title: Changes and predictive and prognostic value of the mitotic index, Ki-67, cyclin D1, and cyclo-oxygenase-2 in 710 operable breast cancer patients treated with neoadjuvant chemotherapy.
abstract: The current study expands upon previous work using a database of 710 patients treated with neoadjuvant chemotherapy. First, we studied phenotypic characteristics of tumors before and after chemotherapy using the following factors: the mitotic index of the Scarff-Bloom-Richardson grade, Ki-67, cyclin D1, and cyclo-oxygenase-2. Second, the predictive value of these factors on response was assessed. Third, we measured the prognostic impact of these markers post-therapy in comparison with clinical and pathological responses according to the Chevallier and Sataloff classifications. Patients were treated using different neoadjuvant chemotherapy combinations, mainly in successive prospective phase II trials. They received a median number of six cycles (range, 1-9). After neoadjuvant chemotherapy, patients underwent surgery and radiotherapy. In cases of important residual disease, some received additional courses of chemotherapy. In addition, menopausal patients with hormone receptor-positive tumors received tamoxifen for 5 years. According to our analysis, we found significant variations before and after neoadjuvant chemotherapy only for cyclin D1 and the mitotic index. Concerning the predictive value of biomarkers for response, Ki-67 and the mitotic index were predictive on univariate analysis, both for objective clinical and pathological complete responses. Because these two factors were correlated, no multivariate analyses were conducted. We then assessed the prognostic impact of the biopathological factors. When the factors were measured before chemotherapy, all were prognostic. When evaluated after chemotherapy, the mitotic index, objective clinical response, and pathological complete response were prognostic. Because these factors were correlated, no multivariate model was done. The main clinical fact is that there were significant correlations between clinical and pathological responses and variations in the biological factors studied.
authors.affiliation: Centre Jean Perrin, Bureau de Recherche Clinique, Clermont-Ferrand Cedex 1, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: Catherine
authors.initials: C
authors.lastname: Abrial
authors.forename: Inès
authors.initials: I
authors.lastname: Raoelfils
authors.forename: Philippe
authors.initials: P
authors.lastname: Chollet
authors.forename: Anne
authors.initials: A
authors.lastname: Cayre
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Mouret-Reynier
authors.forename: Emilie
authors.initials: E
authors.lastname: Thivat
authors.forename: Florence
authors.initials: F
authors.lastname: Mishellany
authors.forename: Pierre
authors.initials: P
authors.lastname: Gimbergues
authors.forename: Xavier
authors.initials: X
authors.lastname: Durando
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019938:Cyclin D1 / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis
chemical_list: D019394:Ki-67 Antigen; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human