Assessment of histologic features and expression of biomarkers in predicting pathologic response to anthracycline-based neoadjuvant chemotherapy in patients with breast carcinoma.
BACKGROUND
There is significant variability in the response of tumors to neoadjuvant chemotherapy, and the underlying mechanism for this variability is unknown. In this study, the authors investigated the roles of tumor nuclear grade, mitotic activity, and biomarker expression profiles in predicting the pathologic response of breast tumors to preoperative chemotherapy.


METHODS
Eighty-two patients with breast carcinoma participated in two clinical trials and were treated with neoadjuvant chemotherapy, which consisted of either a conventional dose of fluorouracil, doxorubicin, and cyclophosphamide (FAC) or dose-escalated FAC. The mean age of the patients was 46 years (range, 24-69 years). Nuclear grade, mitotic activity, and biomarker profile (Her2-neu and mitosin expression patterns) in pretreatment tumors were correlated with the postchemotherapy pathologic response.


RESULTS
Twelve patients (15%) had a complete pathologic response (CPR), 23 patients (28%) had a near complete response (NCR), and 47 patients (57%) had significant residual disease present either at the primary site or in the axillary lymph nodes. The authors found that the nuclear grade and mitotic activity of pretreatment tumors were correlated significantly with CPR and NCR (P = 0.002 and P = 0.004). Mitosin also was correlated significantly with CPR and NCR (P = 0.028). A higher percentage of patients with Her2-neu-positive tumors had a CPR or an NCR (P = 0.152). CPR and NCR were not correlated significantly with disease stage (P = 0.186) or lymph node positivity (P = 0.498).


CONCLUSIONS
The current results indicate that tumor nuclear grade and tumor proliferative activity (mitotic activity and mitosin immunostaining) of pretreatment tumors in patients with breast carcinoma may serve as important indicators for the pathologic responsiveness of tumors to neoadjuvant, anthracycline-based chemotherapy.
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Jianzhou
J
Wang
Thomas A
TA
Buchholz
Lavinia P
LP
Middleton
D Craig
DC
Allred
Susan L
SL
Tucker
Henry M
HM
Kuerer
Francisco J
FJ
Esteva
Gabriel N
GN
Hortobagyi
Aysegul A
AA
Sahin
D000328:Adult; D000367:Age Factors; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins; D008875:Middle Aged; D009367:Neoplasm Staging
D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; C094772:centromere protein F