Ki-67 (or Ki67) is a measure of the proliferative activity of breast cancer cells, i.e., the proportion of dividing cells. Ki-67 normally can be found in breast cancer pathology reports, including biopsy reports. High Ki-67 has been linked to unfavorable breast cancer outcomes in numerous breast cancer studies.
It provides prognostic information in addition to that given by tumor size, grade, hormone receptor status and number of positive lymph nodes. In other words, tumors of a given size, grade, and receptor and lymph node status with low Ki-67 tend to have better outcomes than tumors with the same characteristics and high Ki-67. Now a new study has affirmed that Ki-67 is a valuable prognostic indicator for luminal breast cancer and that values over 14% indicate poor prognosis.
While women with small, lymph node negative, estrogen receptor positive (ER+) tumors generally have a very favorable prognosis, some do relapse. Ki-67 can help determine which of these women might benefit from chemotherapy. In addition, Ki-67 can help predict progression of LCIS to invasive breast cancer. The effectiveness of adjuvant (presurgical) systemic treatment also can be evaluated by comparing Ki-67 before treatment (in the biopsy tissue sample) to Ki-67 after breast cancer surgery.
Ki-67 is a marker of breast cancer cell proliferation
Ki-67 is an antigen, a compound that causes the immune system to produce antibodies against it. Ki-67 is a protein found only in growing, dividing cells and not in cells in the resting phase of the cell cycle. Although it is apparent that Ki-67 has an important role in cell division, its exact function is not well understood. Nevertheless, it appears to be a useful measure of proliferation. High Ki-67 is defined variously by different researchers. Generally speaking, Ki-67 levels over 14% to 25% are considered high (depending on breast cancer type and biopsy type) whereas levels over 40% are considered very high.
Luminal breast cancer
Breast cancer has traditionally been classified by breast cancer cell receptor status. Receptors are proteins found on some cells to which hormones such as estrogen and other compounds will attach. For example, estrogen receptor positive (ER+) cancer cells incorporate the estrogen receptor protein. However, researchers are increasingly categorizing breast cancer according to whether it is luminal, basal (also known as basal-like) or HER2 positive. These are molecular phenotypes determined by gene expression profiling.
Luminal cells are designed to secrete water and nutriments to produce breast milk. Luminal tumors can be subdivided into luminal A and luminal B. Up to 60% of breast cancer patients have luminal A tumors. Luminal A breast cancer is normally strongly estrogen receptor positive (ER+) and progesterone receptor positive (PR+) and not HER2 overexpressing, with low tumor grade and low proliferation. ER+/PR+/HER2- tumors are usually luminal A. Luminal B breast cancer is characterized by weak to moderate ER and PR positivity. It can be HER2- or HER2+ and may have low tumor grade, but has higher proliferation and DNA instability than luminal A. ER+/PR- and ER-/PR+ tumors normally have luminal B phenotype.
Latest research finds Ki-67 predicts luminal BC prognosis
The study referenced at the beginning of this news story was designed to investigate the prognostic significance of Ki-67. The authors also wanted to establish the most accurate and useful prognostic cut-off for high Ki-67. To conduct the study, the authors used data regarding 495 fine needle biopsies from patients with luminal breast cancer who underwent surgery between 2005 and 2011 at Hospital de la Santa Creu i Sant Pau, Barcelona. The study excluded women with stage IV or HER2+ disease. Clinical records were used to obtain pathology data such as tumor grade and Ki-67.
Ki-67 was found to be a continuous variable associated with both unfavorable overall survival and unfavorable breast cancer-specific survival. In other words, generally speaking, the higher the Ki-67 percentage, the worse the outcome. The authors determined that breast cancer-specific survival was poor when Ki-67 exceeded 14%. On the other hand, relapse-free survival was not found to be associated with Ki-67 during the study period. The authors conclude that the prognosis of luminal breast cancer can be predicted using Ki-67 and that a standard cut-off value of 14% for fine needle biopsies makes sense. The authors note that information about the specimen type used to determine Ki-67 should be recorded in the pathological report.