Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is expressed in a wide range of cancer cells and plays important roles in cancer progression and metastasis. Recently, the intracellular function of TF has been revealed to be involved in cancer invasion, independent of the blood coagulation pathway. To evaluate the clinical significance of TF expression, we performed an enzyme-linked immunosorbent assay (ELISA) in the plasma of 67 breast cancer patients and immunohistochemistry in 213 breast cancer tissues. In the ELISA study, we showed an up-regulation of plasma TF concentration in breast cancer patients compared with normal controls. Immunohistochemistry demonstrated that TF was expressed in tumour cells and stromal cells and tumour TF expression closely correlated with stromal TF expression ( P = 0.0005). The concentration of plasma TF was associated with tissue TF expression in both tumour and stroma. The multivariate analysis demonstrated that tumour TF expression was an independent prognostic indicator for overall survival ( P = 0.0452). Our data show that plasma TF concentration reflects tissue TF expression and tumour TF expression can provide some predictive value for prognosis and distant metastasis, which indicates the importance of TF function in tumour progression. © 2000 Cancer Research Campaign

Purpose: Many studies suggest that Her2/neu play an important role in neoadjuvant endocrine therapy. This study aimed to determine whether the level of Her2/neu expression in advanced breast cancer changes after antiaromatase neoadjuvant treatment, as well as to identify the relationship between Her2/neu expression and response to this kind of therapy.Experimental Design: Thirty-six postmenopausal patients with hormonal receptor-positive primary breast cancer were included in a study of three monthly cycles of neoadjuvant endocrine therapy with either Aromasin (25 mg daily) or Femara (2.5 mg daily). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for Her2/neu were conducted both on pretreatment biopsies and surgical tumors.Results: Using IHC, 5 of 36 (13.9%) of the patients had a Her2/neu overexpression after treatment, as compared with 16 of 36 (44.4%) before. Meanwhile, there was no change in 21 (58.3%) patients, and through FISH, there was a change from amplification to no amplification in 15 (41.7%) patients. The response rate to the treatment was 75% for Her2/neu (؉) tumors and 35% for Her2/neu (؊) tumors (P ‫؍‬ 0.017) while FISH was performed. The response rate was also significantly affected by the decrease in Her2/neu status after the treatment, with 73% of the tumors showing decreased Her2/neu expression and with 38% of the tumors showing no change of Her2/neu expression (P ‫؍‬ 0.037).Conclusions: Using both IHC and FISH, advanced breast cancers show statistical evidence of decreasing incidence of Her2/neu expression after antiaromatase neoadjuvant treatment. Our data also suggest that Her2/neu expression and its change during the treatment might be predictive markers for this kind of therapy.

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Background: Abemaciclib, an oral, selective inhibitor of cyclin-dependent kinases 4 and 6 dosed on a twice daily continuous schedule, has demonstrated clinical efficacy and tolerability in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer when administered as monotherapy (MONARCH 1) and in combination with endocrine therapy (ET) in MONARCH 2 and MONARCH 3. In neoMONARCH, abemaciclib plus anastrozole as neoadjuvant therapy reduced the breast tumor cell proliferation marker Ki67 to a greater extent than anastrozole alone after 2 weeks of treatment. Endocrine monotherapy is the current standard of care in the adjuvant setting. However, a proportion of pts relapse despite this therapy. A population with a higher risk of recurrence (15% at 5 years) may be identified based on the clinical and pathological characteristics of disease. Optimizing adjuvant therapy for these pts is an important need. Trial Design: MonarchE (NCT03155997) is a multicenter, randomized, open-label Phase 3 trial that will evaluate the potential for abemaciclib to enhance adjuvant ET. Pts will be randomized 1:1 to abemaciclib 150 mg twice daily continuous schedule plus standard of care (SOC) adjuvant ET versus SOC adjuvant ET alone and stratified by prior chemotherapy (neoadjuvant, adjuvant, or none), menopausal status (pre- or post-), and region (N. America/Europe, Asia, or other). Pts may have started ET within 8 weeks prior to randomization. Pts will receive abemaciclib for up to 2 years in combination with ET per physician's choice (such as tamoxifen or an aromatase inhibitor, +/- ovarian suppression). ET alone will be continued as clinically indicated. All randomized pts will be followed for a total of 10 years. Eligibility Criteria: Eligible pts (male or female) must have early stage resected HR+, HER2- invasive breast cancer with either ≥ 4 positive pathological axillary lymph nodes (pALNs), or 1 to 3 positive pALNs and at least one of the following high risk markers: primary tumor size ≥5 cm, histological grade 3 tumor, or centrally assessed Ki67 index of ≥20% (in a subset of pts). Pts must have completed definitive locoregional therapy (+/- (neo)adjuvant chemotherapy) and be randomized no more than 12 weeks after completion of last non-ET (surgery, chemotherapy, or radiotherapy). Pts must have tumor tissue available for biomarker analysis prior to randomization. Specific Aims: The primary objective of monarchE is to evaluate invasive disease-free survival (IDFS) per the STEEP System.1 Secondary objectives include evaluation of IDFS in pts with Ki67 index of ≥20%, distant relapse-free survival, overall survival, safety, pharmacokinetics, and pt health outcomes. Statistical Methods: Assuming an IDFS hazard ratio of .73, the study is powered to approximately 80% to test the superiority of abemaciclib plus standard ET at a 1-sided α=0.025 using a stratified log-rank test. Target accrual: Approximately 3580 pts Contact information: 1-877-285-4559 Reference: 1. Hudis et al. J Clin Oncol. 2007;25(15):2127-2132. Citation Format: Rastogi P, Toi M, Harbeck N, Bourayou N, Frenzel M, Johnston S. MonarchE: A randomized, open-label, phase 3 study of abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone in patients with high risk, node positive, early stage, HR+, HER2- breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-05-05.