Background Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neo... more Background Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. Methods A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0–III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. Results 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR =...
INTRODUCTION Autologous fat grafting (AFG) for the purpose of breast reconstruction presents diff... more INTRODUCTION Autologous fat grafting (AFG) for the purpose of breast reconstruction presents difficulties during follow-up radiological exams and the oncological potential of grafted fat is uncertain. Coleman et al in 2007 confirmed that, provided a rigorous protocol is respected, the fatty tissue could be transferred under good conditions and would not interfere with mammographic follow-up, although the issue remains controversial about the oncological safety. This study aims to analyze the oncological safety of lipofilling through a meta-analysis of the current literature. METHODS We conducted a meta-analysis to evaluate the oncological safety of AFG after breast cancer (BC) surgery. We reviewed the literature published until 07/05/2020. The outcomes were overall survival (OS), disease free-survival (DFS) and local recurrence (LR). We included RCTs, cohort studies, case-control studies that evaluated women with BC diagnosis who undergone surgery followed by reconstruction with AFG...
Current treatment options in oncology, Jan 16, 2018
Neoadjuvant endocrine therapy (NET) with Ki67-based response monitoring is a practical, cost-effe... more Neoadjuvant endocrine therapy (NET) with Ki67-based response monitoring is a practical, cost-effective approach to the management of clinical stage II and III estrogen receptor-positive (ER+) breast cancer. In addition to marked improvements in rates of breast conservation, the identification of extreme responders on the basis of the preoperative endocrine prognostic index (PEPI) provides a rationale to avoid chemotherapy on the basis of highly favorable prognosis in some patients. Finally, samples accrued from patients treated with neoadjuvant therapy are providing valuable insights into the molecular basis for intrinsic resistance to endocrine therapy and promise a more rational basis and precise approach to the systemic treatment of ER+ breast cancer.
Background. We previously reported an alternative ESR1 somatic gain-of-function chromosomal trans... more Background. We previously reported an alternative ESR1 somatic gain-of-function chromosomal translocation event in a patient presenting with aggressive, endocrine therapy resistant estrogen receptor (ER) positive disease, producing an in-frame fusion gene consisting of N-terminal ESR1 and the C-terminus of the Hippo pathway coactivator YAP1 (ESR1-YAP1). We recently identified another ESR1 fusion through RNA sequencing (RNA-seq) in advanced stage ER+ disease from a chest wall recurrence in a male patient that was refractory to multiple lines of treatment. Two examples of fusions discovered in primary breast cancer samples include ESR1 fused in-frame to C-terminal sequences from NOP2 (ESR1-NOP2), identified in a resistant cohort from a RNA-seq screen focused on 81 primary breast cancers from aromatase inhibitor clinical trials, and a second ESR1 fusion, fused in-frame to the entire coding sequence of POLH (ESR1-POLH), that was identified from RNA-seq analysis of 728 Cancer Genome Atla...
Current treatment options in oncology, Jan 17, 2018
Endocrine treatment resistance eventually develops during adjuvant and even more often during hor... more Endocrine treatment resistance eventually develops during adjuvant and even more often during hormonal treatment for advanced breast cancer (ABC). An ESR1 gene mutation, which encodes for the estrogen receptor (ER) protein, is one of the potential mechanisms of therapy resistance. The ESR1 mutations result in conformational changes in the ER leading to subsequent estrogen-independent transcriptional activity. These mutations are found at a lower level in early stage when compared to metastatic BC, more often through selective pressure after aromatase inhibitor (AI) treatment. Recent studies have explored the role of ESR1 mutations as potential prognostic and predictive biomarkers and showed that ESR1 mutations are likely associated with a more aggressive disease. However, definitive associations with outcome in order to make a specific treatment recommendation are yet to be found. The development of targeted therapy directed to ESR1-mutated clones is an appealing concept, and precli...
Objective To present a systematic review of the literature and a meta-analysis evaluating the onc... more Objective To present a systematic review of the literature and a meta-analysis evaluating the oncological safety of autologous fat grafting (AFG). Summary background data: AFG for breast reconstruction presents difficulties during follow-up radiological exams, and the oncological potential of grafted fat is uncertain. Previous studies confirmed that the fatty tissue could be transferred under a good condition suitable would not interfere with mammographic follow-up, although the issue of oncological safety remains. Methods We reviewed the literature published until 01/18/2021. The outcomes were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). We included studies that evaluated women with breast cancer who undergone surgery followed by reconstruction with AFG. We synthesized data using the inverse variance method on the log-HR (log of the hazard ratio) scale for time-to-event outcomes using RevMan. We assessed heterogeneity using the Chi2 and I2 statisti...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 3, 2017
Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -posit... more Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratifi...
AimsTo correlate the ‘Residual Cancer Burden’ (RCB) index with overall survival (OS) and disease-... more AimsTo correlate the ‘Residual Cancer Burden’ (RCB) index with overall survival (OS) and disease-free survival (DFS) in women undergoing neoadjuvant chemotherapy at the Cancer Institute of the State of São Paulo.MethodsWe analysed the medical records of patients with breast cancer who underwent neoadjuvant chemotherapy and breast surgery, from 2011 to December 2017. Variables analysed were age, clinical and pathological staging, molecular subtype, number of recurrences or metastases, number of deaths, value and class of the RCB index. We used the Kaplan-Meier and the log-rank statistics to evaluate the possible association between RCB and OS and DFS. A regression model was used to determine the independent association of the RCB with the outcomes controlling for confounding factors.Results347 patients were included in the analysis with a mean age of 49.39 years. Initial clinical staging was T3 in 57.9% of patients and 43.8% of patients had N1 axillary status. Survival analysis showe...
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), Jul 14, 2017
The distinction between benign and malignant papilloma of the breast through percutaneous needle ... more The distinction between benign and malignant papilloma of the breast through percutaneous needle biopsy can be difficult because of limited samples; the underestimation rate can be up to 25%. The aim of this study is to identify clinical and histological factors associated with underestimation, invasive ductal carcinoma, or ductal in-situ carcinoma (DCIS) of the breast found in surgical specimens from papillary lesions. This may contribute toward selection of patients for a follow-up strategy without the need for surgical excision. From a database of 3563 patients, we identified 85 with intraductal papilloma between 2007 and 2013 who had undergone breast-imaging studies, percutaneous needle biopsy, and surgical resection of the lesion. Central papillomas normally present with a palpable mass, whereas peripheral papillomas generally do not have clinical manifestations (microcalcifications); both central and peripheral papillomas were related to atypical lesions, 13.5 and 15.4%, respe...
Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia, Jan 21, 2016
Breast cancer is the most common type of cancer and the leading cause of cancer-related death amo... more Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Ad...
Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Deeper understanding ... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Deeper understanding the mechanisms by which luminal-type breast cancer develops resistance to endocrine therapy and development of novel strategies to treat these patients requires model systems recapitulate human breast cancer as accurately as possible. An increasing body of work suggests patient derived xenografts (PDX) may represent an informative model for development of novel therapeutics. We therefore established seven xenograft tumor lines from late-stage breast cancer patients with estrogen positive (ER+) disease. To date five ER+ PDX lines have been tested for responses to estradiol treatment in overiectomized NOD/SCID mice. Three showed estradiol independent-growth, one estrogen-stimulated growth and in one estradiol-induced a regression. These patterns mimicked the clinical phenotypes of each patient, tracking survival and responses to serial endocrine treatments. To define new mechanisms for resistance, whole genome DNA sequencing, RNA sequencing and Reverse Phase Protein Assay analysis was conducted. These studies identified an ESR1/YAP1 balanced translocation in a PDX model and tumor of origin showing low levels of ER, paradoxical high level expression form luminal genes and extreme ET resistance. The ESR1 YAP1 fusion maintained the N terminal DNA binding motif of ESR1, but the hormone binding and AF2 motifs were replaced with the C terminal transactivation domain of YAP1. Expression ESR1 YAP1 in ER+ breast cancer models down-regulated ER and induced estrogen independent growth. PDX endocrine phenotypes parallel tumor of origin responses to endocrine therapy and revel novel mechanism for endocrine therapy resistance. Citation Format: Matthew J. Ellis, Shunqiang Li, Dong Shen, Li Ding, Robert Crowder, Jeiya Shao, Rodrigo Goncalves, Yu Tao, Jingqin Luo, Aleix Prat, Wenbin Liu, Ana Maria Gonzalez-Angulo, Shuying Liu, Joshua F. McMichael, Chris Miller, Dave Larson, Robert S. Fulton, Tom Mooney, Jeremy Hoog, Li Lin, Therese Giuntoli, Caroline Bumb, Crystal Cooper, Rebecca Aft, Robert T. Kitchens, Stephen N. Johnson, Chanpheng Phommaly, Megha Shiyam Kavuri, Katherine DeSchryver, Austin Lin, YiYu Dong, Cynthia X. Ma, Timothy Pluard, Michael Naughton, Ron Bose, Rama Suresh, Reida G. McDowell, Loren Michel, Richard Wilson, Shaomeng Wang, Christopher Maher, Gordon B. Mills, Charles Perou, Elaine R. Mardis. Patient-derived xenografts from advanced luminal-type breast cancer: insights into endocrine therapy resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-265. doi:10.1158/1538-7445.AM2013-LB-265
To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome co... more To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that a...
Background Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neo... more Background Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. Methods A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0–III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. Results 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR =...
INTRODUCTION Autologous fat grafting (AFG) for the purpose of breast reconstruction presents diff... more INTRODUCTION Autologous fat grafting (AFG) for the purpose of breast reconstruction presents difficulties during follow-up radiological exams and the oncological potential of grafted fat is uncertain. Coleman et al in 2007 confirmed that, provided a rigorous protocol is respected, the fatty tissue could be transferred under good conditions and would not interfere with mammographic follow-up, although the issue remains controversial about the oncological safety. This study aims to analyze the oncological safety of lipofilling through a meta-analysis of the current literature. METHODS We conducted a meta-analysis to evaluate the oncological safety of AFG after breast cancer (BC) surgery. We reviewed the literature published until 07/05/2020. The outcomes were overall survival (OS), disease free-survival (DFS) and local recurrence (LR). We included RCTs, cohort studies, case-control studies that evaluated women with BC diagnosis who undergone surgery followed by reconstruction with AFG...
Current treatment options in oncology, Jan 16, 2018
Neoadjuvant endocrine therapy (NET) with Ki67-based response monitoring is a practical, cost-effe... more Neoadjuvant endocrine therapy (NET) with Ki67-based response monitoring is a practical, cost-effective approach to the management of clinical stage II and III estrogen receptor-positive (ER+) breast cancer. In addition to marked improvements in rates of breast conservation, the identification of extreme responders on the basis of the preoperative endocrine prognostic index (PEPI) provides a rationale to avoid chemotherapy on the basis of highly favorable prognosis in some patients. Finally, samples accrued from patients treated with neoadjuvant therapy are providing valuable insights into the molecular basis for intrinsic resistance to endocrine therapy and promise a more rational basis and precise approach to the systemic treatment of ER+ breast cancer.
Background. We previously reported an alternative ESR1 somatic gain-of-function chromosomal trans... more Background. We previously reported an alternative ESR1 somatic gain-of-function chromosomal translocation event in a patient presenting with aggressive, endocrine therapy resistant estrogen receptor (ER) positive disease, producing an in-frame fusion gene consisting of N-terminal ESR1 and the C-terminus of the Hippo pathway coactivator YAP1 (ESR1-YAP1). We recently identified another ESR1 fusion through RNA sequencing (RNA-seq) in advanced stage ER+ disease from a chest wall recurrence in a male patient that was refractory to multiple lines of treatment. Two examples of fusions discovered in primary breast cancer samples include ESR1 fused in-frame to C-terminal sequences from NOP2 (ESR1-NOP2), identified in a resistant cohort from a RNA-seq screen focused on 81 primary breast cancers from aromatase inhibitor clinical trials, and a second ESR1 fusion, fused in-frame to the entire coding sequence of POLH (ESR1-POLH), that was identified from RNA-seq analysis of 728 Cancer Genome Atla...
Current treatment options in oncology, Jan 17, 2018
Endocrine treatment resistance eventually develops during adjuvant and even more often during hor... more Endocrine treatment resistance eventually develops during adjuvant and even more often during hormonal treatment for advanced breast cancer (ABC). An ESR1 gene mutation, which encodes for the estrogen receptor (ER) protein, is one of the potential mechanisms of therapy resistance. The ESR1 mutations result in conformational changes in the ER leading to subsequent estrogen-independent transcriptional activity. These mutations are found at a lower level in early stage when compared to metastatic BC, more often through selective pressure after aromatase inhibitor (AI) treatment. Recent studies have explored the role of ESR1 mutations as potential prognostic and predictive biomarkers and showed that ESR1 mutations are likely associated with a more aggressive disease. However, definitive associations with outcome in order to make a specific treatment recommendation are yet to be found. The development of targeted therapy directed to ESR1-mutated clones is an appealing concept, and precli...
Objective To present a systematic review of the literature and a meta-analysis evaluating the onc... more Objective To present a systematic review of the literature and a meta-analysis evaluating the oncological safety of autologous fat grafting (AFG). Summary background data: AFG for breast reconstruction presents difficulties during follow-up radiological exams, and the oncological potential of grafted fat is uncertain. Previous studies confirmed that the fatty tissue could be transferred under a good condition suitable would not interfere with mammographic follow-up, although the issue of oncological safety remains. Methods We reviewed the literature published until 01/18/2021. The outcomes were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). We included studies that evaluated women with breast cancer who undergone surgery followed by reconstruction with AFG. We synthesized data using the inverse variance method on the log-HR (log of the hazard ratio) scale for time-to-event outcomes using RevMan. We assessed heterogeneity using the Chi2 and I2 statisti...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 3, 2017
Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -posit... more Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratifi...
AimsTo correlate the ‘Residual Cancer Burden’ (RCB) index with overall survival (OS) and disease-... more AimsTo correlate the ‘Residual Cancer Burden’ (RCB) index with overall survival (OS) and disease-free survival (DFS) in women undergoing neoadjuvant chemotherapy at the Cancer Institute of the State of São Paulo.MethodsWe analysed the medical records of patients with breast cancer who underwent neoadjuvant chemotherapy and breast surgery, from 2011 to December 2017. Variables analysed were age, clinical and pathological staging, molecular subtype, number of recurrences or metastases, number of deaths, value and class of the RCB index. We used the Kaplan-Meier and the log-rank statistics to evaluate the possible association between RCB and OS and DFS. A regression model was used to determine the independent association of the RCB with the outcomes controlling for confounding factors.Results347 patients were included in the analysis with a mean age of 49.39 years. Initial clinical staging was T3 in 57.9% of patients and 43.8% of patients had N1 axillary status. Survival analysis showe...
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), Jul 14, 2017
The distinction between benign and malignant papilloma of the breast through percutaneous needle ... more The distinction between benign and malignant papilloma of the breast through percutaneous needle biopsy can be difficult because of limited samples; the underestimation rate can be up to 25%. The aim of this study is to identify clinical and histological factors associated with underestimation, invasive ductal carcinoma, or ductal in-situ carcinoma (DCIS) of the breast found in surgical specimens from papillary lesions. This may contribute toward selection of patients for a follow-up strategy without the need for surgical excision. From a database of 3563 patients, we identified 85 with intraductal papilloma between 2007 and 2013 who had undergone breast-imaging studies, percutaneous needle biopsy, and surgical resection of the lesion. Central papillomas normally present with a palpable mass, whereas peripheral papillomas generally do not have clinical manifestations (microcalcifications); both central and peripheral papillomas were related to atypical lesions, 13.5 and 15.4%, respe...
Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia, Jan 21, 2016
Breast cancer is the most common type of cancer and the leading cause of cancer-related death amo... more Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Ad...
Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Deeper understanding ... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Deeper understanding the mechanisms by which luminal-type breast cancer develops resistance to endocrine therapy and development of novel strategies to treat these patients requires model systems recapitulate human breast cancer as accurately as possible. An increasing body of work suggests patient derived xenografts (PDX) may represent an informative model for development of novel therapeutics. We therefore established seven xenograft tumor lines from late-stage breast cancer patients with estrogen positive (ER+) disease. To date five ER+ PDX lines have been tested for responses to estradiol treatment in overiectomized NOD/SCID mice. Three showed estradiol independent-growth, one estrogen-stimulated growth and in one estradiol-induced a regression. These patterns mimicked the clinical phenotypes of each patient, tracking survival and responses to serial endocrine treatments. To define new mechanisms for resistance, whole genome DNA sequencing, RNA sequencing and Reverse Phase Protein Assay analysis was conducted. These studies identified an ESR1/YAP1 balanced translocation in a PDX model and tumor of origin showing low levels of ER, paradoxical high level expression form luminal genes and extreme ET resistance. The ESR1 YAP1 fusion maintained the N terminal DNA binding motif of ESR1, but the hormone binding and AF2 motifs were replaced with the C terminal transactivation domain of YAP1. Expression ESR1 YAP1 in ER+ breast cancer models down-regulated ER and induced estrogen independent growth. PDX endocrine phenotypes parallel tumor of origin responses to endocrine therapy and revel novel mechanism for endocrine therapy resistance. Citation Format: Matthew J. Ellis, Shunqiang Li, Dong Shen, Li Ding, Robert Crowder, Jeiya Shao, Rodrigo Goncalves, Yu Tao, Jingqin Luo, Aleix Prat, Wenbin Liu, Ana Maria Gonzalez-Angulo, Shuying Liu, Joshua F. McMichael, Chris Miller, Dave Larson, Robert S. Fulton, Tom Mooney, Jeremy Hoog, Li Lin, Therese Giuntoli, Caroline Bumb, Crystal Cooper, Rebecca Aft, Robert T. Kitchens, Stephen N. Johnson, Chanpheng Phommaly, Megha Shiyam Kavuri, Katherine DeSchryver, Austin Lin, YiYu Dong, Cynthia X. Ma, Timothy Pluard, Michael Naughton, Ron Bose, Rama Suresh, Reida G. McDowell, Loren Michel, Richard Wilson, Shaomeng Wang, Christopher Maher, Gordon B. Mills, Charles Perou, Elaine R. Mardis. Patient-derived xenografts from advanced luminal-type breast cancer: insights into endocrine therapy resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-265. doi:10.1158/1538-7445.AM2013-LB-265
To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome co... more To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that a...
S3-05: Patient-derived xenograft study reveals endocrine … cancer caused by distinct ESR1 gene ab... more S3-05: Patient-derived xenograft study reveals endocrine … cancer caused by distinct ESR1 gene aberrations | Cancer Research Página 1 de 2 Abstract S3-05: Patient-derived xenograft study reveals endocrine therapy resistance of ER+ breast cancer caused by distinct ESR1 gene aberrations
P3-13-09: Improved frozen section examination of the retro…rediction of nipple involvement in bre... more P3-13-09: Improved frozen section examination of the retro…rediction of nipple involvement in breast cancer | Cancer Research Página 1 de 2 Abstract P3-13-09: Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer Abstract Introduction: Development of the nipple-sparing mastectomy (NSM) technique has constituted a
OT2-1-02: A phase 2 study of neoadjuvant goserelin and le…sitive HER2 negative stage 2 and 3 brea... more OT2-1-02: A phase 2 study of neoadjuvant goserelin and le…sitive HER2 negative stage 2 and 3 breast cancer | Cancer Research Página 1 de 2 Abstract OT2-1-02: A phase 2 study of neoadjuvant goserelin and letrozole for premenopausal women with estrogen receptor positive HER2 negative stage 2 and 3 breast cancer Abstract Background: More than half of premenopausal women with breast cancer have tumors that are
P4-11-13: Validation of the preoperative endocrine prognos…nce) Z1031 neoadjuvant aromatase inhib... more P4-11-13: Validation of the preoperative endocrine prognos…nce) Z1031 neoadjuvant aromatase inhibitor trial | Cancer Research Página 1 de 2 Abstract P4-11-13: Validation of the preoperative endocrine prognostic index in the ACOSOG (Alliance) Z1031 neoadjuvant aromatase inhibitor trial Abstract Background: The Preoperative Endocrine Prognostic Index (PEPI) is a method to predict outcome
PD2-03: Recurrent functionally diverse in-frame ESR1 gene …ions drive endocrine resistance in bre... more PD2-03: Recurrent functionally diverse in-frame ESR1 gene …ions drive endocrine resistance in breast cancer | Cancer Research Página 1 de 2 Abstract PD2-03: Recurrent functionally diverse in-frame ESR1 gene fusions drive endocrine resistance in breast cancer Abstract Background. We previously reported an alternative ESR1 somatic gain-of-function chromosomal
LB-265: Patient-derived xenografts from advanced luminal-t…cer: insights into endocrine therapy r... more LB-265: Patient-derived xenografts from advanced luminal-t…cer: insights into endocrine therapy resistance. | Cancer Research Página 1 de 2 Abstract LB-265: Patient-derived xenografts from advanced luminal-type breast cancer: insights into endocrine therapy resistance. Abstract Deeper understanding the mechanisms by which luminal-type breast cancer develops resistance to
PD6-4: ESR1 gene fusions implicated in endocrine therapy resistance of ER+ breast cancer | Cancer... more PD6-4: ESR1 gene fusions implicated in endocrine therapy resistance of ER+ breast cancer | Cancer Research Página 1 de 2 Abstract PD6-4: ESR1 gene fusions implicated in endocrine therapy resistance of ER+ breast cancer Abstract Background. We recently identified an in-frame ESR1 translocation in a tumor and PDX pair from a
Uploads
Papers by Rodrigo Goncalves