title: BRCAness predicts resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy.
abstract: BACKGROUND
  To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.
  
  
  METHODS
  We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information.
  
  
  RESULTS
  We obtained 45 CNB and 60 surgical specimens from the 73 patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14 had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P = .03) and for TNBC (50% vs. 100%, P = .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8% vs. 14.3%, P = .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P = .002) and in TNBC cases (P = .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P = .049).
  
  
  CONCLUSIONS
  Identifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue.
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan. Electronic address: sakashi@med.showa-u.ac.jp.
authors.forename: Sadako
authors.initials: S
authors.lastname: Akashi-Tanaka
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Watanabe
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takamaru
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuwayama
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Murasaki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Ohyama
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Rikako
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Sawada
authors.initials: S
authors.lastname: Terumasa
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Enokido
authors.affiliation: Department of Pathology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Department of Pharmacy, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Okuyama
authors.affiliation: Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage*; D064726:Triple Negative Breast Neoplasms / Q000151:congenital / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D043823:Taxoids
keywords: Multiplex ligation-dependent probe amplification; Platinum salts; Predictive marker; Prognostic marker; Taxane resistance