Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information.
The objectives of this study were to determine the prognostic significance of subgrouping estrogen receptor (ER)-positive breast tumors into low- and high-risk luminal categories using Ki67 index, TP53, or progesterone receptor (PR) status. The study group comprised 540 patients with lymph node negative, invasive breast carcinoma. Luminal A subtype was defined as being ER positive, HER2 negative, and Ki67 low (<14% cells positive) and luminal B subtype as being ER positive, HER2 negative, and Ki67 high (≥ 14% cells positive). Luminal tumors were also subgrouped into risk categories based on the PR and TP53 status. Survival analysis was performed. Patients with luminal B tumors (n=173) had significantly worse disease-free survival compared to those with luminal A tumors (n=186) (log rank P-value=0.0164; univariate Cox regression relative risk 2.00; 95% CI, 1.12-3.58; P=0.0187). Luminal subtype remained an independent prognostic indicator on multivariate analysis including traditional prognostic factors (relative risk 2.12; 95% CI, 1.16-3.88; P=0.0151). Using TP53 status or PR negativity rather than Ki67 to classify ER-positive luminal tumors gave similar outcome results to those obtained using the proliferation index. However, it was a combination of the three markers, which proved the most powerful prognostically. Ki67 index, TP53 status, or PR negativity can be used to segregate ER-positive, HER2-negative tumors into prognostically meaningful subgroups with significantly different clinical outcomes. These biomarkers particularly in combination may potentially be used clinically to guide patient management.
Department of Pathology, Cork University Hospital, Cork, Ireland.
Linda P
LP
Feeley
1] Laboratory Medicine Program, University Health Network, Toronto, ON, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
Anna M
AM
Mulligan
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Dushanthi
D
Pinnaduwage
1] Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada [2] Dalla Lana School of Public Health, University of Toronto, ON, Canada.
Shelley B
SB
Bull
1] Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada [2] Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada [3] Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada [4] Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Irene L
IL
Andrulis
D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000737:chemistry* / Q000145:classification / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016009:Chi-Square Distribution; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009864:Ontario; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis*; D012307:Risk Factors; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C508053:ERBB2 protein, human