Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy

Experimental laboratory data suggest that tumour growth is a balance between apoptosis and proliferation and that suppression of drug-induced apoptosis by oncogenes such as bcl-2 may be an important cause of intrinsic chemoresistance. The aims of this study were to assess the in vivo relationship of apoptosis to proliferation and Bcl-2 protein in human breast tumours both prior to chemotherapy and in the residual resistant cell population at the completion of treatment. We examined apoptotic index (AI), Ki67 and Bcl-2 protein expression in the tissue of 40 patients with operable breast cancer immediately before ECF preoperative chemotherapy, and in 20 of these patients with residual tumour, at the completion of treatment. There was a significant positive association between AI and Ki67 both before and after chemotherapy, and in their percentage change with treatment. In the residual specimens AI and Ki67 were significantly reduced compared with pre-treatment biopsies, while Bcl-2 expression showed a significant increase. No differences were seen in the pre-treatment levels of any of the variables measured between patients obtaining pathological complete response and those who did not, although numbers were small. These data suggest that apoptosis and proliferation are closely related in vivo. It is possible that the phenotype of reduced apoptosis and proliferation, and increased Bcl-2 may be associated with breast cancer cells resistant to cytotoxic chemotherapy, although this can only be proven by assessing larger numbers of patients in relation to pathological response.     

23例乳腺派杰氏病诊治体会

目的总结23例乳腺派杰氏(Paget’s)病患者的诊断及治疗。方法收集我院自1984～2004年23例经病理确诊的乳腺Paget’s病例，通过对病人的临床资料及治疗方法的分析，总结该病的诊治经验。结果乳腺Paget’s病以慢性乳头皮肤改变为主要特点，钼靶X线多显示导管区恶性改变。细胞学检查见到Paget’s细胞。术后7例失访，余16例随访时间最长13年，最短6月，其中3例出现术后远处转移。结论早期诊断及手术为主的综合治疗预后较佳。     

乳腺癌分期辨证规范化——一个中医乳房病学与时俱进的重要课题

乳腺癌的发病率近年来呈上升趋势,在经济发达地区已经成为女性发病率最高的恶性肿瘤。长期的临床实践表明中医药在乳腺癌治疗中有着不可或缺的作用。但其理论模式比较滞后,制约着中医药治疗乳腺癌的临床、教学与科研的发展。本文从临床疾病谱的变化、现代医学治疗乳腺癌存在的不足以及目前临床实际存在的问题,阐述了中医药治疗乳腺癌分期辨证规范化的制订和实施的重要性与迫切性,同时也分析了乳腺癌分期辨证规范化研究的基础、思路和方法。     

Role of axillary surgery in early breast cancer: review of the current evidence

BACKGROUND: Controversy continues to surround the best practice for management of the axilla in patients with early breast cancer (EBC), particularly the clinically negative axilla. The balance between therapeutic and staging roles of axillary surgery (with the consequent morbidity of the procedures utilized) has altered. This is due to the increasing frequency of women presenting with early stage disease, the more widespread utilization of adjuvant chemoendocrine therapy and, more recently, the advent of alternative staging procedures, principally sentinel node biopsy (SNB). The aim of the present review is to critically analyse the current literature concerning the preferred management of the axilla in early breast cancer and make evidence-based recommendations on current management. METHODS: A review was undertaken of the English language medical literature, using MEDLINE database software and cross-referencing major articles on the subject, focusing on the last 10 years. The following combinations of key words have been searched: breast neoplasms, axilla, axillary dissection, survival, prognosis, and sentinel node biopsy. RESULTS: Despite the trend to more frequent earlier stage diagnosis, levels I and II axillary dissection remain the treatment of choice in the majority of women with EBC and a clinically negative axilla. CONCLUSIONS: Sentinel node biopsy has no proven superiority over axillary dissection because no randomized controlled trials have been completed to date. Despite this, SNB will become increasingly utilized due to encouraging results from major centres responsible for its development, and patient demand. Therefore if patients are not being enrolled in clinical trials strict quality controls need to be established at a local level before SNB is allowed to replace standard treatment of the axilla. Unless this is strictly adhered to there is a significant risk of an increase in the frequency of axillary relapse and possible increased understaging and resultant inadequate treatment of patients.     

Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists.

PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. RESULTS: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.     

Evaluation of a breast cancer nomogram for prediction of non-sentinel lymph node positivity.

AIMS: This study evaluates the breast cancer nomogram (BCN), an online tool developed by Memorial Sloan-Kettering Cancer Center to determine the rate of non-SLN positivity, in an independent cohort of SLN positive patients. MATERIAL AND METHODS: Available data between 02/2000 and 06/2004 in two prospective databases, 749 cases had successful SLN biopsy including 149 axillary-SLN metastases study cases. These cases had accurately graded tumours up to 9 cm in size and CAD with a minimum total 10 nodes removed. Histopathological assessment of nodes included hematoxylin and eosin staining and/or immunohistochemistry. Computerized BCN was used to estimate probability of non-SLN positivity and compared with actual probability after grouping into deciles. RESULTS: The trend of actual probability in various decile groups was comparable to the predicted probability. An area under the receiver operating characteristic curve was 0.75 as compared to 0.76 in the original study. CONCLUSION: Although this study is small, the results are encouraging and suggest the nomogram is a useful tool to estimate the likelihood of positive axillary non-SLN. However, variations in pathological assessment between centres are the major impediment to widespread application of BCN. If SLN positive patients decline the standard recommendation of CAD or entry into clinical trials evaluating the significance of CAD then the BCN could help in decision making.     

Oncological and cosmetic outcomes of oncoplastic breast conserving surgery.

BACKGROUND: Breast-conserving surgery and radiotherapy is firmly established as a good and safe option for most women with early breast cancer. The important outcome measures of breast conservation are survival, local recurrence, cosmesis and patient satisfaction. Partial breast reconstructive techniques may improve cosmesis and patient satisfaction without compromising the oncological outcomes. METHODS: A search of the Medline and Pubmed databases of studies on breast conserving surgery where partial breast reconstructive techniques were employed. The keywords used were breast conserving surgery, oncoplastic breast surgery, partial breast reconstruction and reduction mammoplasty. The oncological and cosmetic outcomes of these studies were analysed. RESULTS: Studies on partial breast reconstructive techniques often lack oncological outcomes and long-term results are not available. On intermediate follow-up (up to 4.5 years) local recurrence rates vary from 0 to 1.8% per year. Cosmetic failure rates vary from 0 to 18%. To date, detailed studies are small and outcome measures vary. CONCLUSIONS: Breast surgeons should be aware of the range of surgical techniques that may enhance the aesthetic results of breast-conserving surgery as well as expand the indications for its use. There is a need for routine assessment of oncological and cosmetic outcomes and long-term results of partial breast reconstructive techniques in relation to these outcomes are awaited.     

原发性乳腺鳞状细胞癌临床病理分析

回顾性分析11例原发性乳腺鳞状细胞癌（primary squamous cell careinoma of the breast,PSCCB）患者的临床病理资料.11例均行手术治疗,术后病理检查4例发生腋窝淋巴结转移,生存超过5年的7例,3例死于肿瘤复发和转移.回顾性研究的结果提示,PSCCB患者的临床表现与普通类型的乳腺癌比较无特异性,确诊需依据病理诊断,由于其发病率低,规范的治疗和预后评价有待进一步研究.     

BREAST CONSERVING THERAPY IN STAGE T_1 & T_2 BREAST CANCER PATIENTS

There have been several well-established multi-centered clinical trails about breast conserving therapy (BCT) published their results and showed that for appropriately selected and staged patients with early invasive carcinoma of the breast, breast conservation therapy has been shown to result in survival rates and local recurrence rates comparable to those achieved with mastectomy while preserving the breast[1,2]. In 1995, our hospital began breast conserving therapy of early stage breast can…     

Evaluation of 118 Thyroid Cancer Patients Who Underwent a Re-operation after Local Resection

OBJECTIVE To evaluate the incidence of residual thyroid cancer and cervical lymph node metastasis following a previous local resection for thyroid cancer, and to discuss methods of a reoperation.METHODS From 1994～2005, 118 patients with thyroid cancer who had previously been treated with a nodule-resection or subtotal Iobectomy in other hospitals underwent a surgical re-operation.RESULTS The incidence of residual cancer at the primary site was 38.1%. The lymph node metastasis rate at the central area was 39.8%.The rate of lymph node metastasis in patients with enlarged lymph nodes in the ipsilateral internal jugular chain was 37.5%. The rate of laryngeal recurrent nerve injury was 15.2% in other hospitals while that of the second operation in our hospital was 1.6%.CONCLUSION Nodule-resection or subtotal Iobectomy alone is not indicated for patients with thyroid cancer because of the high rate of local residual cancer. It is important to be familiar with the anatomy of the laryngeal recurrent nerve for thyroid surgery. Exploration to the central area is necessary for differentiated thyroid cancer.