Invasive breast cancer treated with taxol and epirubicin neo-adjuvant chemotherapy: the role in the outcome of the "crosstalk" between Erb receptors and p53.
OBJECTIVE
To correlate p53 and ErbB receptors status with disease-free survival (DFS) and overall survival (OS) in locally advanced breast cancer.


METHODS
Sixty patients were included in a single-center, open-label, phase II trial (1998-2003). Analysis of Erb receptors and p53 status and estrogen receptor/progesterone receptor data were available for 33 patients. Neoadjuvant epirubicin 75 mg/m2 and paclitaxel 175-200 mg/m2 were administered every 21 days. The patients underwent surgery and radiation therapy and adjuvant chemo/hormonotherapy.


RESULTS
Approximately two thirds of the patients demonstrated overexpression of ErbB receptors and had mutant p53 overexpression. The disease recurred in 11/33 patients and 7 died (median follow-up 56 months). Detrimental effects on OS were established in cases of combined defective p53 expression and ErbB1-ErbB3 heterodimeric receptor overexpression. In contrast, normal p53 together with the same overexpressed heterodimeric combination of ErbB receptors showed no statistically significant effect.


CONCLUSIONS
In terms of the clinical impact of combinations of ErbB receptors with or without mutant p53, only the overexpressed various ErbB1-ErbB3 dimeric combinations and the ErbB1/ErbB2/ErbB3 triplet combination with mutated p53 were related to a significantly poorer outcome. This observation may help in the development of new strategies required for blocking these molecular pathways and improving the outcome of patients with locally advanced breast cancer.
Sarid
David
D
Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Ron
Ilan G
IG
Shoshan
Lior
L
Barnea
Itai
I
Shina
Sima
S
Baratz
Mimi
M
Greenberg
Julia
J
Merimsky
Ofer
O
Ben-Yosef
Rami
R
Lev-Ari
Shahar
S
Keidar
Yaffa
Y
Yaal-Hahoshen
Neora
N
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018739:Oncogene Proteins v-erbB / Q000096:biosynthesis / Q000378:metabolism*; D020239:Receptor Cross-Talk; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018739:Oncogene Proteins v-erbB; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53