BACKGROUND: TNBC represents a heterogeneous subgroup of BC with poor prognosis and frequently resistant to CT. MATERIAL AND 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). CONCLUSION: 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.
BACKGROUND: TNBC represents a heterogeneous subgroup of BC with poor prognosis and frequently resistant to CT. MATERIAL AND 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). CONCLUSION: 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.
Entities:
Keywords:
Bcl2; anthracyclin chemotherapy; predictive marker; prognostic marker; theraputic targets; triple negative breast cancer
Authors: Tarek M A Abdel-Fatah; Fiona K Middleton; Arvind Arora; Devika Agarwal; Tao Chen; Paul M Moseley; Christina Perry; Rachel Doherty; Stephen Chan; Andrew R Green; Emad Rakha; Graham Ball; Ian O Ellis; Nicola J Curtin; Srinivasan Madhusudan Journal: Mol Oncol Date: 2014-11-06 Impact factor: 6.603
Authors: Álvaro Ruibal; Pablo Aguiar; María Carmen Del Río; Primitiva Menéndez; José Ignacio Arias; Michel Herranz Journal: Med Oncol Date: 2014-07-10 Impact factor: 3.064
Authors: Tarek M A Abdel-Fatah; Roslin Russell; Nada Albarakati; David J Maloney; Dorjbal Dorjsuren; Oscar M Rueda; Paul Moseley; Vivek Mohan; Hongmao Sun; Rachel Abbotts; Abhik Mukherjee; Devika Agarwal; Jennifer L Illuzzi; Ajit Jadhav; Anton Simeonov; Graham Ball; Stephen Chan; Carlos Caldas; Ian O Ellis; David M Wilson; Srinivasan Madhusudan Journal: Mol Oncol Date: 2014-05-13 Impact factor: 6.603