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Pathologic complete response and outcomes by intrinsic subtypes in NSABP B-41, a randomized neoadjuvant trial of chemotherapy with trastuzumab, lapatinib, or the combination.
Swain, Sandra M; Tang, Gong; Lucas, Peter C; Robidoux, André; Goerlitz, David; Harris, Brent T; Bandos, Hanna; Geyer, Charles E; Rastogi, Priya; Mamounas, Eleftherios P; Wolmark, Norman.
Afiliação
  • Swain SM; National Surgical Adjuvant Breast and Bowel Project (NSABP), Nova Tower 2, 100 Allegheny Square, Pittsburgh, PA, 15212, USA. sandra.swain@georgetown.edu.
  • Tang G; Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 4000 Reservoir Road NW, 120 Building D, Washington, DC, 20057, USA. sandra.swain@georgetown.edu.
  • Lucas PC; National Surgical Adjuvant Breast and Bowel Project (NSABP), Nova Tower 2, 100 Allegheny Square, Pittsburgh, PA, 15212, USA.
  • Robidoux A; University of Pittsburgh, 4200 Fifth Ave, Pittsburgh, PA, 15260, USA.
  • Goerlitz D; National Surgical Adjuvant Breast and Bowel Project (NSABP), Nova Tower 2, 100 Allegheny Square, Pittsburgh, PA, 15212, USA.
  • Harris BT; University of Pittsburgh, 4200 Fifth Ave, Pittsburgh, PA, 15260, USA.
  • Bandos H; National Surgical Adjuvant Breast and Bowel Project (NSABP), Nova Tower 2, 100 Allegheny Square, Pittsburgh, PA, 15212, USA.
  • Geyer CE; Centre Hospitalier de L'Universite ́ de Montréal, 3840 St Urbain St, Montreal, QC, H2W 1T8, Canada.
  • Rastogi P; Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 4000 Reservoir Road NW, 120 Building D, Washington, DC, 20057, USA.
  • Mamounas EP; Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 4000 Reservoir Road NW, 120 Building D, Washington, DC, 20057, USA.
  • Wolmark N; National Surgical Adjuvant Breast and Bowel Project (NSABP), Nova Tower 2, 100 Allegheny Square, Pittsburgh, PA, 15212, USA.
Breast Cancer Res Treat ; 178(2): 389-399, 2019 Nov.
Article em En | MEDLINE | ID: mdl-31428908
ABSTRACT

PURPOSE:

NSABP B-41, a phase three randomized trial, evaluated neoadjuvant lapatinib, trastuzumab, or the combination with chemotherapy in patients with HER2-positive operable breast cancer. Though no significant difference in pathologic complete response (pCR) was found among the three arms, pCR was associated with prolonged survival. We analyzed tumor intrinsic subtypes with Prediction Analysis of Microarray 50 in a subset of B-41 patients to determine their value in predicting HER2-targeting benefit.

METHODS:

Pearson's Chi square test and logistic regression were used to compare pCR in the breast and nodes (ypT0/Tis ypN0). Kaplan-Meier estimates and Cox models were used to compare event-free and overall survival among subtypes.

RESULTS:

Intrinsic subtypes were determined in 271 baseline core biopsy samples. The pCR rate among patients with HER2-enriched (HER2E) subtype was greater compared to other subtypes combined (120/197, 60.9% versus 19/74, 25.7%; p < 0.001). In multivariate analysis among patients receiving trastuzumab-containing regimens (with clinical factors and HER2E subtype as factors), HER2E subtype was most strongly associated with pCR [OR 8.41 (95% CI 2.52-28.1) p < 0.001]. Patients with HER2E tumors did not benefit more from dual HER2-targeted therapy versus trastuzumab. The pCR rate was higher among HER2E tumors versus other subtypes in both estrogen receptor-positive and -negative tumors (p ≤ 0.001). Higher ESR1 gene expression was associated with lower pCR rate. No association was observed between subtype and long-term outcomes.

CONCLUSION:

Patients with HER2E tumors were most likely to attain pCR versus other subtypes. HER2E subtype represents a favorable marker for predicting HER2-targeting benefit, particularly with trastuzumab-based therapies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica Tipo de estudo: Clinical_trials / Diagnostic_studies / Etiology_studies / Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica Tipo de estudo: Clinical_trials / Diagnostic_studies / Etiology_studies / Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article