Multi-gene panel testing at the hereditary breast and ovarian cancer (HBOC) unit of the Hospital Clinic of Barcelona

Date 03 May 2019
Event ESMO Breast Cancer 2019
Session Poster lunch
Topics Breast Cancer
Hereditary Syndromes
Presenter Barbara Adamo
Citation Annals of Oncology (2019) 30 (suppl_3): iii39-iii44. 10.1093/annonc/mdz098
Authors B. Adamo1, L. Moreno2, L. Gaba2, M. Vidal1, T. Pascual3, N. Chic1, I. Alonso4, J.A. Puig-Butillé2, M. Muñoz3, A. Prat2
  • 1Medical Oncology And Traslational Genomic And Targeted Therapeutic In Solid Tumors, Hospital Clínic de Barcelona and August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 - Barcelona/ES
  • 2Medical Oncology  , Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 3Medical Oncology, Hospital Clinic de Barcelona, 08036 - Barcelona/ES
  • 4Gynecology, Hospital Clinic de Barcelona, 08036 - Barcelona/ES



The variety and clinical characteristics of BRCA1/2 and non-BRCA1/2 mutations in women with a suspicion of HBOC before the implementation of multi-gene panels in our referral population was unknown.


This is an exploratory study of all consecutive women tested at the HBOC Unit between 2016-2018. TruSight Cancer panel (Illumina) was used and 16 genes were analyzed: BRCA1, BRCA2, PALB2, ATM, CDH1, CHEK2, TP53, NBN, PTEN, STK11, BRIP1, MLH1, MSH2, MSH6, RAD51D and RAD51C. The main objective was to determine the prevalence of pathogenic mutations (PM) and variants of uncertain significance (VUS). Other secondary objectives were explored such as the distribution of the breast cancer (BC) subtypes and the pathological complete response (pCR) rates following neoadjuvant anthracycline/taxane-based chemotherapy in BRCA1/BRCA2/PALB2-PM BC.


451 women were tested. PM and a VUS were found in 60 (12.7%) and 42 (8.9%) patients, respectively. Among PM cases, 37 (62%) had BC and 23 (38%) had OC. The PMs identified in BC were BRCA2 (35.1%), BRCA1 (21.6%), PALB2 (24.3%), TP53 (8.1%), ATM (5.4%), BRIP1 (2.7%) and PTEN (2.7%). All women with PALB2 PM had BC. Within BRCA2-PM BC, the most common subtype was Luminal B (54%), followed by triple-negative (23%), Luminal A (15%) and HER2-positive (8%). Within cases with BRCA1-PM BC, the most common subtype was triple-negative (88%) followed by Luminal B (12%). Within cases with PALB2-PM BC, the most common subtype was Luminal B (56%), followed triple-negative (33%) and Luminal A (11%). Interestingly, within patients BRCA1/BRCA2/PALB2-PM BC (n = 30), only 1 (3.3%) case had HER2+ BC. Following neoadjuvant chemotherapy, 11 of 17 (58%) cases with BRCA1/BRCA2/PALB2-PM BC achieved a pCR. Within cases with OC, PM identified were BRCA2 (39.1%), BRCA1 (39.1%), TP53 (4.3%), BRIP1 (4.3%), CHEK2 (4.3%), RAD51D (4.3%) and MSH6 (4.3%).


Our in-house clinical guidelines detect >10% of tested cases with HBOC. Non-BRCA1/2 PM are found in 35% of the cases. BRCA1/BRCA2/PALB2-PM BC is associated with aggressive tumor biology and high chemotherapy sensitivity.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Hospital Clinic of Barcelona.


Has not received any funding.


A. Prat: Advisory role/lecture fees: NanoString Technologies, Roche, Pfizer, MSD, Novartis, Lilly; Funding: NanoString Technologies, Novartis; Scientific advisory role: Oncolytics Biotech. All other authors have declared no conflicts of interest.