title: A close association between alteration in growth kinetics by neoadjuvant chemotherapy and survival outcome in primary breast cancer.
abstract: Few surrogate markers are available for predicting the survival benefit from chemotherapy in primary breast cancer. We examined tumor growth kinetics by assessing cytokeratin 18 neo-epitope (CK18NE), an apoptosis marker detected by M30 antibody and Ki-67 antigen, a proliferation marker detected by MIB-1 antibody in 72 primary breast cancer patients who underwent pre-operative anthracycline-based chemotherapy. Increase in M30 index and decrease in MIB-1 index after the exposure of 2 to 4 cycles of chemotherapy correlated significantly with pathological tumor response. Univariate survival analysis, conducted in the subgroup of 42 patients who underwent CAF (cyclophosphamide, adriamycin and 5-FU) therapy alone, showed that the patients with the high levels of M30 index (>35 counts/1000 tumor cells) and the low levels of MIB-1 index (<140 counts/1000 tumor cells) after chemotherapy had a remarkably favorable prognosis as compared with patients in other categories. In addition, the alteration in growth kinetics by the treatment showed a significant prognostic value. Multivariate analysis also confirmed that the post-treatment growth kinetics was an independent prognostic indicator. These findings suggest that the alteration in growth kinetics revealed by CK18NE and MIB-1 might be a surrogate marker for predicting the survival benefit from chemotherapy in primary breast cancer.
authors.affiliation: Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takada
authors.forename: Akemi
authors.initials: A
authors.lastname: Kataoka
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Bando
authors.forename: Kazumi
authors.initials: K
authors.lastname: Toyama
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ueno
authors.forename: Stig
authors.initials: S
authors.lastname: Linder
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Funata
authors.forename: Junko
authors.initials: J
authors.lastname: Kinoshita
authors.forename: Sigeru
authors.initials: S
authors.lastname: Murakami
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohono
mesh_terms: D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007633:Keratins / Q000032:analysis / Q000276:immunology; D019394:Ki-67 Antigen / Q000032:analysis / Q000276:immunology; D007700:Kinetics; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000912:Antibodies, Neoplasm; D019394:Ki-67 Antigen; D007633:Keratins; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil