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Start Over Author "Eric P Winer" Publisher american association for cancer research (aacr)
268 results on '"Eric P Winer"'

1. Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer

Author

Junko Tsuji, Tianyu Li, Albert Grinshpun, Tim Coorens, Douglas Russo, Leilani Anderson, Rebecca Rees, Agostina Nardone, Candace Patterson, Niall J. Lennon, Carrie Cibulskis, Ignaty Leshchiner, Nabihah Tayob, Sara M. Tolaney, Nadine Tung, Donald P. McDonnell, Ian E. Krop, Eric P. Winer, Chip Stewart, Gad Getz, and Rinath Jeselsohn

Subjects
Cancer Research, Treatment Outcome, Receptors, Estrogen, Oncology, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols, Exome Sequencing, Liquid Biopsy, Humans, Female, Breast Neoplasms, Article
Abstract

Purpose: Sensitivity to endocrine therapy (ET) is critical for the clinical benefit from the combination of palbociclib plus ET in hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer. Bazedoxifene is a third-generation selective estrogen receptor (ER) modulator and selective ER degrader with activity in preclinical models of endocrine-resistant breast cancer, including models harboring ESR1 mutations. Clinical trials in healthy women showed that bazedoxifene is well tolerated. Patients and Methods: We conducted a phase Ib/II study of bazedoxifene plus palbociclib in patients with HR+/HER2− advanced breast cancer who progressed on prior ET (N = 36; NCT02448771). Results: The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression-free survival (PFS) was 3.6 months [95% confidence interval (CI), 2.0–7.2]. An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR = 4.4; 95% CI, 1.5–13; P = 0.0026), but activating ESR1 mutations did not impact the PFS. Longitudinal plasma circulating tumor DNA whole-exome sequencing (WES; N = 68 plasma samples) provided an overview of the tumor heterogeneity and the subclonal genetic evolution, and identified actionable mutations acquired during treatment. Conclusions: The combination of palbociclib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HR+/HER2− breast cancer. These results merit continued investigation of bazedoxifene in breast cancer.

Published
2022

2. Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases

Author

Sheheryar Kabraji, Jing Ni, Sarah Sammons, Tianyu Li, Amanda E.D. Van Swearingen, Yanzhi Wang, Alyssa Pereslete, Liangge Hsu, Pamela J. DiPiro, Chris Lascola, Heather Moore, Melissa Hughes, Akshara S. Raghavendra, Maria Gule-Monroe, Rashmi K. Murthy, Eric P. Winer, Carey K. Anders, Jean J. Zhao, and Nancy U. Lin

Subjects
Cancer Research, Immunoconjugates, Receptor, ErbB-2, Brain Neoplasms, Breast Neoplasms, Trastuzumab, Antibodies, Monoclonal, Humanized, Article, Cohort Studies, Treatment Outcome, Oncology, Humans, Female, Camptothecin, Prospective Studies, Retrospective Studies
Abstract

Purpose: Brain metastases can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from previous pivotal clinical trials, the central nervous system (CNS) activity of the antibody–drug conjugate trastuzumab deruxtecan (T-DXd) is not well characterized. Experimental Design: We studied how T-DXd affects growth and overall survival in orthotopic patient-derived xenografts (PDX) of HER2-positive and HER2-low breast cancer brain metastases (BCBM). Separately, we evaluated the effects of T-DXd in a retrospective cohort study of 17 patients with stable or active brain metastases. Results: T-DXd inhibited tumor growth and prolonged survival in orthotopic PDX models of HER2-positive (IHC 3+) and HER2-low (IHC 2+/FISH ratio < 2) BCBMs. T-DXd reduced tumor size and prolonged survival in a T-DM1–resistant HER2-positive BCBM PDX model. In a retrospective multi-institutional cohort study of 17 patients with predominantly HER2-positive BCBMs, the CNS objective response rate (ORR) was 73% (11/15) while extracranial response rate was 45% (5/11). In the subset of patients with untreated or progressive BCBM at baseline, the CNS ORR was 70% (7/10). The median time on treatment with T-DXd was 8.9 (1.3–16.2) months, with 42% (7/17) remaining on treatment at data cutoff. Conclusions: T-DXd demonstrates evidence of CNS activity in HER2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM. Prospective clinical trials to further evaluate CNS activity of T-DXd in patients with active brain metastases are warranted. See related commentary by Soffietti and Pellerino, p. 8

Published
2022

3. A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer

Author

Agostina Nardone, Xintao Qiu, Sandor Spisak, Zsuzsanna Nagy, Ariel Feiglin, Avery Feit, Gabriela Cohen Feit, Yingtian Xie, Alba Font-Tello, Cristina Guarducci, Francisco Hermida-Prado, Sudeepa Syamala, Klothilda Lim, Miguel Munoz Gomez, Matthew Pun, MacIntosh Cornwell, Weihan Liu, Aysegul Ors, Hisham Mohammed, Paloma Cejas, Jane B. Brock, Matthew L. Freedman, Eric P. Winer, Xiaoyong Fu, Rachel Schiff, Henry W. Long, Otto Metzger Filho, and Rinath Jeselsohn

Subjects
Carcinoma, Lobular, Tamoxifen, Cancer Research, Receptors, Estrogen, Oncology, Drug Resistance, Neoplasm, Carcinoma, Ductal, Breast, Humans, Breast Neoplasms, Female, Prognosis, Chromatin, Article
Abstract

Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor–positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1–estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1–ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1–ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype. Significance: A unique FOXA1–ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668

Published
2022

4. Supplemental Figure 9 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S9

Published
2023

5. Data from Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial

Author

Jeffrey A. Meyerhardt, Charles S. Fuchs, Frank B. Hu, Pamela S. Douglas, Tara Sanft, Thomas A. Abrams, Kimmie Ng, Eric P. Winer, Sara M. Tolaney, Maura Harrigan, Brenda Cartmel, Alexandra Sorrentino, Michael N. Pollak, Nancy Campbell, Lee W. Jones, Melinda L. Irwin, Jennifer A. Ligibel, Sui Zhang, and Justin C. Brown

Abstract

Observational studies report that physical activity and metformin are associated with improved clinical outcome in patients with cancer. Inflammation is one biological mechanism hypothesized to mediate these associations. In this phase II, multicenter, 2 × 2 factorial trial, 139 patients with breast and colorectal cancer who completed standard therapy were randomized to one of four treatment groups for 12 weeks: exercise alone, metformin alone, exercise and metformin, or control. Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), soluble tumor necrosis factor alpha receptor two (sTNFαR2), and IL6. The primary modeling strategy evaluated the trial product estimand that was quantified using a generalized linear mixed model. Compared with control, exercise alone reduced hs-CRP [−30.2%; 95% confidence interval (CI), −50.3, −1.0] and IL6 (−30.9%; 95% CI, −47.3, −9.5) but did not change sTNFαR2 (1.0%; 95% CI, −10.4, 13.9). Compared with control, metformin alone did not change hs-CRP (−13.9%; 95% CI, −40.0, 23.4), sTNFαR2 (−10.4%; 95% CI, −21.3, 2.0), or IL6 (−22.9%; 95% CI, −42.3, 2.0). Compared with control, exercise and metformin reduced sTNFαR2 (−13.1%; 95% CI, −22.9, −1.0) and IL6 (−38.7%; 95% CI, −52.3, −18.9) but did not change hs-CRP (−20.5%; 95% CI, −44.0, 12.7). The combination of exercise and metformin was not synergistic for hs-CRP, sTNFαR2, or IL6. In survivors of breast and colorectal cancer with low baseline physical activity and without type 2 diabetes, exercise and metformin reduced measures of inflammation that are associated with cancer recurrence and mortality.

Published
2023

6. Supplementary Fig. S1 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Pattern of HER2 amplification in the subset of HER2 heterogeneous tumors. Heatmap generated using data from central pathology evaluation of HER2 heterogeneity. The graphic includes patients classified as HER2 heterogeneous depicted in each row. The color code to the right of the heatmap refers to the percentage of HER2 amplified cells per core biopsy tumor area. Core biopsy tumor areas, A, B and C were obtained from core biopsy site 1 and D, E and F from core biopsy site 2.

Published
2023

7. Data from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Mechanisms driving resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor–positive (HR+) breast cancer have not been clearly defined. Whole-exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate resistance mechanisms including RB1 loss, activating alterations in AKT1, RAS, AURKA, CCNE2, ERBB2, and FGFR2, and loss of estrogen receptor expression. In vitro experiments confirmed that these alterations conferred CDK4/6i resistance. Cancer cells cultured to resistance with CDK4/6i also acquired RB1, KRAS, AURKA, or CCNE2 alterations, which conferred sensitivity to AURKA, ERK, or CHEK1 inhibition. Three of these activating alterations—in AKT1, RAS, and AURKA—have not, to our knowledge, been previously demonstrated as mechanisms of resistance to CDK4/6i in breast cancer preclinically or in patient samples. Together, these eight mechanisms were present in 66% of resistant tumors profiled and may define therapeutic opportunities in patients.Significance:We identified eight distinct mechanisms of resistance to CDK4/6i present in 66% of resistant tumors profiled. Most of these have a therapeutic strategy to overcome or prevent resistance in these tumors. Taken together, these findings have critical implications related to the potential utility of precision-based approaches to overcome resistance in many patients with HR+ metastatic breast cancer.This article is highlighted in the In This Issue feature, p. 1079

Published
2023

8. Supplementary Table S2 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

FISH raw counts

Published
2023

9. Supplementary Fig. S4 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Relationship between ERBB2 copy number and pCR. A, Median HER2/CEP17 ratio for the overall population acording to pCR results. P-value is from a Wilcoxon test. B, Median HER2/CEP17 ratio for the hormone receptor-positive and hormone receptor-negative subsets according to pCR results. P-value is from a Wilcoxon test. C, Median HER2/CEP17 ratio for each of the six core biopsy areas from each tumor and association with pCR. A-C, Red represents patients without pCR, and blue represents patients with pCR.

Published
2023

10. Supplementary Table S4 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Logistic Regression Results

Published
2023

11. Supplemental Figure 8 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S8

Published
2023

12. Supplementary Table S3 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets

Author

William C. Hahn, Gad Getz, David N. Louis, José Baselga, Tracy T. Batchelor, Rameen Beroukhim, Eric S. Lander, Stacey Gabriel, Levi Garraway, Matthew Meyerson, Anat Stemmer-Rachamimov, Eric P. Winer, Nancy U. Lin, Michael S. Rabin, Carrie Sougnez, Sabina Signoretti, Toni K. Choueiri, Mai P. Hoang, Bruce E. Johnson, Aaron R. Thorner, Paul Van Hummelen, Corey M. Gill, Frederick G. Barker, Mara Rosenberg, Aaron Chevalier, Aaron McKenna, Sung-Hye Park, Sun Ha Paek, Ian F. Dunn, William T. Curry, Elena Martinez-Saez, Joan Seoane, Josep Tabernero, Keith L. Ligon, Kristian Cibulskis, Peleg M. Horowitz, Michael S. Lawrence, Eliezer M. Van Allen, Robert T. Jones, Amaro Taylor-Weiner, Daniel P. Cahill, Sandro Santagata, Scott L. Carter, and Priscilla K. Brastianos

Abstract

Summary of clinically informative (TARGET) genes.

Published
2023

13. Supplemental Figure 5 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S5

Published
2023

14. Supplemental Figure 4 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S4

Published
2023

15. Supplementary Methods, Figures S1 - S20 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets

Author

William C. Hahn, Gad Getz, David N. Louis, José Baselga, Tracy T. Batchelor, Rameen Beroukhim, Eric S. Lander, Stacey Gabriel, Levi Garraway, Matthew Meyerson, Anat Stemmer-Rachamimov, Eric P. Winer, Nancy U. Lin, Michael S. Rabin, Carrie Sougnez, Sabina Signoretti, Toni K. Choueiri, Mai P. Hoang, Bruce E. Johnson, Aaron R. Thorner, Paul Van Hummelen, Corey M. Gill, Frederick G. Barker, Mara Rosenberg, Aaron Chevalier, Aaron McKenna, Sung-Hye Park, Sun Ha Paek, Ian F. Dunn, William T. Curry, Elena Martinez-Saez, Joan Seoane, Josep Tabernero, Keith L. Ligon, Kristian Cibulskis, Peleg M. Horowitz, Michael S. Lawrence, Eliezer M. Van Allen, Robert T. Jones, Amaro Taylor-Weiner, Daniel P. Cahill, Sandro Santagata, Scott L. Carter, and Priscilla K. Brastianos

Abstract

Supplementary Methods, Figures S1 - S20. Figure S1. Branched evolution leads to tissue-sampling bias in primary tumor samples. Figure S2. Results of ABSOLUTE on samples from patient 418. Figure S3. 2D Bayesian clustering analysis of point-mutation CCF distributions in case 418. Figure S4. Bayesian clustering of private point-mutation CCF distributions in all sequenced tissue samples from case 418. Figure S5. Genetic alterations supporting phylogeny construction in case 418. Figure S6. Phylogenetic tree for case 418 Figure S7. Evolutionary relationships between primary tumor-samples and brain metastasis samples Figure S8. Detection of homozygous deletion in CDKN2A in the brain metastasis of case 24. Figure S9. Amplification of FGFR1 and MYC detected in the brain metastasis of case 331. Figure S10. Additional alterations under investigation for association with various targeted therapies. Figure S11. Power for paired-detection of somatic mutations. Figure S12. Amplification of CCNE1 detected in the brain metastasis of case 314. Figure S13. Amplification of EGFR detected in the brain metastasis of case 314. Figure S14. Amplification of MYC detected in the brain metastasis of case 308. Figure S15. Amplification of MYC detected in the brain metastasis of case 138. Figure S16. Amplifications of CDK6 and MET detected in the brain metastasis of case 138. Figure S17. Amplifications of CCNE1 and AKT2 detected in the brain metastasis of case 138. Figure S18. Amplification of EGFR detected in a regional lymph node from case 296. Figure S19. Power for somatic mutation detection in 86 matched primary-tumor and brain-metastasis samples. Figure S20. Calling of amplifications in primary-tumor samples and paired brain metastases.

Published
2023

16. Supplemental Table 1 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 1

Published
2023

17. Supplemental Figure 7 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S7

Published
2023

18. Supplemental Table 2 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 2

Published
2023

19. Supplementary Table S1 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

List of all AEs

Published
2023

20. Supplemental Figure 10 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S10

Published
2023

21. Supplemental Table 5 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 5

Published
2023

22. Supplemental Table 7 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 7

Published
2023

23. Supplemental Table 4 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 4

Published
2023

24. Supplementary File 1 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets

Author

William C. Hahn, Gad Getz, David N. Louis, José Baselga, Tracy T. Batchelor, Rameen Beroukhim, Eric S. Lander, Stacey Gabriel, Levi Garraway, Matthew Meyerson, Anat Stemmer-Rachamimov, Eric P. Winer, Nancy U. Lin, Michael S. Rabin, Carrie Sougnez, Sabina Signoretti, Toni K. Choueiri, Mai P. Hoang, Bruce E. Johnson, Aaron R. Thorner, Paul Van Hummelen, Corey M. Gill, Frederick G. Barker, Mara Rosenberg, Aaron Chevalier, Aaron McKenna, Sung-Hye Park, Sun Ha Paek, Ian F. Dunn, William T. Curry, Elena Martinez-Saez, Joan Seoane, Josep Tabernero, Keith L. Ligon, Kristian Cibulskis, Peleg M. Horowitz, Michael S. Lawrence, Eliezer M. Van Allen, Robert T. Jones, Amaro Taylor-Weiner, Daniel P. Cahill, Sandro Santagata, Scott L. Carter, and Priscilla K. Brastianos

Abstract

Supplementary File 1. Power for detection of somatic point mutations in coding exons of TARGET genes. The description for the plots in Supplementary File 1 can be found in the Legend of Supplementary Figure S1.

Published
2023

25. Supplementary Fig. S3 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Assessment of spatial HER2 heterogeneity. A, The maximum area fraction of HER2 non-amplified cells in each patient. P-value is from a Wilcoxon test. The lower and upper hinges correspond to the 1st and 3rd quartiles, respectively. The lower and upper whiskers extend to the smallest and largest values, respectively, no further than 1.5*IQR from the hinge, where the IQR is the distance between the 1st and 3rd quartiles. All data points are plotted. B, Association between the minimum and maximum area fractions of HER2 non-amplified cells in each patient. R and p-value are from a Pearson correlation test of association. C, Asso-ciation between the overall and minimum area fractions of HER2 non-amplified cells in each patient. R and p-value are from a Pearson correlation test of association. D, Association between the overall and maximum area frequencies of HER2 non-amplified cells in each patient. R and p-value are from a Pearson correlation test of association. A-D, Red represents patients without pCR and blue represents patients with pCR.

Published
2023

26. Data from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Intratumor heterogeneity is postulated to cause therapeutic resistance. To prospectively assess the impact of HER2 (ERBB2) heterogeneity on response to HER2-targeted therapy, we treated 164 patients with centrally confirmed HER2-positive early-stage breast cancer with neoadjuvant trastuzumab emtansine plus pertuzumab. HER2 heterogeneity was assessed on pretreatment biopsies from two locations of each tumor. HER2 heterogeneity, defined as an area with ERBB2 amplification in >5% but P < 0.0001, adjusted for hormone receptor status). Single-cell ERBB2 FISH analysis of cellular heterogeneity identified the fraction of ERBB2 nonamplified cells as a driver of therapeutic resistance. These data suggest HER2 heterogeneity is associated with resistance to HER2-targeted therapy and should be considered in efforts to optimize treatment strategies.Significance:HER2-targeted therapies improve cure rates in HER2-positive breast cancer, suggesting chemotherapy can be avoided in a subset of patients. We show that HER2 heterogeneity, particularly the fraction of ERBB2 nonamplified cancer cells, is a strong predictor of resistance to HER2 therapies and could potentially be used to optimize treatment selection.See related commentary by Okines and Turner, p. 2369.This article is highlighted in the In This Issue feature, p. 2355

Published
2023

27. Supplementary Table S2 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets

Author

William C. Hahn, Gad Getz, David N. Louis, José Baselga, Tracy T. Batchelor, Rameen Beroukhim, Eric S. Lander, Stacey Gabriel, Levi Garraway, Matthew Meyerson, Anat Stemmer-Rachamimov, Eric P. Winer, Nancy U. Lin, Michael S. Rabin, Carrie Sougnez, Sabina Signoretti, Toni K. Choueiri, Mai P. Hoang, Bruce E. Johnson, Aaron R. Thorner, Paul Van Hummelen, Corey M. Gill, Frederick G. Barker, Mara Rosenberg, Aaron Chevalier, Aaron McKenna, Sung-Hye Park, Sun Ha Paek, Ian F. Dunn, William T. Curry, Elena Martinez-Saez, Joan Seoane, Josep Tabernero, Keith L. Ligon, Kristian Cibulskis, Peleg M. Horowitz, Michael S. Lawrence, Eliezer M. Van Allen, Robert T. Jones, Amaro Taylor-Weiner, Daniel P. Cahill, Sandro Santagata, Scott L. Carter, and Priscilla K. Brastianos

Abstract

Data describing results of deep targeted sequencing.

Published
2023

28. Supplementary Fig. S6 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Logistic regression model calibration. A, Model 1. B, Model 2. C, Model 3. D, Model 4. E, Model 5. F, Model 6. G, Model 7. A-G, Calibration curves with summary statistics. Dxy is the Somer's rank correlation between the predicted and observed values; C (ROC) is the area under the curve; R2 is the Nagelkerke-Cox-Snell-Maddala-Magee R-squared index; D is the discrimination index; U is the Unreliability index; Q is the Quality index; the Brier score is the average squared difference in the predicted and observed values; Emax is the maximum absolute difference in predicted and loess-calibrated probabili-ties; Eavg is the average absolute difference in predicted and loess-calibrated probabilities; E90 is the 0.9 quantile of the absolute difference in predicted and loess-calibrated probabilities; S:z and S:p are the Spiegelhalter Z-test for calibration accuracy and its two-tailed p-value.

Published
2023

29. Supplementary Fig. S5 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Predicting pathological complete response (pCR) from single cell HER2 FISH and clinical data. A, Receiver operating characteristic (ROC) curves for the prediction models using the frequency of HER2 unamplified cells to predict pathological response. Blue: the model results using all patients, green: model results for the subet of hormone receptor positive cases, and orange: model results for the subset of hormone receptor negative cases. AUC is the area under the corresponding ROC curve. B, ROC curves for the logistic regression models 1 (blue), 2 (orange), 3 (green), 4 (red), 5 (purple), 6 (brown), 7 (pink) to predict pathological response. AUC is the area under the corresponding ROC curve.

Published
2023

30. Supplementary Tables 1 and 2 from Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial

Author

Jeffrey A. Meyerhardt, Charles S. Fuchs, Frank B. Hu, Pamela S. Douglas, Tara Sanft, Thomas A. Abrams, Kimmie Ng, Eric P. Winer, Sara M. Tolaney, Maura Harrigan, Brenda Cartmel, Alexandra Sorrentino, Michael N. Pollak, Nancy Campbell, Lee W. Jones, Melinda L. Irwin, Jennifer A. Ligibel, Sui Zhang, and Justin C. Brown

Abstract

Supplementary Tables 1 and 2

Published
2023

31. Supplemental Figure 3 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S3

Published
2023

32. Supplemental Figure 2 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S2

Published
2023

33. Supplemental Figure 1 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S1

Published
2023

34. Supplementary Fig. S2 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

Assessment of HER2 copy number dispersion. A, The Gini coefficient measuring the dispersion of HER2/CEP17 ratio in each patient. P-value is from a Kolmogorov-Smirnov test. B, Association between the Gini coefficient and Shan-non equitability index in each patient. R and p-value are from a Pearson correlation test of association. C, Association between the Gini coefficient and percent of HER2 non-amplified cells in each patient. R and p-value are from a Pearson correlation test of association. A-C, Red represents patients without pCR and blue represents patients with pCR.

Published
2023

35. Supplementary File 3 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets

Author

William C. Hahn, Gad Getz, David N. Louis, José Baselga, Tracy T. Batchelor, Rameen Beroukhim, Eric S. Lander, Stacey Gabriel, Levi Garraway, Matthew Meyerson, Anat Stemmer-Rachamimov, Eric P. Winer, Nancy U. Lin, Michael S. Rabin, Carrie Sougnez, Sabina Signoretti, Toni K. Choueiri, Mai P. Hoang, Bruce E. Johnson, Aaron R. Thorner, Paul Van Hummelen, Corey M. Gill, Frederick G. Barker, Mara Rosenberg, Aaron Chevalier, Aaron McKenna, Sung-Hye Park, Sun Ha Paek, Ian F. Dunn, William T. Curry, Elena Martinez-Saez, Joan Seoane, Josep Tabernero, Keith L. Ligon, Kristian Cibulskis, Peleg M. Horowitz, Michael S. Lawrence, Eliezer M. Van Allen, Robert T. Jones, Amaro Taylor-Weiner, Daniel P. Cahill, Sandro Santagata, Scott L. Carter, and Priscilla K. Brastianos

Abstract

Supplementary File 3. Detailed plots of the data used for phylogenetic inference in each case. The description for the plots in Supplementary File 3 can be found in the Legend of Supplementary Figure S13-S17.

Published
2023

36. Supplementary Table S1 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets

Author

William C. Hahn, Gad Getz, David N. Louis, José Baselga, Tracy T. Batchelor, Rameen Beroukhim, Eric S. Lander, Stacey Gabriel, Levi Garraway, Matthew Meyerson, Anat Stemmer-Rachamimov, Eric P. Winer, Nancy U. Lin, Michael S. Rabin, Carrie Sougnez, Sabina Signoretti, Toni K. Choueiri, Mai P. Hoang, Bruce E. Johnson, Aaron R. Thorner, Paul Van Hummelen, Corey M. Gill, Frederick G. Barker, Mara Rosenberg, Aaron Chevalier, Aaron McKenna, Sung-Hye Park, Sun Ha Paek, Ian F. Dunn, William T. Curry, Elena Martinez-Saez, Joan Seoane, Josep Tabernero, Keith L. Ligon, Kristian Cibulskis, Peleg M. Horowitz, Michael S. Lawrence, Eliezer M. Van Allen, Robert T. Jones, Amaro Taylor-Weiner, Daniel P. Cahill, Sandro Santagata, Scott L. Carter, and Priscilla K. Brastianos

Abstract

Clinical characteristics of the 86 patients.

Published
2023

37. Supplementary Data from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplementary material

Published
2023

38. Supplementary File 2 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets

Author

William C. Hahn, Gad Getz, David N. Louis, José Baselga, Tracy T. Batchelor, Rameen Beroukhim, Eric S. Lander, Stacey Gabriel, Levi Garraway, Matthew Meyerson, Anat Stemmer-Rachamimov, Eric P. Winer, Nancy U. Lin, Michael S. Rabin, Carrie Sougnez, Sabina Signoretti, Toni K. Choueiri, Mai P. Hoang, Bruce E. Johnson, Aaron R. Thorner, Paul Van Hummelen, Corey M. Gill, Frederick G. Barker, Mara Rosenberg, Aaron Chevalier, Aaron McKenna, Sung-Hye Park, Sun Ha Paek, Ian F. Dunn, William T. Curry, Elena Martinez-Saez, Joan Seoane, Josep Tabernero, Keith L. Ligon, Kristian Cibulskis, Peleg M. Horowitz, Michael S. Lawrence, Eliezer M. Van Allen, Robert T. Jones, Amaro Taylor-Weiner, Daniel P. Cahill, Sandro Santagata, Scott L. Carter, and Priscilla K. Brastianos

Abstract

Supplementary File 2. Detailed plots of SCNA calls in TARGET genes. The description for the plots in Supplementary File 2 can be found in the Legend of Supplementary Figure S3.

Published
2023

39. Supplemental Figure 6 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Figure S6

Published
2023

40. Supplemental Table 8 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 8

Published
2023

41. Supplemental Table 3 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 3

Published
2023

42. Supplemental Table 6 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer

Author

Nikhil Wagle, Sean G. Buchanan, Nancy U. Lin, Sara M. Tolaney, Eric P. Winer, Levi A. Garraway, Jill D. Kremer, Melissa E. Hughes, Gerald Batist, Quincy S. Chu, Gerard J. Oakley, Patricia S. Smith, John R. Stille, Valerie M. Jansen, Chunping Yu, Xiang S. Ye, Lacey M. Litchfield, Ricardo Martinez, Stephen H. Parsons, Adrienne G. Waks, Utthara Nayar, Kailey J. Kowalski, Karla Helvie, Pingping Mao, Flora Luo, Dewey Kim, Maxwell R. Lloyd, Jorge E. Buendia-Buendia, Gabriela N. Johnson, Xueqian Gong, Ofir Cohen, and Seth A. Wander

Abstract

Supplemental Table 6

Published
2023

43. Supplementary Table S3 from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab

Author

Ian E. Krop, Eric P. Winer, Franziska Michor, Kornelia Polyak, Tari A. King, Leila Russo, Patrizia Dell'Orto, Aditya Bardia, Michelle K. DeMeo, Eileen Wrabel, Adrienne G. Waks, Laura M. Spring, Carlos L. Arteaga, Vandana G. Abramson, Ingrid A. Mayer, Denise A. Yardley, Lorenzo Trippa, Shayna Stein, Giuseppe Viale, and Otto Metzger Filho

Abstract

HER2 counting at a single cell level

Published
2023

44. Supplementary Figure from Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers

Author

Gerburg M. Wulf, Peter J. Park, Hans P. Eikesdal, Helen Won, David B. Solit, Panagiotis A. Konstantinopoulos, Ursula A. Matulonis, Per E. Lønning, Stian Knappskog, Erica L. Mayer, Eric P. Winer, Nadine M. Tung, Nabihah Tayob, Niya Xiong, Madeline Polak, Antuan Tran, Victor Mao, Doga C. Gulhan, and Felipe Batalini

Abstract

Supplementary Figure from Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers

Published
2023

45. Supplemental Figure 1 from Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer

Author

Rinath Jeselsohn, Gad Getz, Chip Stewart, Eric P. Winer, Ian E. Krop, Donald P. McDonnell, Nadine Tung, Sara M. Tolaney, Nabihah Tayob, Ignaty Leshchiner, Carrie Cibulskis, Niall J. Lennon, Candace Patterson, Agostina Nardone, Rebecca Rees, Leilani Anderson, Douglas Russo, Tim Coorens, Albert Grinshpun, Tianyu Li, and Junko Tsuji

Abstract

Supplemental Figure 1: Consort diagram

Published
2023

46. Data from Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers

Author

Gerburg M. Wulf, Peter J. Park, Hans P. Eikesdal, Helen Won, David B. Solit, Panagiotis A. Konstantinopoulos, Ursula A. Matulonis, Per E. Lønning, Stian Knappskog, Erica L. Mayer, Eric P. Winer, Nadine M. Tung, Nabihah Tayob, Niya Xiong, Madeline Polak, Antuan Tran, Victor Mao, Doga C. Gulhan, and Felipe Batalini

Abstract

Purpose:The identification of patients with homologous recombination deficiency (HRD) beyond BRCA1/2 mutations is an urgent task, as they may benefit from PARP inhibitors. We have previously developed a method to detect mutational signature 3 (Sig3), termed SigMA, associated with HRD from clinical panel sequencing data, that is able to reliably detect HRD from the limited sequencing data derived from gene-focused panel sequencing.Experimental Design:We apply this method to patients from two independent datasets: (i) high-grade serous ovarian cancer and triple-negative breast cancer (TNBC) from a phase Ib trial of the PARP inhibitor olaparib in combination with the PI3K inhibitor buparlisib (BKM120; NCT01623349), and (ii) TNBC patients who received neoadjuvant olaparib in the phase II PETREMAC trial (NCT02624973).Results:We find that Sig3 as detected by SigMA is positively associated with improved progression-free survival and objective responses. In addition, comparison of Sig3 detection in panel and exome-sequencing data from the same patient samples demonstrated highly concordant results and superior performance in comparison with the genomic instability score.Conclusions:Our analyses demonstrate that HRD can be detected reliably from panel-sequencing data that are obtained as part of routine clinical care, and that this approach can identify patients beyond those with germline BRCA1/2mut who might benefit from PARP inhibitors. Prospective clinical utility testing is warranted.

Published
2023

47. Supplementary Data from Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer

Author

Rinath Jeselsohn, Gad Getz, Chip Stewart, Eric P. Winer, Ian E. Krop, Donald P. McDonnell, Nadine Tung, Sara M. Tolaney, Nabihah Tayob, Ignaty Leshchiner, Carrie Cibulskis, Niall J. Lennon, Candace Patterson, Agostina Nardone, Rebecca Rees, Leilani Anderson, Douglas Russo, Tim Coorens, Albert Grinshpun, Tianyu Li, and Junko Tsuji

Abstract

Supplementary tables 1-4 and supplementary figure legend

Published
2023

48. Data from Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases

Author

Nancy U. Lin, Jean J. Zhao, Carey K. Anders, Eric P. Winer, Rashmi K. Murthy, Maria Gule-Monroe, Akshara S. Raghavendra, Melissa Hughes, Heather Moore, Chris Lascola, Pamela J. DiPiro, Liangge Hsu, Alyssa Pereslete, Yanzhi Wang, Amanda E.D. Van Swearingen, Tianyu Li, Sarah Sammons, Jing Ni, and Sheheryar Kabraji

Abstract

Purpose:Brain metastases can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from previous pivotal clinical trials, the central nervous system (CNS) activity of the antibody–drug conjugate trastuzumab deruxtecan (T-DXd) is not well characterized.Experimental Design:We studied how T-DXd affects growth and overall survival in orthotopic patient-derived xenografts (PDX) of HER2-positive and HER2-low breast cancer brain metastases (BCBM). Separately, we evaluated the effects of T-DXd in a retrospective cohort study of 17 patients with stable or active brain metastases.Results:T-DXd inhibited tumor growth and prolonged survival in orthotopic PDX models of HER2-positive (IHC 3+) and HER2-low (IHC 2+/FISH ratio < 2) BCBMs. T-DXd reduced tumor size and prolonged survival in a T-DM1–resistant HER2-positive BCBM PDX model. In a retrospective multi-institutional cohort study of 17 patients with predominantly HER2-positive BCBMs, the CNS objective response rate (ORR) was 73% (11/15) while extracranial response rate was 45% (5/11). In the subset of patients with untreated or progressive BCBM at baseline, the CNS ORR was 70% (7/10). The median time on treatment with T-DXd was 8.9 (1.3–16.2) months, with 42% (7/17) remaining on treatment at data cutoff.Conclusions:T-DXd demonstrates evidence of CNS activity in HER2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM. Prospective clinical trials to further evaluate CNS activity of T-DXd in patients with active brain metastases are warranted.See related commentary by Soffietti and Pellerino, p. 8

Published
2023

50. Supplemental Figure 5 from Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer

Author

Rinath Jeselsohn, Gad Getz, Chip Stewart, Eric P. Winer, Ian E. Krop, Donald P. McDonnell, Nadine Tung, Sara M. Tolaney, Nabihah Tayob, Ignaty Leshchiner, Carrie Cibulskis, Niall J. Lennon, Candace Patterson, Agostina Nardone, Rebecca Rees, Leilani Anderson, Douglas Russo, Tim Coorens, Albert Grinshpun, Tianyu Li, and Junko Tsuji

Abstract

Supplemental Figure 5: SSNVs detected in the cancer-related genes across 68 ctDNA WES samples

Published
2023

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