Annals of Oncology Advance Access originally published online on March 5, 2008
Annals of Oncology 2008 19(7):1261-1265; doi:10.1093/annonc/mdn039
breast cancer |
p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes
,*
1 Department of Pathology, Institut Gustave Roussy, Villejuif
2 Department of Medical Oncology
3 Department of Pathology, Centre Jean Perrin, Clermont-Ferrand
4 Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France
* Correspondence to: Dr F. Andre, Department of Medical Oncology, Institut Gustave Roussy, 94805 Villejuif, France. Tel: +33142-114-371; Fax: +33142115274; E-mail: fandre{at}igr.fr
Background: We hypothesized that, among molecular subclasses of breast cancer, p53 status may have a differential predictive value for the efficacy of anthracyclines/alkylating agents-based regimen. We analysed the efficacy of a preoperative combination between 5-fluorouracil, anthracyclines and cyclophosphamide according to both p53 status and molecular classification.
Patients and methods: Oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) expression and p53 status were determined by immunohistochemistry in 293 samples from two different centres. A logistic regression model was used for multivariate analysis of predictors for pathological complete response (pCR).
Results: p53 immunostaining (54%) was associated with high grade (P = 0.002) and ER negativity (P = 0.04). p53 was detected in 59% of triple-negative tumours (ER–/PgR–/HER2–, n = 120 patients). In the overall population, pCR (9.6%) was independently predicted by high tumour grade (P = 0.002) and ER/PgR/HER2 triple negativity (P = 0.0004), but not by p53 status (P = 0.12). p53 immunostaining was associated with a trend for a higher rate of pCR in triple-negative tumours [relative risk (RR) = 2.5, 95% confidence interval (CI) = 0.8–7.5, P = 0.09], but not in non-triple-negative tumours (RR = 0.73, 95% CI = 0.16–3.3, P = 0.69).
Conclusion: p53 status may have a different predictive value for efficacy of anthracycline/alkylating agents-based regimen in each molecular subclass, a result which may explain the different results reported in literature.
Key words: anthracycline, p53, primary chemotherapy, triple-negative breast cancer
These two authors equally contributed to this work as senior author. Received for publication December 4, 2007. Revision received January 22, 2008. Accepted for publication January 24, 2008.