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Intrinsic subtyping provided significant prognostic information
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CHICAGO — Intrinsic subtyping using a panel of ER, PR, HER-2 and Ki67 provided significant prognostic information that could better direct patient treatment during early-stage breast cancer.
Based on prior data in which gene expression profiles had identified four main intrinsic subtypes of breast cancer that had distinct clinical behaviors and responses to therapy, Ewan K.A. Millar, MD, FRCPath, FRCPA, of the Garvan Institute of Medical Research in Sydney, Australia, and colleagues used tissue microarrays created from two randomized trials of adjuvant chemo-endocrine therapy in node-negative early breast cancer to review intrinsic subtype.
In the study, 1,220 patients were assessed for intrinsic subtype, including 1) luminal A: ER and/or PR present, Ki-67 low (,19% median) and HER-2–negative; 2) luminal B: ER and/or PR present, Ki-67 high (>19% median) and/or HER-2–positive; 3) HER-2 enriched: ER- and/or PR-negative, HER-2–positive; or 4) triple-negative: ER, PR and HER-2–negative.
Additionally, p53-positive and high cyclin D1 protein expression were evaluated to determine whether they provided further additive discriminatory value.
According to the study results, standard definitions of intrinsic subtype demonstrated a significant difference in DFS between the subtypes in both randomized trials (P=.02); however, this was not significant in multivariate analysis. The discrimination between luminal A and B tumors could not be improved upon by the addition of p53 or cyclin D1 expression. The standard definitions demonstrated that triple-negative and HER-2–enriched tumors benefited from the addition of chemotherapy to endocrine therapy, but luminal A and luminal B did not.
“[Immunohistochemical] subtype can provide meaningful information regarding the prognosis in treatment decisions, but is of inferior predictive value to pathological grade and the presence of lymphatic vascular invasion,” Millar said in a press conference. “This study has confirmed previous findings that triple-negative and HER-2 patients benefit from the addition of [cyclophosphamide, methotrexate and fluorouracil] chemotherapy, but not luminal B patients.”
Although p53-positive was associated with a poorer prognosis in ER-positive luminal tumors, it improved prognosis in ER-negative non-luminal tumors (interaction P =.002).
According to Millar, “p53-positive appears to have a divergent associated effect on outcome, which appears to be dependent on ER status.”
For more information:
Millar EK. Abstract #504. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: The researchers report no relevant financial disclosures.