title: Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings.
abstract: BACKGROUND
  TNBC represents a heterogeneous subgroup of BC with poor prognosis and frequently resistant to CT.
  
  
  METHODS
  The relationship between Bcl2 immunohistochemical protein expression and clinico-pathological outcomes was assessed in 736 TNBC-patients: 635 patients had early primary-TNBC (EP-TNBC) and 101 had primary locally advanced (PLA)-TNBC treated with neo-adjuvant- ATC-CT.
  
  
  RESULTS
  Negative Bcl2 (Bcl2-) was observed in 70% of EP-TNBC and was significantly associated with high proliferation, high levels of P-Cadherin, E-Cadherin and HER3 (P's < 0.01), while Bcl2+ was significantly associated with high levels of p27, MDM4 and SPAG5 (P < 0.01). After controlling for chemotherapy and other prognostic factors, Bcl2- was associated with 2-fold increased risk of death (P = 0.006) and recurrence (P = 0.0004). Furthermore, the prognosis of EP-TNBC/Bcl2- patients had improved both BC-specific survival (P = 0.002) and disease-free survival (P = 0.003), if they received adjuvant-ATC-CT. Moreover, Bcl2- expression was an independent predictor of pathological complete response of primary locally advanced triple negative breast cancer (PLA-TNBC) treated with neoadjuvant-ATC-CT (P = 0.008).
  
  
  CONCLUSIONS
  Adding Bcl2 to the panel of markers used in current clinical practice could provide both prognostic and predictive information in TNBC. TNBC/Bcl2- patients appear to benefit from ATC-CT, whereas Bcl2+ TNBC seems to be resistant to ATC-CT and may benefit from a trial of different type of chemotherapy with/without novel-targeted agents.
authors.affiliation: Clinical Oncology Department, Nottingham University Hospitals, Nottingham.
authors.forename: T M A
authors.initials: TM
authors.lastname: Abdel-Fatah
authors.forename: C
authors.initials: C
authors.lastname: Perry
authors.forename: P
authors.initials: P
authors.lastname: Dickinson
authors.forename: G
authors.initials: G
authors.lastname: Ball
authors.forename: P
authors.initials: P
authors.lastname: Moseley
authors.forename: S
authors.initials: S
authors.lastname: Madhusudan
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
authors.forename: S Y T
authors.initials: SY
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D018943:Anthracyclines; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: Bcl2; anthracyclin chemotherapy; predictive marker; prognostic marker; theraputic targets; triple negative breast cancer