What does proliferation mean in breast cancer?

Cancer cells do not obey the normal signals to stop growing. They continue to grow and divide in situations in which healthy cells would stop growing. Proliferation is a word to describe the way cancer cells grow and multiply.

How reliable is the Ki-67 proliferation marker test?

Some researchers have found the Ki-67 test to be an accurate indicator of how fast breast cancer is likely to grow. However, other researchers have found that the ability of lab workers to score the test the same is poor. Scientists continue to work to find ways to make the test more reliable and useful for patients.

What does a low Ki-67 mean for breast cancer treatment?

Each person with breast cancer needs an individualized treatment plan from their healthcare team. Overall, a low Ki-67 generally means a less aggressive cancer, A low score is correlated with a better chance of survival. Finally, researchers are working to see if Ki-67 can help guide decisions about treatment choices for breast cancer.

How the Ki-67 Test Is Used in Breast Cancer Treatment

Tumor markers are special lab tests that help doctors diagnose, stage, and monitor cancer. Sometimes these are referred to as biomarkers. There are many different tumor markers, and some are specific to the type of cancer. For breast cancer, Ki-67 is one of the tumor markers that your doctor may check.

Ki-67 is a protein found in the nucleus of cancer cells. The protein exists only in cells that are actively growing and dividing. However, the protein is not detectable when the cells are not growing but are in their resting phase. Because of the way cancer cells produce this protein, a higher level is an indicator that cancer cells are rapidly growing and dividing.

Cancer cells are different from normal, healthy body cells. One of the things that indicates a cell has mutated (been altered) into a cancer cell is that the cell does not stop growing and dividing. Because Ki-67 is associated with cells that are rapidly growing and dividing, it is sometimes considered a good marker of proliferation (rapid increase in the number of cells).

Knowing how much Ki-67 is produced by your tumor can help your healthcare team estimate how likely the cancer is to grow and spread. However, the use of this test in breast cancer is controversial.

This article will describe how the Ki-67 test works, how it is used in cancer care, and what different results may mean.

Verywell / Madelyn Goodnight

How the Ki-67 Test Works

When diagnosing and staging breast cancer, your oncologist (doctor specializing in cancer diagnosis and treatment) will likely recommend a biopsy. During a biopsy, a sample of the breast cancer tissue is removed and sent to the lab for analysis. Your oncologist will request different tests, and you will get your results in a pathology report.

There are many different subtypes of breast cancer, so identifying tumor markers and your specific kind of cancer will help your doctor to find the best treatment.

The test uses an antibody that attaches to antigen receptors on the Ki-67 protein. The higher the concentration of Ki-67, the more the cells will “stain,” or absorb the antibody material and be visible under the microscope.

While healthcare providers increasingly order the Ki-67 proliferation marker test, its overall benefit is not certain. Research is underway to determine how to best apply the information from the test to patient care. Currently, doctors disagree on how to use the test results to guide cancer treatment.

Why It's Used

Your Ki-67 score may help you and your healthcare provider better understand your cancer. The test may help determine your cancer prognosis or your chance of recovery. Your oncologist usually takes several test results into account when trying to understand your unique cancer.

Some studies have found that tumors with higher levels of Ki-67 may have a worse prognosis than tumors with lower levels. There is ongoing research to better understand how to use and apply this information to patient care.

On a more positive note, research has also found that tumors with a high level of Ki-67 may respond particularly well to chemotherapy. Chemotherapy attacks all rapidly growing cells (including healthy cells, such as hair follicles). Therefore, tumors that are more aggressive (divide more rapidly) may respond particularly well to these regimens.

Some researchers are suggesting that Ki-67 testing may be helpful in avoiding unnecessary chemotherapy depending on the cancer's characteristics.

Currently, the American Society of Clinical Oncology (ASCO) clinical practice guidelines recommends that Ki-67 protein levels should not be used to guide decisions about chemotherapy choices after surgery.

Luminal A vs. Luminal B

There are many types of breast cancer. Oncologists recommend treatment based on several different characteristics of the cancer cells. Often, doctors will look at the genes of the cancer cells to better identify and treat the disease. There are several different groupings of cancer types. According to the Mayo Clinic, these are called “luminal” groups.

Among breast cancers that are hormone-positive, there are two distinct subtypes that have different prognoses and may respond differently to treatment regimens.

Ki-67 has been used as part of the data to separate tumors into these two categories. There are many other tests being studied to help with this classification system. One type, MCM2 appears to be a promising alternative. The two categories are:

Luminal A tumors : are estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), HER2-negative (HER2-) and have a Ki-67 index less than 14%.
Luminal B tumors: Luminal B tumors are estrogen receptor and/or progesterone receptor-positive, HER2-negative, and have a Ki-67 index greater than 14%. Or, they are estrogen receptor and/or progesterone receptor-positive, HER2-positive, and have any Ki-67 index.

Your healthcare team will consider your pathology report, the genetic traits of your cancer, and your overall health, to work with you to make a treatment plan for your breast cancer. Scientists are studying the genetic makeup of cancer hoping better understanding will lead to more effective treatments.

Understanding Your Ki-67 Results

In test results, you will see the Ki-67 findings expressed as a percentage. This is the percentage of the total sample that has active Ki-67 proteins. This is used to estimate how many cells are actively dividing, as follows:

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

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

Even though it can be helpful, not all healthcare providers order the Ki-67 test. Do not be alarmed if it is not on your pathology report. Your healthcare team will look at the overall results from all of your tests to assess your breast tumor.

There are other tests that researchers are developing to help understand how cancer behaves. For example, a different test used to assess the growth of breast cancer is called the S-phase fraction. The test measures how many cancer cells are in the process of copying their DNA. This test is also reported as a percentage of the cells. For this test, a percentage greater than 10 is considered high.

Again, the Ki-67 test result is only one piece of the puzzle, so look at the whole picture of your pathology results. Talk to your healthcare provider about how to best interpret your personal test results, and how they may (or may not) affect your treatment plan.

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Controversy

In the medical community, questions about the best cut-off points for the test results are being researched and discussed. The overall importance of this test as a marker and prognostic factor remain undetermined. Ki-67 testing remains controversial.

A 2017 study set out to settle some lingering questions. Researchers report findings that support the use of neoadjuvant (before surgery) chemotherapy for those with Ki-67 results above 20%. However, they concluded that Ki-67 is not effective for determining the prognosis of tumors that do not respond to neoadjuvant chemotherapy.

It is likely that guidelines and use of Ki-67 will change over time as more research is done. Talk with your healthcare team about your questions and concerns.

Summary

Tumor markers can help doctors understand the stage, growth, and seriousness of your cancer. Ki-67 is a biomarker test for people with breast cancer. It is one of many different tests available. Cancer research continues to help medical professionals make the best decisions they can when developing treatment plans.

A Word From Verywell

While gaining information about breast cancer through reading is an excellent way to gain knowledge about breast cancer, if you have breast cancer, consider joining a local breast cancer support group or an online breast cancer community.

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.

Frequently Asked Questions

What does proliferation mean in breast cancer?

Cancer cells do not obey the normal signals to stop growing. They continue to grow and divide in situations in which healthy cells would stop growing. Proliferation is a word to describe the way cancer cells grow and multiply.
How reliable is the Ki-67 proliferation marker test?

Some researchers have found the Ki-67 test to be an accurate indicator of how fast breast cancer is likely to grow. However, other researchers have found that the ability of lab workers to score the test the same is poor. Scientists continue to work to find ways to make the test more reliable and useful for patients.
What does a low Ki-67 mean for breast cancer treatment?

Each person with breast cancer needs an individualized treatment plan from their healthcare team. Overall, a low Ki-67 generally means a less aggressive cancer, A low score is correlated with a better chance of survival. Finally, researchers are working to see if Ki-67 can help guide decisions about treatment choices for breast cancer.

Originally written by

Pam Stephan

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