title: Ki-67 index as a prognostic factor of subsequent lapatinib-based therapy in HER2-positive metastatic breast cancer with resistance to trastuzumab.
abstract: Prognostic factor analysis has been conducted to determine whether the parameters of clinical data and biomarkers would predict differential progression-free survival (PFS) or overall survival (OS) from lapatinib-based therapy in patients with primary or acquired resistance to trastuzumab. Treatment with lapatinib plus capecitabine for HER2-positive metastatic breast cancer (MBC) with primary or acquired resistance to trastuzumab was analyzed retrospectively. Tumor biomarkers, which came from the biopsies before the starting of lapatinib therapy, were evaluated by immunohistochemistry (IHC). Prognostic factors related to PFS or OS of the lapatinib therapy were assessed by univariate and multivariate analysis. Ki-67 index and liver metastases were the significant prognostic factors for predicting PFS of subsequent lapatinib therapy in the univariate analysis and the multivariate analysis. The risk for disease progression in patients who had a Ki-67 index<40% was 59% less than that in patients had Ki-67 ≥ 40 (HR = 0.41, 95% CI, 0.23-0.74, P = 0.003). TTP of prior trastuzumab therapy, liver metastases, and the number of metastatic sites were three independent prognostic factors of subsequent lapatinib therapy. Ki-67 index was the significant prognostic factors for predicting PFS of the subsequent second line targeted therapy in patients with trastuzumab resistance.
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Hui-Qiang
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Guo
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Ge
authors.initials: G
authors.lastname: Du
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Shi-Kai
authors.initials: SK
authors.lastname: Wu
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: San-Tai
authors.initials: ST
authors.lastname: Song
authors.affiliation: Department of Breast Cancer; Affiliated Hospital of Academy of Military Medical Sciences; Beijing, PR China.
authors.forename: Ze-Fei
authors.initials: ZF
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2 positive; Ki-67; lapatinib; metastatic breast cancer; prognostic factor; resistance; trastuzumab