95P - Gene signatures as potential predictive markers of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Breast Cancer
Translational Research
Presenter Emanuela Risi
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors E. Risi1, A. Grilli2, I. Migliaccio3, C. Biagioni1, C. Guarducci3, M. Bonechi3, A. McCartney1, S. Vitale4, L. Biganzoli1, S. Bicciato2, A. di Leo1, L. Malorni1
  • 1Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Istituto Toscano Tumori, 59100 - Prato/IT
  • 2Center For Genome Research, Department Of Life Science, Univeristy of Modena and Reggio Emilia, 41121 - Modena/IT
  • 3Sandro Pitigliani Translational Research Unit, Hospital of Prato, Istituto Toscano Tumori, 59100 - Prato/IT
  • 4Department Of Medical Biotechnologies, University of Siena, 53100 - Siena/IT



Chemotherapy (CT) combined with anti-HER2 drugs (H) is the treatment of choice for HER2+ early breast cancer (BC) patients (pts). However HER2+ tumors are clinically and biologically heterogeneous, and treatment response largely varies according to ER status. Predictive biomarkers are urgently needed in this context. We have recently developed a meta-dataset of clinical trials of neoadjuvant CT +/− H (trastuzumab, lapatinib, or both) in HER2+ BC pts annotated for gene expression, hormone receptor status and pathological complete response (pCR) rates. We have shown that a gene-signature (GS) of RB-1 loss-of-function (RBsig) seems to be predictive of response to neoadjuvant CT +/− H in ER+/HER2+ BC pts in this meta-dataset. Here we report the results of additional analyses aimed to evaluate RBsig’s predictive value against 10 previously developed GSs in the subset of ER+/HER2+ BC pts.


The association of RBsig with pCR was evaluated in comparison with previously described GSs of: low ER signaling, p53 mutation, high PI3K pathway signaling, high expression of HER2 amplicon genes, PAM 50 and 5 immune-related GSs. For each GS, samples were classified as High or Low group using a previously described classifier. Odds Ratio (OR) performance was calculated using the ROCR (v. 1.0) package in R and plotted by forest plot using the survcomp (v. 1.24) package.


RBsig and the HER2 amplicon GS were best at predicting response to neoadjuvant CT +/− H (211 pts; p:0.017). In the subgroup of pts treated with CT alone (n = 94), only the PI3K pathway GS was significantly associated with pCR (p:0.026). In pts treated with CT + H (n = 117) only the HER2 amplicon GS significantly correlated with pCR (p:0.042). RBsig showed a similar trend in both these subgroups (p: 0.078 and 0.104, respectively) The immune GSs and PAM50 were not associated with pCR, independent of treatment received.


RBsig and HER2 amplicon GS are strongly associated with pCR in ER+/HER2+ tumors unselected for treatment. These results support the potential use of such GSs as predictive markers of response to CT +/−H in ER+/HER2+ BC pts. Validation studies are warranted.

Clinical trial identification

Legal entity responsible for the study

Angelo Di Leo




A. Di Leo: Consultant/Advisory Board: Novartis, Pfizer, Lilly. All other authors have declared no conflicts of interest.