Marker Helps Identify Most Aggressive Metastasized Breast Tumors

Rosemary Frei, MSc

January 2013, Vol 4, No 1 - ASH Annual Meeting

Boston, MA—Researchers believe they are closing in on a better way to identify breast cancers that are particularly dangerous and therefore require more aggressive therapy.

High levels of the proliferation marker Ki-67 in axillary lymph node metastases from a primary breast tumor are associated with reduced survival, according to a study presented at the American Society for Clinical Pathology’s 2012 meeting.

“This is the first indication for us that a tumor with high proliferative activity and that has metastasized behaves much worse than one with low proliferative activity. Nobody has shown this before,” said lead investigator Ossama Tawfik, MD, PhD, Vice Chairman for Education and Outreach, and Director of Anatomic and Surgical Pathology, University of Kansas Hospital, Kansas City. “We’re trying to get closer to identifying in a clinical way which tumor is going to behave nastier or nicer, so each can be treated with appropriate therapy.”

Dr Tawfik and his colleagues sought to solidify previous research that indicates that Ki-67 is a robust prognostic marker for breast cancer survival.
The team reviewed the outcomes and expression of Ki-67 and other markers in 103 patients (average age, 54.5 years) with primary breast cancers and axillary lymph node metastases. Overall, 17 cancers were Scarff-Bloom-Richardson grade I, 32 were grade II, and 54 were grade III. The average tumor size was 3.3 cm, and 86% of the tumors were ductal.

Expression of Ki-67 correlated with epidermal growth factor receptor (EGFR), p53, HER2 status, and tumor grade. Furthermore, there was an association between primary and lymph node Ki-67 expression and the frequency and the number of positive nodes.

There was no difference in overall survival (OS) in patients whose primary tumor had Ki-67 levels below or above 10%. However, those with lymph nodes with Ki-67 expression <10% had significantly better OS.

The majority of patients whose primary tumors had a Ki-67 expression of <10% also had lymph nodes with a low level of Ki-67 expression, and they had relatively favorable survival rates. The converse was also true, except the 12 patients with Ki-67 expression that was ≥10% in the primary tumor who had Ki-67 expression of <10% in the lymph nodes; those women had relatively better survival.

Other markers predictive of OS were progesterone receptor (PgR) ≥10% in the primary tumor; EGFR ≥10% in the primary tumor; and PgR ≥1%, 5%, and 10% in the lymph nodes. However, a multivariate analysis showed that only Ki-67 ≥10% expression in the lymph nodes was a statistically significant predictor of OS.

“Simply put, the other markers also appear to predict overall survival. But at the end of the day, only Ki-67 had the most power,” coinvestigator Bruce Kimler, PhD, Associate Director, Breast Cancer Prevention Center, University of Kansas Hospital and Medical Pavilion, Westwood, KS, told Value-Based Cancer Care.