Patient Care

What is Ki-67 in Breast Cancer? It Can Spell the Difference in Treatment Options

Mar. 14, 2022

At first glance, two 50-something women with breast cancer appear to have similar cases. But an article by Wilmot Cancer Institute experts points out that technically, only one woman is eligible for a newer, potentially lifesaving treatment due to slight differences in tumor markers.

The article raises questions about rules around using the latest therapies — and illustrates how nuances in tumor biology can have a major influence on treatment choices. It also speaks to the critical need for consistent, high standards for pathology testing across the U.S.

Dr. Ruth O'Regan leans against a laboratory bench
Ruth O'Regan, MD

Co-author Ruth O’Regan, M.D., a national thought-leader in breast cancer and executive at Wilmot, would like to see the U.S. follow Europe and loosen the limitations for the breast cancer treatment in question, known as CDK inhibitors.

“We believe that restricting the use of these drugs is controversial and deserves more discussion,” she said.

O’Regan and David Hicks, M.D., a professor of Pathology and Laboratory Medicine who has devoted his career to innovations in breast tumor analysis, described two cases of breast cancer in postmenopausal women in a “Grand Rounds” article in the Journal of Clinical Oncology.

Both women were diagnosed with stage 2 breast cancer, which had begun to spread to the lymph nodes. Each woman faced a high risk of the cancer recurring after initial treatment was completed. Testing also showed that the hormones estrogen and progesterone were largely fueling each person’s disease.

A key fact separated these Wilmot patients, however: Only one was eligible for CDK therapy, which has a proven survival advantage.

The reason? Her tumor had a higher level of a cancer-related gene known as Ki-67, indicating rapid reproduction of cancer cells.

A mixed bag of clinical trial data has shown that certain levels of Ki-67 in breast tumors support better outcomes for patients who are treated with CDK inhibitors. The FDA approved the use of CDK inhibitors for individuals whose tumors have Ki-67 levels of 20 percent or higher.

But, O’Regan said, this leaves out women whose tumors have Ki-67 markers at 15-to-19 percent, for example, even though other factors in their cases may indicate that treatment with the drug would help.

One clinical trial in the U.S. does, in fact, support the use of the newer drug for tumors with lower levels of Ki-67, and Europe’s equivalent of the FDA approved the CDK treatment without limitations, O’Regan noted.

headshot of Dr. David Hicks, pathologist
David Hicks, MD

The lynchpin in the U.S. is that measurement of Ki-67 is notoriously inconsistent across hospital systems and clinical laboratories. Many institutions do not routinely check for this tumor marker — although all breast cancer patients at Wilmot receive Ki-67 testing in optimal, standardized laboratory conditions, O’Regan said.

It will take time to overcome the testing hurdle nationwide, Hicks and O’Regan wrote, due to variability among practices and materials available.

Meanwhile, O’Regan continues to assess cases on an individual basis, often in collaboration with Wilmot’s tumor board, and has achieved insurance approval for CDK therapy for a few patients that fell outside of current FDA eligibility requirements, she said. 

CDK inhibitors are also available to women with stage 4 breast cancer; limitations only exist for earlier-stage disease. Breast cancer patients should ask their doctors about this newer form of treatment, O'Regan said.   

O’Regan is the Charles A. Dewey Professor and Chair of Medicine at the University of Rochester Medical Center, as well as the Associate Director of Wilmot’s education and mentoring program. Hicks has studied tumor markers in breast cancer for several years at URMC and helped to develop national guidelines on estrogen-receptor and HER2 gene testing.