The Arsenal of Metastatic Breast Cancer Imaging Modalities Continues to Expand

Rena D. Callahan, MD

A range of imaging modalities are crucial to diagnosing metastatic breast cancer and assessing treatment response, including standard computed tomography (CT) scans and nuclear medicine bone scans, as well as positron emission tomography (PET)/CT, which is growing in use, according to Rena D. Callahan, MD. However, repeat biopsies are the key to accurately following metastases, she emphasized.

“This area of biopsies, tissue biopsies, liquid biopsies, and better imaging is in evolution.” Callahan said. “We need to do more studies to prove that these [imaging modalities] are not just costly, but actually useful.”

In an interview with OncLive®, Callahan discussed the current standards for breast cancer imaging modalities, the complexities of using bone biopsy, and the importance of continuing to study nonstandard imaging modalities to increase the accessibility of breast cancer imaging for metastatic disease.

Callahan is an associate professor of medicine at the David Geffen School of Medicine at the University of California Los Angeles.

OncLive: What imaging modalities are available in breast cancer, and what are some of the distinguishing features between them?

Callahan: For breast cancer, there are standard imaging modalities [we can use] if we’re looking for metastases, or we’re looking in a patient with metastatic breast cancer to determine response to treatment. These include CT scans, such as a CT scan of the chest with contrast and a CT scan of the abdomen and pelvis with and without contrast, and nuclear medicine bone scans. These are considered standard imaging [tools] and are generally used in clinical trials to make these assessments because they are widely available and generally covered by insurance and agreed upon across the United States and international study sites.

However, we often use other imaging modalities as well, such as PET/CT. Although not technically considered standard imaging, PET/CT is widely used in assessing metastatic breast cancer, because in 1 study, you can assess organ involvement, lymph nodes, and bones. That can be more convenient for the patient. Additionally, it generally covers from the base of the skull to the middle of the thigh, so you get a bit more information than just a CT [of the] chest, abdomen, and pelvis. That’s usually what we’re talking about when we’re using imaging.

Sometimes we use magnetic resonance imaging [MRI]. The utility of MRI is primarily for central nervous system metastases. PET scans and CTs of the head are not sufficient to evaluate for brain metastases, especially when brain metastases are small. You need to do a brain MRI with contrast to look for these types of metastases. Sometimes, if you’re looking at the spine and need to evaluate for spinal cord compression with the tumor or leptomeningeal metastases, that is another situation in which MRI of the spine and the brain is useful and better than other imaging modalities.

What workup elements are required for bone biopsy, and what are some of the challenges associated with this?

Before a bone biopsy, you need to have your interventional radiologist, who is usually performing this type of biopsy, identify the target. This cannot be done with a bone scan. Logistically, they can’t use a nuclear medicine bone scan in real time and target the metastatic focus. Generally, they’re using CT guidance.

Sometimes, there is a metastatic focus with a soft tissue component, which makes it easier for them to identify, as well as easier to obtain sufficient material to analyze. However, there are other bone lesions that don’t have that soft tissue component. They may be sclerotic. Those bone lesions may represent treated metastases. You may try to biopsy 1 of these lesions and get nothing, [because there are] no cancer cells in there that you can analyze.

When feasible, and when you do get cancer cells from bone biopsy, there’s an additional challenge. Sometimes you can identify adenocarcinoma in a specimen, but that’s not good enough for us. For breast cancer, we need to be able to analyze estrogen receptor [ER] and HER2 status. Then, there’s next-generation sequencing [NGS] that we perform to look for mutations that are targetable with some newer therapies.

Also, the bones need to go through a decalcification process, generally, to be analyzed. Unfortunately, 1 of the issues with decalcification is that proteins are degraded. Some of these proteins are what you’re looking for, so you can miss a mutation that’s targetable with a bone biopsy, even if you can find cancer cells. It could lead you astray. For example, you may do a bone biopsy and the ER returns negative, and you’re in a situation where you’re not sure whether the tumor lost its ER or whether [this result is] just an artifact from the bone biopsy and the technical issues associated with biomarker testing.

How do you use bone biopsy in your practice?

When I’m deciding where to biopsy, I will typically do a scan and try to find a non-bone lesion. Sometimes, patients have bone-only disease, so you have no choice. In those situations, I will often try to biopsy a bone lesion. We’ll review with the radiologist what we think may be the most high-yield and approachable location. [The location needs] to be technically feasible. If a patient has a spot in their vertebrae, those are tricky to approach. However, I will routinely send liquid biopsies because often circulating tumor DNA [ctDNA] is shed into the bloodstream, and we can pick up targetable mutations, for example, ESR1, with the liquid biopsy, at a rate that’s triple [the rate] we can find with the bone biopsy or tissue biopsy.

What is the importance of using diagnostic imaging to determine bone dominance in metastatic breast cancer?

Sometimes, it is hard to find all the metastatic disease. When we use CT scans, we might miss bone metastases. That’s why it is important either to do a nuclear medicine bone scan to look for these bone metastases or potentially a PET/CT or an MRI to find them. It guides therapy because we use bone-directed therapies, such as denosumab or zoledronic acid when a patient has bone metastases, so we need to look for them.

Are the guidelines around bone biopsy and these diagnostic imaging modalities complete, or do you feel there are gaps that still need to be evaluated and discussed?

This is in evolution. There will always be some gaps because science moves at a rapid pace. These imaging modalities are upgraded. We still don’t consider PET/CT standard imaging, even though many of us use it in our practice. That’s certainly not uniform. There are other kinds of PET scans with different labels, such as an fluoroestradiol PET/CT, that’s not considered standard imaging either, [However], that is on the horizon [to help] look for difficult-to-find estrogen-positive metastases in patients with trickier cancers, for example, lobular breast cancer, where you see a tumor marker going up, and you can’t find the cancer. These nonstandard imaging modalities will be increasingly used for this purpose.

What main message would you emphasize for your community partners who do not see patients with breast cancer as frequently?

We often think of tissue biopsies as the gold standard for cancer. Although that is true for initial diagnosis, when we are talking about metastatic disease, we need to be able to keep up with the cancer. Using archival tumor specimens will not give us a complete picture, because the cancer is in evolution over the course of metastatic disease. We need to repeat biopsies and send liquid biopsies to perform NGS on ctDNA, or we will miss some targetable mutations.

What ongoing or planned breast cancer imaging research would you like to highlight, and what additional research still needs to be done in this area?

Looking for ctDNA to pick up recurrence of cancer or progression of cancer is an exciting field. It’s easy to do because you just need a few vials of blood. Where we fall short right now is: What do we do with this information? Do we make a change based on these biopsies prior to being able to see changes on our standard imaging? Ongoing studies are investigating an intervention when we see ctDNA either change and acquire a new mutation or increase in number, indicating early signs of progression.

With insurance, there’s a lot of heterogeneity and payers. Interestingly, with more modalities, some insurers are tightening restrictions on what they will approve, because these modalities, for example, PET/CT, are becoming more widely available, and we want to use them. I’ve often run into a challenge where an insurer will say that first, I need to get the standard imaging, and then if there are equivocal lesions, I can get the PET scan.

We need more studies that show how we can use these other nonstandard imaging modalities, such as fluorodeoxyglucose PET/CT or fluoroestradiol PET/CT PET/CT, and how they can affect physician and patient decision making and outcomes. An interesting study was presented recently at a national meeting that [evaluated the efficacy of] PET/CT in predicting response to preoperative therapy and making a treatment change based on that. There are other cancers for which PET/CT has been a standard imaging modality, such as lymphoma. That is not the case with breast cancer yet because the data have not yet shown utility but could.