Breast Cancer: Molecular Testing Terms To Know

“These gene changes may be responsible for how the tumor is behaving in terms of its growth, response to therapy, and prognosis,” Dr. Tkaczuk says. “Molecular testing of the tumor tissue may help us to identify treatment targets and essentially identify targeted therapies for our patients.”

Why is Molecular Profiling Important?

• It can determine how fast your tumor may grow.
• It can indicate your potential response to certain treatments and therapies.
• It can predict the likelihood that your cancer may come back.

What is Next-Generation Sequencing (NGS)?

One of the more common tests used for molecular profiling is called next-generation sequencing (NGS).  This is a new large-scale test that can look at hundreds of different alterations and mutations in your tumor in a relatively short time period.

While one day it may be standard to do tumor-based NGS testing on all stages of breast cancer, at the moment it is more commonly used in advanced breast cancer.

“In advanced stage cancer or metastatic breast cancer, next-generation sequencing should be part of routine care,” Dr. Tao says. “It is not always necessary at the outset, meaning right away at diagnosis, but it can often change or influence what’s next after first-line treatment.”

Once diagnosed with advanced or metastatic breast cancer, your doctor should send a sample of your tumor off for next-generation sequencing (NGS). Its results may not be relevant in your first round of treatments, but it could come into play later on if your cancer comes back or you develop resistance to the treatment you are on.

Dr. Tkaczuk agrees: “We definitely do next-gen sequencing on patient’s tumors, but also next-gen sequencing can be done on the blood of patients.”

What is Liquid Biopsy?

The “blood” test Dr. Tkaczuk is referring to is actually another type of NGS called liquid biopsy. It is a newer technology that takes a blood sample and tests it for the DNA from dead cancer cells circulating in your bloodstream called circulating tumor DNA (ctDNA).

It is easier and faster to do than testing a sample of your tumor biopsy. And results can come back within a day or a week, whereas tumor-based NGS results can typically take a few weeks.

But it does have some limitations.

“It is not a perfect blood test, meaning that they can be less sensitive than tumor-based next-generation sequencing,” Dr. Tao says. “But obviously it’s easier and much more straightforward than getting another tumor sample or a tissue sample to send for this specialized testing.”

And as Dr. Tkaczuk reasserts — NGS testing is done only rarely for early stage breast cancer and more commonly for advanced or metastatic disease.

“Next-gen sequencing currently in breast cancer, in particular, is primarily used in patients who have stage four breast cancer,” Dr. Tkaczuk says. “Some of the genetic testing may be actually applicable in treatment of early stage breast cancer, but this is actually not tumor-genetic testing, but germline testing.”

What is Germline Testing?

Germline testing is a kind of genetic testing. But unlike NGS, which specifically looks at alterations or mutations in your cancer (either in your tumor or circulating in your bloodstream), germline testing looks at the inheritable DNA you were born with and was passed down from your parents or other family members that could put you and your family at higher risk for certain cancers.

“These are cancer predisposing genes in your lineage that you got from mom or dad, and have potential to pass on to your children,” Dr. Tao explains.

Germline testing is done via blood or sometimes a sample of your saliva, typically when you are diagnosed. Your results can help you and your family know if you have certain genetic mutations, some of which have effective targeted therapies available, like the BRCA1 and BRCA2 mutations.

“The majority of the patients who present with early stage breast cancer now may already be tested for BRCA1, BRCA2 germline mutations,” Dr. Tkaczuk says. “(They) may have additional treatment options in the early stage situation when they may be eligible for treatments with PARP inhibitors specifically.”

PARP inhibitors are a kind of targeted therapy that has been proven to be very effective for BRCA-positive breast cancers. On top of germline testing, from the time of your diagnosis, there is one other essential testing that your doctor should do at the time of diagnosis: pathology testing or what your doctor may sometimes refer to as “tumor marker,” “biomarker” or “marker” testing.

What is Pathologic Testing?

In advanced breast cancer, NGS testing should be routine, according to Dr. Tao and Dr. Tkaczuk. And in both early and advanced breast cancer, germline testing may be done as well depending on certain patient specific factors.

But is there any additional testing you should expect?

“There is pathologic testing on the tumor that helps us understand what specific type of tumor you have and what the features are and what we call the biology of the tumor,” Dr. Tao says.

Pathology testing is done in early and advanced breast cancer. The type of test is called immunohistochemistry (IHC). It typically looks at these four tumor markers, which can help define what subtype of breast cancer you have:

• Estrogen receptor (ER)
• Progesterone receptor (PR)
• Human epidermal growth factor receptor 2 (HER2)
• Ki67

“Immunohistochemistry is a type of staining that looks at proteins on pathology slides. Essentially the pathologist would take a piece of the tumor, create a slide out of it, and then use antibodies to stain to see how much of this protein is expressed on the cancer cells,” Dr. Tao explains.

Measuring these markers will give your doctor a much better understanding of how your tumor will act, as well as which targeted therapies may work best.

“From this testing, we have information about whether the cancer is estrogen positive or triple negative,” Dr. Tkaczuk explains. For example, “in triple negative breast cancer there will be absence of expression of these three primary markers: the estrogen receptor, the progesterone receptor, and the HER2. And the Ki67 proliferation marker for those tumors is typically very high. It could be as high as 80-90%. So these are tumors that are more rapidly growing.”

Additionally, Dr. Tao recommends testing for Lymphovascular Invasion (LVI), which can indicate if your cancer has spread.

“The pathologist looks under the microscope and sees whether the tumor cells are invading into the nearby lymph and vessel structures. It is a way of giving us a general sense of how the tumor behaves,” Dr. Tao says.

The test results will become a reference point for you and your doctor throughout this round of treatment. They will also be closely looked at if you are diagnosed with breast cancer again. Dr. Tkaczuk also recommends re-testing those markers if the cancer returns to monitor its evolution.

“It is extremely important to recheck the primary markers, which are the ER, the PR, and the HER2. And of course, the availability of the tumor biopsy and the tumor tissue is also important from the point of view of sending next-generation sequencing testing on the tissue.”

That will help determine if the new disease has come back or if it is a new, separate breast cancer.

Questions To Ask Your Doctor

• What testing should be done for my breast cancer?
• Should tumor-based NGS testing be done for my breast cancer?
• Have we done germline testing?
• Have we tested levels of my primary markers (ER, PR, HER2, Ki67)?
• How can the results from these tests help guide my treatment options?

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