Distinguishing Luminal Breast Cancer Subtypes by Ki67 Index, PR Negativity or p53 Status Provides Prognostic Information?
Linda Feeley, Dushanthi Pinnaduwage, Anna Marie Mulligan, Irene Andrulis. Cork University Hospital, Cork, Ireland; Samuel Lunenfeld Research Institute, Toronto, Canada; St Michael's Hospital, Toronto, Canada
Background: The principal objectives of this study were to determine the prognostic significance when subgrouping estrogen receptor positive breast tumors (i) into immunohistochemically defined luminal A and B categories using Ki67 and ii) according to p53 or PR status.
Design: The study group comprised of a consecutive series of 609 patients with node negative invasive breast carcinoma (median follow-up 107 months). 81 recurrences were observed. The luminal A subtype was defined as being ER and/or PR positive, HER-2 negative, and Ki67 low (<14%) and the luminal B subtype as being ER and/or PR positive, HER-2 negative, and Ki67 high (≥ 14%) as proposed by Cheang et al. For this study, all HER-2 positive tumors were classified in the HER-2 group. ER negative, HER-2 negative, and CK5 positive tumors were classified as basal. Survival analysis was performed. In addition the luminal A and B subgroups were correlated with various clinical, pathological and molecular markers.
Results: Luminal A tumors had a significantly better disease free survival than their high proliferation luminal B counterparts. Furthermore the luminal B subtype was more prone to late relapse with consequent poorer long-term survival than the basal subtype which was at significantly higher risk of early relapse.
When the luminal subgroups were compared pre-menopausal status, larger tumor size, higher tumor grade, presence of LVI, administration of chemotherapy, Bcl-2 negativity and p53 positivity were all significantly associated with luminal B tumors. Using p53 status or progesterone negativity instead of Ki67 to classify the ER+ luminal tumors further refined the luminal group and gave similar outcome results to that obtained using Ki67.
Conclusions: The Ki67 index can used to segregate hormone receptor positive, HER-2 negative tumors into prognostically meaningful subgroups. Utilization of p53 status or PR negativity can also separate the ER+ luminal group into subgroups with different clinical outcomes. These IHC biomarkers offer a potential alternative to expensive molecular tests such as Oncotype Dx in guiding patient management.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 13, Wednesday Afternoon