Prognosis of node-positive breast cancer patients who underwent parasternal lymph node biopsy during surgery followed by doxorubicin- or mitoxantrone-containing adjuvant chemotherapy

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.     

Clinicopathological features and treatment sensitivity of elderly Chinese breast cancer patients

This study aimed to determine the clinicopathological features and treatment sensitivity of elderly breast cancer patients in China. The clinical data of 594 elderly breast cancer patients of 70 or more years of age were collected and compared to those of 657 patients of less than 70 years of age to analyze whether breast cancer in the elderly is different and whether the difference affected outcome. The median age was 75.2 years in the elderly patients and 49.8 years in the young patients. Age of menarche, parous status and body mass index were similar in the two groups. A higher frequency of steroid receptor-positive rate, a lower expression of HER-2 and p53, less axillary node-positive rate and earlier tumor stage were found in patients of 70 years or older. The 5-year relapse-free survival (RFS) and overall survival (OS) was 77 and 82% in the elderly and 86 and 93% in the young patients, respectively. Patients with estrogen receptor (ER)-positive or lymph node (LN)-negative cancers showed a more favorable outcome in the elderly patients. RFS and OS were increased in elderly patients who underwent endocrine therapy or omitted chemotherapy. Breast cancer in the elderly had more favorable tumor features, using estrogen receptor and lymph node status as prognostic factors. It was therefore concluded that adjuvant endocrine therapy may benefit elderly patients, while chemotherapy may not.     

3H-thymidine-labeling index as a prognostic indicator in node-positive breast cancer

The prognostic relevance of 3H-thymidine-labeling index (3H-TdR-LI) was retrospectively evaluated in 523 women with resectable node-positive breast cancer given adjuvant combination chemotherapy consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) +/- Adriamycin (doxorubicin; Farmitalia, Carlo Ezba, Italy). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were significantly higher for patients with slowly proliferating tumors (3H-TdR-LI less than or equal to 2.8%) compared with rapidly proliferating tumors (RFS, 66% v 50%, P = .0007; OS, 85% v 73%, P = .0012). In the analysis of RFS, 3H-TdR-LI provided prognostic information independent of axillary node involvement, tumor size, and estrogen receptor (ER) status, with an estimated lower hazard ratio compared with the degree of nodal involvement, but equivalent to that of the other indicators. Conversely, nodal involvement was found to interact with 3H-TdR-LI and receptors on survival. Present findings confirm that tumor cell kinetics represents a prognostic indicator also in an adjuvant situation. 3H-TdR-LI can substantially contribute to a more precise definition of high-risk patients within subsets having the traditionally favorable prognostic characteristics.     

118例小肿块多腋窝淋巴结转移乳腺癌患者的临床特征和预后分析

目的分析小肿块多腋窝淋巴结转移(肿块直径≤2 cm、腋窝淋巴结转移≥4个)乳腺癌患者的临床特征和预后。方法1993年1月至2003年12月我院共收治小肿块多腋窝淋巴结转移乳腺癌患者118例,对其临床病理特征、辅助治疗进行分析,以发现相关的预后因素。结果全组患者的5年总生存率为75.0%。腋窝淋巴结转移4～9个及≥10个者的5年生存率分别为89.5%和59.8%(P=0.009),术后化疗患者与未化疗患者的5年生存率分别为82.1%和53.3%(P=0.001),术后内分泌治疗者与未行内分泌治疗者的5年生存率分别为89.2%和61.9%(P=0.001)。单因素Kaplan-Merier生存分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的重要因素。Cox多因素预后分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的独立因素。结论小肿块多腋窝淋巴结转移的乳腺癌患者具有易于转移的趋势,患者预后较差,尤其是腋窝淋巴结转移≥10个的患者;肿瘤分期、辅助化疗和内分泌治疗是影响患者预后的独立因素;合理的综合治疗有可能改善小肿块多腋窝淋巴结转移乳腺癌患者的预后。     

淋巴结转移数和淋巴结转移率与乳腺癌预后关系的分析比较

  目的  探讨淋巴结转移率(lymph node ratio, LNR)是否能更优于淋巴结转移数(positive lymph nodes, PLN), 用于评价乳腺癌术后患者的复发风险和总生存时间。  方法  回顾性分析1089例淋巴结清扫数目为10枚或以上、术后经病理证实淋巴结转移阳性的原发性浸润性乳腺癌患者临床病理资料。  结果  单因素生存分析, 肿瘤大小分期, 组织学分级、ER/PR/HER-2状态、PLN、LNR、切检淋巴结总数、结外软组织侵犯、辅助治疗与患者RFS(relapse free survival, RFS)、OS(overall survival, OS)均具有明显的相关性(P < 0.05);多因素生存分析, 当PLN和LNR作为协变量分别进入Cox比例风险模型时, PLN和LNR均为患者RFS和OS的独立预测指标(P < 0.001);当PLN和LNR作为协变量同时进入Cox比例风险模型时, LNR依然是患者RFS和OS的独立预测指标(RFS: P < 0.001.OS: P=0.001), 而PLN不再是其独立预测指标(RFS: P=0.944, 0S: P=0.315)。  结论  相对于PLN而言, LNR能更好的评价乳腺癌术后患者的复发风险和总生存时间, 为乳腺癌危险度分级和临床医生制定辅助治疗方案提供更有力的参考依据。      

Adjuvant cytotoxic and endocrine therapy in pre- and postmenopausal patients with breast cancer and one to nine infiltrated nodes: five-year results of the Hellenic Cooperative Oncology Group randomized HE 10/92 study

SUMMARY: The present randomized phase III trial was designed to detect a 15% benefit in relapse-free survival (RFS) or overall survival (OS) from the incorporation of adjuvant tamoxifen to the combination of CNF [cyclophosphamide, 500 mg/m2; mitoxantrone (Novantrone), 10 mg/m2; fluorouracil, 500 mg/m2 chemotherapy and ovarian ablation in premenopausal patients with node-positive breast cancer and conversely from the incorporation of CNF chemotherapy to adjuvant tamoxifen in node-positive postmenopausal patients. From April 1992 until March 1998, 456 patients with operable breast cancer and one to nine infiltrated axillary nodes entered the study. Premenopausal patients were treated with six cycles of CNF chemotherapy followed by ovarian ablation with monthly injections of triptoreline 3.75 mg for 1 year (Group A, 84 patients) or the same treatment followed by 5 years of tamoxifen (Group B, 92 patients). Postmenopausal patients received 5 years of tamoxifen (Group C, 145 patients) or 6 cycles of CNF followed by 5 years of tamoxifen (Group D, 135 patients). Adjuvant radiation was administered to all patients with partial mastectomy. After a median follow-up period of 5 years, 125 patients (27%) relapsed and 79 (17%) died. The 5-year actuarial RFS for premenopausal patients was 65% in Group A and 68% in Group B (p = 0.86) and for postmenopausal patients 70% in Group C and 67% in Group D (p = 0.36). Also, the respective OS rates were 77% and 80% (p = 0.68) for premenopausal and 84% and 78% (p = 0.10) for postmenopausal patients. Severe toxicities were infrequently seen, with the exception of leukopenia (18%), among the 311 patients treated with CNF. In conclusion, the present study failed to demonstrate a 15% difference in RFS in favor of node-positive premenopausal patients treated with an additional 5 years of tamoxifen after CNF adjuvant chemotherapy and ovarian ablation. Similarly, six cycles of CNF preceding 5 years of tamoxifen did not translate to a 15% RFS benefit in node-positive postmenopausal patients.     

Sentinel Lymph Node Biopsy in Breast Cancer Patients With Pathological Complete Response in the Axillary Lymph Node After Neoadjuvant Chemotherapy

PurposeSentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph node-positive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC.MethodsThis single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND.ResultsThis study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6–155) in the SLNB group and 99 (range 2–159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001).ConclusionAs an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.     

Adjuvant Chemotherapy with a Combination of Mitoxantrone,Methotrexate, 5-Fluorouracil for Node-Positive Breast Cancer: Phase II Pilot Study

Abstract

A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m², methotrexate 40 mg/m², and 5-fluorouracil 600 mg/m² administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/ml; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapsefree survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.     

２９３例乳腺癌患者术后预后因素分析

目的：探讨２９３例乳腺癌患者月经情况、术后Ｔ分期、Ｎ分期、受体、术后放疗、化疗及内分泌治疗等因素对患者无病生存时间及总生存时间的影响。方法：收集我院２００２～２００６年２９３例乳腺癌患者术后的完整随访资料,选择可能对乳腺癌术后患者预后产生影响的非重复特征因素,包括月经情况、术后病理的Ｔ分期、Ｎ分期、受体的免疫组化分型、术后放疗、化疗及内分泌治疗,采用Ｃｏｘ风险回归模型分析影响无复发生存率（ＲＦＳ）和总生存率（ＯＳ）的预后因素。对具有统计学意义的独立预后因素进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析。结果：本组病例中Ｎ分期是影响患者ＲＦＳ及ＯＳ的独立因素,相对危险度（ＯＲ）分别为１.４５３（９５％ＣＩ：１.０９６～１.９２６,Ｐ＜０.０１）、１.４５８（９５％ＣＩ：１.０９９～１.９９３,Ｐ＜０.０１）。对Ｎ分期进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析表明,Ｎ０期患者的ＲＦＳ及ＯＳ优于Ｎ１～Ｎ３期患者（Ｐ＜０.０５）,而Ｎ１～Ｎ３期患者之间ＲＦＳ及ＯＳ无差异（Ｐ＞０.０５）。结论：乳腺癌术后患者Ｎ分期与患者的预后有关,淋巴结阴性患者的预后好于淋巴结阳性患者预后,建议对淋巴结阳性患者加强术后辅助治疗。     

The prognostic significance of expression of the multidrug resistance-associated protein (MRP) in primary breast cancer.

In the present study, we determined the frequency and intensity of MRP protein expression by monoclonal antibody immunohistochemistry in a series of 259 resected invasive primary breast carcinomas, and we evaluated MRP immunoreactivity in relation to patient and tumour characteristics, relapse-free (RFS) and overall survival (OS). The immunostaining was graded on a semiquantitative scale that ranged from (-) to ( ). Overall, 34% of the tumours were positive for anti-MRP antibody: 19% showed weak cytoplasmic staining (+), 14% had clear cytoplasmic staining (++) and only 1% of the tumours had a strong cytoplasmic as well as membranous staining ( ). MRP expression was not related to patient''s age, menopausal status, tumour size, differentiation grade, oestrogen and progesterone receptor level or lymph node involvement. In an exploratory univariate analysis of all patients, only primary tumour size and number of lymph nodes involved were significantly associated with shortened RFS (P < 0.001 and P < 0.001 respectively) and OS (P = 0.02 and P < 0.001 respectively). In Cox univariate analysis for RFS in subgroups of patients stratified by menopausal status, tumour size, nodal status, adjuvant systemic therapy and oestrogen and progesterone receptor status, MRP expression was associated with increased risk for failure in patients with small tumours (T1), in node-negative patients and in node-positive patients who received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF); the relative hazard rate (RHR) for relapse was increased in the presence of MRP, with RHR values with 95% confidence limits (CL) of 2.8 (1.2-6.9), 2.1 (1.0-4.2) and 2.8 (0.8-9.9) respectively. In analysis for OS, expression of MRP was also associated with increased risk for failure in patients with small tumours (T1) [RHR (95% CL) 2.3 (0.9-6.0)] and in node-positive patients who received adjuvant systemic chemotherapy with CMF [RHR (95% CL) 3.7 (0.8-17.1)] but not in node-negative patients [RHR (95% CL) 1.1 (0.4-2.6)]. In conclusion, our results show that MRP is frequently overexpressed in primary breast cancer and suggest that MRP expression might be of prognostic significance in the subgroups of patients with the more favourable prognosis, i.e. patients with small tumours and node-negative patients, as well as in the setting of adjuvant systemic chemotherapy. In primary breast cancer, MRP might be related to altered cell biological behaviour, including a more aggressive phenotype, and resistance to adjuvant systemic chemotherapy.     

Association of angiogenesis in lymph node metastases with outcome of breast cancer

BACKGROUND: Microvessel density (MVD) is a measure of the extent of new blood vessel growth or angiogenesis, which is required for tumor progression. Increased MVD in primary breast cancers appears to adversely affect disease-free survival and overall survival in patients with breast cancer. However, the clinical implications of angiogenesis in breast cancer metastases have not been well studied. The purpose of this study was to compare intratumoral MVD in primary breast cancer tissues with MVD in axillary lymph node metastases and to evaluate the relationships among primary- and metastatic-tumor MVD, disease-free survival, and overall survival in patients with lymph node-positive, stage II breast cancer who were treated with adjuvant chemotherapy in Cancer and Leukemia Group B Protocol 8082. METHODS: Immunostaining for factor VIII-related antigen was performed on tissue sections from 47 primary tumors and 91 axillary lymph nodes containing metastases from 110 patients with lymph node-positive breast cancer. Sections were examined for the presence or absence of focal areas of relatively intense neovascularization (vascular hot spots), and a quantitative assessment of intratumoral MVD was performed. RESULTS: The presence of vascular hot spots in axillary lymph node metastases, but not primary breast cancers, was associated with statistically significantly decreased disease-free survival (P =.006) and overall survival (P =.004) by univariate analysis. Similarly, increased MVD in metastases, but not in primary tumors, was statistically significantly associated with diminished overall survival in these patients (P =.02). In multivariate analysis, the number of positive axillary lymph nodes and the presence of vascular hot spots in axillary lymph node metastases predicted decreased disease-free survival (P =.0001 and.02, respectively) and overall survival (P =.0001 and.007, respectively). All P values were two-sided. CONCLUSION: This pilot study suggests that assessing neovascularization in axillary lymph node metastases may provide clinically useful information regarding survival in patients with primary breast cancer.     

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

Background

We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC).

Methods

A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013.

Results

Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered.

Conclusions

Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.     

Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF.

BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.     

Adjuvant chemotherapy with a combination of mitoxantrone, methotrexate, 5-fluorouracil for node-positive breast cancer: phase II pilot study

A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/microl; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapse-free survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.     

Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for patients with operable breast cancer: a randomised phase III trial of the European Organisation for Research and Treatment of Cancer Breast Group

BackgroundThe contribution of adjuvant tamoxifen in breast cancer patients after receiving adjuvant chemotherapy is not fully established. We investigated the impact of tamoxifen, given sequentially after completion of adjuvant chemotherapy in patients with operable breast cancer.Patients and methodsBetween March 1991 and June 1999, 1863 women with stages I–IIIA operable breast cancer who had undergone surgery and completed six cycles of adjuvant combination chemotherapy with either CMF, CAF, CEF, FAC or FEC were randomised to receive either tamoxifen 20 mg daily for 3 years or no further treatment. Irrespective of menstrual status and hormone receptor content of the primary tumour, patients were stratified by institute, chemotherapy scheme and age (above 50 years or younger). The main end-point was to detect a 5% increase in the 5 year survival (from 80% to 85%) in favour of antioestrogen therapy. Secondary end-points were relapse free survival (RFS), local control, incidence of second primary breast cancer and correlation of results with hormone receptor content.ResultsAfter exclusion of all patients from three sites because of inadequate documentation, a total of 1724 patients (93%) were analysed (Tam 861 and Control 863). At a median follow-up of 6.5 years, 5-year RFS on tamoxifen was 73% versus 67% in controls (p = 0.035). No difference was seen in overall survival. The benefit of tamoxifen therapy was mainly seen in the subgroup of patients with histologically documented positive axillary nodes (5-year RFS on tamoxifen 71% versus 64% in the control group, p = 0.044) and in patients with tumours expressing the ER and PR positive phenotype (5-year RFS on tamoxifen 77% versus 70% in the control group, p = 0.014).ConclusionsTamoxifen administered for 3 years after completion of adjuvant chemotherapy in this otherwise unselected group of patients for endocrine sensitivity had a limited impact on relapse and had no detectable effect on overall survival. The beneficial effect of tamoxifen is mainly confined to the subgroup of patients with node-positive disease and to patients with tumours expressing the ER and PR positive phenotype.     

Adjuvant therapy approaches to breast cancer: Should taxanes be incorporated?

The triplet of docetaxel, doxorubicin, and cyclophosphamide (TAC) has emerged as an alternative chemotherapy regimen for adjuvant management of node-positive breast cancer. Based on recently reported 3-year data from the Breast Cancer International Research Group (BCIRG) 001, disease-free survival was significantly higher in patients who underwent adjuvant chemotherapy with TAC rather than the established regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). TAC reduced the risk of disease recurrence in estrogen receptor-positive and -negative patients. Whereas overall survival was not significantly different between the two groups, TAC led to a significant reduction in mortality in the subset of patients with one to three involved axillary lymph nodes. Overall, these interim BCIRG 001 results, coupled with those from Cancer and Leukemia Group B-9344 and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 (phase III trials of sequential adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel), suggest that taxanes are a valuable component of adjuvant chemotherapy for patients with node-positive breast cancer, including those with estrogen receptor positivity and/or extensive lymph node involvement. Accumulating data in the neoadjuvant setting lend further support to the view that the taxanes confer clinically meaningful benefits in the management of early-stage breast cancer. Such ongoing studies as NSABP B-30 will be instrumental in establishing the relative merits of sequential versus concurrent taxane-anthracycline adjuvant regimens for patients with node-positive breast cancer.     

Axillary lymph node ratio and total number of removed lymph nodes: predictors of survival in stage I and II breast cancer.

AIMS: Presence of axillary lymph node metastases is considered the most important prognostic factor for breast cancer survival. In a period of increasing popularity for the sentinel node procedure, clarity about the possible relation between axillary dissection and survival is essential. This study investigated whether the total number of removed lymph nodes and the ratio of invaded/removed lymph nodes (lymph node ratio (LNR) would prove to be independent prognostic factors for survival. METHODS: Data from 453 consecutive patients with stage I or II breast cancer were studied retrospectively. The total number of removed lymph nodes and the LNR were analysed for their prognostic value in comparison with known prognostic factors. RESULTS: Node-negative patients with < 14 lymph nodes removed had a 10 year survival of 79% compared with 89% in patients with > or = 14 lymph nodes removed (P=0.005). The 10 year survival for patients with an LNR > or = 0.2 was 52%, compared with 73% for patients with an LNR < 0.2 (P<0.0001). A Cox proportional hazards model showed that, for node-negative patients, only age and total number of removed lymph nodes were significant prognostic factors. For node-positive patients, age, total number of removed lymph nodes and the LNR were significant risk factors for survival outcome. The LNR was also significantly associated with the presence of distant metastases during follow-up (hazard ratio 3.56, range 1.63-7.77). CONCLUSIONS: In stage I and II breast cancer, a favourable prognosis was found for node-negative patients with > or = 14 removed lymph nodes. Before axillary lymph node dissection with its well-defined survival prognosis is replaced by less invasive staging methods, long-term survival using new staging techniques needs to be defined. For node-positive patients, the LNR proved to be an excellent predictor for survival outcome or development of metastatic disease. Selection of lymph node-positive patients based on the LNR may guide specific adjuvant treatment choices.     

Obesity,diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients

BackgroundTo determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy.Patients and methodsWe identified 6342 patients with stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status.ResultsIn a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02–1.36], 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively.ConclusionsIn patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.     

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis

Background: Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. Methods: A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. Results: The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. Conclusion: ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.     

Prediction of relapse and survival in breast cancer patients by pS2 protein status

Application of systemic adjuvant therapy for primary breast cancer patients requires a more accurate identification of patients at high risk for recurrence. We have quantitatively assessed the cytosolic levels of estrogen-regulated pS2 protein in tumors of 205 breast cancer patients (median follow-up, 47 mo). There were no significant associations between the level of pS2 protein and tumor size, lymph node status, and differentiation grade. Using length of relapse-free survival (RFS) and overall survival (OS) as end points, 11 ng of pS2 protein/mg of cytosol protein were found as the best cutoff level to discriminate between positive (pS2+) and negative (pS2-). Patients with pS2- tumors showed significantly shorter RFS and OS (P less than 0.0001) than patients with pS2+ tumors. Also after adjustment for tumor size, lymph node status, and estrogen receptor (ER) status, pS2 negativity was associated with earlier recurrence and death. Tumors positive for pS2 (55 of 205, 27%) were almost exclusively confined to the subclass of ER+ tumors (53 of 55, 96%). The death rate for patients with pS2+ tumors was one-tenth of the death rate for patients with pS2-/ER- tumors. In the patients with ER+ tumors, the prognostic power of the pS2 status was especially present in patients whose tumors were also positive for the progesterone receptor (5-yr RFS and OS, 85% and 97% for ER+/PgR+/pS2+ tumors compared with 50% and 54% for the patients with ER+/PgR+/pS2- tumors). In patients with axillary lymph node involvement (N+), pS2 status could discriminate strongly between a good and bad prognosis group (5-yr RFS and OS, 65% and 88% for N+/pS2+ compared with 32% and 34% for N+/pS2-). A similar phenomenon was observed in patients without axillary lymph node involvement (5-yr RFS and OS, 89% and 95% for N0/pS2+ compared with 58% and 82% for N0/pS2-). We conclude that the pS2 status of human primary breast tumors is an important variable for the identification of patients at high risk for recurrence and death. Knowledge of the cytosolic pS2 status appeared of particular importance to identify patients at high risk in the ER+/PgR+ subclass of tumors, and in both the N0 and N+ subclasses of patients.