BACKGROUND: Pathological complete response (pCR) after neoadjuvant systemic chemotherapy (NST) is strongly associated with improved long-term clinical outcomes, even among the patients with inflammatory breast cancer (IBC). In this study, we examined the clinical factors determining long-term outcome in patients with IBC who did and did not achieve pCR. METHODS: We identified patients with primary IBC treated with NST who received definitive surgery within 1 year and were evaluable for pathological tumor response, and whose hormone receptor and HER2 status was available at baseline. pCR was defined as no evidence of invasive cancer in the breast and ipsilateral axillary lymph nodes. We also investigated the relationship between clinical outcome and the ratio of positive to excised lymph nodes (lymph node ratio) in the non-pCR group. The Kaplan-Meier method was used to estimate disease-free survival (DFS) and overall survival (OS); groups were compared using the log-rank test. Multivariate Cox proportional hazards models were fit to identify predictors of DFS and OS. RESULTS: Among 517 patients treated at MDACC between 1998 and 2011, 79 (15.2%) achieved pCR. A total of 50.3% had hormone receptor-positive disease, 37.5% had HER2-positive disease, and 26.3% had triple-negative disease. NST included an anthracycline and a taxane in 72.9% of the patients, an anthracycline only in 17.3% and others in 9.8%. A total of 83.7% of patients received adjuvant radiation therapy. The median follow-up period was 3.9 years in the pCR group and 2.4 years in the non-pCR group. Two-year DFS for pCR and non-pCR groups are 74% and 40%, respectively (p<.0001). In the pCR group, only triple-negative disease was significantly associated with decreased OS (P = 0.006) and DFS (P = 0.024). In the non-pCR group, high lymph node ratio, triple-negative disease, vascular invasion, and positive surgical margins were associated with decreased OS and DFS, and adjuvant radiation and hormonal therapies were associated with increased OS and DFS in the multivariate model. As shown in the table, increased lymph node ratios were associated with increased estimated hazard ratios for OS and DFS in the non-pCR group. Relationship between node ratio increase and clinical outcome Hazard ratio (95% confidence interval)Increase in node ratio,%OSDFS101.07 (1.02-1.12)1.09 (1.05-1.14)201.15 (1.05-1.25)1.20 (1.11-1.29)301.23 (1.08-1.41)1.32 (1.17-1.48)401.32 (1.11-1.58)1.45 (1.24-1.68)501.42 (1.14-1.77)1.59 (1.31-1.92) CONCLUSIONS: In patients who do not achieve pCR, high lymph node ratio and positive surgical margins predict poor outcome after NST. Use of an optimized tri-modality treatment plan (chemotherapy, surgery, radiation therapy) is important to achieve the best outcomes in patients with IBC; Surgery including total mastectomy with clear margins and axillary dissection to remove all nodal tissue are critical for achieving optimal clinical outcomes in IBC. Even in the pCR group, some patients with triple negative disease still had a poor prognosis suggesting a need for more effective systemic therapy such as innovative agents tailored to the Lehmann subtypes. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-03.
Background: Entinostat is a novel, potent, orally bioavailable, class I selective histone deacetylase inhibitor. Pre-clinical data has shown that Entinostat can enhance the activity of Lapatinib in HER2+ metastatic inflammatory and non-inflammatory breast cancer. The primary objective of the phase I portion of this study is to determine the recommended phase II dose for Entinostat in combination with Lapatinib in patients who have received Trastuzumab for HER2+ metastatic breast cancer. Methods: This is a single center, open-label study to evaluate the safety and tolerability of every other week entinostat in combination with a 28-day cycle of Lapatinib. Patients with metastatic breast cancer in whom trastuzumab has failed were included. The phase I portion of the study is a conventional 3+3 dose-escalation design. Dose levels include 0 (starting dose) Entinostat 10 mg orally every other week, I Entinostat 12 mg, and II Entinostat 15 mg. Lapatinib 1,250 mg orally is given every day without dose escalation. Toxicities are evaluated at the end of each cycle. Results: Here we report the phase I portion of the study. To date, 9 patients were enrolled, 3 were in level 0, and 6 were in level I. In Level 0, 2 patients were taken off study due to disease progression (PD) at the end of cycle one and 1 patient was taken off study due to PD at the end of cycle two. In Level I, 1 patient was taken off study due to PD at the end of cycle one and 2 patients were taken off study due to PD at the end of cycle 2. 1 patient had stable disease. The median age is 41 (range, 26–69). Seven of the nine patients are evaluable for toxicity. Most common toxicities reported by the patients are nausea grade 3 (1), fatigue grade 3 (1), muscle aches/pain grade 2 (3), skin rash grade 3 (1), paresthesias grade 2 (2), heartburn grade 1 (4), and diarrhea Grade 2 (1). Lapatinib dose was reduced in 2 patients. The most common hematological toxicities were neutropenia grade 1 (3), anemia grade 2 (1), and thrombocytopenia grade 4 (1). Conclusions: Overall, patients have tolerated the combination regimen relatively well. We have not reached the maximum tolerated dose, so patient enrollment will continue until the phase I portion of the study is complete, most likely in July 2012. We plan to proceed with phase II portion in two parallel cohorts (HER2+ inflammatory and non-inflammatory metastatic breast cancer). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-13.
Background: Inflammatory breast cancer (IBC) is the most aggressive form breast cancer. NST, followed by local therapy (surgery and radiation therapy), is considered the current standard therapy for IBC. Among noninflammatory breast cancers, sensitivity to NST differs based on ER and HER2 status. However, whether the sensitivity to NST also differs in primary IBC based on ER status or other prognostic factors has not been studied in a large cohort. Methods: We retrospectively reviewed 1078 patients (pts) newly diagnosed with IBC from April 1989 to January 2011. Of these, 838 pts met our inclusion criterion of stage III disease at diagnosis, and 713 of these pts had received NST and surgery. Among this population, 545 pts had information available on both ER and HER2 status. We compared pathological complete response (pCR) rates (defined as no evidence of invasive disease in the breast and ipsilateral axillary limph nodes) and clinical characteristics between ER and HER2-status subgroups and analyzed their clinical outcome. We used the Kaplan-Meier method to estimate the median recurrence-free survival (RFS) after surgery and overall survival (OS), and the Cox proportional hazards regression model to test the statistical significance of potential prognostic factors in each group. Results: Overall 177 pts had ER+HER2− tumors; 75, ER+HER2+; 134, ER-HER2+; and 159, ER-HER2−. NST consisted of anthracycline-based [A] alone, a taxane [T] alone or with A+T; HER2 targeting therapies (H) were administered to 117 patients with HER2-positive breast cancer after 1998. Overall pCR rate was 14.7%. pCR rates are shown by marker subtype and NST received in the table below. pCR rate, nuclear grade, vascular invasion, clinical response to NST, adjuvant treatment, radiation therapy, and adjuvant hormonal therapy differed significantly among subgroups. The median RFS and OS for all patients was 19.2 and 33.2 months, respectively. In multivariate analysis, BMI, ER status, lymphatic invasion, radiation therapy, and pCR rate were associated with RFS, and ER status, vascular invasion, radiation therapy, and pCR rate were associated with OS. Except in the ER+HER2− group, pCR was associated with better prognosis compared to non-pCR. Adjuvant hormonal therapy improved RFS both in ER+HER2+ and ER+HER2− groups, but did not improve OS in the ER+HER2+ group. Among 209 patients with HER2+ IBC, 134 received HER2 targeting therapies in neoadjuvant or adjuvant chemotherapy, and had a trend to improvement in RFS compared to chemotherapy alone (p = 0.082). The ER-HER2− group showed poorest outcome compared to other subgroups (P < 0.001). Conclusions: Sensitivity to NST differs depending on the ER and HER2 status in IBC pts. pCR rates based on these subgroups appear to be low. There is a need more effective treatments in the neoadjuvant and adjuvant therapies for all subgroups of IBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-05.
Primary Objective: To assess the efficacy of MK-3475 as a single agent in patients with MIBC and non-IBC TNBC. The primary endpoint is disease control rate at the end of 4 months after receiving the treatment. We will also investigate the association between biomarkers in the peripheral blood and tumor tissue, safety and efficacy. Background: The extensive invasion of lymphatic vessels by tumor emboli in patients with IBC suggests that the host immune surveillance system is suboptimal or that the tumor cells have decreased immunogenicity through immune editing to avoid detection by the host. In the immune-competent host, tumor cells must overcome both innate and adaptive immunologic defenses of the host. The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control. MK-3475 is a potent and highly selective humanized mAb designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. MK-3475 strongly enhances T lymphocyte immune responses in cultured blood cells from healthy human donors, cancer patients, and primates. Mouse anti-PD-1, as a monotherapy, demonstrated efficacy in several syngeneic mouse tumor models. To date, no specific targeted therapeutic options exist for the treatment of MIBC and TNBC. After patients achieving a clinical response to systemic therapy, the maintenance of disease control is not guaranteed. Further, our recent publication suggests that IBC has immune dysfunction. Chemotherapies can debulk the disease volume but cannot be used for maintenance due to their toxicities. Using an anti PD-1 monoclonal antibody is a promising approach for this patient population. Study Design and Treatment Plan: This is a single arm phase II study. Up to 35 patients with HER2 negative MIBC or metastatic TN-IBC (MTNBC) who have achieved clinical response or stable disease after receiving any prior systemic therapy for metastatic/recurrent disease, and meet all other criteria will be eligible. Patients will receive MK-3475 200 mg IV every 3 weeks for up to 2 years. Statistical Considerations: The trial will be conducted using Simon's optimal two-stage design and the rate of disease control will be estimated accordingly. It is assumed that the MK-3475 single agent will have a disease control rate of 30%. A disease control rate of 10% or lower will be considered treatment failure and the regimen will be rejected under this circumstance. Status of the study: Activation Date: June 2015. 13 patients have been enrolled. Enrollment continues. Sponsor: Merck Sharp & Dohme Corp. State of Texas appropriation for rare and aggressive breast cancer research. Citation Format: Willey JS, Parker CA, Valero V, Lim B, Reuben JM, Krishnamurthy S, Gong Y, Scoggins ME, Dryden MJ, Liu DD, Woodward WA, Ueno NT. A phase II study of anti-PD-1 (MK-3475) therapy in patients with metastatic inflammatory breast cancer (MIBC) or non-IBC triple negative breast cancer (non-IBC TNBC) who have achieved clinical response or stable disease to prior chemotherapy [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 OT1-02-01.
Background: Detection of high number of CTCs (>5) before initiation of first-line therapy in patients with metastatic breast cancer is associated with shorter progression free survival and overall survival. The most widely used method is CellSearch (Veridex, Raritan, NJ). It relies on immunomagnetic capture of CTCs, using antibodies against the epithelial cell adhesion molecule (EpCAM). Although the US Food and Drug Administration approved CellSearch assay for clinical use. In addition to isolation and enumeration, a promising area of research is genomic CTCs characterization which entails phenotyping and molecular expression profiling of CTC subsets consisting of those of epithelial origin (CTC-Epi), others undergoing epithelial to mesenchymal transition (CTC-EMT), or expressing cancer stem cell-like phenotype (CTC-CSC; CD44+ CD24low, ALDH+), respectively. EMT is a molecular process to acquire the traits needed to execute the multiple steps of metastasis. Through the EMT process, epithelial cells lose cell-cell contacts and cell polarity, downregulate epithelial-associated genes, acquire mesenchymal gene expression and undergo major changes in their cytoskeleton. Currently, a CTC detection kit is available to detect CTCs expressing EMT-associated genes by semiquantitative RT-PCR (Adna EMT2/Stem Cell test). EMT will be detected by measuring EMT-inducing transcription factors such as TWIST1, SNAIL1, SLUG, ZEB1 and FOXC2) by RT-PCR Objectives. Primary objective: To investigate if activated pathways in CTCs are correlated with clinical outcome of patient with stage III breast cancer. Secondary objective: To prospectively determine if assessment of the pathways profiling in CTCs can be used to stratify NED breast cancer patients Patients Eligibility: Inclusion: histologically confirmed invasive breast cancer (any subtype), clinical stage III, no evidence of distant metastasis by PET-CT or CT scan of chest and abdomen, and body scan, age 18 years or older, pts must be scheduled to start neoadjuvant/adjuvant therapy, ECOG PS 0-2. Pts must sign a written informed consent. Exclusion: distant metastasis, investigational therapy, prior history of other malignancies within the last 2 years, except non-melanoma skin cancer. This study (PA12-0097) was approved by IRB of UT MD Anderson Cancer Center. Trial Design. This is a pilot, international, multicenter, prospective, blood sample collection from 200 patients with clinical or pathologic stage III breast cancer. Statistical Analysis: This study is a 7-year study (84 months). Pts will be classified as to the presence [negative (neg) vs. positive (pos)] of CTC and as to the expression of a biomarker (neg vs. pos). The primary endpoint of the study is breast cancer recurrence. Time to recurrence curves for the four breast cancer patient groups (neg/neg, neg/pos, pos/neg, or pos/pos) will be estimated using the Kaplan-Meier method and differences in the recurrence rates will be evaluated by the log-rank test at the end of the study (84 months). The confidence intervals for the quantiles of the recurrence distribution will be based on the sign test as described by Brookmeyer and Crowley. Citation Format: Alvarez RH, Gao H, Ensor JE, Gomez HL, Ruiz-Garcia EB, Arce C, Sun H, Willey JS, Ueno NT, Valero V, Reuben JM. Pilot study of prognostic utility of circulating tumor cells (CTCs) assessed by AdnaGen technology and clinical outcome of patients with stage III breast cancer who completed locoregional and systemic treatment. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-02-01.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.