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.
Resources from the same session
1025 - Liver metastases (LM) from intrahepatic cholangiocarcinoma (iCCA): Outcomes from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry and implications on current American Joint Committee on Cancer (AJCC) staging.
Presenter: Angela Lamarca
Session: Poster Display session 2
Resources:
Abstract
5813 - Is MGMT methylation a new therapeutic target for Biliary Tract Cancer?
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5839 - Biliary Tract Cancers in Portuguese families with BRCA gene mutation: a retrospective study.
Presenter: Patricia Pereira
Session: Poster Display session 2
Resources:
Abstract
4338 - Selection of patients with hepatocellular carcinoma for selective internal radiation therapy based on tumour burden and liver function: a post-hoc analysis of the SARAH trial
Presenter: Daniel Palmer
Session: Poster Display session 2
Resources:
Abstract
1700 - Second-line chemotherapy (SLC) in Patients with Advanced Biliary tract and Gallbladder Cancers (ABGC) Prolongs Survival: A Retrospective Population-based Cohort Study
Presenter: Adnan Zaidi
Session: Poster Display session 2
Resources:
Abstract
5562 - Overall survival of patients with hepatocellular carcinoma receiving sorafenib versus selective internal radiation therapy with predicted dosimetry in the SARAH trial
Presenter: Neil Hawkins
Session: Poster Display session 2
Resources:
Abstract
1838 - Multicenter phase II trial of axitinib monotherapy for advanced biliary tract cancer refractory to gemcitabine-based chemotherapy
Presenter: Naohiro Okano
Session: Poster Display session 2
Resources:
Abstract
3641 - Soluble Programmed Death-ligand 1 indicate poor prognosis in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization
Presenter: Xiaolu Ma
Session: Poster Display session 2
Resources:
Abstract
2733 - The Prognostic Nutritional Index (PNI) is an independent predictor of survival in advanced biliary cancers (ABC) receiving first-line chemotherapy (1L).
Presenter: Francesco Caputo
Session: Poster Display session 2
Resources:
Abstract
3773 - Impact of centralisation of national cancer services on patient outcomes for hepatobiliary cancers in Ireland 2000 – 2016
Presenter: David O Reilly
Session: Poster Display session 2
Resources:
Abstract