Evaluation of HER-2/neu amplification and other biological markers as predictors of response to neoadjuvant anthracycline-based chemotherapy in primary breast cancer: the role of anthracycline dose intensity.
OBJECTIVE
The value of HER-2/neu status as a predictor of response to anthracycline-based chemotherapy is still a matter of debate. We evaluated the contribution of HER-2/neu gene amplification and other biologic markers in predicting response to different doses of neoadjuvant anthracycline-based chemotherapy.


METHODS
Clinical and pathologic records of 115 primary breast cancer patients were reviewed. Forty-eight and 67 patients received high (doxorubicin > or =20 mg/m2/wk; epirubicin > or =30 mg/m2/wk) and moderate-low anthracycline dose intensity regimens, respectively. Pathologic diagnosis, hormonal receptor status (HR), Ki67, and HER-2/neu status were assessed on tumor samples before neoadjuvant chemotherapy. HER-2/neu was determined by fluorescence in situ hybridization (FISH).


RESULTS
HER-2/neu amplification was observed in 29/115 (25%) tumors, 18 from moderate-low-dose and 11 from high-dose group. In the univariate analysis, a high Ki67 index (> or =20%) and positive clinical axillary nodes were predictive of an objective tumor response (P = 0.033 and 0.001, respectively). In the multivariate analysis, Ki67 was the only factor predictive of response (OR = 3.08, 95% CI = 1.1-8.5, P = 0.03). HER-2/neu status was not a factor in predicting objective response to different anthracycline dose intensities. The same finding was observed with regards to HR and Ki67.


CONCLUSIONS
In our series, no significant dose-response relationship was found according to HER-2/neu status.
Bozzetti
Cecilia
C
Deparment of Medical Oncology, University Hospital, Parma, Italy. cbozzetti@ao.pr.it
Musolino
Antonino
A
Camisa
Roberta
R
Bisagni
Giancarlo
G
Flora
Marcella
M
Bassano
Cristina
C
Martella
Eugenia
E
Lagrasta
Costanza
C
Nizzoli
Rita
R
Personeni
Nicola
N
Leonardi
Francesco
F
Cocconi
Giorgio
G
Ardizzoni
Andrea
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D019394:Ki-67 Antigen; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
D018943:Anthracyclines; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen