p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes.
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.


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).


CONCLUSIONS
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.
Bidard
F-C
FC
Department of Pathology, Institut Gustave Roussy, Villejuif.
Matthieu
M-C
MC
Department of Pathology, Institut Gustave Roussy, Villejuif.
Chollet
P
P
Department of Medical Oncology.
Raoefils
I
I
Department of Pathology, Centre Jean Perrin, Clermont-Ferrand.
Abrial
C
C
Department of Medical Oncology.
Dômont
J
J
Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France.
Spielmann
M
M
Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France.
Delaloge
S
S
Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France.
André
F
F
Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France. Electronic address: fandre@igr.fr.
Penault-Llorca
F
F
Department of Pathology, Centre Jean Perrin, Clermont-Ferrand.
D000230:Adenocarcinoma / Q000145:classification / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018943:Anthracyclines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53