BCL2 is a predictive marker of adjuvant CMF regimen in triple negative breast cancer (TNBC) patients.

Konference: 2012 XXXVI. Brněnské onkologické dny a XXVI. Konference pro sestry a laboranty

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: 22. Základní a aplikovaný výzkum v onkologii

Číslo abstraktu: 199

Autoři: MUDr. Kateřina Bouchalová (Špačková), Ph.D.; MUDr. Magdalena Čížková; RNDr. Radek Trojanec, Ph.D.; Mgr. Lenka Radová, Ph.D.; Mgr. Jana Fürstová; prof. MUDr. Bohuslav Melichar, Ph.D.; MUDr. Karel Cwiertka, Ph.D.; MUDr. Gvantsa Kharaishvili; prof. MUDr. Zdeněk Kolář, CSc.; doc. MUDr. Marián Hajdúch, Ph.D.

   Background

   Tumors in TNBC patients are aggressive and the prognosis is poor. Patients cannot benefit from targeted treatment based on hormonal or HER2 receptors positivity. Moreover, little is known which TNBC patients will benefit from „non-targeted“ adjuvant treatment. The classical CMF adjuvant chemotherapy regimen [cyclophosphamide, methotrexate, 5-fluorouracil (5-FU)] was first used in 1973 (Bonadonna et al., NEJM 1976) and it improved the prognosis of breast cancer patients. Recent publications suggest that CMF may be a good adjuvant strategy for TNBC.

   Purpose

   The overall objective of this analysis was search for predictors of adjuvant chemotherapy in TNBC pts.

   Patients/Methods

   This study included 67 TNBC patients diagnosed from 1998 to 2005 with clinical stages I, II and III. All but 22 patients had undergone adjuvant chemotherapy (CMF-27 patients). Fluorescent in situ hybridization (FISH) using p53, HER1, centromere 7 and 17 probes was performed on formalin-fixed paraffin-embedded tumor tissue. BCL2 was detected by immunohistochemistry.

   Results

   HER1 amplification was found in 23.9 % (16/67), p53 deletion was detected in 29.7 % (11/37) and BCL2 positivity was present in 34.3 % (23/67) tumors. A lower p53/chromosome 17 ratio correlated with higher grading (p=0.003) and showed a strong trend toward HER1/chromosome 7 ratio (p=0.053). Patients with a chromosome 17 copy number ≥1.9 had better overall survival than patients with a copy number <1.9 (Kaplan-Meier, p=0.014). BCL2 positive patients treated with adjuvant CMF had significantly better relaps free survival than BCL2 negative patients treated with adjuvant CMF (Kaplan-Meier, p<0.035).

   Conclusions

   These initial data support the use of the classical CMF regimen in TNBC patients. It is relatively non-toxic, has a high response rate, low frequency of multidrug resistance and it is cost-effective. However, the biomarker of CMF responsiveness is needed for clinical practice. We confirmed that BCL2 positivity is a useful predictor of adjuvant CMF in TNBC patients. Our results concur with the data presented by Abdel-Fatah et al., ASCO meeting 2011. However, validation of this marker in a larger prospective study is needed. Higher chromosome 17 copy number was associated with better outcome, suggesting the importance of its assessment.

Grants: IGA NS10286-3, NS9956, MSM6198959216 and Biomedreg CZ.1.05/2.1.00/01.0030.

Datum přednesení příspěvku: 19. 4. 2012