Abstract 1369
Background
HER2-positive (HER2+) breast cancer (BC) comprises all the intrinsic molecular subtypes, with the HER2-enriched (HER2-E) usually being the most represented. Data coming from neoadjuvant trials of HER2+ BC treated with anti-HER2 containing regimens, with or without chemotherapy (CT), have shown that HER2-E tumors are more likely to achieve pathologic complete response (pCR) than non-HER2-E tumors. We decided to perform a meta-analysis combining all the available data in attempt to validate the ability of the HER2-E signature to predict pCR.
Methods
A systematic literature search was performed to identify clinical studies exploring the correlation between BC subtypes and pCR after neoadjuvant therapy (NAT) with anti-HER2 containing regimens in patients affected by HER2+ early BC. Primary analysis compared the association of gene signatures with pCR. Secondary analyses compared the association of gene signatures with pCR within hormone receptor (HR) positive (+) or negative (-) BC. Odds Ratio (OR) and 95% confidence intervals (CI) for pCR were extracted from each trial. A random-effect model was applied. The Higgins’ I2 was used to quantify heterogeneity.
Results
Sixteen studies (2,857 patients) were included; 4 investigated CT-free regimens. Various methods for assessing BC intrinsic subtypes were used across all trials. HER2-E subtype was significantly associated with pCR in all patients (OR: 3.32, 95% CI: 2.70-4.07, p < 0.001, I2=25%) and in HR + (OR: 3.40, 2.51-4.61, p < 0.001, I2=0%) and HR- (OR: 1.97, 1.10-3.54, p = 0.02, I2=46%) disease. In CT-free studies, HER2-E subtype was significantly associated with pCR in all patients (OR: 4.43, 2.34-8.38, p < 0.001, I2=0%) and in HR+ disease (OR: 4.79, 2.23-10.29, p < 0.001, I2=0%), but not within HR- tumors (OR: 2.18, 0.66-7.26, p = 0.20).
Conclusions
HER2-E subtype identifies patients with a higher likelihood of achieving a pCR following anti-HER2-based NAT, with or without CT. In the latter case, albeit limited by small casuistry, the association seems stronger in HR+ tumors. This suggests that strategies to escalate or de-escalate systemic therapy in HER2+ tumors would benefit from incorporating intrinsic subtypes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Schettini: Travel / Accommodation / Expenses: Pfizer and Celgene. T. Pascual: Advisory / Consultancy: Roche. P.F. Conte: Honoraria (self): BMS, Roche, EliLilly, Novartis, AstraZeneca; Advisory / Consultancy: Novartis, EliLilly, AstraZeneca, Tesaro; Research grant / Funding (self): Novartis, Roche, BMS, Merck-KGa; Research grant / Funding (self): Italian Ministry of Health, Veneto Secretary of Health, University of Padua. S. De Placido: Honoraria (self): Roche, Pfizer, AstraZeneca, Novartis, Celgene, Lilly and Eisai. L. Carey: Research grant / Funding (institution): Genentech / Roche, Novartis, Seattle Genetics, G1 Therapeutics, Immunomedics, Innocrin. C.M. Perou: Shareholder / Stockholder / Stock options: BioClassifier LLC; Advisory / Consultancy: BioClassifier LLC; Licensing / Royalties: Breast PAM50. A. Prat: Full / Part-time employment, An immediate family member employed: Novartis; Honoraria (self): Pfizer, Novartis, Roche, MSD Oncology, Lilly and Daiichi Sankyo; Advisory / Consultancy: NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb; Research grant / Funding (self): Roche, Novartis; Travel / Accommodation / Expenses: Daiichi Sankyo. All other authors have declared no conflicts of interest.
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