10 results on '"Symmans, W. Fraser"'
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2. Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.
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Symmans, W. Fraser, Yau, Christina, Chen, Yunn-Yi, Balassanian, Ron, Klein, Molly E., Pusztai, Lajos, Nanda, Rita, Parker, Barbara A., Datnow, Brian, Krings, Gregor, Wei, Shi, Feldman, Michael D., Duan, Xiuzhen, Chen, Beiyun, Sattar, Husain, Khazai, Laila, Zeck, Jay C., Sams, Sharon, Mhawech-Fauceglia, Paulette, and Rendi, Mara
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- 2021
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3. Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial
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Yee, Douglas, DeMichele, Angela M., Yau, Christina, Isaacs, Claudine, Symmans, W. Fraser, Albain, Kathy S., Chen, Yunn-Yi, Krings, Gregor, Wei, Shi, Harada, Shuko, Datnow, Brian, Fadare, Oluwole, Klein, Molly, Pambuccian, Stefan, Chen, Beiyun, Adamson, Kathi, Sams, Sharon, Mhawech-Fauceglia, Paulette, Magliocco, Anthony, and Feldman, Mike
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- 2020
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4. Association of Residual Cancer Burden After Neoadjuvant Therapy and Event-Free Survival in Breast Cancer—Reply.
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Mukhtar, Rita, Symmans, W. Fraser, and Esserman, Laura J.
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- 2022
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5. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.
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Boughey, Judy C, Suman, Vera J, Mittendorf, Elizabeth A, Ahrendt, Gretchen M, Wilke, Lee G, Taback, Bret, Leitch, A Marilyn, Kuerer, Henry M, Bowling, Monet, Flippo-Morton, Teresa S, Byrd, David R, Ollila, David W, Julian, Thomas B, McLaughlin, Sarah A, McCall, Linda, Symmans, W Fraser, Le-Petross, Huong T, Haffty, Bruce G, Buchholz, Thomas A, and Nelson, Heidi
- Abstract
Importance: Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies.Objective: To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer.Design, Setting, and Patients: The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged.Main Outcomes and Measures: The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease.Results: Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%).Conclusions and Relevance: Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND.Trial Registration: clinicaltrials.gov Identifier: NCT00881361. [ABSTRACT FROM AUTHOR]- Published
- 2013
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6. Cenomic Predictor of Survival After Chemotherapy for Breast Cancer.
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Burke, Harry B., Symmans, W. Fraser, and Hatzis, Christos
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LETTERS to the editor , *ANTHRACYCLINES ,BREAST cancer chemotherapy - Abstract
A letter to the editor is presented in response to the article "A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer," by Christos Hatzis and colleagues which appeared in a previous issue.
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- 2011
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7. Association of Immunophenotype With Pathologic Complete Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: A Secondary Analysis of the BrighTNess Phase 3 Randomized Clinical Trial.
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Filho OM, Stover DG, Asad S, Ansell PJ, Watson M, Loibl S, Geyer CE Jr, Bae J, Collier K, Cherian M, O'Shaughnessy J, Untch M, Rugo HS, Huober JB, Golshan M, Sikov WM, von Minckwitz G, Rastogi P, Maag D, Wolmark N, Denkert C, and Symmans WF
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- Carboplatin, Female, Humans, Immunophenotyping, Paclitaxel, Antineoplastic Combined Chemotherapy Protocols, Neoadjuvant Therapy, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms pathology
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Importance: Adding carboplatin to standard neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) likely benefits a subset of patients; however, determinants of benefit are poorly understood., Objective: To define the association of molecular subtype, tumor proliferation, and immunophenotype with benefit of carboplatin added to NAC for patients with stages II to III TNBC., Design, Setting, and Participants: This was a prespecified secondary analysis of a phase 3, double-blind, randomized clinical trial (BrighTNess) that enrolled 634 women across 145 centers in 15 countries. Women with clinical stages II to III TNBC who had undergone pretreatment biopsy were eligible to participate. Whole transcriptome RNA sequencing was performed on the biopsy specimens. The prespecified end point was association of pathologic complete response (pCR) with gene expression-based molecular subtype, with secondary end points investigating established signatures (proliferation, immune) and exploratory analyses of immunophenotype. Data were collected from April 2014 to March 2016. The study analyses were performed from January 2018 to March 2019., Interventions: Neoadjuvant chemotherapy with paclitaxel followed by doxorubicin and cyclophosphamide, or this same regimen with carboplatin or carboplatin plus veliparib., Main Outcomes and Measures: Association of gene expression-based molecular subtype (PAM50 and TNBC subtypes) with pCR., Results: Of the 634 women (median age, 51 [range, 22-78] years) enrolled in BrighTNess, 482 (76%) patients had evaluable RNA sequencing data, with similar baseline characteristics relative to the overall intention-to-treat population. Pathologic complete response was significantly more frequent in PAM50 basal-like vs nonbasal-like cancers overall (202 of 386 [52.3%] vs 34 of 96 [35.4%]; P = .003). Carboplatin benefit was not significantly different in basal-like vs nonbasal-like subgroups (P = .80 for interaction). In multivariable analysis, proliferation (hazard ratio, 0.36; 95% CI, 0.21-0.61; P < .001) and immune (hazard ratio, 0.62; 95% CI, 0.49-0.79; P < .001) signatures were independently associated with pCR. Tumors above the median for proliferation and immune signatures had the highest pCR rate (84 of 125; 67%), while those below the median for both signatures had the lowest pCR rate (42 of 125; 34%). Exploratory gene expression immune analyses suggested that tumors with higher inferred CD8+ T-cell infiltration may receive greater benefit with addition of carboplatin., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, triple-negative breast cancer subtyping revealed high pCR rates in basal-like and immunomodulatory subsets. Analysis of biological processes related to basal-like and immunomodulatory phenotypes identified tumor cell proliferation and immune scores as independent factors associated with achieving pCR; the benefit of carboplatin on pCR was seen across all molecular subtypes. Further validation of immunophenotype with existing biomarkers may help to escalate or de-escalate therapy for patients with TNBC., Trial Registration: ClinicalTrials.gov Identifier: NCT02032277.
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- 2021
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8. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial.
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Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van 't Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, and Esserman LJ
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- Antibodies, Monoclonal, Humanized pharmacology, Breast Neoplasms pathology, Female, Humans, Neoplasm Staging, Antibodies, Monoclonal, Humanized therapeutic use, Breast Neoplasms drug therapy, Neoadjuvant Therapy methods, Programmed Cell Death 1 Receptor therapeutic use
- Abstract
Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed., Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial., Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with ERBB2 (formerly HER2)-negative breast cancer were eligible for randomization to pembrolizumab between November 2015 and November 2016., Interventions: Participants were randomized to receive taxane- and anthracycline-based NACT with or without pembrolizumab, followed by definitive surgery., Main Outcomes and Measures: The primary end point was pathologic complete response (pCR). Secondary end points were residual cancer burden (RCB) and 3-year event-free and distant recurrence-free survival. Investigational arms graduated when demonstrating an 85% predictive probability of success in a hypothetical confirmatory phase 3 trial., Results: Of the 250 women included in the final analysis, 181 were randomized to the standard NACT control group (median [range] age, 47 [24.77] years). Sixty-nine women (median [range] age, 50 [27-71] years) were randomized to 4 cycles of pembrolizumab in combination with weekly paclitaxel followed by AC; 40 hormone receptor (HR)-positive and 29 triple-negative. Pembrolizumab graduated in all 3 biomarker signatures studied. Final estimated pCR rates, evaluated in March 2017, were 44% vs 17%, 30% vs 13%, and 60% vs 22% for pembrolizumab vs control in the ERBB2-negative, HR-positive/ERBB2-negative, and triple-negative cohorts, respectively. Pembrolizumab shifted the RCB distribution to a lower disease burden for each cohort evaluated. Adverse events included immune-related endocrinopathies, notably thyroid abnormalities (13.0%) and adrenal insufficiency (8.7%). Achieving a pCR appeared predictive of long-term outcome, where patients with pCR following pembrolizumab plus chemotherapy had high event-free survival rates (93% at 3 years with 2.8 years' median follow-up)., Conclusions and Relevance: When added to standard neoadjuvant chemotherapy, pembrolizumab more than doubled the estimated pCR rates for both HR-positive/ERBB2-negative and triple-negative breast cancer, indicating that checkpoint blockade in women with early-stage, high-risk, ERBB2-negative breast cancer is highly likely to succeed in a phase 3 trial. Pembrolizumab was the first of 10 agents to graduate in the HR-positive/ERBB2-negative signature., Trial Registration: ClinicalTrials.gov Identifier: NCT01042379.
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- 2020
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9. The Neo-Bioscore Update for Staging Breast Cancer Treated With Neoadjuvant Chemotherapy: Incorporation of Prognostic Biologic Factors Into Staging After Treatment.
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Mittendorf EA, Vila J, Tucker SL, Chavez-MacGregor M, Smith BD, Symmans WF, Sahin AA, Hortobagyi GN, and Hunt KK
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- Adult, Aged, Breast Neoplasms genetics, Breast Neoplasms pathology, Disease-Free Survival, Female, Humans, Middle Aged, Neoadjuvant Therapy, Neoplasm Grading, Neoplasm Staging, Predictive Value of Tests, Breast Neoplasms drug therapy, Estrogen Receptor alpha genetics, Prognosis, Receptor, ErbB-2 genetics
- Abstract
Importance: We previously described and validated a breast cancer staging system (CPS+EG, clinical-pathologic scoring system incorporating estrogen receptor-negative disease and nuclear grade 3 tumor pathology) for assessing prognosis after neoadjuvant chemotherapy using pretreatment clinical stage, posttreatment pathologic stage, estrogen receptor (ER) status, and grade. Development of the CPS+EG staging system predated routine administration of trastuzumab in patients with ERBB2-positive disease (formerly HER2 or HER2/neu)., Objective: To validate the CPS+EG staging system using the new definition of ER positivity (≥1%) and to develop an updated staging system (Neo-Bioscore) that incorporates ERBB2 status into the previously developed CPS+EG., Design, Setting, and Participants: Retrospective review of data collected prospectively from January 2005 through December 2012 on patients with breast cancer treated with neoadjuvant chemotherapy at The University of Texas MD Anderson Cancer Center., Main Outcomes and Measure: Prognostic scores were computed using 2 versions of the CPS+EG staging system, one with ER considered positive if it measured 10% or higher, the other with ER considered positive if it measured 1% or higher. Fits of the Cox proportional hazards model for the 2 sets of prognostic scores were compared using the Akaike Information Criterion (AIC). Status of ERBB2 was added to the model, and the likelihood ratio test was used to determine improvement in fit., Results: A total of 2377 patients were included; all were women (median age, 50 years [range, 21-87 years]); ER status was less than 1% in 28.9%, 1% to 9% in 8.3%, and 10% or higher in 62.8%; 591 patients were ERBB2 positive. Median follow-up was 4.2 years (range, 0.5-11.7 years). Five-year disease-specific survival was 89% (95% CI, 87%-90%). Using 1% or higher as the cutoff for ER positivity, 5-year disease-specific survival estimates determined using the CPS+EG stage ranged from 52% to 98%, thereby validating our previous finding that the CPS+EG score facilitates more refined categorization into prognostic subgroups than clinical or final pathologic stage alone. The AIC value for this model was 3333.06, while for a model using 10% or higher as the cutoff for ER positivity, it was 3333.38, indicating that the model fits were nearly identical. The improvement in fit of the model when ERBB2 status was added was highly significant, with 5-year disease-specific survival estimates ranging from 48% to 99% (P < .001). Incorporating ERBB2 into the staging system defined the Neo-Bioscore, which provided improved stratification of patients with respect to prognosis., Conclusions and Relevance: The Neo-Bioscore improves our previously validated staging system and allows its application in ERBB2-positive patients. We recommend that treatment response and biologic markers be incorporated into the American Joint Committee on Cancer staging system.
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- 2016
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10. A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
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Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, Vidaurre T, Holmes F, Souchon E, Wang H, Martin M, Cotrina J, Gomez H, Hubbard R, Chacón JI, Ferrer-Lozano J, Dyer R, Buxton M, Gong Y, Wu Y, Ibrahim N, Andreopoulou E, Ueno NT, Hunt K, Yang W, Nazario A, DeMichele A, O'Shaughnessy J, Hortobagyi GN, and Symmans WF
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- Adult, Algorithms, Anthracyclines therapeutic use, Antineoplastic Agents, Hormonal pharmacology, Antineoplastic Agents, Hormonal therapeutic use, Biopsy, Needle, Breast Neoplasms mortality, Bridged-Ring Compounds therapeutic use, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Forecasting, Genes, erbB-2, Genomics, Humans, Middle Aged, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Oligonucleotide Array Sequence Analysis, Predictive Value of Tests, Prognosis, Prospective Studies, Receptors, Estrogen analysis, Risk, Taxoids therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Gene Expression Profiling, Genes, Neoplasm genetics
- Abstract
Context: Prediction of high probability of survival from standard cancer treatments is fundamental for individualized cancer treatment strategies., Objective: To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer., Design, Setting, and Patients: Prospective multicenter study conducted from June 2000 to March 2010 at the M. D. Anderson Cancer Center to develop and test genomic predictors for neoadjuvant chemotherapy. Patients were those with newly diagnosed ERBB2 (HER2 or HER2/neu)-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens (then endocrine therapy if estrogen receptor [ER]-positive). Different predictive signatures for resistance and response to preoperative (neoadjuvant) chemotherapy (stratified according to ER status) were developed from gene expression microarrays of newly diagnosed breast cancer (310 patients). Breast cancer treatment sensitivity was then predicted using the combination of signatures for (1) sensitivity to endocrine therapy, (2) chemoresistance, and (3) chemosensitivity, with independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response., Main Outcome Measures: Distant relapse-free survival (DRFS) if predicted treatment sensitive and absolute risk reduction ([ARR], difference in DRFS between 2 predicted groups) at median follow-up (3 years)., Results: Patients in the independent validation cohort (99% clinical stage II-III) who were predicted to be treatment sensitive (28%) had 56% (95% CI, 31%-78%) probability of excellent pathologic response and DRFS of 92% (95% CI, 85%-100%), with an ARR of 18% (95% CI, 6%-28%). Survival was predicted in ER-positive (30% predicted sensitive; DRFS, 97% [95% CI, 91%-100%]; ARR, 11% [95% CI, 0.1%-21%]) and ER-negative (26% predicted sensitive; DRFS, 83% [95% CI, 68%-100%]; ARR, 26% [95% CI, 4%-48%]) subsets and was significant in multivariate analysis. Other genomic predictors showed paradoxically worse survival for patients predicted to be responsive to chemotherapy., Conclusion: A genomic predictor combining ER status, predicted chemoresistance, predicted chemosensitivity, and predicted endocrine sensitivity identified patients with high probability of survival following taxane and anthracycline chemotherapy.
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- 2011
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