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Assessment of histologic features and expression of biomarkers in predicting pathologic response to anthracycline‐based neoadjuvant chemotherapy in patients with breast carcinoma
Author(s) -
Wang Jianzhou,
Buchholz Thomas A.,
Middleton Lavinia P.,
Allred D. Craig,
Tucker Susan L.,
Kuerer Henry M.,
Esteva Francisco J.,
Hortobagyi Gabriel N.,
Sahin Aysegul A.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10585
Subject(s) - medicine , anthracycline , chemotherapy , breast carcinoma , breast cancer , lymph node , oncology , biomarker , neoadjuvant therapy , cyclophosphamide , doxorubicin , pathology , cancer , biology , biochemistry
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. Cancer 2002;94:3107–14. © 2002 American Cancer Society. DOI 10.1002/cncr.10585