Prognostic, predictive abilities and concordance of BCL2 and TP53 protein expression in primary breast cancers and axillary lymph-nodes: a retrospective analysis of the Belgian three arm study evaluating anthracycline vs CMF adjuvant chemotherapy.
Given recent data on genetic heterogeneity within and individual's tumor, we investigated if there were differences in the prognostic and predictive abilities of BCL2 and TP53 protein expression in primary breast cancer (TU) and corresponding axillary lymph-nodes (LN). We used patient samples from the adjuvant Belgian three-arm study which randomized between anthracycline containing regimens and traditional CMF. The endpoints analyzed were overall survival (OS), event-free survival (EFS) and interactions between chemotherapy regimens. At a median follow-up of 15.6 years, BCL2 and TP53 (in both TU and LN) were significantly associated with OS but only in the first 5 years. Likewise, BCL2 and TP53 (in both TU and LN) were associated with EFS in the first 2 years after randomization, with no association after 2 years. BCL2 and TP53 remained statistically significant after adjustment for the standard clinical-pathological characteristics in regard to OS and EFS in the respective first years after randomization, (p value < 0.001 for both markers). Furthermore, an interaction was found between high BCL2 expression in the TU (but not in LN) and benefit to CMF over anthracycline-based chemotherapy (interaction p value EFS: 0.042; OS = 0.01). No interaction was found for TP53 expression neither in TU nor in LN. We conclude that BCL2 and TP53 were predictive biomarkers for better and worse survival respectively, but only in the first two to five years after diagnosis. BCL2 expression in the TU but not in the LN was predictive of increased benefit to CMF vs anthracycline-based chemotherapy.
Breast Data Center, Medical Oncology Department, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels, Belgium; Medical Oncology Department, Institute for Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia. Electronic address: ivanabs@borde.be.
Ivana
I
Bozovic-Spasojevic
Data Centre, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels, Belgium. Electronic address: lieveke.ameye@bordet.be.
Lieveke
L
Ameye
Data Centre, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels, Belgium. Electronic address: marianne.peasmans@bordet.be.
Marianne
M
Paesmans
Pathological Department, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels, Belgium. Electronic address: denis.larsimont@bordet.be.
Denis
D
Larsimont
Department of Medical Oncology, "Sandro Pitigliani" Hospital of Prato, Prato, Italy. Electronic address: adileo@usl4.toscana.it.
Angelo
A
Di Leo
Breast Data Center, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels, Belgium. Electronic address: stella.dolci@bordet.be.
Stella
S
Dolci
Medical Oncology Department, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels, Belgium. Electronic address: martine.piccart@bordet.be.
Martine
M
Piccart
Breast Data Center, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels, Belgium. Electronic address: evando.azambuja@bordet.be.
Evandro
E
de Azambuja
Breast Cancer Translational Research Laboratory JC Heuson, Institut Jules Bordet, Boulevard de Waterloo 125, Brussels, Belgium; Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Electronic address: sherene.loi@petermac.org.
Sherene
S
Loi
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001365:Axilla; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate
BCL2; Biomarkers; Breast cancer; Expression; Prognosis; TP53