title: The search for optimal cutoff points for apoptosis and proliferation rate in prognostification of early stage breast cancer patients treated with anthracyclines in adjuvant settings.
abstract: Cancer growth is determined by the proportion of proliferating to dying cells; thus, the aim of the study was to analyze how proliferation rate and apoptosis level affect disease-free survival (DFS) of breast cancer (BC) patients treated with anthracycline-based chemotherapy. For 172 BC, proliferation rate was investigated by Ki-67 labeling index (Ki-67 LI)-assessed immunohistochemically. Apoptosis level was analyzed by apoptotic index (AI) estimated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. To stratify patients into subgroups with higher and lower DFS and to achieve optimal categorization, optimal cutoff points were searching by minimal P value method. The best separation of DFS curves (P = 0.001) was observed for three categories of AI: (i) AI >1.8 % (DFS = 100 %), (ii) AI ≤0.3 % (DFS = 84.6 %), and (iii) 1.8 % <= AI >0.3 % (DFS = 64.0 %). The highest DFS (86.1 %) was shown for the subgroup with low-proliferating BC (Ki-67 LI ≤18.0 %), intermediate (73.9 %) for patients characterized by Ki-67 LI in the range 18.0-37.0 % and the lowest (60.0 %) for women with fast-proliferating tumors (Ki-67 LI >37.0 %) (P = 0.022). Summarized, minimal P value method allows for optimal separation of survival curves. Apoptosis level and proliferation rate have some prognostic potential for early stage breast cancer patients treated with anthracyclines in adjuvant setting, however, as suggested by multivariate analysis, not as independent prognostic factors.
authors.affiliation: Department of Applied Radiobiology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow Branch, 11 Garncarska Street, Cracow, 31-115, Poland. z5biesag@cyfronet.pl.
authors.forename: Beata
authors.initials: B
authors.lastname: Biesaga
authors.affiliation: Department of Applied Radiobiology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow Branch, 11 Garncarska Street, Cracow, 31-115, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Niemiec
authors.affiliation: Department of Tumor Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow Branch, 11 Garncarska Street, Cracow, 31-115, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wysocka
authors.affiliation: Department of Applied Radiobiology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow Branch, 11 Garncarska Street, Cracow, 31-115, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Słonina
authors.affiliation: Department of Medical Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow Branch, 11 Garncarska Street, Cracow, 31-115, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Ziobro
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; D019394:Ki-67 Antigen; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil
keywords: Anthracyclines; Apoptosis; Early stage breast cancer patients; Proliferation rate