Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy
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ABSTRACT:
PROVIDER: PRJNA418709 | ENA |
REPOSITORIES: ENA
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Project description:Triple negative breast cancer is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study was to explore the clinical relevance of Lehmann triple negative breast cancer subtypes by identifying any differences in response to neoadjuvant chemotherapy among them.
2017-11-17 | GSE106977 | GEO
Project description:Purpose:The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. We hypothesized that due to similarities between radiation and chemotherapy induced cellular response mechanisms, radiation responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Materials and Methods: Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiation responsive genes. These murine radiation induced genes were then converted to their human orthologs. These genes were then used to develop a predictor of pathologic complete response (pCR) that was validated on two independent published neoadjuvant chemotherapy data sets of genomic data with response. Results: A radiation induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples in two independent published datasets and was found to be significantly predictive of pathologic complete response. Multivariate logistic regression analysis in both independent datasets showed that this 30 gene signature added significant predictive information independent of that provided by standard clinical predictors and other gene expression based predictors of pathologic complete response. Conclusion: This study provides new biologic information regarding response to neoadjuvant chemotherapy and a means of possibly improving the prediction of pathologic complete response. reference x sample
2015-01-21 | E-GEOD-48073 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5995183 | biostudies-literature
Project description:Purpose:The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. We hypothesized that due to similarities between radiation and chemotherapy induced cellular response mechanisms, radiation responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Materials and Methods: Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiation responsive genes. These murine radiation induced genes were then converted to their human orthologs. These genes were then used to develop a predictor of pathologic complete response (pCR) that was validated on two independent published neoadjuvant chemotherapy data sets of genomic data with response. Results: A radiation induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples in two independent published datasets and was found to be significantly predictive of pathologic complete response. Multivariate logistic regression analysis in both independent datasets showed that this 30 gene signature added significant predictive information independent of that provided by standard clinical predictors and other gene expression based predictors of pathologic complete response. Conclusion: This study provides new biologic information regarding response to neoadjuvant chemotherapy and a means of possibly improving the prediction of pathologic complete response.
2015-01-21 | GSE48073 | GEO
Project description: Not available
| S-EPMC7475504 | biostudies-literature
Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors. Neoadjuvant study of 50 HER2-positive breast cancer cases treated with trastuzumab-based chemotherapy pre-operatively. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to Affymetrix microarrays according to manufacturer protocol. Pathologic response was assessed at the end of neoadjuvant treatment.
2012-05-11 | E-GEOD-37946 | biostudies-arrayexpress
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant validation cohort of 198 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
2011-05-11 | E-GEOD-25065 | biostudies-arrayexpress
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant study of 310 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
2011-05-11 | E-GEOD-25055 | biostudies-arrayexpress
Project description:In a cohort study of 7 women with primary invasive breast cancer, we obtained a tumor specimen before (biopsy) and after (tumorectomy) 4 cycles of NAC with epirubicine and cyclophosphamide, followed by 4 cycles of taxanes. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. Molecular functions changing during chemotherapy were searched. Whole genome expression of triple negative breast cancer tissues were measured before and after four cycles neoadjuvant chemotherapy
2016-03-24 | E-GEOD-43816 | biostudies-arrayexpress
Project description:For patients with muscle-invasive bladder cancer, there are no biomarkers in clinical use that can identify patients that are sensitive or resistant to neoadjuvant chemotherapy. This study investigates how molecular subtypes impact pathological response and survival in 149 patients receiving preoperative cis-platin based chemotherapy by tumor classification using transcriptomic profiling and a 13-marker immunostaining panel. Furthermore, we explored to what extent gene expression signatures can predict chemotherapy response beyond molecular subtypes. We observed improved pathological response rates and survival outcomes for patients presenting with genomically unstable (GU) and urothelial-like (Uro) subtypes compared to the basal-squamous (BASQ) subtype following neoadjuvant chemotherapy and radical cystectomy. Also, SPP1, coding for osteopontin, displayed a clear subtype-dependent effect on chemotherapy response, confirmed at the protein level. Based on our findings, we hypothesize that urothelial cancer of the luminal-like GU- and Uro-subtypes are more responsive to cisplatin-based chemotherapy which may influence patient selection pending further research.
2021-11-19 | GSE169455 | GEO