Pathologic complete response (pCR) rates for patients with HRD/HER2L high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial

被引:3
作者
Huppert, L. A. [1 ]
Wolf, D. [2 ]
Yau, C. [3 ]
Brown-Swigart, L. [2 ]
Hirst, G. L. [3 ]
Isaacs, C. [4 ]
Pusztai, L. [5 ]
Pohlmann, P. R. [6 ]
Demichele, A. [7 ]
Shatsky, R. [8 ]
Yee, D. [9 ]
Thomas, A. [10 ]
Nanda, R. [11 ]
Perlmutter, J.
Heditsian, D.
Hylton, N. [3 ,12 ]
Symmans, F. [4 ,13 ]
van't Veer, L. J. [2 ]
Esserman, L. [2 ]
Rugo, H. S. [1 ]
机构
[1] Univ Calif San Francisco, Dept Med, 1825 Fourth St, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA USA
[3] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA
[4] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA
[5] Yale Univ, Yale Sch Med, New Haven, CT USA
[6] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Div Canc Med, Houston, TX USA
[7] Univ Penn, Perelman Sch Med, Philadelphia, PA USA
[8] Univ Calif San Diego, Div Hematol & Oncol, San Diego, CA 92037 USA
[9] Univ Minnesota, Div Hematol Oncol & Transplantat, Minneapolis, MN USA
[10] Duke Univ, Med Ctr, Durham, NC 27710 USA
[11] Univ Chicago, Sect Hematol Oncol, Chicago, IL USA
[12] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA
[13] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA
关键词
neoadjuvant therapy; molecular subtype; luminal; basal; MammaPrint; intrinsic subtype; NEOADJUVANT CHEMOTHERAPY; ADAPTIVE RANDOMIZATION; POSTMENOPAUSAL WOMEN; INTRINSIC SUBTYPES; LETROZOLE;
D O I
10.1016/j.annonc.2024.10.018
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (EBC) is a heterogenous disease. Identification of better clinical and molecular biomarkers is essential to guide optimal therapy for each patient. Patients and methods: We analyzed rates of pathologic complete response (pCR) and distant recurrence-free survival (DRFS) for patients with HR+/HER2-negative EBC in eight neoadjuvant arms in the I-SPY2 trial by clinical/molecular features: age, stage, histology, percentage estrogen receptor (ER) positivity, ER/progesterone receptor status, MammaPrint (MP)-High1 (0 to-0.57) versus MP-High2 (<-0.57), BluePrint (BP)-Luminal-type versus BP-Basal-type, and ImPrint immune signature. We quantified the clinical/molecular heterogeneity, assessed overlap among these biomarkers, and evaluated associations with pCR and DRFS. Results: Three hundred and seventy-nine patients with HR+/HER2-negative EBC were included in this analysis, with an observed pCR rate of 17% across treatment arms. pCR rates were higher in patients with stage II versus III disease (21% versus 9%, P = 0.0013), ductal versus lobular histology (19% versus 11%, P = 0.049), lower %ER positivity (<66% versus >66%) (35% versus 9%, P = 3.4E-09), MP-High2 versus MP-High1 disease (31% versus 11%, P = 1.1E-05), BP-Basal-type versus BP-Luminal-type disease (34% versus 10%, P = 1.62E-07), and ImPrint-positive versus-negative disease (38% versus 10%, P = 1.64E-09). Patients with lower %ER were more likely to have MP-High2 and BP-Basal-type disease. At a median follow-up of 4.8 years, patients who achieved pCR had excellent outcomes irrespective of clinical/ molecular features. Among patients who did not achieve pCR, DRFS events were more frequent in patients with MP-High2 and BP-Basal-type disease than those with MP-High1 and BP-Luminal-type disease. Conclusions: Among patients with high molecular-risk HR+/HER2-negative EBC, the MP-High2, BP-Basal-type, and ImPrint-positive signatures identified a partially overlapping subset of patients who were more likely to achieve pCR in response to neoadjuvant chemotherapy +/- targeted agents or immunotherapy compared to patients with MPHigh1, BP-Luminal-type, and ImPrint-negative disease. I-SPY2.2 is incorporating the use of these biomarkers to molecularly define specific patient populations and optimize treatment selection.
引用
收藏
页码:172 / 184
页数:13
相关论文
共 42 条
[1]   Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery [J].
Albain, Kathy S. ;
Yau, Christina ;
Petricoin, Emanuel F. ;
Wolf, Denise M. ;
Lang, Julie E. ;
Chien, A. Jo ;
Haddad, Tufia ;
Forero-Torres, Andres ;
Wallace, Anne M. ;
Kaplan, Henry ;
Pusztai, Lajos ;
Euhus, David ;
Nanda, Rita ;
Elias, Anthony D. ;
Clark, Amy S. ;
Godellas, Constantine ;
Boughey, Judy C. ;
Isaacs, Claudine ;
Tripathy, Debu ;
Lu, Janice ;
Yung, Rachel L. ;
Gallagher, Rosa I. ;
Wulfkuhle, Julia D. ;
Brown-Swigart, Lamorna ;
Krings, Gregor ;
Chen, Yunn Yi ;
Potter, David A. ;
Stringer-Reasor, Erica ;
Blair, Sarah ;
Asare, Smita M. ;
Wilson, Amy ;
Hirst, Gillian L. ;
Singhrao, Ruby ;
Buxton, Meredith ;
Clennell, Julia L. ;
Sanil, Ashish ;
Berry, Scott ;
Asare, Adam L. ;
Matthews, Jeffrey B. ;
Demichele, Angela M. ;
Hylton, Nola M. ;
Melisko, Michelle ;
Perlmutter, Jane ;
Rugo, Hope S. ;
Symmans, W. Fraser ;
van't Veer, Laura J. ;
Yee, Douglas ;
Berry, Donald A. ;
Esserman, Laura J. .
CLINICAL CANCER RESEARCH, 2024, 30 (04) :729-740
[2]  
[Anonymous], 2022, NCCN Guidelines Version 1.2022 Breast Cancer Risk Reduction
[3]  
Brown L, 2023, ASCO
[4]  
Cardoso F, 2023, ESMO EUROPEAN SOC ME
[5]   Phase 3 study of neoadjuvant pembrolizumab or placebo plus chemotherapy, followed by adjuvant pembrolizumab or placebo plus endocrine therapy for early-stage high-risk ER+/ HER2-breast cancer: KEYNOTE-756 [J].
Cardoso, Fatima ;
O'Shaughnessy, Joyce ;
McArthur, Heather ;
Schmid, Peter ;
Cortes, Javier ;
Harbeck, Nadia ;
Telli, Melinda ;
Cescon, David ;
Fasching, Peter A. ;
Shao, Zhimin ;
Loirat, Delphine ;
Park, Yeon Hee ;
Fernandez, Manuel Gonzalez ;
Rubovszky, Gabor ;
Im, Seock-Ah ;
Hui, Rina ;
Takano, Toshimi ;
Andre, Fabrice ;
Yasojima, Hiroyuki ;
Liu, Zhenzhen ;
Ding, Yu ;
Jia, Liyi ;
Karantza, Vassiliki ;
Tryfonidis, Konstantinos ;
Bardia, Aditya .
CANCER RESEARCH, 2024, 84 (09)
[6]   MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial [J].
Chien, A. Jo ;
Tripathy, Debasish ;
Albain, Kathy S. ;
Symmans, W. Fraser ;
Rugo, Hope S. ;
Melisko, Michelle E. ;
Wallace, Anne M. ;
Schwab, Richard ;
Helsten, Teresa ;
Forero-Torres, Andres ;
Stringer-Reasor, Erica ;
Ellis, Erin D. ;
Kaplan, Henry G. ;
Nanda, Rita ;
Jaskowiak, Nora ;
Murthy, Rashmi ;
Godellas, Constantine ;
Boughey, Judy C. ;
Elias, Anthony D. ;
Haley, Barbara B. ;
Kemmer, Kathleen ;
Isaacs, Claudine ;
Clark, Amy S. ;
Lang, Julie E. ;
Lu, Janice ;
Korde, Larissa ;
Edmiston, Kirsten K. ;
Northfelt, Donald W. ;
Viscusi, Rebecca K. ;
Yee, Douglas ;
Perlmutter, Jane ;
Hylton, Nola M. ;
van't Veer, Laura J. ;
DeMichele, Angela ;
Wilson, Amy ;
Peterson, Garry ;
Buxton, Meredith B. ;
Paoloni, Melissa ;
Clennell, Julia ;
Berry, Scott ;
Matthews, Jeffrey B. ;
Steeg, Katherine ;
Singhrao, Ruby ;
Hirst, Gillian L. ;
Sanil, Ashish ;
Yau, Christina ;
Asare, Smita M. ;
Berry, Donald A. ;
Esserman, Laura J. .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (10) :1059-+
[7]   Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [J].
Cortazar, Patricia ;
Zhang, Lijun ;
Untch, Michael ;
Mehta, Keyur ;
Costantino, Joseph P. ;
Wolmark, Norman ;
Bonnefoi, Herve ;
Cameron, David ;
Gianni, Luca ;
Valagussa, Pinuccia ;
Swain, Sandra M. ;
Prowell, Tatiana ;
Loibl, Sibylle ;
Wickerham, D. Lawrence ;
Bogaerts, Jan ;
Baselga, Jose ;
Perou, Charles ;
Blumenthal, Gideon ;
Blohmer, Jens ;
Mamounas, Eleftherios P. ;
Bergh, Jonas ;
Semiglazov, Vladimir ;
Justice, Robert ;
Eidtmann, Holger ;
Paik, Soonmyung ;
Piccart, Martine ;
Sridhara, Rajeshwari ;
Fasching, Peter A. ;
Slaets, Leen ;
Tang, Shenghui ;
Gerber, Bernd ;
Geyer, Charles E., Jr. ;
Pazdur, Richard ;
Ditsch, Nina ;
Rastogi, Priya ;
Eiermann, Wolfgang ;
von Minckwitz, Gunter .
LANCET, 2014, 384 (9938) :164-172
[8]   The Neoadjuvant Model Is Still the Future for Drug Development in Breast Cancer [J].
DeMichele, Angela ;
Yee, Douglas ;
Berry, Donald A. ;
Albain, Kathy S. ;
Benz, Christopher C. ;
Boughey, Judy ;
Buxton, Meredith ;
Chia, Stephen K. ;
Chien, Amy J. ;
Chui, Stephen Y. ;
Clark, Amy ;
Edmiston, Kirsten ;
Elias, Anthony D. ;
Forero-Torres, Andres ;
Haddad, Tufia C. ;
Haley, Barbara ;
Haluska, Paul ;
Hylton, Nola M. ;
Isaacs, Claudine ;
Kaplan, Henry ;
Korde, Larissa ;
Leyland-Jones, Brian ;
Liu, Minetta C. ;
Melisko, Michelle ;
Minton, Susan E. ;
Moulder, Stacy L. ;
Nanda, Rita ;
Olopade, Olufunmilayo I. ;
Paoloni, Melissa ;
Park, John W. ;
Parker, Barbara A. ;
Perlmutter, Jane ;
Petricoin, Emanuel F. ;
Rugo, Hope ;
Symmans, Fraser ;
Tripathy, Debasish ;
Veer, Laura J. Van't ;
Viscusi, Rebecca K. ;
Wallace, Anne ;
Wolf, Denise ;
Yau, Christina ;
Esserman, Laura J. .
CLINICAL CANCER RESEARCH, 2015, 21 (13) :2911-2915
[9]   Randomized Phase II Neoadjuvant Comparison Between Letrozole, Anastrozole, and Exemestane for Postmenopausal Women With Estrogen Receptor-Rich Stage 2 to 3 Breast Cancer: Clinical and Biomarker Outcomes and Predictive Value of the Baseline PAM50-Based Intrinsic Subtype-ACOSOG Z1031 [J].
Ellis, Matthew J. ;
Suman, Vera J. ;
Hoog, Jeremy ;
Lin, Li ;
Snider, Jacqueline ;
Prat, Aleix ;
Parker, Joel S. ;
Luo, Jingqin ;
DeSchryver, Katherine ;
Allred, D. Craig ;
Esserman, Laura J. ;
Unzeitig, Gary W. ;
Margenthaler, Julie ;
Babiera, Gildy V. ;
Marcom, P. Kelly ;
Guenther, Joseph M. ;
Watson, Mark A. ;
Leitch, Marilyn ;
Hunt, Kelly ;
Olson, John A. .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (17) :2342-2349
[10]   Estrogen receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers [J].
Groenendijk, Floris H. ;
Treece, Tina ;
Yoder, Erin ;
Baron, Paul ;
Beitsch, Peter ;
Audeh, William ;
Dinjens, Winand N. M. ;
Bernards, Rene ;
Whitworth, Pat .
NPJ BREAST CANCER, 2019, 5 (1)