表阿霉素联合紫杉醇的新辅助化疗治疗乳腺癌的临床观察

目的 评价表阿霉素(EPI)联合紫杉醇(TAX)进行新辅助化学治疗乳腺癌的疗效及不良反应。方法用EPI联合TAX治疗Ⅱ、Ⅲ期乳腺癌26例,其中EPI 60 mg/m2,第1天静注,TAX 150 mg/m2,第2天持续3 h静滴,4周为1个疗程。所有患者化疗2个周期后行乳腺癌改良根治术,术后继续以原方案化疗4~6个周期。化疗前给予地塞米松、蒽丹西酮、苯海拉明和西米替丁预防胃肠道不良反应及过敏反应。结果乳腺癌有效率(RR)81％(21/26),其中Ⅱ期乳腺癌达94％(15,16),Ⅲ期为60％(6,10)。无病理完全缓解病例,1例(4％)临床完全缓解(cCR),20例(77％)部分缓解(PR),5例(19％)无变化(NC),无进展病例。腋窝肿大淋巴结中62％(16/26)新辅助化疗后不能触及,其中N1达75％(15/20),N2为17％(1/6)。主要不良反应为白细胞下降、关节肌肉痛、神经毒性、胃肠道反应、脱发和面色潮红,均可耐受。结论EPI联合TAX进行新辅助化疗是一种安全、有效、可行的方法,能明显缩小乳腺癌的原发肿瘤及腋窝淋巴结转移灶。     

新辅助化疗后乳腺癌病理变化31例分析

目的研究乳腺癌新辅助化疗后的病理改变，及其对于预后判断和后续治疗的意义。方法31例局部进展期乳腺癌患者，以TA方案进行新辅助化疗，化疗前的粗针穿刺标本和化疗后的根治术标本均进行病理检测。结果新辅助化疗后，原发病灶与淋巴结出现蜕变坏死、钙化、玻璃样变性、纤维性变等改变；临床体检、B超及钼靶评价新辅助化疗的疗效与病理评价的符合率分别为58.1%、71.0%和51.6%；新辅助化疗后原发肿瘤病理缓解程度高的患者转移淋巴结数目低于病理缓解程度低的患者（P=0.009）。结论①临床评价（体检、超声或钼靶）不能准确体现病灶在新辅助化疗后的变化；②新辅助化疗后原发肿瘤的病理评价可以在一定程度上预测腋窝淋巴结状态。     

乳腺癌激素受体的表达与新辅助化疗疗效的相关性

目的 研究乳腺癌雌孕激素受体的表达与新辅助化疗疗效之间的相关性。方法 用免疫组化的方法检测46例乳腺癌患者在接受新辅助化疗之前雌孕激素受体的表达情况，新辅助化疗结束后进行疗效评价。结果 46例患者中，临床完全缓解(cCR)17例，部分缓解(PR)21例，无变化(NC)8例，其中病理完全缓解(pCR)9例，总有效率为82．6％，pCR率为19．57％。在受体双阴的22例患者中，20例有效(cCR PR)，总有效率为90．9％，NC2例；pCR6例(27．3％)，受体单阳或双阳的2，4例患者中，18例有效(cCR PR)，总有效率为75．0％，NC6例。pCR3例(12．5％)。受体双阴组患者的pCR率及总有效率都高于受体单阳或双阳组患者，但未见显著性差异。结论 受体双阴的患者可能较受体单阳或双阳的患者对化疗的敏感性更高。     

后ACSOGZ0011时代术中冰冻病理评估乳腺癌前哨淋巴结转移的价值

目的探讨后ACSOG Z0011时代术中冰冻病理诊断在乳腺癌前哨淋巴结活检中的价值。方法连续收集就诊于北京大学人民医院乳腺中心的浸润性乳腺癌患者,术中前哨淋巴结行冰冻病理检查,按术后石蜡病理结果统计分析冰冻病理的准确性;按Z0011入组标准分析前哨淋巴结冰冻病理诊断对后续腋窝处理的影响。结果 395例入组患者中前哨淋巴结术中冰冻病理阳性59例,阴性336例,冰冻切片的假阴性率为21.3%,敏感度为78.7%。在59例阳性患者中,按Z0011入组标准统计分析,26人(44.1%)可避免腋窝淋巴结清扫术;而在接受保乳手术患者中,该比例为92.9%。结论对于T1-2期、术前腋窝淋巴结临床阴性、拟行保乳手术的乳腺癌患者,可不行术中冰冻切片检查。     

乳腺癌术后伤口并发症的探讨--附164例报告

目的 探讨乳腺癌术后伤口并发症发生的原因和相关危险因素及其防治措施。方法2004年1月-2004年11月我院接受乳腺癌手术治疗的164例连续乳腺癌患者。手术方式包括乳腺癌改良根治术和保留乳房手术。术中常规留置负压引流直至24h引流量小于20ml后拔除。记录每口引流量、患者住院天数、术后皮瓣积液、皮瓣坏死、伤口感染情况。结果164例患者发生共发生皮下积液30例（18．3％）；电刀游离皮瓣明显增加了皮瓣积液的发生率（OR=2．39，P=0．014）；腋窝淋巴结转移数目1-4个（OR值=2．56，P〈0．05）和5-10个（OR值=6．20，P〈0．05）时其发生皮瓣积液危险均高于腋窝淋巴结阴性的患者。电刀游离皮瓣的患者总引流量多于手术刀游离皮瓣组，改良根治术后的总引流量也多于保乳手术组（P〈0．01）。乳腺癌术后发生皮瓣积液明显延长了患者的住院时间（P〈0．01）。患者的年龄、肿瘤分期、接受新辅助化疗及腋窝淋巴结清扫数目都和术后是否发生皮瓣积液无关（P〉0．05）。结论保持通畅引流、合理使用电刀和恰当加压包扎是预防切口并发症的关键。     

三苯氧胺对人乳腺癌的雌激素受体的上调作用

东莞氧胺(TMX)为一非固醇类雌激素拮抗剂,广泛用于晚期和复发乳腺癌。TMX使约60％雌激素受体(ER)阳性和10％ER阴性的乳腺癌肿缩小。一些临床试验表明,对ER阳性的绝经后乳腺癌患者TMX可作为一有效辅助治疗。目前尚未阐明在体内TMX治疗对人乳腺癌ER和孕激素受体(PR)水平的影响。在本研究中,作者试图从同一乳腺癌中获得系列细针穿刺吸引(FNA)标本,用酶联免疫法(EIA)检测TMX对人乳腺癌ER水平的影响及对PR的影响。     

射频消融技术对子宫肌瘤组织中ER、PR表达影响的临床试验研究

目的 :开腹直视下射频消融子宫肌瘤后 ,观察射频消融对子宫肌瘤组织中ER、PR表达的影响 ,初探射频治疗子宫肌瘤的机制。方法 :30例需开腹行子宫切除术的多发性子宫肌瘤患者 ,分别用 0 .5cm、1.2cm长的射频自凝刀行肌瘤部位射频消融 ,治疗后立即切除子宫 ,作为试验组 ,并于消融灶中心 (A组 )、边缘 (B组 )、边缘外 1cm(C组 )、边缘外 2cm(D组 )处取材 ,HE染色观察病理变化 ,免疫组化检测ER、PR水平 ;选同一子宫上未做射频治疗的肌瘤组织作为对照组。结果 :射频治疗后 ,消融灶中心肌瘤组织呈凝固性坏死 ,ER、PR无表达 ;消融灶边缘肌瘤细胞变性 ,ER、PR表达减少 (P <0 .0 5 ) ;消融灶边缘外1cm ,肌瘤细胞无变性、坏死 ,但ER、PR表达低于对照组 (P <0 .0 5 ) ;消融灶边缘外 2cm ,ER、PR与对照组差异无显著性 (P >0 .0 5 )。结论 :射频消融技术使肌瘤组织凝固性坏死 ,ER、PR的表达丧失及低表达是射频消融技术能够治疗子宫肌瘤的循证依据     

子宫内膜癌组织中环氧化酶-2与雌、孕激素受体的表达及相关性研究

目的:探讨子宫内膜癌组织中环氧化酶-2(COX-2)、雌激素受体(ER)和孕激素受体(PR)的表达及相关性。方法:应用免疫组化SP法检测56例子宫内膜癌中COX-2、ER和PR的表达。结果:COX-2在子宫内膜癌中的表达率随病理分级的增高而升高,与患者年龄、临床分期和淋巴结转移情况无关。ER和PR在子宫内膜癌的表达与临床分期及病理分级、淋巴结转移有关,表达率随临床分期增加、病理分级增高及淋巴结转移而降低。COX-2的表达与ER和PR无关。结论:COX-2可能介导不同的生物学途径,可以联合内分泌药物与特异性COX-2抑制剂治疗转移或复发的子宫内膜癌。     

新辅助化疗在宫颈癌治疗中的应用及疗效观察

目的探讨术前新辅助化疗对局部晚期宫颈癌的治疗效果。方法对55例Ib2～Ⅱb期的宫颈癌患者行新辅助化疗，并对治疗效果进行评价。以同期未行新辅助化疗的33例宫颈癌患者作为对照，比较两组患者术中出血量、宫旁浸润率、阴道切缘阳性率及淋巴结转移率的差异。对患者进行随访，分析新辅助化疗对远期预后的影响。结果新辅助化疗组总有效率为94．6％，病理完全缓解者5例（9．1％）。有效的52例患者接受了手术。新辅助化疗组淋巴结转移率为36．5％，对照组为48．5％，两组比较，无差异（P〉0．05）。但新辅助化疗组中Ⅱ期患者淋巴结转移率（35．3％）低于对照组（69．2％），两者比较，差异有显著性（P〈0．05）。两组的宫旁浸润率分别为1．9％和18．2％，经精确概率法计算，两者比较，差异有显著性（P〈0．05）。术中出血量分别为（874．0±675．6）ml和（493．9±316．7）ml，两者比较，差异有显著性（P〈0．05）。NACT组与对照组的1年无瘤生存率分别为77．78％和81．04％，5年无瘤生存率分别为75．41％和81．04％，1年总生存率分别为93．91％和96．88％，5年总生存率分别为84．37％和88．03％，两组比较，差异均无显著性（P〉0．05）。结论新辅助化疗对局部晚期宫颈癌患者近期疗效显著，但对无瘤生存时间和总生存时间无明显影响。术后化疗、淋巴结转移是影响患者无瘤生存时间的主要因素。     

乳腺癌中survivin表达及变化与紫杉醇疗效的相关性

目的探讨乳腺癌中survivin的表达水平及其在化疗前后表达水平的变化与紫杉醇作用效果之间的相关性。方法选取60例接受新辅助化疗的乳腺癌，用免疫组织化学的方法分别检测化疗前后survivin的表达情况，并评价化疗的疗效。结果Survivn阴性和强阳性组相比及弱阳性组与强阳性组相比，前者的化疗效果优于后者，差异有统计学意义。获得临床稳定（SD）的患者与获得临床部分缓解（PR）、临床完全缓解（cCR）的患者相比，前者化疗后survivin上调的比例要明显高于后者，两者之间存在统计学差异。结论survivin的过表达可能与紫杉醇的耐药性相关。     

Ultrasound-guided fine needle aspiration cytology in staging clinically node-negative invasive breast cancer

The aim of this study was to evaluate the value of ultrasound (US)-guided axillary lymph node fine needle aspiration cytology (FNAC) in staging clinically node-negative invasive breast cancer. Based on retrospective data, we analyzed sensitivity, specificity, and positive and negative predictive value and efficacy of preoperative axillary US-guided FNAC. A total of 108 consecutive female patients with histological-confirmed invasive breast cancer between January 2006 and December 2010 were included. The management decisions were based on cytological results. Twenty-two patients underwent neoadjuvant chemotherapy and 86 remaining patients benefited of primary surgery. Patients with positive cytology or included in neoadjuvant regimens were scheduled for axillary lymph node dissection (ALND), while patient with negative or nondiagnostic cytology underwent sentinel lymph node biopsy. Axillary US-guided FNAC was compared with definitive pathology of surgically removed lymph nodes. Axillary metastases were found in 55 out of 108 patients (50.9%). In these cases we proceeded with ALND. Excluding the group benefiting from neoadjuvant chemotherapy, we could spare a second surgical intervention for 37 out of 86 patients (43%). The axillary US with FNAC has a sensitivity of 73%, a specificity of 85%, a positive predictive value of 89%, and a negative predictive value of 66%. Without taking into account the neoadjuvant chemotherapy group, in which the statistical analyzes might be biased by the complete histological response, specificity and positive predictive value increased to 100% and negative predictive value to 71%. US combined with FNAC of axillary lymph nodes is a simple, minimally invasive, and reproducible diagnostic approach in improving the preoperative axillary staging of invasive breast cancer patients.     

Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancer

AIM: To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix. METHODS: From January 1999 to December 2001, 106 women with cervical cancer stage IB received neoadjuvant chemotherapy (n = 52) or primary surgery (n = 54). These were randomly assigned. Clinical effects and pathological changes were simultaneously recorded. RESULTS: The overall clinical response rate was 84.6% and included a complete response (CR) in four patients (7.7%), partial response (PR) in 40 patients (76.9%), and stable disease (SD) in the remaining eight patients (15.4%). Surgery revealed positive nodes in 9.6% neoadjuvant chemotherapy group patients and in 29.6% primary surgery group patients (P = 0.014). Similar results occurred with vascular space involvement: 27.8% in the primary surgery group compared to 9.6% in the neoadjuvant chemotherapy group (P = 0.024). However, parametrial infiltration was found in 7.4% of the patients in the primary surgery group, while only 3.8% showed it in the neoadjuvant chemotherapy group (P = 0.679). The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy (84.6%) than for the control group (75.9%) (P = 0.0112). The median survival time in patients with complete response and partial response to chemotherapy (83.3 months) was significantly higher than that of patients with stable disease to chemotherapy (55.2 months) (P = 0.0049). 27.3% of patients developed recurrent disease within 5 years of the primary treatment. The women with recurrence included partial response in six patients (60.0%), and stable disease in four patients (40.0%). For the other patients there was partial response and complete response in 38 patients (90.5%), and stable disease in the remaining four patients (9.5%) (P = 0.035). CONCLUSION: Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer.     

Detection of axillary metastases in breast cancer patients using ultrasound and colour Doppler combined with fine needle aspiration cytology

The aims of this study were to evaluate the diagnostic value of ultrasonography and colour Doppler combined with fine needle aspiration (FNA) cytology for the detection of non-palpable axillary lymph node metastases in breast cancer patients. Forty patients with operable breast cancer (T1/T2), invasive carcinoma, not submitted to neo-adjuvant therapy, underwent axillary ultrasonography and colour Doppler preoperatively. FNA cytology was performed on axillary lymph nodes presenting ultrasonographic and/or Doppler suspicious features. A total of 542 lymph nodes were surgically removed from the 40 patients; 19 were metastatic lymph nodes. Ultrasound-guided FNA detected metastases in six out of 11 histologically node-positive patients. Sensitivity and specificity in this preliminary study was 55% and 100%, respectively. These are the preliminary results of a prospective study that has the purpose of reducing the sentinel node procedures in breast cancer patients with clinically negative axillae, but positive FNA cytology.     

Gene expression profiles of breast cancer obtained from core cut biopsies before neoadjuvant docetaxel, adriamycin, and cyclophoshamide chemotherapy correlate with routine prognostic markers and could be used to identify predictive signatures

BACKGROUND: Neoadjuvant administration of chemotherapy provides a unique opportunity to monitor response to treatment in breast cancer and assesses response exactly. Global gene expression profiling by microarrays has been used as a valuable tool for the identification of prognostic and predictive marker genes. Even though this technology is now wide spread and relatively standardized, there are only few data available which compare established parameters with expression values to determine reliability of this method. Therefore we analyzed gene expression data of pretreatment biopsies of breast cancer patients and compared them with the results of the immunohistochemical receptor expression for ER/ PR and Her-2, as well as FISH testing for HER-2 amplification. We analyzed the change of expression of these markers before and after neoadjuvant chemotherapy. Furthermore we evaluated the predictive significance of prognostic gene signatures as described by Sorlie, van't Veer and Ahr for response to neoadjuvant chemotherapy. METHODS: Pretherapeutic core biopsies were obtained from 70 patients undergoing neoadjuvant TAC chemotherapy within the GEPARTRIO-trial. Samples were characterized according to standard pathology including ER, PR and HER2 IHC and amount of cancer cells. Only biopsies with more than 80 % tumor cells were considered for further examination. RNA was isolated and expression profiling performed using Affymetrix Hg U133 Arrays (22 500 genes). GeneData's Expressionist software was used for bioinformatic analyses. RESULTS: More than two thirds of the biopsies yielded sufficient amounts (> 5 microg) of RNA for expression profiling and high quality data were obtained for 50 samples. Unsupervised clustering broadly revealed a correlation with hormone receptor status. When ER-alpha, PR and HER2 as analyzed by immunohistochemistry were compared to the corresponding mRNA data from gene chips more than 90 % concordance was observed. We could observe a switch of receptor expression for ER, PR or HER-2 from positive to negative and vice versa in 16/35 cases (45.7 %) and 5/22 cases (22.7 %) respectively. The prognostic marker sets of Sorlie, van't Veer and Ahr could not discriminate responders from non-responders in our patient group. CONCLUSIONS: Our results demonstrate that reliable expression profiles can be achieved by using limited amounts of tissue obtained during neoadjuvant chemotherapy. Microarray data capture conventional prognostic markers but might contain additional informative gene sets correlated with treatment outcome. Prognostic marker sets are not suitable to predict tumor response in the neoadjuvant setting, suggesting the necessity of class prediction methods to identify marker sets predictive for the type of therapy used.     

Circulating tumor cells in breast cancer

PURPOSE OF REVIEW: To critically review the latest findings concerning the detection and characterization of circulating tumor cells in breast cancer. RECENT FINDINGS: Various studies have used different methods and markers for circulating tumor cell detection in breast cancer. Data on the prognostic value of circulating tumor cell monitoring by the CellSearch system are now available in patients with measurable metastatic breast cancer receiving chemotherapy, whereas no such data are still available for adjuvant or neoadjuvant settings. The detection of cytokeratin 19 mRNA-positive cells before the initiation of adjuvant chemotherapy was shown to be an independent prognostic factor for worse clinical outcome in patients with early breast cancer. Interestingly, this was mainly observed in patients with triple-negative and HER2-positive, but not estrogen receptor-positive/HER2-negative, early breast cancer. Finally, gene-expression profiling of single cells was reported to be feasible with important implications for eliminating circulating tumor cells. Pilot studies have shown that phenotyping of circulating tumor cells could be used to predict response to targeted therapies. SUMMARY: Circulating tumor cells might become a valuable tool to refine prognosis in early and metastatic breast cancer. Circulating tumor cell phenotyping/profiling may serve as a real-time tumor biopsy for individually-tailored targeted therapies.     

Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable,advanced-stage ovarian cancer

OBJECTIVE: The aim of this review is to report our experience and the feasibility of neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer. METHODS: Forty-five patients with primarily unresectable advanced-stage epithelial ovarian cancer were treated in our center between 1995 and 2002 by platinum-based neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Their files were reviewed retrospectively. RESULTS: At the end of neoadjuvant chemotherapy, according to RECIST criteria, 1 patient (2.2%) had achieved a clinical complete response (CR), 33 (73.4%) a partial response (PR), and 8 (17.8%) had stable disease (SD). Only 3 (6.6%) patients showed disease progression (PD). Surgery was performed in patients with objective response or SD after a median number of 4 courses (range: 2-6) of induction chemotherapy. A complete macroscopic debulking was achieved in 24 (53.3%) out of 39 patients in whom cytoreductive surgery was performed. For the entire group, median overall survival was 29 months. Survival was significantly improved in patients with optimal debulking compared to patients with persistent tumor after surgery: 41 months versus 23 months (P = 0.0062). Median survival for patients responding to neoadjuvant chemotherapy (CR and PR) was 44 months compared to 27 months for patients with SD or PD after initial chemotherapy (P = 0.01). Neither treatment-related deaths nor significant toxicities were observed. CONCLUSION: Neoadjuvant chemotherapy followed by optimal debulking may be a safe and valuable treatment alternative in patients with primarily unresectable advanced-stage bulky ovarian cancer. Patients with an objective response to chemotherapy or absence of macroscopic residual tumor after surgery have a better outcome. This approach is currently being tested in large, prospective randomized clinical trials.     

The use of aminoglutethimide in the treatment of metastatic breast cancer]

It has been demonstrated that AG inhibits the peripheric conversion of androstenedione into estrogens and produces an adrenal suppression, equivalent to surgical adrenalectomy. As breast cancer is responsive to hormonal therapy, AG has been used in the treatment of metastatic breast cancer. Since 1984, at I Clinica Ostetrica e Ginecologica of University of Torino, 48 patients with advanced breast cancer, previously treated with chemotherapy and hormonotherapy, have been given AG 1 g/day and hydrocortisone 40 mg/day. Six patients (12%) obtained CR, nine (19%) a PR, eleven (23%) a SD, twenty two (46%) a PD. The efficacy of AG has been evaluated as related to the following prognostic factors: menopausal status, hormone receptors, disease free interval, age, prior tamoxifen exposure. This study shows that bone involvement is the most responsive localization to AG. In conclusion AG is still an effective therapeutic choice in metastatic breast cancer treatment.