术前化疗诱导乳腺癌细胞凋亡的临床意义

目的 研究乳腺癌术前化疗是否能引起肿瘤细胞的细胞凋亡,以及肿瘤细胞凋亡的改变是否和术前化疗的疗效及生存率有关。方法 应用原位杂交和免疫组化法,检测术前化疗和对照肝瘤细胞的凋亡指数（ＡＩ）和肿瘤铁雌激纱受体状态,采用学生检验法（ｔａｉｌｅｄｓｔｕｄｅｎｔ‘ｓ ｔ－ｔｅｓｅ）。比较术前化疗组和对照组ＡＩ的差要用ａｐｌａｎ－Ｍｅｉｅｒ方法,计算术前化疗组和对照组的总生存率（ＯＳ）和无病生存率（ＲＦＳ）     

Early changes in apoptosis and proliferation following primary chemotherapy for breast cancer

Patients undergoing primary chemotherapy for invasive breast cancer consented to a core biopsy of the invasive breast primary pre- and 24 h postchemotherapy. The resulting tissue was analysed for apoptosis, Ki67, ER and HER-2 using immunohistochemical techniques. These data were then used to evaluate the relationship between these biological markers and response to chemotherapy and overall survival. Response rate to chemotherapy in this group was 86%, 16 patients (25%) achieved a clinical complete response and 41 (63%) a partial response. Prechemotherapy there was a significant correlation between Ki67 and apoptotic index (AI), r=0.6, (P<0.001). A significant rise in AI (P<0.001), and fall in Ki67 (P=0.002) was seen 24 h following chemotherapy. No relationship was seen between pretreatment AI and clinical response, but higher Ki67 and growth index (Ki67/AI ratio, GI) did correlate with clinical response (both r=0.31, P<0.025). No correlation was seen between the change in AI or Ki67 at 24 h and clinical response or survival. Significant changes in apoptosis and proliferation can be demonstrated 24 h following chemotherapy, but these changes do not relate to clinical response or outcome in this study. Pretreatment proliferation and GI are however predictive of response to chemotherapy in breast cancer.     

新辅助化疗后乳腺癌组织中survivin表达及其与Ki-57、AI的相关性研究

目的探讨采用CTF方案新辅助化疗后乳腺癌组织中凋亡抑制蛋白survivin的表达及其与肿瘤细胞凋亡、增殖的相互关系和临床意义。方法采用免疫组化SABC法,检测60例行新辅助化疗和60例未行新辅助化疗的乳腺癌组织中survivin和Ki-67的表达,并采用原位细胞末端转移标记法（TUNEL法）测定细胞凋亡指数（AI）。结果新辅助化疗组survivin阳性表达率为36．7％（22／60）,明显低于对照组（71．7％,43／60）（X^2=14．821,P〈0．001）。新辅助化疗组Ki-67阳性表达率（38．3％,23／60）明显低于对照组（61．7％,37／60,0=6．533,P〈0．05）。新辅助化疗组AI均数为（9．34±3．12）％,对照组AI均数为（5．27±3．16）％,两组比较差异有统计学意义（y=1．998,P〈0．05）。新辅助化疗组survivin表达与AI呈负相关（γ=-0．36,P〈0．05）,而与Ki-67表达呈正相关（γ=0．47,P〈0．05）。新辅助化疗组化疗总有效率为73．3％（44／60）,化疗后部分缓解（Ⅱ级）病例survivin表达水平（18．2％,8／44）明显低于无效（Ⅲ级）病例（81．3％,13／16）（X^2=20．514,P〈0．001）。结论应用CTF方案新辅助化疗,缓解率高,近期疗效明显。Sur-vivin表达水平可作为预测乳腺癌新辅助化疗疗效的指标。     

Randomized trial comparing neo-adjuvant versus adjuvant chemotherapy in operable locally advanced breast cancer (T4b N0-2 M0)

BACKGROUND AND OBJECTIVES: Locally advanced breast cancer (LABC) remains a major problem in developing countries. While trials utilizing neo-adjuvant chemotherapy demonstrate superior survival rates compared to historic controls, randomized studies evaluating the precise role of neo-adjuvant chemotherapy in LABC are lacking. In the present trial, neo-adjuvant chemotherapy was compared against adjuvant chemotherapy to assess survival advantage in operable T4b N0-2 M0 breast cancer. METHODS: A total of 101 women with operable LABC (T4b N0-2 M0) were randomized. In arm A, 50 patients received 3 cycles of CEF chemotherapy before and 3 cycles following surgery. In arm B, 51 patients had primary surgery followed by 6 cycles of CEF chemotherapy. In both arms, loco-regional radiotherapy was given after completion of CEF. RESULTS: The response of primary tumor to neo-adjuvant chemotherapy was 66%, complete response (CR) 14% and partial response (PR) 52%. Clinical nodal response occurred in 95% of node positive patients. Only two (4%) patients had pathologic CR both in tumor and axilla. There was a significant (P = 0.02) increase in incidence of pathologically negative nodes in arm A. At a median follow up of 25 months, there was no significant difference in overall and disease free survival (DFS) in both arms (P = 0.42 and 0.18). Patients showing a response to neo-adjuvant chemotherapy had better DFS (P = 0.04) compared to those who had no response. CONCLUSIONS: Early results of the study indicate no survival benefit with the inclusion of neo-adjuvant chemotherapy in LABC (T4b N0-2 M0). Neo-adjuvant chemotherapy resulted in significant down staging; good responders had a better DFS compared to those who did not respond.     

可手术乳腺癌新辅助化疗近期疗效观察

目的 研究可手术乳腺癌患者手术前给予新辅助化疗(NCT)的安全性、近期疗效以及对手术方式的影响。方法 我院于1997年3月～2001年12月收治的224例可手术乳腺癌患者(Ⅱ～Ⅲ期)术前随机给予CMF(CTX+MIX+5-Fu)方案或CAF(CTX+ADM+5-Fu)方案化疗两个周期,全部患者治疗前均经针吸细胞学检查确诊,评价其近期疗效和毒性反应,将临床原发肿瘤对化疗的反应按WHO标准分为完全缓解(CR)、部分缓解(PR)、无效(NR)或进展(PD)。结果 全部224例化疗患者中,CR 17例,PR 136例,总有效率68.3％,无恶化病例;毒性反应主要表现为胃肠道反应和骨髓抑制。胃肠道反应主要表现为恶心、呕吐,其中Ⅱ～Ⅲ级为65.6％;骨髓抑制以白细胞减少为主,Ⅲ～Ⅳ级白细胞减少发生率为60.3%,经对症治疗后均可缓解。全部患者无因为化疗的毒性反应而终止治疗的病例。结论 对于可手术乳腺癌的患者手术前给予新辅助化疗(NCT)可以使原发灶明显缩小,能够为预测化疗效果提供实体依据,降低手术复杂性,缩小手术范围,提高患者术后的生活质量,并且安全可行,是一种提高治疗效果的重要治疗方法。     

Prognostic role of p27Kip1 and apoptosis in human breast cancer

Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from an indolent slowly progressive one to a course associated with rapid progression and metastatic spread. It is important to establish prognostic factors which will define subgroups of patients with low vs high risk of recurrence so as to better define the need for additional therapy. Additional characterization of the molecular make-up of breast cancer phenotypes should provide important insights into the biology of breast cancer. In the present study, we investigated apoptosis, expression of p27Kip1 and p53 retrospectively in 181 human breast cancer specimens. In addition, their relevance to the biological behaviour of breast cancer was examined. Our studies found a significant association among high histological grade, high p53, low apoptosis and low p27. Our results also demonstrated that, in human breast cancer, low levels of p27 and apoptotic index (AI) strongly correlated with the presence of lymph node metastasis and decreased patient survival. In node-negative patients, however, p27 also had prognostic value for relapse-free and overall survival in multivariate analysis. Furthermore p27 and AI had predictive value for the benefits of chemotherapy. These latter observations should prompt prospective randomized studies designed to investigate the predictive role of p27 and AI in determining who should receive chemotherapy in node-negative patients.     

Role of combination therapy with aromatase and cyclooxygenase-2 inhibitors in patients with metastatic breast cancer

Aromatase inhibitors (AIs) are well established in the treatment of metastatic hormone-sensitive breast cancer in postmenopausal women. Cyclooxygenase (COX)-2 inhibitors have demonstrated efficacy in reducing cancer risk in animal and human studies. In several preclinical studies, combination AI plus COX-2 inhibitor therapy has shown a synergistic antitumor effect. This review describes the utility of AI plus COX-2 inhibitor therapy and discusses the completed and ongoing clinical trials investigating treatment with the AI exemestane and the COX-2 inhibitor celecoxib in the neo-adjuvant and metastatic breast cancer settings. In general, combination therapy had comparable or better efficacy compared with AI monotherapy using the end points of progression-free survival, overall response rate, clinical benefit rate, time to progression, and duration of clinical benefit. All therapies were well tolerated. There appeared to be a beneficial impact on serum lipid levels for patients receiving combination therapy in a neo-adjuvant trial despite the known cardiovascular toxicity risk associated with COX-2 inhibitors. In conclusion, AIs plus COX-2 inhibitors have shown promising efficacy and safety for the treatment of patients with metastatic breast cancer. Careful monitoring during future trials will be necessary to accurately assess the risk–benefit ratio of combination therapy.     

18F-FDG PET/CT融合显像对乳腺癌新辅助化疗疗效的预测价值

背景与目的:既往研究表明,18F-FDG PET显像结果与肿瘤新辅助治疗后的临床或病理反应密切相关.本研究拟探讨乳腺癌新辅助化疗前后18F-FDGPET/CT融合显像与细胞凋亡间的关系,以求进一步明确PET/CT对乳腺癌新辅助化疗疗效的预测价值.方法:45例原发性乳腺癌患者细针穿刺确诊后给予新辅助化疗三个周期,新辅助化疗前后行PET/CT融合显像检查并计算肿瘤区与非肿瘤区放射性比值(tumor to non-tumor activity ratio,T/N),dTUP末端标记技术检测穿刺及手术标本的癌细胞凋亡指数(apoptotic index,AI).结果:新辅助化疗后临床疗效评价完全缓解4例(8.9%),部分缓解29例(64.4%),疾病稳定10例(22.2%),疾病进展2例(4.4%).化疗前后肿瘤平均T/N值分别为3.23±0.63、2.31±0.49(P=0.006),下降6.4%～50.8%.化疗前后AI分别为(2.81±0.76)%、(17.31±6.85)%(P＜0.001),增高1.9%～41.3%.T/N值下降率与AI变化值间存在直线相关关系(r(.)=0.850,P＜0.001).以化疗后T/N值下降≥20%为阈值,PET/CT预测肿瘤临床缓解的灵敏度、特异度分别为90.9%、83.3%,阳性、阴性预测值分别为93.8%、76.9%,准确率为92.1%.结论:18F-FDG PET/CT融合显像与乳腺癌新辅助化疗后的细胞凋亡状态密切相关,对预测化疗疗效具有一定的应用价值.     

Response and Long-Term Effect of Patients with Triple-Negative Breast Cancer Receiving Neo-Adjuvant Anthracycline-Based

OBJECTIVE The breast cancer lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) is defined as the Triple-negative breast cancer (TNBC). Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up (median, 5.4 years) of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival (RFS) and overall survival (OS) rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triple- negative phenotype (TNP), tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission (pCR) rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 (21.5%) of the 326 patients suffered TNBC. Compared with the subjects in non- TNBC group, the patients with TNBC had a significantly higher pCR rate (P=0.046) and clinical response rate (P＝0.037), but also decreased 5-year RFS (P=0.001) and OS (P=0.004) rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression (P＝0.007, P＝0.028), but negatively correlated with level of E-cadherin (P＝0.034).CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor.The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.     

Platinum-based chemotherapy in triple-negative breast cancer

BackgroundExperimental data suggest that triple-negative (TN) breast cancer may have increased sensitivity to platinum-based chemotherapy but clinical data are limited. We present our long-term results with platinum-based chemotherapy for TN breast cancer.Patients and methodsIn all, 94 (17 TN), 79 (11 TN) and 155 (34 TN) patients receiving platinum-based chemotherapy in neo-adjuvant/adjuvant and advanced setting were included. Response rates and outcome were compared for TN tumours versus others.ResultsNeo-adjuvant complete response rates were significantly higher for TN tumours (88%) than others (51%; P = 0.005). The 5-year overall survival (OS) for TN tumours following adjuvant/neo-adjuvant chemotherapy was 64% [95% confidence interval (CI) 44% to 79%] compared with 85% (95% CI 79% to 90%) for others. Five-year disease-free survival for TN tumours was 57% (95% CI 37% to 73%) compared with 72% (95% CI 64% to 78%) for others. For patients with advanced breast cancer, overall response rates were 41% for TN tumours and 31% for others (P = 0.3). Patients with TN tumours had a significantly prolonged progression-free survival of 6 months compared with 4 months for others (P = 0.05), though the OS was not significantly different between the two groups (11 versus 7 months).ConclusionPlatinum-based chemotherapy achieves increased response rates for TN tumours, with a trend towards worse survival in early breast cancer through an improved survival in advanced disease. Prospective randomised trials are warranted.     

Identification of residual breast tumour localization after neo-adjuvant chemotherapy using a radioactive 125 Iodine seed

Introduction

The use of neo-adjuvant chemotherapy has increased in the treatment of loco-regionally advanced primarily operable breast cancer. As a result of improved neo-adjuvant chemotherapy regimes the number of clinical as well as radiological responses have increased. In case of a complete response it is difficult to identify residual disease and to perform an adequate radical breast-conserving surgery. Therefore localization of the original tumour bed is mandatory. In this study we propose a novel technique with a seed containing radioactive 125 Iodine (¹²⁵I). The ¹²⁵I has a half-time of 60 days and is therefore still recognisable with a gamma probe after admittance of several courses of neo-adjuvant chemotherapy.

Material and Methods

In the period from July 2003 and November 2008, 47 consecutive patients had successful ¹²⁵I seed localization of a breast tumour before starting neo-adjuvant chemotherapy.

Results

The overall clinical response rate to neo-adjuvant chemotherapy was 100%. Complete clinical response occurred in 34 patients, partial clinical response occurred in 13 patients. Complete radiological response occurred in 18 patients, partial radiological response occurred in 29 patients. The initial surgical treatment consisted of breast-conserving surgery for all 47 patients, after a mean of 170 days (range: 70–220) after ¹²⁵I seed localization. In 19 patients pathology revealed no residual tumour, 23 patients showed a partial response. Only 3 lumpectomies were irradical.

Conclusion

This study has shown that ¹²⁵I seed localization is a novel and highly successful technique in localizing the tumour bed in patients who receive neo-adjuvant chemotherapy for breast cancer leading to a high percentage of radical margins in case of breast-conserving surgery.     

新辅助化疗诱导乳腺癌细胞凋亡与化疗疗效关系

[目的]探讨乳腺癌采用CEF方案新辅助化疗肿瘤组织标本中凋亡指数(apopto-sis index,AI)及其与化疗疗效的关系.[方法]确诊乳腺癌58例患者经予3个周期CEF方案新辅助化疗.化疗前后均检测AI值资料完整的42例.凋亡指数测定采用原位细胞末端转移标记法(TUNEL法).[结果]CEF方案化疗有效率为62.1%.化疗后AI值显著降低(P＜0.05).AI变化和术前化疗疗效密切相关(P＜0.05).[结论]化疗后凋亡指数高低可以作为预测新辅助化疗效果的指标.     

CAF方案新辅助化疗对乳腺癌组织BCSG1蛋白表达的影响

目的:探讨CAF联合化疗方案的新辅助化疗对乳腺癌组织BCSG1蛋白表达的影响.方法:采用免疫组化SP法分别检测34例行CAF联合方案新辅助化疗患者(新辅助化疗组)和同期110例未行新辅助化疗惠者(对照组)手术切除的乳腺癌组织BCSG1蛋白的表达.同时对新辅助化疗组疗效进行病理形态学评价,并分析BCSG1蛋白表达与病理形态学变化的关系.结果:新辅助化疗组化疗总有效率为79.4%.新辅助化疗组BCSG1蛋白高表达率明显低于对照组(29.4%比64.5%,P＜0.01),化疗后部分缓解(Ⅱ级)病例BCSG1蛋白高表达水平明显低于无效(Ⅲ级)病例(P=0.002).结论:采用CAF方案新辅助化疗近期疗效明显,可抑制乳腺癌BCSG1蛋白的表达.     

Response and long-term effect of patients with triple-negative breast cancer receiving neo-adjuvant anthracycline-based chemotherapy

OBJECTIVE The breast cancer lack of expression of estrogen receptor （ER）, progesterone receptor （PR）, and human epidermal growth factor receptor 2 （HER-2） is defined as the Triple-negative breast cancer （TNBC）. Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up （median, 5.4 years） of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival （RFS） and overall survival （OS） rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triplenegative phenotype （TNP）, tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission （pCR） rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 （21.5%） of the 326 patients suffered TNBC. Compared with the subjects in non-TNBC group, the patients with TNBC had a significantly higher pCR rate （P = 0.046） and clinical response rate （P = 0.037）, but also decreased 5-year RFS （P = 0.001） and OS （P = 0.004） rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression （P = 0.007, P = 0.028）, but negatively correlated with level of E-cadherin （P = 0.034）. CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor. The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.     

Consensus development conference on the medical treatment of non-small cell lung cancer: treatment of the early stages

Surgery remains the mainstay of treatment for early non-small cell lung cancer (NSCLC) but more than 80% of recurrences occur within 2 years from radical surgery. The pattern of recurrence may differ by histology with more local recurrences seen for patients with squamous cell carcinoma and more distant metastases seen in patients with adenocarcinoma. A number of studies demonstrate that dissemination of cancer cells at levels much below those detected by any current available imaging techniques, including PET scanning also, affect prognosis of patients with clinical early-stage NSCLC. The current clinical evidence does not recommend adjuvant chemotherapy and/or radiotherapy in completely resected stage I-II-IIIA for N1. There are few randomised trials available for analysis of neo-adjuvant chemotherapy involving patients with resectable stage III disease; overall these trials suggest that induction chemotherapy (with or without radiation) improves survival, particularly in those patients who undergo significant downstaging. Heterogeneous study populations limit the ability to define the optimal patient population who would most benefit from this approach. There is no conclusive evidence that neo-adjuvant chemotherapy in early NSCLC is associated with an increased post surgical morbility and mortality. Additional trials are needed. More recently neo-adjuvant chemotherapy has been tested in resectable stage I-II NSCLC and proved to be feasible and better tolerated than adjuvant chemotherapy. Several randomised trials are currently ongoing. In the next future the role of targeted biological therapies as agents acting on minimal residual disease should be explored.     

乳腺癌新辅助化疗86例临床观察

目的：观察乳腺癌新辅助化疗的临床效果,并探讨其临床价值。方法：2004年6月-2007年2月收治乳腺癌患者86例,予以新辅助化疗（rIThpC方案）,即：多西紫杉醇（艾素）100mg,d1;吡柔比星60mg,d1;环磷酰胺0．8g,d1。21d为1周期,2—5个周期后观察客观有效率、病理缓解率及新辅助化疗前后免疫组化指标的变化。结果：新辅助化疗后临床完全缓解（cCR）者19例,占22．09％,部分缓解（cPR）者51例,占59．30％,病情稳定（SD）者16例,占18．60％,无疾病进展（PD）患者;病理学完全缓解（pCR）者7例,占8．14％。21例患者新辅助化疗后的ER、PR、C-erbB-2的阳性表达率均低于新辅助化疗前,但未达到统计学差异（P〉0．05）。结论：乳腺癌新辅助化疗可以有效的缩小肿瘤,降低肿瘤分期,提高行改良根治术及保乳术几率,逆转可能存在的全身转移,为化疗方案提供药敏依据;新辅助化疗可使乳腺癌患者ER、PR、C-erbB-2的阳性表达降低,临床应根据术前免疫组化结果制定相关术后辅助治疗方案,才可能使患者有更大的获益。     

Prognostic Factors for Triple-Negative Breast Cancer Patients Receiving Preoperative Systemic Chemotherapy

BackgroundTriple-negative breast cancer patients are more likely to achieve a pathologic complete response after preoperative chemotherapy but they have still poor prognosis. The aim of this study was to identify prognostic factors in triple-negative breast cancer patients receiving preoperative chemotherapy.Patients and MethodsTriple-negative breast cancer patients who underwent preoperative chemotherapy were retrospectively analyzed. Significant prognostic factors among clinical and pathologic variables were investigated with Kaplan–Meier analysis and Cox proportional hazards modeling for disease-free survival and overall survival.ResultsAmong the 135 triple-negative breast cancer patients, the median age was 54 years, median tumor diameter on palpation was 4.5 cm, and there were 62 clinically node positive patients. The clinical response rate was 76% (103 patients) and pathologic complete response rate was 21% (29 patients). Median disease-free survival was 44.4 months and median overall survival was 49.2 months. Univariate and multivariate analysis showed that that completion of chemotherapy, better clinical response, fewer positive nodes, and lower histologic grades were significant factors associated with both disease-free and overall survival.ConclusionsOur data demonstrated that clinical response of preoperative systemic chemotherapy is an important independent favorable prognostic factor for triple-negative breast cancer.     

Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers

Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging and predictive biomarkers.     

Androgen receptors in breast cancer

Androgen receptor assays have been performed on 1371 specimens of histologically confirmed primary and recurrent breast cancer. Forty-two patients who had received tamoxifen as treatment for advanced disease were assessed for objective response. Another 42 patients who had received chemotherapy were similarly studied. Patients with androgen receptor-negative tumors had a significantly poorer response rate to hormone therapy than those with receptor-positive tumors (P less than 0.05). This clinical correlation is supported by survival data of 1181 patients with primary breast cancer which showed that patients with androgen receptor-negative tumors had a highly significant trend toward shorter overall survival than those with receptor-positive tumors (P less than 0.001). Androgen receptor data added significantly to the information provided by estrogen receptor data both in terms of response to hormone treatment and survival.     

Expression of Senescence and Apoptosis Biomarkers in Synchronous Bilateral Breast Cancer: A Case Report

Background: Synchronous bilateral breast cancer (SBBC) provides a special condition where two independent breast tumors are exposed to cancer pharmacotherapy within a uniform pharmacokinetic milieu. Both senescence and apoptosis are established responses to therapy; however, they have potentially variable contributions to the overall outcome of treatment, which are yet to be determined. Methods: In this report, we describe the clinicopathological picture of two SBBC cases that received standard anticancer treatment and assess their expression profile of several molecular hallmarks of senescence and apoptosis. Results: Our analysis identified that synchronous tumors have variable expression profiles of both senescence- and apoptosis-associated biomarkers, despite comparable pathological responses to neoadjuvant chemotherapy and current survival rates. Conclusions: Our results highlight the variable expression of senescence- and apoptosis-associated markers in breast tumors (despite the shared somatic genetic background) and invites a large-scale assessment of both senescence and apoptosis in breast cancer tissue in vivo and their contribution to the pathological response and overall survival.