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

Ki-67 is a protein found in the nucleus of cancer cells that are actively growing and dividing. For breast cancer, Ki-67 is one of the main tumor biomarkers that your healthcare provider will check for when diagnosing, staging, and monitoring the cancer.

A higher level of Ki-67 means that the cancer cells are multiplying at a faster rate. Thus, 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.

Use of the Ki-67 test in breast cancer remains controversial. This article explains why, along with how the Ki-67 test works, and what different results may mean for your care.

Verywell / Madelyn Goodnight

What Is the Ki-67 Protein?

Normal living cells divide in two to produce new cells. The process of cell division (mitosis) is strictly regulated, occurring in controlled stages so that only certain groups of cells are dividing at any given time.

Occasionally, cells escape the strict controls of mitosis and develop gene mutations that cause them to no longer understand their instructions. If the cells continue to mutate and rapidly divide, they can become cancerous.

The protein Ki-67, also called the MKI67 gene, is present during all active phases of mitosis, and absent in cells that are resting (not dividing). Thus, a higher-than-normal volume of Ki-67 means that cells are dividing at an abnormal rate.

How the Ki-67 Test Works

When diagnosing and staging breast cancer, your oncologist (a 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 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 recommend 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, known as “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 are two categories:

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 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 to better understand 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 5% is considered low.
Thirty percent 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.

The overall importance of Ki-67 as a marker and prognostic factor in breast cancer remains undetermined and somewhat controversial.

Many researchers support the use of neoadjuvant (before surgery) chemotherapy for those with Ki-67 results above 20%. However, there is some evidence that Ki-67 may not be effective in 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.

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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.

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.

19 Sources

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