic effect.     

术后辅助化疗起始时间影响乳腺癌患者的预后

美国MD Anderson癌症中心的de Melo Gagliato等于2014年第8期《Journal of Clinical Oncology》在线发表了题为《Clinical impact of delaying initiation of adjuvant chemotherapy in patients with breast cancer》的论著,阐述了乳腺癌术后化疗起始时间对患者预后的影响。     

辅助化疗对提高胃癌根治术后远期疗效的临床研究

我们将２３５例胃癌根治术病例随机分为两组，根治术后加辅助化疗的综合组（１１２例）和单纯根治术组（１２３例），研究辅助化疗的临床意义，总的５年生存率综合组为５１．８％，明显高于单纯根治术组的３０．９％（ｐ＜０．０１）．其中Ⅱ期胃癌５年生存率综合组与单纯根治术组相比，为７０．７％：４１．３％，差异有非常显著意义（ｐ＜０．０１）；Ⅲ期胃癌为４８．７％：２６．８％，差异亦有显著意义（ｐ＜０．０５）；而Ⅰ、Ⅳ期胃癌两组间差异无显著意义（ｐ＞０．０５）．本研究结果表明，辅助化疗对提高各期胃癌根治术后远期疗效的作用不同，并分析了其原因．     

乳腺癌腋窝淋巴结清扫术后阴性淋巴结数目的临床意义(英文)

Objective: The purpose of this study was to evaluate the impact of the negative lymph node (LN) count on the survival of the breast cancer patients in early stage after the axillary dissection. Methods: The breast cancer patients with T1-2N0-1M0 stage between January 2001 and December 2005 in Jiangsu Cancer Hospital, who underwent the axillary LNs dissection, were enrolled in this study. We analyzed the data of these patients including information of follow-up and postoperative pathological results. All patients were divided into two groups according to the axillary LN status and each group was divided into four subgroups according to the negative LN count. Cox regression analysis was performed to screen the pathological factor including the negative LN count on the survival and to compare the different negative LN count on the survival. Results: COX proportional hazard regression model showed that the survival of the breast cancer was significantly associated with the negative LN count. In T1-2N0 group, when the negative LN count was 3 or less, 4 to 5, 6 to 9 and 10 or more, the median survival time was (82.6 ± 4.1) months, (101.5 ± 1.3) months, (104.7 ± 1.0) months, and (110.5 ± 0.9) months respectively (P < 0.05). In T1-2N1 group, when the negative LN count was 6 or less, 7 to 8, 9 to 10 and 11 or more, the median survival time was (95.4 ± 1.9) months, (101.8 ± 1.1) months, (104.9 ± 1.0) months, and (106.5 ± 0.9) months respectively (P < 0.05). Conclusion: The negative LN count can reflect the adequacy of the axillary dissection. Increasing negative LN count is independently associated with improved survival in pT1-2N0M0 or pT1-2N1M0 staging breast cancer patients. The negative LN count should be considered for incorporation into staging for breast cancer with the axillary LN dissection.     

声脉冲辐射力成像技术评价乳腺癌新辅助化疗疗效的价值研究

目的 探讨声脉冲辐射力成像技术(ARFI)在乳腺癌新辅助化疗疗效评价中的应用价值.方法 选取42例原发性浸润性乳腺癌患者(共42个病灶),所有患者均于新辅助化疗后行外科手术治疗.应用ARFI技术测量新辅助化疗前后病灶最大弹性值变化率.以Millen-Payne(MP)分级系统作为病理反应的评价依据,Ⅰ~Ⅲ级为组织学非显著反应,Ⅳ~Ⅴ级为组织学显著反应.以手术病理诊断为金标准,应用受试者工作特征曲线(ROC)评价ARFI的诊断价值.结果 42例乳腺癌组织中,69.05%(29/42)为组织学显著反应,30.95%(13/42)为组织学非显著反应.通过ROC曲线确定的评价新辅助化疗有效和无效的VTQ值变化率诊断界值为29%(曲线下面积为0.925,95%CI:0.863~0.987),敏感度为91.1%,特异度为83.3%,准确度为87.7%.新辅助化疗后,组织学显著反应组乳腺癌患者的VTQ值(弹性值)明显低于化疗前,差异有统计学意义(P﹤0.01).结论 ARFI技术可通过定量测量新辅助化疗前后乳腺癌硬度变化,为乳腺癌新辅助化疗的疗效评估提供新方向.     

Impact of haemoglobin levels during adjuvant chemotherapy on the survival of patients with primary breast cancer

Tumour anaemia is a common symptom in cancer patients, particularly in those receiving chemotherapy. The aim of the current study was to analyse the impact of haemoglobin levels on the prognosis of patients with primary breast cancer receiving adjuvant chemotherapy. A total of 129 patients were available for analysis. The estimated median five-year overall survival rate was 76.6%. Mean Hb prior to primary surgery was 13.8 g/dl (SD 1.09), pre-chemotherapy Hb 12.8 g/dl (SD 1.2), and nadir Hb during chemotherapy 11.0 g/dl (SD1.1), respectively. Hb values were analysed as continuous variables in the Cox model. Survival analyses did not show a correlation between preoperative and pre-chemotherapy Hb levels with patient outcome. However, univariate analysis identified low nadir Hb (p=0.008), larger tumours (p=0.042), and hormone-receptor-negative tumours (p=0.022) to be significantly associated with poor patient survival. This result was persistent when analysis was adjusted for relevant prognostic factors in a multivariate Cox proportional hazards model. Nadir Hb, 1.54-fold increased risk for death (95% CI 1.03-2.32), and tumour size, 3.2-fold increased risk (95% CI 1.17-8.77) remained as independent variables, whereas hormone-receptor status failed to retain significance. The present data showed anaemia during adjuvant chemotherapy to be associated with poor survival in patients with primary breast cancer. Prospective randomized trials are warranted to examine the value of correcting anaemia with regard to improve disease control and survival.     

The effect of prior adjuvant chemotherapy on survival in metastatic breast cancer

Some adjuvantly treated patients develop recurrent breast cancer and little is known about the effect of prior adjuvant chemotherapy on subsequent response rates to systemic therapy or on overall survival. We describe our retrospective comparison of 179 patients who received doxorubicin containing adjuvant chemotherapy and developed recurrent breast cancer on University of Arizona Cancer Center clinical trials with 202 non-adjuvantly treated patients entered onto clinical protocols for recurrent or metastatic breast cancer during the same period. Adjuvant failures had a shorter median survival from the date of onset of recurrent disease (18 months versus 28 months, P less than 0.001), a lower response rate to initial combination chemotherapy (38% versus 69%, P = 0.001), and a high incidence of CNS involvement at the time of relapse (11%). In patients having recurrent or metastatic breast cancer, a history of prior adjuvant chemotherapy appears to identify a subgroup who will have a higher incidence of CNS involvement, a lower response rate to chemotherapy and a shorter survival with metastatic disease. These findings may help explain the failure of improved relapse free survival seen in many adjuvant chemotherapy trials to result in improved overall survival.     

Feasibility of adjuvant chemotherapy for breast cancer patients

To evaluate the feasibility of adjuvant chemotherapy, we analyzed the toxicities of chemotherapy for primary breast cancer in Japanese women. Since the opening of the National Cancer Center Hospital East, 180 female breast cancer patients have received adjuvant chemotherapy or chemo-hormonal therapy following surgical treatment between June 1992 and December 1995. On the basis of informed consent about prognosis and adjuvant therapy, most patients decided to choose the type of cytotoxic chemotherapy themselves. Adjuvant chemotherapy consisted of oral fluoropyrimidine compounds (OFP), cyclophosphamide + adriamycin +/- 5-fluorouracil [CA(F)] or cyclophosphamide + methotrexate + 5-fluorouracil (CMF). Toxicity was determined using the Toxicity Grading Criteria of the Japan Clinical Oncology Group (JCOG). Sixty-six patients received OFP, 59 CA(F) and the rest 55 CMF. The toxicity grading of leukocytes and neutrophils was significantly higher in patients treated with CA(F) or CMF than in those treated with OFP. Similar results were also seen relating to the toxicity of nausea/vomiting and alopecia. There was no statistical difference in the toxicity grading of hemoglobin, glutamic oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT) and stomatitis/ gastritis between the three groups of patients. Interestingly, the number of patients that were forced to discontinue chemotherapy was higher in those receiving OFP than in those receiving CA(F) or CMF. Cytotoxic chemotherapy of CA(F) or CMF results in greater toxicity than OFP, but is tolerated and feasible in the adjuvant setting used in Japanese breast cancer patients from the viewpoint of toxicities by anticancer chemotherapy.      

不同术后辅助化疗方案对胃癌患者远期生存的影响

目的:比较奥沙利铂(L-OHP)联合5-FU/LV与羟基喜树碱(HCPT)联合5-FU/LV两种不同辅助化疗方案对可切除胃癌术后远期生存的影响.方法:85例Ⅰ-Ⅳ期胃癌术后(R0切除)患者接受治疗,其中奥沙利铂组(L-OHP组)43例,羟基喜树碱组(HCPT组)42例,比较两组不良反应和生存率.结果:不良反应两组血小板减少、外周神经毒性及腹泻有显著性差异(P<0.05),其它不良反应无统计学差异(P>0.05).L-OHP组及HCPT 组1、3、5年总生存率(OS)分别为 95.4%、67.4%、18.6%和92.9%、64.3%、21.4%,两组比较无显著性差异(P>0.05),L -OHP组及HCPT组1、3、5年无病生存率(DFS)分别为83.7%、41.9%、9.3%和80.5%、45.2%、19.1%,随着时间延长,HCPT组5年DFS似有升高趋势,但均无统计学差异(P>0.05).结论:两种化疗方案均可作为胃癌患者术后辅助治疗的选择.     

不同术后辅助化疗方案对胃癌患者远期生存的影响

目的：比较奥沙利铂（L—OHP）联合5-FU／LV与羟基喜树碱（HCPT）联合5-FU／LV两种不同辅助化疗方案对可切除胃癌术后远期生存的影响。方法：85例I-Ⅳ期胃癌术后（R0切除）患者接受治疗,其中奥沙利铂组（L—OHP组）43例,羟基喜树碱组（HCPT组）42例,比较两组不良反应和生存率。结果：不良反应两组血小板减少、外周神经毒性及腹泻有显著性差异（P〈0．05）,其它不良反应无统计学差异（P〉0．05）。L—OHP组及HCPT组1、3、5年总生存率（OS）分别为95．4％、67．4％、18．6％和92．9％、64．3％、21．4％,两组比较无显著性差异（P〉Q05）,L—OHP组及HCPT组1、3、5年无病生存率（DFS）分别为83．7％、41．9％、9．3％和80．5％、45．2％、19．1％,随着时间延长,HCPT组5年DFS似有升高趋势,但均无统计学差异（P〉0．05）。结论：两种化疗方案均可作为胃癌患者术后辅助治疗的选择。     

Oncoplastic breast conservation does not lead to a delay in the commencement of adjuvant chemotherapy in breast cancer patients

Introduction

There is hardly any evidence that oncoplastic breast conservation surgery (OBCS) does not lead to a delay in the commencement of adjuvant chemotherapy. Although this is an integral part of overall oncological safety, no controlled studies have been published so far. Therefore, our aim was to determine whether OBCS led to a delay when compared to simple wide local excision (WLE), mastectomy (Ms) or mastectomy with immediate reconstruction (MsIR).

Methods

Breast cancer patients who required adjuvant chemotherapy after OBCS, WLE, Ms and MsIR were identified from prospectively maintained institutional databases. Time between multidisciplinary team decision to offer chemotherapy and delivery of first cycle of chemotherapy was measured and compared among the four groups of patients.

Results

time to chemotherapy of breast cancer patients (n = 169) treated with OBCS (n = 31) were 29 [16–58] days, while it was 29.5 [15–105] days after WLE (n = 66), 29 [15–57] days after Ms (n = 56) and 31 [15–58] days after MsIR (n = 16). A combined analysis involving all four groups demonstrated no statistically significant difference (p = 0.524). Similarly, inter-group analysis revealed no significant differences in between patients treated with OBCS compared to any of the three control groups (OBCS to WLE: p = 0.433; OBCS to Ms: p = 0.800; OBCS to MsIR: p = 0.405).

Conclusion

OBCS seems as safe as WLE, Ms or MsIR in terms of delivery of adjuvant chemotherapy, and, therefore, should not adversely affect breast cancer outcome in this respect.     

Effect of timing of initiation of adjuvant chemotherapy on disease-free survival in breast cancer

Summary Four hundred and sixty patients with stage II or III breast cancer following regional therapy were treated with an adjuvant combination chemotherapy consisting of fluorouracil, doxorubicin, and cyclophosphamide (FAC). The relationship between the length of disease-free survival and length of delays in initiation of chemotherapy after surgery was evaluated. Patients were divided into four subgroups according to the length of delay in initiation of chemotherapy (< 10 weeks, 10–13, 14–17, and 18 weeks). Overall four year diseasefree survival was 64%, 68%, 60%, and 63% for patient groups with delays of < 10 weeks, 10–13, 14–17, or 18 weeks respectively (p = 0.39). There was no trend for longer delay in treatment to be associated with shorter disease-free survival, except in poor prognosis patients.     

Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of primary breast cancer patients

The UK audit was undertaken in primary breast cancer patients receiving adjuvant chemotherapy to: (1) record the incidence of neutropenic events (hospitalisation due to febrile neutropenia, dose delay of > or =1 week or dose reduction of > or =15% due to neutropenia); (2) evaluate the impact of neutropenic events on overall dose intensity (DI) received and (3) review the use of granulocyte colony-stimulating factor (G-CSF) in clinical practice. Data from 422 patients with Stage I-III breast cancer were collected from 15 centres. Cyclophosphamide, methotrexate and 5-fluorouracil(CMF)- or anthracycline-based regimens were the most commonly used. Only 5.2% of patients received G-CSF. Overall, 29% of patients experienced a neutropenic event, most frequently dose delay. Neutropenic events had a significant impact on the ability to deliver planned DI. Out of 422 patients, 17% did not achieve 85% of their planned DI; due to neutropenia in 11% of patients. Of the neutropenic patients receiving CMF- or anthracycline-based regimens, around 40 and 32% of patients, respectively, did not achieve 85% of their planned DI. Patients who experienced one neutropenic event had a higher risk of a second event. During adjuvant chemotherapy of primary breast cancer, neutropenic events are common, likely to occur in subsequent chemotherapy cycles, and have a significant impact on receiving planned DI.     

Incidence of anaemia in breast cancer patients receiving adjuvant chemotherapy

Anaemia is frequent in breast cancer patients but often remains undiagnosed and untreated. To determine the incidence of anaemia a prospective survey of primary non-metastatic breast cancer patients who received at least four cycles of adjuvant, non-platinum multi-agent chemotherapy was conducted at 47 centres in Austria. Two hundred and forty seven patients were prospectively included between October 1999 and December 1999. Haemoglobin (Hb) levels were determined after surgery and prior to each cycle of chemotherapy. Treatment of anaemia (blood transfusion or epoetin alfa) during the observation period was at the physician's discretion. For the purpose of this study, patients were considered to be anaemic if their Hb was below 12 g/dl. At baseline (after surgery and before the first cycle of chemotherapy), 28.7% of all patients were anaemic. The only significant differentiating factor was the type of surgery. 37.9% of patients who underwent mastectomy were anaemic, whereas only 22.8% of patients who underwent breast conserving surgery were anaemic. Forty two percent of 176 patients with a Hb level of 12 g/dl at baseline developed anaemia during adjuvant chemotherapy. The only factor that significantly influenced the development of anaemia during chemotherapy was the Hb level at baseline. The total incidence of anaemia in patients with primary breast cancer who underwent surgery followed by adjuvant multi-agent chemotherapy was 58.7%. Forty nine patients (20.2%), 48 patients (19.2%) and 48 patients (19.2%) showed a decrease in Hb levels by 1 g/dl, 1–2 g/dl and >2 g/dl, respectively. Only 18.6% of the patients who were found to be anaemic received anaemia treatment. The two most important factors for developing anaemia are the kind of surgery and the Hb level prior to chemotherapy.