Personalized Medicine and Imaging Triple-Negative versus Non–Triple-Negative Breast Cancers in High-Risk Women: Phenotype Features and Survival from the HIBCRIT-1 MRI-Including Screening Study Franca Podo 1 , Filippo Santoro 1 , Giovanni Di Leo 2 , Siranoush Manoukian 3 , Clelia de Giacomi 4 , Stefano Corcione 5 , Laura Cortesi 6 , Luca A. Carbonaro 2 , Rubina M. Trimboli 2 , Anna Cilotti 7 , Lorenzo Preda 8 , Bernardo Bonanni 9 , Matilde Pensabene 10 , Laura Martincich 11 , Antonella Savarese 12 , Alma Contegiacomo 10 , and Francesco Sardanelli 2,13 Abstract Purpose: To compare phenotype features and survival of triple-negative breast cancers (TNBC) versus non-TNBCs detected during a multimodal annual screening of high-risk women. Experimental Design: Analysis of data from asymptomatic high-risk women diagnosed with invasive breast cancer during the HIBCRIT-1 study with median 9.7-year follow-up. Results: Of 501 enrolled women with BRCA1/2 mutation or strong family history (SFH), 44 were diagnosed with invasive breast cancers: 20 BRCA1 (45%), 9 BRCA2 (21%), 15 SFH (34%). Magnetic resonance imaging (MRI) sensitivity (90%) outper- formed that of mammography (43%, P < 0.001) and ultrasonog- raphy (61%, P ¼ 0.004). The 44 cases (41 screen-detected; 3 BRCA1-associated interval TNBCs) comprised 14 TNBCs (32%) and 30 non-TNBCs (68%), without significant differences for age at diagnosis, menopausal status, prophylactic oophorectomy, or previous breast cancer. Of 14 TNBC patients, 11 (79%) were BRCA1; of the 20 BRCA1 patients, 11 (55%) had TNBC; and of 15 SFH patients, 14 (93%) had non-TNBCs (P ¼ 0.007). Invasive ductal carcinomas (IDC) were 86% for TNBCs versus 43% for non-TNBCs (P ¼ 0.010), G3 IDCs 71% versus 23% (P ¼ 0.006), size 16  5 mm versus 12  6 mm (P ¼ 0.007). TNBC patients had more frequent ipsilateral mastectomy (79% vs. 43% for non- TNBCs, P ¼ 0.050), contralateral prophylactic mastectomy (43% vs. 10%, P ¼ 0.019), and adjuvant chemotherapy (100% vs. 44%, P < 0.001). The 5-year overall survival was 86%  9% for TNBCs versus 93%  5% (P ¼ 0.946) for non-TNBCs; 5-year disease-free survival was 77%  12% versus 76%  8% (P ¼ 0.216). Conclusions: In high-risk women, by combining an MRI- including annual screening with adequate treatment, the usual reported gap in outcome between TNBCs and non-TNBCs could be reduced. Clin Cancer Res; 22(4); 895–904. Ó2015 AACR. Introduction Triple-negative breast cancers (TNBC), defined as breast cancers testing negative to estrogen receptor (ER) and proges- terone receptor (PR) in the absence of HER2 overexpression, form a heterogeneous clinical subset partially overlapping with the basal-like subtype (1) and frequently occurring in women with germline deleterious BRCA1 mutations (2–5). Most population-based studies report a TNBC prevalence of 10% to 20%, but higher values can be found in some ethnic groups (5–9). While often presenting in premenopausal age, TNBCs also appear as interval cancers in population-based mammography screening programs (10). Frequent phenotype features of TNBCs in the general female population are high 1 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit a, Rome, Italy. 2 Unit of Radiology, IRCCS Policlinico San Donato, Milan, Italy. 3 Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 4 Department of Medical Oncology, CRO—Centro di Riferimento Oncologico, Aviano (PN), Italy. 5 Breast Imaging Unit, Sant'Anna Universitary Hospital, Cona (FE), Italy. 6 Department of Oncology and Haematology, Azienda Ospedaliera Policlinico, Modena, Italy. 7 Radiological Section, Ospedale Santa Chiara, University of Pisa, Pisa, Italy. 8 Division of Radiology, European Institute of Oncology, Milan, Italy. 9 Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy. 10 Department of Clinical Medicine and Surgery, Clinical Unit of "Hereditary and Familial Cancers", University Hospital Federico II, Naples, Italy. 11 Unit of Radi- ology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo (TO), Italy. 12 Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy. 13 Dipartimento di Scienze Biomediche per la Salute, Universit a degli Studi di Milano, Milan, Italy. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/). Prior presentation: Preliminary results of this study were presented at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16–19; Anaheim, CA. Cancer Prev Res 2012;5(11 Suppl): Abstract nr B13, Philadelphia (PA): AACR. F. Podo and F. Santoro share first authorship and contributed equally to this article. Corresponding Author: Franca Podo, Istituto Superiore di Sanit a, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 3906-4990-2686; Fax: 3906-4938-7144; E-mail: franca.podo@alice.it doi: 10.1158/1078-0432.CCR-15-0459 Ó2015 American Association for Cancer Research. Clinical Cancer Research www.aacrjournals.org 895 Downloaded from http://aacrjournals.org/clincancerres/article-pdf/22/4/895/2034599/895.pdf by guest on 24 June 2022