Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Basic science

2230 - Tumor microenvironment biomarkers as therapeutic strategies for TNBC


10 Sep 2017


Basic science


Translational Research;  Breast Cancer


Federico Rojo


Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391


F. Rojo1, M. Ruíz-Borrego2, M. Hui3, J.M. Trigo Perez4, A. Cazet3, M.A. Karsdal5, A. Urruticoechea6, S. Antolin7, J.A. García-Saenz8, S. O’toole3, A. Blach9, L. Perez-Ramos10, S. Bezares11, M. Sánchez-Aragó12, R. Caballero13, C.L. Bager5, A. Swarbrick14, M. Martin Jimenez15

Author affiliations

  • 1 Cancer Institute, Hospital Universitario Fundación Jimenez Diaz, GEICAM, CIBERONC-ISCIII, 28040 - Madrid/ES
  • 2 Clinical Oncology, Hospital Virgen del Rocío, Sevilla/ES
  • 3 Translational Breast Cancer Research, Garvan Institute of Medical Research, Darlinghurst, New South Wales/AU
  • 4 Clinical Oncology, Hospital Universitario Virgen de la Victoria, IBIMA, 29010 - Malaga/ES
  • 5 Biomarkers & Research, Nordic Bioscience A/S, 2730 - Herlev/DK
  • 6 Clinical Oncology, Fundación Onkologikoa, Donosti/ES
  • 7 Clinical Oncology, Complejo Hospitalario U A Coruña, Coruña/ES
  • 8 Medical Oncology, Hospital Universitario Clínico San Carlos, Madrid/ES
  • 9 Translational Research, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 10 Statistics, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 11 Medical Lead, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 12 Traslational Research, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 13 Traslational Research Director, GEICAM, 28703 - San Sebastian de los Reyes/ES
  • 14 Tumour Progression, Garvan Institute of Medical Research, Darlinghurst, New South Wales/AU
  • 15 Medical Oncology, Hospital General Universitario Gregorio Marañón, GEICAM, CIBERONC-ISCIII, 28009 - Madrid/ES


Abstract 2230


Patients with triple negative breast cancer (TNBC) comprise a heterogeneous and poor-prognosis subgroup. Biomarkers for targeted therapy development remains a challenge. Progression of TNBC is associated with extracellular matrix (ECM) remodeling and reactivation of the paracrine Hedgehog (Hh) pathway, highlighting the relevance of tumor micronvironment (TME) in tumorigenesis. We investigated whether TME biomarkers could determine clinical response in TNBC patients treated with the Hh pathway inhibitor sonidegib in combination with docetaxel.


Patients enrolled in GEICAM/2012-12 (EDALINE) trial were included (n = 12). To evaluate Hh pathway activation, the expression of SHH and GLI1 was centrally examined by immunohistochemistry in pre-treatment primary tumors. A Hh Pathway Activation Signature (HPAS) was defined when SHH expression in epithelium and GLI1 in stroma were high (> median). Biomarkers involved in formation and degradation of ECM (C1M, C3M, C4M, C6M, pro-C3, pro-C6, CRPM, Loxl-2 and VCANM) were evaluated by ELISA (Protein Fingerprint™) in sequential plasma samples. ECM signature (ECMS) was defined when C4M and VCANM were high at baseline (> median).


Related to Hh pathway activation, only 10 tumors had IHC results. Three patients had high HPAS, 2 of them experienced a clinical benefit, 1 complete response (CR) and 1 stable disease (SD) lasting 7.3 and 5.5 months, respectively. All patients with low HPAS expression progressed. An additional patient had clinical benefit but the status of Hh pathway activation was unknown. For ECM biomarkers, a maintained reduction was observed in the expression along treatment (C2D1-0.5h, C2D2-25h and C4D1) vs baseline for pro-C3 (12.8, 10.2 and 9.4 vs 16.6, p = 0.05, p = 0.03, p = 0.25, respectively), and pro-C6 (9.2, 7.5 and 8 vs 9.95, p = 0.13, p 


Hh pathway activation and ECM remodeling might be associated with improved benefit to sonidegib in combination with docetaxel in TNBC metastatic patients.

Clinical trial identification


Legal entity responsible for the study

GEICAM Spanish Breast Group.


Australian National Health and Medical Research Council.


M. Hui: Institution conducts research funding by Pfizer. M.A. Karsdal: Employed by Nordic Bioscience in a compensated leadership role and owns interest in the company. A. Urruticoechea: Consulting advisory role in Eisai. Travel accommodation expenses by Roche, Merck and Eisai. S. O’Toole: Honoraria from Bristol Myers. C.L. Bager: Employed by Nordic Bioscience. A. Swarbrick: Institution receives research funding from Novartis Pharmaceuticals. Honoraria from Roche. M. Martin Jimenez: Speaker honoraria and advisory boards of AstraZeneca. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.