The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer.
The aim of this study was to evaluate the prognostic value of Ki67 in relation to established prognostic factors in lymph node-negative breast cancer, and furthermore, whether the prognostic impact was dependent on estrogen receptor (ER) status and histological grade. In 200 premenopausal patients, with 5 years of follow-up, Ki67 was determined on tissue microarrays. In univariate analysis, Ki67 (< or = 20 vs >20%) was a prognostic factor for distant disease-free survival (hazard ratio: 2.7, 95% confidence interval: 1.3-5.4, P=0.005) and overall survival (hazard ratio: 4.9, 95% confidence interval: 1.7-14, P=0.003). When stratifying for ER status and histological grade, Ki67 was a significant prognostic factor for distant disease-free survival and overall survival only in the ER-positive group, and only in patients with histological grade 2, respectively. In multivariate analysis, human epidermal growth factor receptor 2 and age were independent prognostic factors for distant disease-free survival, whereas Ki67, histological grade, and tumor size were not. Ki67 was, however, an independent prognostic factor in the 87% of the patients who had not received adjuvant medical treatment. Agreement between the three readers was very good (kappa-values: 0.83-0.88). Furthermore, Ki67 was a significant prognostic factor for all three investigators (hazard ratio: 2.7-3.2). This study shows that Ki67 is a prognostic factor in node-negative breast cancer. It is noteworthy that the prognostic information of Ki67 is restricted to ER-positive patients, and to patients with histological grade 2. Taken together, Ki67, as an easily assessed and reproducible proliferation factor, may be an alternative or complement to histological grade as a prognostic tool and for selection of adjuvant treatment.
Klintman
Marie
M
Department of Oncology, Clinical Sciences, Lund University and Lund University Hospital, SE 221 85 Lund, Sweden. Marie.Klintman@med.lu.se
Bendahl
Pär-Ola
PO
Grabau
Dorthe
D
Lövgren
Kristina
K
Malmström
Per
P
Fernö
Mårten
M
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D017697:Premenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen