NSABP B-41, a randomized neoadjuvant trial: Genes and signatures associated with pathologic complete response (pCR).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 511-511
Author(s):  
Sandra M. Swain ◽  
Gong Tang ◽  
Heather Ann Brauer ◽  
David Goerlitz ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Epithelial Mesenchymal Transition ◽  
Pathologic Complete Response ◽  
Housekeeping Genes ◽  
Complete Response ◽  
Her2 Positive ◽  
Treatment Benefit ◽  
Mesenchymal Transition ◽  
B 41

511 Background: NSABP B-41 randomly assigned 529 patients (pts) with HER2 positive breast cancer to neoadjuvant trastuzumab (T), lapatinib (L), or combination (T+L), with weekly paclitaxel following doxorubicin and cyclophosphamide. No significant differences in pCR were found, but overall survival was significantly increased for pCR. Methods: RNA was extracted from FFPE tumor specimens, run on the NanoString Breast Cancer 360 Plus panel. Gene counts were normalized to include housekeeping genes, 33 biological signatures from 776 genes across 23 pathways and transformed into logarithm scale with base two. Univariate logistic regression was used to screen candidate genes and signatures that are prognostic of pCR, with false discovery rate controlled at 0.1. Multivariable logistic regression with lasso regularization was used for model selection. Results: 194 core biopsy samples were available; 69 treated with T, 64 with L and 61 with T+L. 20 prognostic genes are selected for trastuzumab-based regimens (TBR), including the epithelial-mesenchymal transition (HEMK1, GRB7, ERBB2, TMPRSS4), adhesion and migration (ITGB6, COL27A1, NRCAM), JAK-STAT (SOCS2), Hedgehog (LRP2), ER signaling (ELOVL2, MAPT), DNA damage and repair (NPEPPS, PRKDC), MAPK (DUSP6, PRKCB), Apoptosis (BCL2), proliferation (TFDP1). ERBB2 expression are associated with pCR in patients on TBR (OR = 1.73), but not for patients on L (interaction p = 0.01). HER2-Enriched correlation (p < 0.001), ESR1 (OR = 0.78, 95% CI = 0.69-0.88, p < 0.001), PD1 (OR = 1.68, 95% CI = 1.12-2.52, p = 0.01) and Tumor Inflammation Score (OR = 1.58, 95% CI = 1.18-2.11, p = 0.002) are associated with pCR in TBR. No genes or signatures were found to be predictive of treatment benefit from L added to T. Conclusions: BC360 highlighted tumor progression and signaling genes prognostic for TBR. HER2-Enriched correlation, ERBB2 and PD1 expression, and immune activation signatures were associated with pCR in TBR and may provide personalized treatment guidance.

scholarly journals Neoadjuvant Pertuzumab plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2 Positive Breast Cancer: Real-World Data from a National Institute of Oncology in Poland.

2022 ◽  
Author(s):  
Agnieszka Irena Jagiełło-Gruszfeld ◽  
Magdalena Rosinska ◽  
Malgorzata Meluch ◽  
Katarzyna Pogoda ◽  
Anna Niwińska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Her2 Positive ◽  
Real World Data ◽  
Cancer Subtypes ◽  
Cancer Management ◽  
Her2 Positive Breast Cancer ◽  
Neoadjuvant Systemic Therapy ◽  
Positive Breast Cancer

Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

scholarly journals Texture Analysis of Dynamic Contrast-Enhanced MRI in Evaluating Pathologic Complete Response (pCR) of Mass-Like Breast Cancer after Neoadjuvant Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Kun Cao ◽  
Bo Zhao ◽  
Xiao-Ting Li ◽  
Yan-Ling Li ◽  
Ying-Shi Sun
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Neoadjuvant Therapy ◽  
Texture Analysis ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Imaging Method ◽  
First Order ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

Objectives. MRI is the standard imaging method in evaluating treatment response of breast cancer after neoadjuvant therapy (NAT), while identification of pathologic complete response (pCR) remains challenging. Texture analysis (TA) on post-NAT dynamic contrast-enhanced (DCE) MRI was explored to assess the existence of pCR in mass-like cancer. Materials and Methods. A primary cohort of 112 consecutive patients (40 pCR and 72 non-pCR) with mass-like breast cancers who received preoperative NAT were retrospectively enrolled. On post-NAT MRI, volumes of the residual-enhanced areas and TA first-order features (19 for each sequence) of the corresponding areas were achieved for both early- and late-phase DCE using an in-house radiomics software. Groups were divided according to the operational pathology. Receiver operating characteristic curves and binary logistic regression analysis were used to select features and achieve a predicting formula. Overall diagnostic abilities were compared between TA and radiologists’ subjective judgments. Validation was performed on a time-independent cohort of 39 consecutive patients. Results. TA features with high consistency (Cronbach’s alpha >0.9) between 2 observers showed significant differences between pCR and non-pCR groups. Logistic regression using features selected by ROC curves generated a synthesized formula containing 3 variables (volume of residual enhancement, entropy, and robust mean absolute deviation from early-phase) to yield AUC = 0.81, higher than that of using radiologists’ subjective judgment (AUC = 0.72), and entropy was an independent risk factor (P<0.001). Accuracy and sensitivity for identifying pCR were 83.93% and 70.00%. AUC of the validation cohort was 0.80. Conclusions. TA may help to improve the diagnostic ability of post-NAT MRI in identifying pCR in mass-like breast cancer. Entropy, as a first-order feature to depict residual tumor heterogeneity, is an important factor.

scholarly journals Novel Molecular Markers for Breast Cancer

2016 ◽  
Vol 8 ◽  
pp. BIC.S38394 ◽  
Author(s):  
Kazushi Inoue ◽  
Elizabeth A. Fry
Keyword(s):  
Breast Cancer ◽  
Molecular Markers ◽  
Hormone Receptors ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Her2 Positive ◽  
Specific Therapy ◽  
Predictive Values ◽  
Mesenchymal Transition

The use of molecular biomarkers assures that breast cancer (BC) patients receive optimal treatment. Established biomarkers, such as estrogen receptor, progesterone receptor, HER2, and Ki67, have been playing significant roles in the subcategorization of BC to predict the prognosis and decide the specific therapy to each patient. Antihormonal therapy using 4-hydroxytamoxifen or aromatase inhibitors have been employed in patients whose tumor cells express hormone receptors, while monoclonal antibody to HER2 has been administered to HER2-positive BCs. Although new therapeutic agents have been developed in the past few decades, many patients still die of the disease due to relapse; thus, novel molecular markers that predict therapeutic failure and those that can be targets for specific therapy are expected. We have chosen four of such molecules by reviewing recent publications, which are cyclin E, B-Myb, Twist, and DMP1β. The oncogenicity of these molecules has been demonstrated in vivo and/or in vitro through studies using transgenic mice or siRNAs, and their expressions have been shown to be associated with shortened overall or disease-free survival of BC patients. The former three molecules have been shown to accelerate epithelial-mesenchymal transition that is often associated with cancer stem cell-ness and metastasis; all these four can be novel therapeutic targets as well. Thus, large prospective studies employing immunohistochemistry will be needed to establish the predictive values of these molecules in patients with BC.

Correlation of quantitative p95HER2, HER2, and HER3 protein expression with pathologic complete response (pCR) in HER2-positive breast cancer patients (pts) treated with neoadjuvant chemotherapy and trastuzumab.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 137-137 ◽  
Author(s):  
Jose Caetano Villasboas ◽  
Judith Hurley ◽  
Jodi Marie Weidler ◽  
Agnes Paquet ◽  
Carmen Gomez Fernandez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Invasive Disease ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Additional Information ◽  
Her2 Breast Cancer ◽  
Poor Outcomes

137 Background: Elevated p95HER2 [HER2-M611-CTF (carboxy-terminal-fragment) also known as p95] expression has been correlated with poor outcomes in HER2+ pts with metastatic breast cancer treated with trastuzumab (T); however, limited data is available on the correlation between p95 and pCR to T in the neoadjuvant (NEO) setting, where p95 was measured by immunohistochemistry. The current study aims to determine whether quantitative p95, HER3 and HER2 expression correlated with pCR in pts treated with T + chemotherapy in the NEO setting. Methods: pCR data and quantitative HER2 (H2T), p95, and HER3 (H3T) results by HERmark/VeraTag assays were available in 45 patient cases with pre-therapy, formalin-fixed, paraffin-embedded breast tumors. pCR was defined as the absence of invasive disease in the breast. Quantitative biomarker data were correlated with pCR according to previously published or presented biomarker cutoffs. Results: The overall pCR rate was 46.7% (ER+: 14.3% vs. ER-: 75%; p<0.0001) and was significantly associated with higher H2T levels (p=0.02) and lower H3T levels (p=0.04). In ER- subjects (N=24), no difference in H2T levels was observed between pCR vs non-pCR groups (median H2T=111.5 vs 150.5, respectively; p=0.721). However, within the ER+ group (N=21), H2T levels were significantly higher in the pCR group vs non-pCR group (median H2T=254 vs 37.3; p=0.024). Using multivariate logistic regression, increasing log(H2T) (p = 0.012), ER-negativity (p = 0.027) and low p95 (p = 0.074) were found to correlate or trend with pCR. Conclusions: pCR was significantly associated with high H2T, particularly in ER+ HER2+ breast cancer pts who received NEO therapy with T + chemotherapy. Lower H3T was also associated with pCR. A trend towards pCR was seen in tumors with low p95. These data suggest that quantitative H2T, H3T and p95 may provide additional information on response to T-based regimens in breast cancer stratified by ER status. Additional investigation into the relationship between quantitative H2T, p95 and H3T expression and T response in the NEO setting in larger cohorts is warranted.

Sign in / Sign up

Export Citation Format

Share Document