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Yunchao Wang,1 Tao Sun,2 Donggui Wan,3 Lijun Sheng,4 Wei Li,5 Huayun Zhu,6 Yanping Li,1 Janice Lu1,7 1Department of Breast Cancer, Beijing Shijitan Hospital, Capital Medical University, Beijing, 2Department of Oncology, Liaoning Cancer Hospital and Institute, Shenyang, 3Department of Oncology, China-Japan Friendship Hospital, Beijing, 4Department of Oncology, Shandong Cancer Hospital, Jinan, 5Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, 6Department of Oncology, Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 7Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA Objectives: Trastuzumab, a humanized monoclonal antibody that binds human epidermal growth factor receptor 2 (HER2), dramatically improves the clinical outcomes of HER2-positive breast cancer. Emerging evidence implied that the clinical behavior and sensitivity to targeted agents in HER2-positive breast cancer differed by hormone receptor (HR) status. The objectiveof this study was to determine the effect of the HR status on survival benefit of HER2-positive metastatic breast cancer when treated with anti-HER2-targeted therapy in People’s Republic of China.Methods: Metastatic breast cancer patients with HER2-positive diseases across six cancer centers in People’s Republic of China were retrospectively analyzed in our study. Patients were classified into four groups according to HR/HER2 status and trastuzumab treatment: HER2+/HR+ patients with first-line trastuzumab treatment, HER2+/HR+ patients with no trastuzumab treatment, HER2+/HR- patients with first-line trastuzumab treatment, and HER2+/HR- patients with no trastuzumab treatment. Kaplan–Meier analysis, log-rank test, and multivariate analysis were performed during analysis.Results: A total of 295 patients were included in the final analysis. The median overall survival was 30 months (95% confidence interval: 27.521–32.479). Among patients with HER2+/HR- disease, significant survival benefit was observed when treated with trastuzumab (30 vs 21months, P=0.000). However, in patients with HER2+/HR+ disease, trastuzumab administration had a survival improvement trend but no significant statistical differences (36 vs 30months, P=0.258). In the multivariate analysis, HR status was an independent predictor of overall survival and trastuzumab treatment had significantly decreased risk of death in HER2+/HR- patients (hazard ratio =0.330).Conclusion: HR status is an independent predictor of overall survival in HER2-positive metastatic breast cancer patients and patients with HER2+/HR- subtype might be associated with more survival benefits when treated with trastuzumab-based regimens. Keywords: HER2-positive, metastatic breast cancer, hormone receptor status

Using archived tumours, those from 1984–1986 and 1996–1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival.

Purpose To evaluate whether hormonal receptor (HR) status can influence the prognostic significance of pathologic complete response (pCR). Patients and Methods This retrospective analysis included 1,731 patients with stage I to III noninflammatory breast cancer treated between 1988 and 2005 with primary chemotherapy (PC). Ninety-one percent of patients received anthracycline-based PC, and 66% received additional taxane therapy. pCR was defined as no evidence of invasive tumor in the breast and axillary lymph nodes. Results Median age was 49 years (range, 19 to 83 years). Sixty-seven percent of patients (n = 1,163) had HR-positive tumors. A pCR was observed in 225 (13%) of 1,731 patients; pCR rates were 24% in HR-negative tumors and 8% in HR-positive tumors (P < .001). A significant survival benefit for patients who achieved pCR compared with no pCR was observed regardless of HR status. In the HR-positive group, 5-year overall survival (OS) rates were 96.4% v 84.5% (P = .04) and 5-year progression-free survival (PFS) rates were 91.1% v 65.3% (P < .0001) for patients with and without pCR, respectively. For the HR-negative group, 5-year OS rates were 83.9% v 67.4% (P = .003) and 5-year PFS rates were 83.4% v 50.0% (P < .0001) for patients with and without pCR, respectively. After adjustment for adjuvant hormonal treatment, HR status, clinical stage, and nuclear grade, patients who achieved a pCR had 0.36 times the risk of death. Conclusion pCR is associated with better outcome regardless of HR status in breast cancer patients who receive PC.

Aims and background This study was aimed at analyzing metastatic involvement in interpectoral (Rotter's) lymph nodes in relation to tumor location, size, grade and hormone receptor status in primary breast cancer. Methods The study included 172 female patients undergoing surgery for breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes were removed in all of the patients. Serum levels of the tumor marker CA 15-3 were determined before surgery and hormone receptor status after surgery. Results Rotter's lymph nodes were identified in 67% of the patients, with metastatic involvement being found in 20% of the Rotter's nodes. Metastatic involvement of Rotter's nodes in patients with negative and positive axillary lymph nodes was 4% and 35%, respectively. When we looked at the location of the tumor in patients with metastatic involvement of Rotter's nodes, we found that tumors located in the upper quadrants were more prone to metastasis to Rotter's nodes; there was a significant positive correlation between tumor location and positive Rotter's nodes (r = 0.953, P = 0.012). As regards tumor size, Rotter's nodes were identified in 15%, 20% and 30% of stage T1 (5 cm) tumors, respectively. Hormone receptor status showed no statistically significant difference in the expression of estrogen and progesterone receptors between patients with and those without positive Rotter's nodes. Of 35 Rotter's node-positive patients, 31.4% had elevated serum levels of CA 15-3; the level was significantly higher in Rotter's-positive patients compared to those with negative (or absent) Rotter's nodes. Conclusions The results show that one-fifth of breast cancer patients, or even one-third of those with positive axillary lymph nodes, are discharged with positive interpectoral lymph nodes that remain undiagnosed. As the nodes can be surgically removed without additional mutilation, exploration of Rotter's lymph nodes should be introduced into routine clinical practice.

The study was aimed at analyzing metastatic involvement in interpectoral (Rotter's) lymph nodes related to tumor marker CA 15-3 and hormone receptor status. The study includes 172 female patients undergoing surgery for breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes were removed in all of the patients. Levels of the serum tumor marker CA 15-3 was determined prior to surgery and hormone receptors status were determined after the surgery. Rotter's lymph nodes were identified in 67% of the patients, with metastatic involvement revealed in 20% of the Rotter's nodes. Metastatic involvement of Rotter's nodes in patients with negative and positive axillary lymph nodes was 4% and 35%, respectively. Of 35 Rotter's node-positive patients, 31.4% had elevated serum levels of tumor marker CA 15-3, with the level statistically significantly higher in Rotter's positive patients compared to those with negative (or absent) Rotter's nodes ( 2=8.22, p= 0.0004). Hormone receptor status showed statistically significant difference in the expression of estrogen receptors and no statistically significant difference in progesteron receptors between patients with and those without positive Rotter's nodes (2=3.68; p=0.05 and 2=0.07;p=0.79). The results show that one-fifth of breast cancer patients, or even one-third of them with positive axillary lymph nodes, are discharged with positive interpectoral lymph nodes that remain undiagnosed and non-extirpated. Tumor marker CA 15-3 is more frequently elevated in patients with positive Rotter's lymph nodes. Estrogen receptors are as well more frequently negative in such patients. Progesteron receptors show no difference in patients with positive or negative Rotter's lymph nodes. As the nodes can be surgically removed without additional mutilation, the exploration of Rotter's lymph nodes should be introduced into routine clinical practice and the elevated values of tumor marker CA 15-3 could be warning for possible positive interpectoral nodes., U radu je analizirana zahvaćenost interpektoralnih (Rotterovih) limfnih čvorova metastazama u odnosu na vrijednosti tumorskog markera CA 15-3 i hormonski status. Analizirane su 172 bolesnice s rakom dojke operirane u Klinici za tumore, Zagreb od studenog 2001. do kolovoza 2003. U svih su bolesnica, uz standardnu operaciju, uklonjeni i interpektoralni (Rotterovi) limfni čvorov. Prije operacije su izmjerene vrijednosti tumorskog markera CA15- 3, a nakon operacije vrijednosti hormonskih receptora. Rotterovi limfni čvorovi otkriveni su u 67% bolesnica, od kojih je 20% bilo zahvaćeno metastazama. U bolesnica s negativnim aksilarnim limfnim čvorovima metastatska zahvaćenost Rotterovih limfnih čvorova iznosila je 4%, a u bolesnica s pozitivnim aksilarnim limfnim čvorovima 35 %. Od 35 bolesnica s pozitivnim Rotterovim limfnim čvorovima u njih 31, 4% bio je i povišen tumorski marker CA 15- 3 što je statistički znakovito viša vrijednost u odnosu na žene s rakom dojke s negativnim (ili neprisutnim) Rotterovim limfnim čvorovima (_2=8,22, p= 0,0004). Hormonski status pokazuje statistički znakovitu razliku u ekspresiji estrogenskih receptora, a u ekspresiji progesteronskih receptora takva razlika između bolesnica sa ili bez pozitivnih Rotterovih čvorova nije uočena (_2=3,68; p=0,05 and _2=0.07;p=0,79). Rezultati pokazuju da je jedna petina bolesnica s rakom dojke, ili čak jedna trećina s pozitivnim aksilarnim limfnimčvorovima otpuštena iz bolnice s pozitivnim interpektoralnim limfnim čvorovima koji nisu dijagnosticirani, pa tako ni uklonjeni. Vrijednosti tumorskog markera češće su povišene u bolesnica s pozitivnim Rotterovim čvorovima. Estrogenski su receptori u tih bolesnica tako|er bili češće negativni, a progesteronski receptori ne pokazuju razlike između bolesnica s pozitivnim i onima s negativnim Rotterovim čvorovima. Kako se ti čvorovi mogu ukloniti bez dodatne mutilacije, otkrivanje Rotterovih limfnih čvorova treba postati redovitom kliničkom praksom, a pritom povišene vrijednosti tumorskog markera CA 15-3 mogu upozoravati na eventualno pozitivne interpektoralne limfne čvorove.

Background The procoagulant state in cancer increases the thrombotic risk, but also supports tumor progression. To investigate the molecular mechanisms controlling cancer and hemostasis, we conducted a case-control study of genotypic and phenotypic variables of the tissue factor (TF) pathway of coagulation in breast cancer. Methods 366 breast cancer patients and 307 controls were genotyped for SNPs (n = 41) in the F2, F3 (TF), F5, F7, F10, TFPI and EPCR genes, and assayed for plasma coagulation markers (thrombin generation, activated protein C (APC) resistance, D-dimer, antithrombin, protein C, protein S, and TF pathway inhibitor (TFPI)). Associations with breast cancer were evaluated using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), or the chi-square test. Results Four SNPs in F5 (rs12120605, rs6427202, rs9332542 and rs6427199), one in F10 (rs3093261), and one in EPCR (rs2069948) were associated with breast cancer. EPCR rs2069948 was associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while the SNPs in F5 appeared to follow hormone receptor negative and triple negative patients. The prothrombotic polymorphisms factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) were not associated with breast cancer. High APC resistance was associated with breast cancer in both factor V Leiden non-carriers (OR 6.5, 95% CI 4.1-10.4) and carriers (OR 38.3, 95% CI 6.2-236.6). The thrombin parameters short lag times (OR 5.8, 95% CI 3.7-9.2), short times to peak thrombin (OR 7.1, 95% CI 4.4-11.3), and high thrombin peak (OR 6.1, 95% CI 3.9-9.5) predicted presence of breast cancer, and high D-dimer also associated with breast cancer (OR 2.0, 95% CI 1.3-3.3). Among the coagulation inhibitors, low levels of antithrombin associated with breast cancer (OR 5.7, 95% CI 3.6-9.0). The increased coagulability was not explained by the breast cancer associated SNPs, and was unaffected by ER, PR and triple negative status. Conclusions A procoagulant phenotype was found in the breast cancer patients. Novel associations with SNPs in F5, F10 and EPCR to breast cancer susceptibility were demonstrated, and the SNPs in F5 were confined to hormone receptor negative and triple negative patients. The study supports the importance of developing new therapeutic strategies targeting coagulation processes in cancer. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-845) contains supplementary material, which is available to authorized users.