Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial

Alba, Emilio; Albanell, Joan; Haba, Juan de la; Barnadas, Agustí; Calvo, Lourdes; Sánchez‐Rovira, Pedro; Ramos, Manuel; Rojo, Federico; Burgués, Octavio; Carrasco, Eva; Caballero, Rosalía; Porras, Ignacio; Tibau, Ariadna; Camara, M.; Lluch, Aña

doi:10.1038/bjc.2013.831

Cited by 61 publications

(56 citation statements)

References 53 publications

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“…In all these trials, patients were treated with anthracycline and taxane-based neoadjuvant chemotherapy; anti-HER2 therapy (trastuzumab or lapatinib) was administered for most patients with HER2 overexpression (Table 1). Detailed descriptions of these trials have been published elsewhere [15][16][17][18][19]. The 262 patients involved represented 73% of the 361 patients participating in the four trials combined.…”

Section: Study Populationmentioning

confidence: 99%

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

Alba

Lluch²,

Ribelles

et al. 2016

The Oncologist

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Background. In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. Patients and Methods. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinicaltrialsofneoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Results. A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 .50% achieved a

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Section: Study Populationmentioning

confidence: 99%

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

Alba

Lluch²,

Ribelles

et al. 2016

The Oncologist

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“…S3). Mechanisms underlying this observation warrant investigation; importantly, these findings have clinical implications, and may explain the superior head-to-head clinical efficacy of trastuzumab versus lapatinib observed in HER2 pos -BC patients (23). …”

Section: Resultsmentioning

confidence: 99%

CD4+ T-Helper Type 1 Cytokines and Trastuzumab Facilitate CD8+ T-cell Targeting of HER2/neu–Expressing Cancers

Datta

Rosemblit

et al. 2015

Cancer Immunology Research

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Vaccination strategies incorporating the immunodominant HLA-A2-restricted HER2/neu-derived peptide 369-377 (HER2369-377) are increasingly utilized in HER2/neu-expressing cancer patients. The failure of post-vaccination HER2369-377-specific CD8+ T cells to recognize HLA-A2posHER2/neu-expressing cells in vitro, however, has been attributed to impaired MHC class I/HLA-A2 presentation observed in HER2/neu-overexpressing tumors. We reconcile this controversy by demonstrating that HER2369-377 is directly recognized by high functional-avidityHER2369-377-specific CD8+ T cells—either genetically modified to express a novel HER2369-377-TCR or sensitized using HER2369-377-pulsed type 1-polarized dendritic cells (DC1)—on class I-abundant HER2low, but not class I-deficient HER2high, cancer cells. Importantly, a critical cooperation between CD4+ T-helper type-1 (Th1) cytokines IFNγ/TNFα and HER2/neu-targeted antibody trastuzumab is necessary to restore class I expression in HER2high cancers, thereby facilitating recognition and lysis of these cells by HER2369-377-specific CD8+ T cells. Concomitant induction of PD-L1 on HER2/neu-expressing cells by IFNγ/TNF and trastuzumab, however, has minimal impact on DC1-sensitized HER2369-377-CD8+ T cell-mediated cytotoxicity. Although activation of EGFR and HER3 signaling significantly abrogates IFNγ/TNFα and trastuzumab-induced class I restoration, EGFR/HER3 receptor blockade rescues class I expression and ensuing HER2369-377-CD8+ cytotoxicity of HER2/neu-expressing cells. Thus, combinations of CD4+ Th1 immune interventions and multivalent targeting of HER family members may be required for optimal anti-HER2/neuCD8+ T cell-directed immunotherapy.

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“…Because we still donot know whether trastuzumab is similarly effective among IBC patients and non-IBC patients, this high proportion of IBC cases should be noted. In previous studies that tested the predictors of trastuzumab response, HR-negative status was revealed to be a predictor of pCR but was also directly associated with poor survival outcomes [10][11][12]. Because we did not know whether the HER2 FISH ratio was a prognostic factor, we included HRpositive patients in the present study.…”

Section: Association Between Her2 Fish Ratio and Survival Outcomementioning

confidence: 99%

High HER2/Centromeric Probe for Chromosome 17 Fluorescence In Situ Hybridization Ratio Predicts Pathologic Complete Response and Survival Outcome in Patients Receiving Neoadjuvant Systemic Therapy With Trastuzumab for HER2-Overexpressing Locally Advanced Breast Cancer

et al. 2015

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Key Words. HER21 breast cancer x HER2/centromeric probe for chromosome 17 fluorescence in situ hybridization ratio x Trastuzumab x Predictive factor x Pathologic complete response ABSTRACTBackground. The present study was performed to determine whether the human epidermal growth factor receptor-related 2 (HER2)/centromeric probe for chromosome 17 fluorescence in situ hybridization (FISH) ratio is a predictor of a pathologic complete response (pCR), recurrence-free survival (RFS), and/or overall survival (OS) in patients receiving neoadjuvant systemic treatment (NST) with trastuzumab (NST-T) for HER21 locally advanced breast cancer (LABC). Patients and Methods. The present retrospective study included 555 patients with HER21 LABC who had undergone NST and definitive surgery (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012); 373 had concurrently received trastuzumab. HER2-positivity was considered present with an immunohistochemical score of 31 and/or HER2 FISH ratio of $2.0. We used logistic regression analysis and Cox proportional hazard modeling to determine whether a high HER2 FISH ratio,

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Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial

Cited by 61 publications

References 53 publications

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

CD4+ T-Helper Type 1 Cytokines and Trastuzumab Facilitate CD8+ T-cell Targeting of HER2/neu–Expressing Cancers

High HER2/Centromeric Probe for Chromosome 17 Fluorescence In Situ Hybridization Ratio Predicts Pathologic Complete Response and Survival Outcome in Patients Receiving Neoadjuvant Systemic Therapy With Trastuzumab for HER2-Overexpressing Locally Advanced Breast Cancer

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