title: Novel biomarkers in primary breast core biopsies to predict poor response to neoadjuvant chemotherapy and appearance of metastases.
abstract: Drug resistance has been one of the major obstacles limiting the success of cancer chemotherapy. In two thirds of breast cancer patients, large (>1cm) residual tumors are present after neoadjuvant chemotherapy (NCT). The residual tumor and involved nodes have been indicators of relapse and survival very important in breast cancer. The goal of this preliminary study was to assess the predictive significance of a panel of molecular biomarkers, related with the response to treatment or drug resistance to NCT, as determined on the diagnostic tumor. The expression of 22 proteins was examined using immunohistochemistry in tissue microarrays (TMA) from 115 patients of stage II-III breast cancer, treated with NCT. Among studied proteins, there are some that are anti-apoptotic, pro-proliferative, cancer stem cell markers and the Vitamin D Receptor. Other proteins are involved in the identification of molecular subtype, cell cycle regulation or DNA repair. Next, a predictive signature of poor response was generated from independent markers of predictive value. Tumors that expressed four or five conditions (biomarkers of chemoresistance with a determinated cutoff) were associated with a 9-fold increase in the chances of these patients of having a poor response to NCT. Additionally, we also found a worse prognostic signature, generated from independent markers of prognostic value. Tumors which expressed two or three conditions of worst prognostic, were associated with a 6-fold reduction in Distant Disease Free Survival. In conclusion, finding biomarkers of chemoresitance (ypTNM II-III) and metastases can become a stepping stone for future studies that will need to be assessed in a bigger scale.
authors.affiliation: Department of Medical Oncology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain. anovellalvarez@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Novell
authors.affiliation: Department of Medical Oncology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
authors.forename: Serafin
authors.initials: S
authors.lastname: Morales
authors.affiliation: Unit of Biostatistics, IRBLleida, Lleida, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Valls
authors.affiliation: Department of Pathology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Panadés
authors.affiliation: Department of Medical Oncology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Salud
authors.affiliation: Department of Surgery (Unit of Breast Pathology), Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
authors.forename: Edelmiro
authors.initials: E
authors.lastname: Iglesias
authors.affiliation: Department of Pathology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
authors.forename: Felip
authors.initials: F
authors.lastname: Vilardell
authors.affiliation: Department of Pathology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: Department of Medical Oncology, Hospital Universitari Arnau de Vilanova, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Cussac
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor