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Anna Maria Storniolo - One of the best experts on this subject based on the ideXlab platform.
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Abstract P3-07-13: Homologous recombination deficiency (HRD) as a predictive biomarker of response to Preoperative Systemic Therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer
Poster Session Abstracts, 2016Co-Authors: Roisin M. Connolly, Anna Maria Storniolo, Ep Elkin, Kirsten Timms, Mp Goetz, Judy C. Boughey, Z Zhang, B Walsh, John T. Carpenter, S WatkinsAbstract:Background: Biomarkers to predict response to platinum-based Therapy in early breast cancer are needed. HRD is a promising predictor of response to DNA damaging agents, such as platinums. We hypothesized that HRD (high HRD score ≥ 42 and/or tumor BRCA [tBRCA] mutation) would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer treated with PST comprising a platinum, regardless of estrogen receptor (ER) status. Methods: TBCRC008 was a multicenter placebo-controlled trial that investigated pCR (no invasive cancer in breast/axilla) following 12 weeks of Preoperative carboplatin and albumin-bound paclitaxel with or without vorinostat in patients with ER-positive or triple-negative breast cancer (TNBC) (Connolly RM. JNM 2015). The pCR rate was similar in both arms (vorinostat 25.8%, placebo 29%). We performed an exploratory biomarker study correlating baseline tumor biopsy HRD status with pCR. The analysis population included all patients with available HRD and pCR data. We compared the proportion of patients with pCR by HRD status using Fisher9s exact test. A subset analysis compared pCR proportions by high (≥42) vs. low ( Results: HRD status and pCR data were available for 48/62 patients (30 ER-positive, 18 TNBC). Of these, 46% of tumors were HR deficient (n=22/48, 33% ER-positive [10/30], 67% TNBC [12/18]). We observed a significantly higher pCR rate in patients with HR deficiency vs not (50% vs 7.7%, p=0.002) in the overall population. A similar trend was observed in ER-positive (30% vs 5%, p=0.095) and TNBC (66.7% vs 16.7%, p=0.13) patients. There was no significant difference when analyzed by treatment arm (vorinostat vs placebo). In a subgroup analysis (n=40) of patients without tBRCA (25 ER-positive, 15 TNBC), a significantly higher pCR rate was observed in those with high vs low HRD score (64.3% vs 7.7%, p Conclusion: This is the first study to evaluate the predictive role of HRD status in patients with ER-positive, HER2-negative breast cancer treated with platinum-based Therapy. Our results also support prior observations that HRD status is a promising predictive biomarker of response to platinum agents in TNBC. Further evaluation of this question is warranted in both TNBC and ER-positive breast cancer. Citation Format: Connolly R, Elkin E, Timms K, Goetz M, Boughey J, Zhang Z, Walsh B, Carpenter J, Storniolo A, Watkins S, Gabrielson E, Hartman A-R, Stearns V. Homologous recombination deficiency (HRD) as a predictive biomarker of response to Preoperative Systemic Therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer. [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 P3-07-13.
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tbcrc 008 early change in 18f fdg uptake on pet predicts response to Preoperative Systemic Therapy in human epidermal growth factor receptor 2 negative primary operable breast cancer
The Journal of Nuclear Medicine, 2015Co-Authors: Roisin M. Connolly, Jeffrey Leal, Matthew P Goetz, Zhe Zhang, Xian C Zhou, Lisa K Jacobs, Joyce Mhlanga, H O Joo, John Carpenter, Anna Maria StornioloAbstract:Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemoTherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods: Participants were randomly assigned to 12 wk of Preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1–3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. Results: In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SULmax 15 d after initiating Preoperative Therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3–22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18F-FDG PET 15 d after the initiation of Preoperative Therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatment-selection biomarker.
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a multi institutional double blind phase ii study evaluating response and surrogate biomarkers to carboplatin and nab paclitaxel cp with or without vorinostat as Preoperative Systemic Therapy pst in her2 negative primary operable breast cancer tbcrc008
Journal of Clinical Oncology, 2010Co-Authors: R M Connolly, Antonio C. Wolff, Anna Maria Storniolo, Matthew P Goetz, Zhe Zhang, Stacie Jeter, Jane Zorzi, D K Armstrong, John H Fetting, V StearnsAbstract:TPS111 Background: Traditionally, Systemic treatment recommendations for women with breast cancer have been based on clinicopathologic factors following definitive surgery. PST allows for improved ...
Roisin M. Connolly - One of the best experts on this subject based on the ideXlab platform.
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Abstract P3-07-13: Homologous recombination deficiency (HRD) as a predictive biomarker of response to Preoperative Systemic Therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer
Poster Session Abstracts, 2016Co-Authors: Roisin M. Connolly, Anna Maria Storniolo, Ep Elkin, Kirsten Timms, Mp Goetz, Judy C. Boughey, Z Zhang, B Walsh, John T. Carpenter, S WatkinsAbstract:Background: Biomarkers to predict response to platinum-based Therapy in early breast cancer are needed. HRD is a promising predictor of response to DNA damaging agents, such as platinums. We hypothesized that HRD (high HRD score ≥ 42 and/or tumor BRCA [tBRCA] mutation) would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer treated with PST comprising a platinum, regardless of estrogen receptor (ER) status. Methods: TBCRC008 was a multicenter placebo-controlled trial that investigated pCR (no invasive cancer in breast/axilla) following 12 weeks of Preoperative carboplatin and albumin-bound paclitaxel with or without vorinostat in patients with ER-positive or triple-negative breast cancer (TNBC) (Connolly RM. JNM 2015). The pCR rate was similar in both arms (vorinostat 25.8%, placebo 29%). We performed an exploratory biomarker study correlating baseline tumor biopsy HRD status with pCR. The analysis population included all patients with available HRD and pCR data. We compared the proportion of patients with pCR by HRD status using Fisher9s exact test. A subset analysis compared pCR proportions by high (≥42) vs. low ( Results: HRD status and pCR data were available for 48/62 patients (30 ER-positive, 18 TNBC). Of these, 46% of tumors were HR deficient (n=22/48, 33% ER-positive [10/30], 67% TNBC [12/18]). We observed a significantly higher pCR rate in patients with HR deficiency vs not (50% vs 7.7%, p=0.002) in the overall population. A similar trend was observed in ER-positive (30% vs 5%, p=0.095) and TNBC (66.7% vs 16.7%, p=0.13) patients. There was no significant difference when analyzed by treatment arm (vorinostat vs placebo). In a subgroup analysis (n=40) of patients without tBRCA (25 ER-positive, 15 TNBC), a significantly higher pCR rate was observed in those with high vs low HRD score (64.3% vs 7.7%, p Conclusion: This is the first study to evaluate the predictive role of HRD status in patients with ER-positive, HER2-negative breast cancer treated with platinum-based Therapy. Our results also support prior observations that HRD status is a promising predictive biomarker of response to platinum agents in TNBC. Further evaluation of this question is warranted in both TNBC and ER-positive breast cancer. Citation Format: Connolly R, Elkin E, Timms K, Goetz M, Boughey J, Zhang Z, Walsh B, Carpenter J, Storniolo A, Watkins S, Gabrielson E, Hartman A-R, Stearns V. Homologous recombination deficiency (HRD) as a predictive biomarker of response to Preoperative Systemic Therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer. [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 P3-07-13.
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tbcrc 008 early change in 18f fdg uptake on pet predicts response to Preoperative Systemic Therapy in human epidermal growth factor receptor 2 negative primary operable breast cancer
The Journal of Nuclear Medicine, 2015Co-Authors: Roisin M. Connolly, Jeffrey Leal, Matthew P Goetz, Zhe Zhang, Xian C Zhou, Lisa K Jacobs, Joyce Mhlanga, H O Joo, John Carpenter, Anna Maria StornioloAbstract:Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemoTherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods: Participants were randomly assigned to 12 wk of Preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1–3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. Results: In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SULmax 15 d after initiating Preoperative Therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3–22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18F-FDG PET 15 d after the initiation of Preoperative Therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatment-selection biomarker.
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early change in 18 fluorodeoxyglucose fdg uptake on positron emission tomography pet to predict response to Preoperative Systemic Therapy pst in her2 negative primary operable breast cancer translational breast cancer research consortium tbcrc008
Journal of Clinical Oncology, 2012Co-Authors: Roisin M. Connolly, Matthew P Goetz, Zhe Zhang, Xian C Zhou, Joyce Mhlanga, Jeffrey P Leal, Stacie Jeter, Bridget Walsh, Penny Powers, Jane ZorziAbstract:10509 Background: PST allows for improved surgical outcomes and response assessment without compromising long term outcomes. PST is an attractive model for assessing surrogate markers of response t...
Matthew P Goetz - One of the best experts on this subject based on the ideXlab platform.
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tbcrc 008 early change in 18f fdg uptake on pet predicts response to Preoperative Systemic Therapy in human epidermal growth factor receptor 2 negative primary operable breast cancer
The Journal of Nuclear Medicine, 2015Co-Authors: Roisin M. Connolly, Jeffrey Leal, Matthew P Goetz, Zhe Zhang, Xian C Zhou, Lisa K Jacobs, Joyce Mhlanga, H O Joo, John Carpenter, Anna Maria StornioloAbstract:Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemoTherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods: Participants were randomly assigned to 12 wk of Preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1–3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. Results: In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SULmax 15 d after initiating Preoperative Therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3–22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18F-FDG PET 15 d after the initiation of Preoperative Therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatment-selection biomarker.
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early change in 18 fluorodeoxyglucose fdg uptake on positron emission tomography pet to predict response to Preoperative Systemic Therapy pst in her2 negative primary operable breast cancer translational breast cancer research consortium tbcrc008
Journal of Clinical Oncology, 2012Co-Authors: Roisin M. Connolly, Matthew P Goetz, Zhe Zhang, Xian C Zhou, Joyce Mhlanga, Jeffrey P Leal, Stacie Jeter, Bridget Walsh, Penny Powers, Jane ZorziAbstract:10509 Background: PST allows for improved surgical outcomes and response assessment without compromising long term outcomes. PST is an attractive model for assessing surrogate markers of response t...
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a multi institutional double blind phase ii study evaluating response and surrogate biomarkers to carboplatin and nab paclitaxel cp with or without vorinostat as Preoperative Systemic Therapy pst in her2 negative primary operable breast cancer tbcrc008
Journal of Clinical Oncology, 2010Co-Authors: R M Connolly, Antonio C. Wolff, Anna Maria Storniolo, Matthew P Goetz, Zhe Zhang, Stacie Jeter, Jane Zorzi, D K Armstrong, John H Fetting, V StearnsAbstract:TPS111 Background: Traditionally, Systemic treatment recommendations for women with breast cancer have been based on clinicopathologic factors following definitive surgery. PST allows for improved ...
Zhe Zhang - One of the best experts on this subject based on the ideXlab platform.
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tbcrc 008 early change in 18f fdg uptake on pet predicts response to Preoperative Systemic Therapy in human epidermal growth factor receptor 2 negative primary operable breast cancer
The Journal of Nuclear Medicine, 2015Co-Authors: Roisin M. Connolly, Jeffrey Leal, Matthew P Goetz, Zhe Zhang, Xian C Zhou, Lisa K Jacobs, Joyce Mhlanga, H O Joo, John Carpenter, Anna Maria StornioloAbstract:Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemoTherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods: Participants were randomly assigned to 12 wk of Preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1–3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. Results: In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SULmax 15 d after initiating Preoperative Therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3–22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18F-FDG PET 15 d after the initiation of Preoperative Therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatment-selection biomarker.
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early change in 18 fluorodeoxyglucose fdg uptake on positron emission tomography pet to predict response to Preoperative Systemic Therapy pst in her2 negative primary operable breast cancer translational breast cancer research consortium tbcrc008
Journal of Clinical Oncology, 2012Co-Authors: Roisin M. Connolly, Matthew P Goetz, Zhe Zhang, Xian C Zhou, Joyce Mhlanga, Jeffrey P Leal, Stacie Jeter, Bridget Walsh, Penny Powers, Jane ZorziAbstract:10509 Background: PST allows for improved surgical outcomes and response assessment without compromising long term outcomes. PST is an attractive model for assessing surrogate markers of response t...
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a multi institutional double blind phase ii study evaluating response and surrogate biomarkers to carboplatin and nab paclitaxel cp with or without vorinostat as Preoperative Systemic Therapy pst in her2 negative primary operable breast cancer tbcrc008
Journal of Clinical Oncology, 2010Co-Authors: R M Connolly, Antonio C. Wolff, Anna Maria Storniolo, Matthew P Goetz, Zhe Zhang, Stacie Jeter, Jane Zorzi, D K Armstrong, John H Fetting, V StearnsAbstract:TPS111 Background: Traditionally, Systemic treatment recommendations for women with breast cancer have been based on clinicopathologic factors following definitive surgery. PST allows for improved ...
Joseph A. Sparano - One of the best experts on this subject based on the ideXlab platform.
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clinical utility of 18f fdg pet ct in staging localized breast cancer before initiating Preoperative Systemic Therapy
Journal of The National Comprehensive Cancer Network, 2020Co-Authors: Yaser Baghdadi, Charito Love, Joseph A. SparanoAbstract:Background 18F-fluorodeoxyglucose PET/CT is recommended as an optional study in the current NCCN Clinical Practice Guidelines in Oncology for Breast Cancer after CT of the chest, abdomen, and pelvis with contrast and bone scan (CTBS) in stage IIA-IIIC breast cancer. We evaluated our experience with the use of PET/CT in this setting before beginning primary Systemic Therapy (PST) prior to planned surgery. Methods We performed medical record abstractions of all adult female patients with clinical stage IIA-IIIC breast cancer diagnosed at Montefiore Medical Center from January 1, 2014, through January 1, 2019, who underwent PET/CT before PST. We calculated the proportion of patients upstaged after PET/CT and examined the cost and radiation exposure associated with PET/CT compared with CTBS. Results A total of 195 patients with 196 breast cancers (bilateral disease in 1 patient) met the study inclusion criteria and had PET/CT as the first imaging study before PST. The overall upstaging rate for regional nodal metastasis and/or distant metastasis was 37% (73/196), including 24% for stage IIA (9/38), 39% for stage IIB (31/79), 54% for stage IIIA (22/41), 27% for stage IIIB (8/30), and 37% for stage IIIC (3/8). The overall upstaging rate for distant metastasis was 14% (27/196), including 0% for stage IIA, 13% for stage IIB (10/79), 22% for stage IIIA (9/41), 17% for stage IIIB (5/30), and 37% for stage IIIC (3/8). Medicare reimbursement rates were $1,604.37 for PET/CT and $1,679.94 for CTBS. The radiation dose for PET/CT was 14 mSv versus 21 mSv for CTBS. Conclusions Approximately 37% of patients with clinical stage IIA-IIIC breast cancer who underwent PET/CT before PST showed more extensive disease, including 23% with more extensive nodal metastasis and 14% with distant metastasis. Given its high detection rate, comparable cost, lower radiation dose, and greater convenience, PET/CT should be considered as an alternative to CTBS rather than "optional" after CTBS, especially in patients who require an efficient and expeditious workup before initiating PST.
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clinical utility of 18f fdg pet ct in staging localized breast cancer prior to initiating Preoperative Systemic Therapy
Journal of Clinical Oncology, 2020Co-Authors: Yaser Baghdadi, Charito Love, Joseph A. SparanoAbstract:563Background: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) is recommended as an optional study in current National Comprehensive Cancer Network (NCCN) guidelines after co...