title: Predictors of pathologic complete response after standard neoadjuvant chemotherapy in triple-negative breast carcinoma.
abstract: The objective of this study was to identify predictors of pathologic complete response and tumor volume reduction in triple-negative breast carcinomas. Consecutive cases of 101 triple-negative carcinomas within the last 3 years treated with standard neoadjuvant chemotherapy were identified. However, 56 cases with sufficient material available (for tissue microarray construction) in the pretherapy core biopsy tissue blocks formed the basis of this study. The pretherapy tumor core biopsy slides were examined for various morphologic features including tumor grade. The tumors were immunohistochemically examined for basal phenotype markers (CK5, CK14, CK17, epidermal growth factor receptor), cell adhesion marker E-cadherin, and proliferation marker Ki-67. The overall rate of pathologic complete response was 34% (19 of 56). Neither any morphologic feature nor any basal marker reactivity predicted for pathologic complete response or >50% tumor volume reduction. Ki-67 proliferation index also failed as a predictive marker. Reduced E-cadherin expression (defined as H score ≤200) was initially seen in 47% of cases with pathologic complete response and in only 6% of cases that failed to achieve pathologic complete response (P=0.001); however, in additional 20 cases from a separate validation set, no such difference was identified. Basal marker reactivity in triple-negative breast carcinomas does not predict pathologic complete response after neoadjuvant chemotherapy. As vast majority of triple-negative tumors are highly proliferative, Ki-67 proliferation index appears to have negligible clinical value in predicting pathologic complete response. E-cadherin expression as a predictor of pathologic complete response in triple-negative tumors should be further assessed on larger number of cases.
authors.affiliation: Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Kraus
authors.forename: Sushil
authors.initials: S
authors.lastname: Beriwal
authors.forename: David J
authors.initials: DJ
authors.lastname: Dabbs
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Ahrendt
authors.forename: Kandace P
authors.initials: KP
authors.lastname: McGuire
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Johnson
authors.forename: Preeti
authors.initials: P
authors.lastname: Badve
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Puhalla
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhargava
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007120:Immunochemistry; D046228:Microarray Analysis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000951:Antigens, Neoplasm; D054316:Biomarkers, Pharmacological; D043823:Taxoids; D004317:Doxorubicin; D003520:Cyclophosphamide