Metastatic Breast Cancer Survival Predicted by Nodal Ki-67?

BOSTON — The presence of high levels of the Ki-67 antigen in axillary lymph node metastases is a significant and clinically useful predictor of survival in breast cancer and may identify subgroups of patients who would benefit from more aggressive treatment, suggests a study presented here at the American Society for Clinical Pathology (ASCP) 2012 Annual Meeting.

Assessment of the Ki-67 antigen has proven to be a simple and dependable method for indirectly measuring cell proliferation, and studies have demonstrated a positive relationship between cell proliferation in breast cancer and tumor grade and size, mitotic activity, hormonal and Her-2 status, and tumor progression, according to Kareem Tawfik, MD, lead author and resident of the University of Cincinnati, Ohio.

In light of a growing body of evidence suggesting that proliferation markers may identify subgroups of patients with breast cancer who are most likely to benefit from adjuvant chemotherapies, senior author Ossama Tawfik, MD, PhD, director of anatomic and surgical pathology, Department of Pathology and Lab Medicine at the University of Kansas Medical Center in Kansas City, Kansas, and colleagues compared the prognostic significance of Ki-67 expression in axillary lymph node metastases to that of patients' matched primary tumors. This research group previously reported a direct correlation between Ki-67 expression in breast cancer cells and prognosis for survival.

In the current study, the investigators evaluated Ki-67 expression (by means of immunohistochemistry via the MIB-1 monoclonal antibody) in the primary breast tumors and corresponding axillary lymph node metastases of 103 patients (median age, 54.5 years) treated at their institution and correlated the data with patient age, tumor grade, tumor size, estrogen receptor, progesterone receptor, p53, epidermal growth factor receptor, Bcl-2, Her-2 status, and overall survival.

Of the 103 primary breast carcinomas, most of which (86%) were ductal type, 17 were Scarff-Bloom-Richardson (SBR) grade I, 32 were SBR grade II, and 54 were SBR grade III, Dr. K. Tawfik said in a poster presentation of the data. The median Ki-67 expression in primary and metastatic tumors, respectively, was 20% and 15%, he said, noting that the latter was significantly lower for cases in which primary tumors were smaller than 2.0 cm.

An analysis of the results showed no difference in overall survival between primary tumors with 10% Ki-67 expression or less, "but there was significantly better overall survival when Ki-67 expression in lymph nodes was less than 10%," Dr. K. Tawfik reported. "For patients whose primary tumors exhibited Ki-67 expression less than 10%, most of their metastatic lesions had a similarly low Ki-67, and they had a favorable outcome." Worse survival was observed in the small subgroup of patients (6 of 34) with low Ki-67 expression in the primary tumor who had a nodal Ki-67 of 10% or higher, he said.

Ki-67 in Lymph Nodes May Tell More Than in Primary Tumors

Of 69 patients whose primary tumors had high Ki-67 expression, most had similarly high nodal Ki-67 expression, with the exception of 12 patients in whom nodal Ki-67 expression was less than 10%. These 12 patients "had significantly better overall survival," Dr. K. Tawfik said, suggesting that the measurement of Ki-67 in metastatic lymph nodes is more telling — and potentially more clinically useful — than its evaluation in primary tumors. "Identifying subgroups of patients with different levels of Ki-67 expression in lymph nodes and primary tumors may help in the selection of therapeutic options," he said. Specifically, "based on our findings, patients with higher proliferative activity in lymph node metastases might require more aggressive therapy and closer clinical monitoring of their disease."

Although Ki-67 is a robust and valuable biomarker of cell proliferation, the clinical utility of measuring its expression is hampered at present by variations in scoring procedures and the lack of standardization for different types of specimens, explains Mitch Dowsett, PhD, head of breast cancer translational research at the Royal Marsden Hospital and Institute of Cancer Research in London, United Kingdom, and co-chair of the International Ki-67 in Breast Cancer Working Group. "The direct application of specific cutoffs for decision making must be considered unreliable" in the absence of intra- and interlaboratory standardization, he told Medscape Medical News. Dr. Dowsett was not involved in this study.

Dr. K. Tawfik and Dr. Dowsett have disclosed no relevant financial relationships.

American Society for Clinical Pathology (ASCP) 2012 Annual Meeting. Poster 361. Presented November 2, 2012.