新辅助化疗诱导的粒细胞减少症对乳腺癌预后的影响

目的 探讨新辅助化疗诱导的粒细胞减少症与采用蒽环类联合紫杉类新辅助化疗方案进行新辅助化疗患者的疗效及远期生存率之间的关系.方法 对接受4个周期蒽环类联合紫杉类新辅助化疗方案治疗的211例乳腺癌患者的资料进行回顾性分析.结果 211例中51(24.2%)例为嗜中性粒减少症患者,160(75.8%)例为非嗜中性粒细胞减少症患者.嗜中性粒细胞减少症患者组的新辅助化疗反应较非嗜中性粒细胞减少症组患者为好(P＜0.05).嗜中性粒细胞减少症患者5年无病生存率为82.4%,5年总生存率为90.2%,而非嗜中性粒细胞减少症患者的5年无病生存率为60%,5年总生存率为67.5%,两者相比差异均有统计学意义(均P＜0.01).结论 蒽环类联合紫杉类新辅助化疗方案诱导的嗜中性粒细胞减少症与可手术乳腺癌患者的预后有良好的相关性,可用来评估肿瘤对此类化疗药物的敏感性,并为个体化的治疗方案提供依据.     

Utility of neoadjuvant chemotherapy in the treatment of operable breast cancer

Neoadjuvant chemotherapy (NAC) is a legitimate alternative to first‐line surgical therapy for the treatment of breast cancer patients, as level one evidence shows the effect on overall survival is equivalent to that of adjuvant chemotherapy. In the treatment of women with operable breast cancer, NAC provides a number of potential advantages including: improving the chance of achieving breast‐conserving surgery, improving cosmesis after breast‐conserving surgery, downstaging the breast and axilla, allowing time to fully consider surgical options, time for genetic testing and facilitating breast reconstruction in otherwise high‐risk patients. However, in Australia, NAC is poorly utilized with less than 3% of women with operable breast cancer receiving NAC. This review discusses the potential harms and benefits of NAC, discusses areas of controversy in the use of NAC and describes how we have used NAC in our own practice. We conclude that if it is obviously necessary for the newly presenting breast cancer patient to have chemotherapy as part of the treatment, it is worth considering NAC. In many patients, the potential benefits of NAC outweigh the harms. However, maximizing these benefits is closely aligned with appropriate patient selection and timely multidisciplinary team communication.     

Development of malignant breast microcalcifications after neoadjuvant chemotherapy in advanced breast cancer

The increased interest in the use of neoadjuvant chemotherapy for patients with locally advanced or large tumors at initial presentation necessitates the recognition of sequelae of this therapy. This article describes the interval appearance of malignant, linear-branching, microcalcifications during neoadjuvant chemotherapy for locally advanced breast cancer. Mammographically the malignant microcalcifications appeared only in the region of the breast where the primary tumor was found. Pathologically only a subpopulation of malignant cells responded to the chemotherapy, demonstrating viability of the majority of the tumor, with cell death only in the subpopulation. With the increased use of neoadjuvant chemotherapy, it is important to recognize previously undescribed mammographic findings secondary to this therapeutic approach.     

Sentinel lymph node mapping following neoadjuvant chemotherapy for breast cancer

The purpose of this study was to evaluate the feasibility of sentinel lymph node mapping in patients undergoing neoadjuvant chemotherapy for breast carcinoma prior to lumpectomy or mastectomy and sentinel lymph node mapping followed by complete axillary dissection. A retrospective analysis of 14 patients from February 1998 to July 2000 with stage I to stage IIIB breast cancer diagnosed by core biopsy underwent neoadjuvant chemotherapy (doxorubicin/cyclophosphamide) prior to definitive surgery, including lumpectomy or mastectomy and sentinel lymph node mapping, followed by full axillary dissection. Thirteen of 14 patients had successful sentinel lymph node identification (93%), and all 14 underwent full axillary dissection. An average of 2.2 sentinel nodes and a median of 16 axillary lymph nodes (including sentinel nodes) were found per patient. Of the 13 patients in whom a sentinel lymph node was identified, 10 were positive for metastases (77%). Only 4 of the 10 had further axillary metastases (40%). Three patients had negative sentinel lymph nodes shown by hematoxylin and eosin and cytokeratin stainings and had no axillary metastases (0% false negative). The single patient in whom a sentinel lymph node could not be identified had stage IIIA disease with extensive lymphatic tumor emboli. Sentinel lymph node mapping is feasible in neoadjuvant chemotherapy breast cancer patients and can spare a significant number of patients the morbidity of full axillary dissection. Further study to evaluate sentinel lymph node mapping in this patient population is warranted.     

分子标记物表达预测乳腺癌蒽环类新辅助化疗疗效价值研究

目的探讨局部晚期乳腺癌病人肿瘤组织分子生物学标记物的表达及其与新辅助化疗有效率的关系。方法采用免疫组化的方法检测2000年1月至2010年12月复旦大学附属肿瘤医院乳腺外科收治的420例乳腺癌新辅助化疗病人化疗术后标本中雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)/neu、p53、Cathepsin-D、p27、cyclinD1、Bax、Ki67、TOPOII、GSTπ、MDR和Bcl-2等分子标记物的表达情况,分析这些分子标记物的表达与新辅助化疗疗效之间的关系。结果 p53或cathepsin-D或GSTπ阴性的病人化疗疗效要显著优于阳性的病人,多因素回归分析提示GSTπ和p53是独立的新辅助化疗疗效预测指标。结论 GSTπ和p53可作为判定乳腺癌蒽环类新辅助化疗方案敏感性的两个独立预测指标。     

循环肿瘤细胞在乳腺癌新辅助化疗中的应用进展

·综 述·     

胃癌新辅助化疗进展

新辅助化疗又称术前化疗,主要目的 在于减小肿瘤负荷,降低临床分期,提高手术根治性切除率,改善治疗效果.胃癌新辅助化疗作为一个相对较新的理念,目前在临床上应用逐渐增多.     

胰腺癌新辅助化疗进展

胰腺癌目前仍然是临床非常棘手的问题,但在一些胰腺外科中心通过手术切除改善了胰腺癌的预后.目前已有结果提示新辅助治疗对胰腺癌患者安全,且能够显著提高手术切除率.但新辅助治疗与手术治疗、术后辅助治疗及姑息治疗相比较其疗效如何,到目前为止,尚缺少高质量的循证医学证据,也没有关于胰腺癌新辅助化疗或放化疗与外科手术后系统化疗间比较的随机对照研究.需要设计完善的随机对照研究对比新辅助化疗和手术治疗,以此来评价新辅助化疗在胰腺癌多种治疗方案中的价值.     

背阔肌肌皮瓣修复新辅助化疗后局部晚期乳腺癌组织缺损的疗效观察

目的:探讨我科12例局部晚期伴有皮肤侵犯导致溃疡形成的乳腺癌患者,术前行新辅助化疗后行改良根治术,即刻应用背阔肌肌皮瓣即时修复组织缺损的疗效观察。方法:12例患者均于术前行4~6周期新辅助化疗TEC方案,后达到临床部分缓解(PR)、创面缩小后,行乳腺癌改良根治术、即刻背阔肌肌皮瓣转移修复胸壁组织缺损。结果:12例患者手术均成功,接受新辅助化疗和术后放疗。随访l0~24个月,术后远处转移l例,无局部复发和死亡病例。结论:局部晚期乳腺癌新辅助化疗后,应用背阔肌肌皮瓣转移至胸壁修复组织缺损切实可行。     

淋巴细胞亚群对乳腺癌新辅助化疗疗效的预测价值

目的 本研究旨在探讨治疗前淋巴细胞亚群对乳腺癌新辅助化疗(NAC)疗效的预测价值.方法 本研究选取2016年4月至2020年6月在中山大学孙逸仙纪念医院接受NAC的乳腺癌患者109例.采用卡方检验及logistics回归分析不同淋巴细胞亚群比例与病理完全缓解(pCR)的相关性,并通过Kaplan-Meier曲线评估其与...     

Preoperative evaluation of residual tumor extent by three-dimensional magnetic resonance imaging in breast cancer patients treated with neoadjuvant chemotherapy

The purpose of this study was to evaluate the usefulness of three-dimensional magnetic resonance imaging (3D MRI) for the preoperative assessment of residual tumor extent in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Thirty-eight breast cancer patients treated with NAC containing taxane and/or anthracycline for 3-6 months were enrolled in this study. Tumor size was measured by means of calipers, ultrasonography, and dynamic MRI before and after NAC. Three-dimensional maximum intensity projection MRIs to measure the tumor size were created for every case. The tumor size determined by calipers, ultrasonography, and 3D MRI after NAC was compared with that determined by pathologic examination. The tumor size determined by 3D MRI showed a strong correlation with that determined by pathologic examination (r = 0.896). Moderate, but significant correlations were found between measurements obtained with calipers and pathology (r = 0.554), and between ultrasonography and pathology (r = 0.484). The response rates to NAC were estimated at 84.2% with calipers, 58.0% with ultrasonography, and 44.7% with 3D MRI. Calipers and ultrasonography thus tended to overestimate the response to NAC compared to 3D MRI (p < 0.001 and 0.240, respectively). Three-dimensional MRI can visualize residual tumor extent after NAC more accurately than calipers and ultrasonography, and seems to be more reliable than other modalities for estimating response to NAC. It should also help surgeons with decision making for breast-conserving surgery after NAC.     

Dose-dense chemotherapy for breast cancer

The concept of dose-dense chemotherapy has emerged and is based on the hypothesis that maximal chemotherapy effectiveness can be achieved by scheduling the interval of chemotherapy to correspond to the period of most rapid tumor growth, as predicted by preclinical models. The granulocyte-colony stimulating factor support has permitted the safe delivery of chemotherapy at shorter ("dose-dense") inter-treatment intervals. Several randomized trials have been conducted to test the feasibility and effectiveness of anthracycline and/or taxanes-based dose-dense strategies. They have been associated with a modest impact on disease recurrence and overall survival of patients with early-stage breast cancer. Subset analyses have suggested increased benefits for specific tumor subtypes such as hormone receptor-negative, highly proliferative or HER2 overexpressing tumors. This review article aims to outline the theoretical framework for dose-dense chemotherapy and summarizes the results of several recent clinical trials addressing this concept within neoadjuvant and adjuvant breast cancer treatment and discuss their implications for clinical practice. Further studies are needed to define the optimal regimen and the patient population that will receive the greatest benefit from dose-dense strategy.     

多西他赛、环磷酰胺与多西他赛、吡柔比星新辅助化疗方案治疗局部晚期乳腺癌疗效分析

目的观察多西他赛、环磷酰胺（DC方案）与多西他赛、吡柔比星（DT方案）新辅助化疗方案治疗局部晚期乳腺癌的临床疗效和不良反应。方法经麦默通穿刺确诊局部晚期乳腺癌可手术患者73例,随机分为DC组（35例）,DT组（38例）,分别给予DC方案,DT方案化疗3个周期,DC组35例,DT组38例化疗结束2周后行乳腺癌改良根治术。比较DC组,DT组疗效和不良反应,治疗前、后TNM分变化、术后并发症及化疗前后ER、PR、HER2变化比较。结果临床疗效比较DT组优于DC组,其差异有统计学意义（P〈0．05）;TNM分期均较新辅助化疗前降低（P〈0．05）,不良反应比较差异无统计学意义（P〉0．05）;术后并发症比较差异无统计学意义（P〉0．05）,ER、PR均为阴性患者对化疗敏感,DT方案对于HER2高表达患者疗更敏感。结论DT及DC新辅助化疗方案疗对局部晚期乳腺癌均有效,DT方案优于DC方案。     

Inflammatory breast cancer: results of antracycline-based neoadjuvant chemotherapy

Abstract: Twenty-three patients with inflammatory breast cancer treated with a combined modality approach including anthracycline-based induction chemotherapy-surgery-chemotherapy-radiotherapy were reviewed. Twelve patients (52.2%) received FAC (5-fluorouracil, adriamycin, cyclophosphamide) and 11 patients (47.8%) were treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) induction chemotherapy for three cycles every 3 weeks. Surgery was followed by the initial chemotherapy or second-line chemotherapy for an additional six cycles to complete nine cycles and radiotherapy, respectively. The median overall survival (OS) time was 27 months and the median disease-free survival (DFS) was 13 months. Furthermore, patients treated with FAC induction chemotherapy have been found to have longer median OS and DFS periods compared to patients with FEC induction chemotherapy in both univariate and multivariate analysis. In conclusion, the superiority of doxorubicin-containing chemotherapy over epirubicin-containing chemotherapy should be established in larger randomized studies and more effective chemotherapeutic agents such as taxans are required for better survival rates in inflammatory breast cancer patients.      

动脉内灌注新辅助化疗治疗晚期乳腺癌

目的探讨动脉内灌注新辅助化疗对晚期乳腺癌疗效及病理特征的影响。方法36例晚期乳腺癌术前超选择动脉置泵灌注化疗。化疗方案为CEF方案:5氟尿嘧啶(5Fu)500mg/m2,环磷酰胺(CTX)400mg/m2,表阿霉素(EPI)60mg/m2。每周1～2次,2～3次为一个疗程,休息2周后可重复灌注化疗,2～3个疗程后进行手术。结果动脉内灌注新辅助化疗后,术前肿瘤病灶临床完全缓解(CR)6例。部分缓解(PR)25例,稳定(MR)5例,有效率(CR PR)86.1%。术后病理学检查发现:癌细胞均有不同程度的核固缩,碎裂,胞浆凝固,变性;细胞间质水肿,纤维增生,炎细胞浸润;血管内膜增厚,血栓形成。结论动脉内灌注新辅助化疗可以明显改变晚期乳腺癌的组织学形态,改善临床症状,提高生存率。     

Diagnosis of complete response to neoadjuvant chemotherapy using diagnostic imaging in primary breast cancer patients

Advances in the therapeutic agents used for neoadjuvant chemotherapy (NAC) have recently achieved higher response rates and induced a greater number of pathologic complete responses (pCR) than ever before. The aim of this study is the diagnosis of pCR after NAC by diagnostic imaging of clinical complete response (cCR) patients. This study included 35 breast cancer patients who demonstrated cCR after receiving NAC with a combination of anthracycline and taxane from May 1998 to August 2003. Surgical treatment included breast-conserving therapy followed by radiotherapy or mastectomy. The identity of post-NAC lesions as either a complete response (CR) or partial response (PR) were made by mammography, ultrasonography, and contrast-enhanced computed tomography (CT). Among the 35 patients, 11 achieved pCR, including the disappearance of both invasive and intraductal components. Of the patients achieving pCR, eight were defined as CR and three were determined to be PR by CT. There was a significant relationship between the pCR and the determination of CR by CT. The determination of CR by ultrasonography was indicative of the disappearance of pathologic invasive components. While mammography appeared to reflect the observed histologic results, we did not observe any statistical differences. A subset of cases exhibited discrepancies between the imaging and pathologic results, likely due to the replacement of destroyed tumor cells by fibrosis and granulomatous tissue. The evaluation of CR by CT was significantly indicative of pCR. The positive predictive value, however, was not large enough to avoid surgical treatment. Further studies will be needed to establish a diagnosis of pCR.     

Accuracy of axillary sentinel lymph node biopsy following neoadjuvant (induction) chemotherapy for carcinoma of the breast

Sentinel lymph node biopsy (SLNB) is widely employed to detect axillary lymph node metastases in breast cancer patients with clinically negative (N0) axillae. One of the few reported contraindications to SLNB is prior treatment with systemic chemotherapy (neoadjuvant/induction chemotherapy). Previous investigators reported difficulty identifying the sentinel node and an unacceptable false-negative rate in this patient cohort. We present one experienced surgeon's experience with SLNB following induction chemotherapy (n = 21). Following treatment with Adriamycin and Cytoxan (AC)-based cyclic chemotherapy, patients underwent SLNB, followed by levels I and II axillary lymph node dissection (ALND). At least one sentinel node was identified in all patients (100%). With respect to metastatic disease, the status of the sentinel node(s) accurately reflected the status of the axilla in 20 of 21 patients (95%). Eleven patients (52%) had axillary metastases identified by ALND. Of this group, SLNB failed to identify metastatic disease in one patient (9%). Previous treatment with induction chemotherapy should not be considered an absolute contraindication to SLNB. An experienced surgeon may utilize the technique in these patients, sparing them the added morbidity of axillary dissection.     

Risk scoring system for predicting breast conservation after neoadjuvant chemotherapy

We developed a risk scoring system (RSS) for predicting breast conservative surgery (BCS) in women receiving neoadjuvant chemotherapy(NAC) for breast cancer. BCS rate in the training set was 32.6%, associated with five variables: age < 50years, primary radiological tumor diameter < 60mm, absence of multifocality, absence of breast inflammation and hormone receptor status. These variables were assigned scores ranging from 0 to 9. The discrimination of the RSS was 0.78(95%CI 0.69‐0.86) in the training set. The area under the curve of the receiver operating characteristics for predicting BCS after internal and external validation was 0.77(95%CI 0.68‐0.85) and 0.75(95%CI 0.66‐0.84), respectively.     

乳腺癌新辅助治疗个体化管理

近年来乳腺癌新辅助治疗作为标准治疗手段之一愈发受到关注,与辅助治疗相比是否有优势存在的争论也颇多。然而经新辅助化疗达到病理完全缓解（PCR）可以显著改善预后这个不争的事实展示了该治疗方式的美好前景,同时也促使外科医生思考哪类病人能够达到PCR,哪些方案能够使病人从新辅助化疗中最大获益。另外,在治疗过程中运用MRI、循环肿瘤细胞测定等手段对疾病进行监测和疗效预测,使乳腺癌新辅助治疗在安全、可控中进行,做到真正的个体化治疗。     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in a patient with operable breast cancer

PURPOSE: This study was undertaken to assess the feasibility of performing a sentinel lymph node biopsy (SLNB) for a patient with operable breast cancer after undergoing neoadjuvant chemotherapy (NAC). METHOD: Between January 2002 and December 2003, women with primary breast cancer who had a breast tumor measuring larger than 3 cm in unilateral diameter were eligible for NAC. All patients who had completed NAC underwent lymphatic mapping with labeled (99m)Tc phytate on the day before surgery. Sentinel lymph node biopsy followed by a full axillary lymph node (AXLN) dissection (ALND) was performed in all patients. Sentinel lymph nodes (SLN) were sent for a frozen-section examination. RESULTS: The rate of SLN identification was 71%. Both the sensitivity and negative predictive value of SLNB were 100%. The false negative rate was 0%. When candidates for SLNB were restricted to patients with a breast tumor measuring less than 3 cm and clinically negative nodes after NAC, the rate of SLN identification increased to 93% from 71% while still maintaining the 0% false negative rate. CONCLUSION: Sentinel lymph node biopsy after NAC is therefore considered to be a feasible and accurate method to predict the AXLN status in patients who have a breast tumor measuring less than 3 cm in unilateral diameter and a clinically negative AXLN status at the time of surgery after NAC.