The Ki-67 Proliferation Marker Test and Breast Cancer Treatment

Ki-67 is a cancer antigen (protein) that's found in growing, dividing cells but is absent in the resting phase of cell growth (when cells are not growing). Because cancer cells grow and divide rapidly, Ki-67 is sometimes considered a good marker of proliferation (tumor marker), helping your doctor follow the progress of cancer. However, its use in breast cancer is controversial.

The Ki-67 test may be performed on a sample of breast cancer tissue to help predict the tumor's aggressiveness. The test, which is performed and interpreted by a doctor called a pathologist, measures the level of Ki-67 expression in the cancer cells through a staining process. 

While the Ki-67 proliferation marker test is increasingly ordered by doctors, its overall benefit, specifically when it comes to making decisions about treatment, is not certain.

Your doctor may order the Ki-67 test as a way to measure how quickly your breast cancers cells are dividing and forming new cells. The test does this by using an antibody called MIB1 on tissue samples. The more cells MIB1 attaches to, the more likely tumor cells are to grow and divide rapidly.

Your Ki-67 score may help you and your doctor determine your cancer prognosis or your chance of recovery. Studies have found that tumors with higher levels of Ki-67 have a worse prognosis than tumors with lower levels.

On a more positive note, research has also found that tumors with a high level of Ki-67 may respond particularly well to chemotherapy. Since chemotherapy is designed to attack all rapidly growing cells (including "normal cells" such as hair follicles), tumors that are more aggressive (divide more rapidly) may respond particularly well to these regimens. This is, in fact, why some very aggressive cancers (such as acute lymphocytic leukemia) that used to be quickly fatal now can often be cured with chemotherapy.

At the current time, one of the most common uses of this test is to predict the response to what's called neoadjuvant chemotherapy—when chemo is used to shrink a tumor and/or lymph nodes in order to make surgery possible—in people with breast cancer that's spread to the chest wall, the skin of the chest, or to many lymph nodes (usually stage 3A or stage 3B tumors). This is called locally advanced breast cancer.

Using Ki-67 as a predictive marker of chemotherapy response, however, is still controversial.

Among breast cancers that are hormone-positive, there are two distinct subtypes that have different prognoses and respond differently to treatment. Ki-67 has been used as an adjunct in separating tumors into these two categories, though MCM2 appears to be a promising alternative.

• Luminal A Tumors: Are estrogen receptor-positive, progesterone receptor-positive, HER2 negative, and have a Ki-67 index less than 14%
• Luminal B Tumors: Are estrogen receptor and/or progesterone receptor-positive, HER2 negative, and have a Ki-67 index greater than 14% or, are estrogen receptor and/or progesterone receptor-positive, HER2 positive, and have any Ki-67 index.

The distinction between luminal A and luminal B tumors can be very confusing if you read breast cancer studies, but it can affect prognosis in several ways.

In test results, you'll see the Ki-67 findings expressed as a percentage:

• Less than 10% is considered low
• 20% or higher is considered high

A "high" score means that the breast tumor is more likely to be aggressive and spread quickly.

Even so, not all doctors order the Ki-67 test, so don't be alarmed if it's not on your pathology report. In addition, it's important to note that other tests are done to assess your breast tumor. These results, along with your Ki-67 Labeling Index (test score) may affect your treatment plan. In other words, your doctor usually takes several test results into account when trying to understand your unique cancer.

For example, another test used to assess the growth of your breast cancer is the S-phase fraction. It's also reported as a percentage and tells you how many cancer cells are in the process of copying their DNA. A percentage greater than 10 is considered high.

Again, the Ki-67 test result is only one piece of the puzzle, so try not to read too much into it. Instead, talk to your doctor about how to best interpret your individual test results, and how they may (or may not) affect your treatment plan.

In the medical community, questions about the best cut-off points for the test and its overall importance as a marker and prognostic factor remain, and that has made Ki-67 testing controversial.

A 2017 test set out to settle some of the lingering questions. Researchers report findings that support the use of neoadjuvant chemotherapy for those with Ki-67 results above 20%.

However, they concluded that Ki-67 isn't effective for determining the prognosis of tumors that don't respond to neoadjuvant chemotherapy.

They also state that Ki-67 should not be used alone in deciding whether to use this form of treatment.

It's possible that guidelines and use of Ki-67 will change over time as more research is done.

While reading is an excellent way to gain knowledge about breast cancer, consider joining a local breast cancer support group or an online breast cancer community. Often, these groups can help you to stay on top of the latest cancer research as well as providing support from people who have faced the uncertainty and controversy surrounding an elevated Ki-67 test.