Q&A: Few options exist to watch for, prevent breast cancer recurrence
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Although an abundance of treatments exist for breast cancer, there are almost no options for screening patients for risk for recurrence or spread of early-stage breast cancer, representing a major unmet need in the field.
Although liquid biopsy procedures are currently being developed in the hopes of changing this landscape, watching for and preventing the recurrence and spread of breast cancer looks to remain a challenge for years to come.
Healio spoke with Heather A. Parsons, MD, MPH, a medical oncologist at Dana-Farber Cancer Institute, to discuss the major risk factors of breast cancer recurrence and spread, what screening options are in development, and how she addresses those fears in her patients.
Healio: When you have a patient diagnosed with breast cancer, what kind of game plan do you put together in order to prevent that from spreading and metastasizing?
Parsons: Breast cancer is not one disease, but many diseases, so the first step is to understand both how extensive the cancer is — in terms of whether it's in the breast, the lymph nodes, how large it is — and then also, what kind of breast cancer it is. Is it hormone receptor positive? Is it HER2 positive? Is it triple negative? Because those guide our treatments, and then, we're lucky in that we have a lot of data over a long history to guide us in terms of what treatments are most effective in patients with breast cancer.
We know that, for instance, hormone receptor-positive breast cancer, even people with the smallest breast cancer will benefit from taking an antihormonal therapy, such as an aromatase inhibitor or tamoxifen. So we guide patients to take those kinds of therapies in addition to obviously local treatment, like radiation and surgery. In more advanced disease or triple-negative or HER2-positive disease, we more often use systemic therapies that include chemotherapy or other targeted therapies too.
But we have so much data —a list of very many effective therapies — and we're able to see the patient in front of us, understand the cancer, and then guide their therapy based on that, all with the goal of making sure the cancer is gone and doesn't come back. And that we do just enough and not too much to be able to make that happen.
Healio: What kind of signs do you look for from a patient with early-stage breast cancer that might show that the cancer is actually spreading?
Parsons: It's surprising to many patients with early breast cancer and their family members — because of the data that we have to support this — that once somebody is finished with their definitive curative-intent treatment for their early breast cancer, the approach to surveilling and watching to make sure the cancer doesn't come back is fairly straightforward and minimal.
We see patients once every 6 months, typically. We do a physical exam and a history to look for any suspicious signs or symptoms, and then, if somebody does develop symptoms or signs that we're worried about, then we do sort of a directed investigation of those symptoms to find out whether the cancer might be coming back or what's causing their symptoms.
We do not do regular interval scans, which is different than some other solid tumor types where every 3 months they might do a CAT scan or a PET scan. And the reason for that is that there are data saying that that is not helpful. It doesn't help people live longer. It doesn't help find the cancer earlier in a meaningful way, and so, right now, that's the standard of care.
It is scary for patients, and we are working on developing better ways, including liquid biopsy tests — which is what I work on — to potentially be able to guide, identify recurrence earlier, and then better take care of patients and help them do better.
Healio: How do you manage communicating with patients who are worried or soothe their fears when they’re at risk for breast cancer recurrence or spread?
Parsons: The reassuring thing about breast cancer overall is the vast majority of patients who have an early breast cancer will do very well and never hear from their breast cancer again. That's really reassuring to patients to hear that.
Even patients who have, for example in HER2-positive breast cancer, a very locally advanced cancer that's involved in the lymph nodes and is a big tumor, because of the effective therapies we have, the likelihood that that's going to come back is actually pretty low. So we can provide reassurance in that way, and also reassure them that if they have a new symptom that they're worried about that persists for more than a few weeks and is getting worse, we want to take them seriously and investigate it.
It's not that because we're not doing these interval scans that we're not going to ever scan or look for something; it's that we will do that based on those symptoms, guided by those symptoms and signs.
Healio: What’s the current state of screening options you have for patients with early-stage breast cancer to watch for spread?
Parsons: We don't do regular tests right now — the tests that we're working on develop — because those tests haven't been shown to make a difference for patients, and that's why it's sort of a need in the field to do that. The hope is that these tests, such as cell-free DNA- or circulating tumor DNA-based — what are sometimes called liquid biopsy tests — may be helpful in understanding whether cancer has come back and whether we can guide our treatment to help that patient not have a metastatic recurrence, but to be able to treat that cancer.
And there are a lot of promising studies — they’re small, but they’re quite encouraging — that if we find this circulating tumor DNA in the blood and all cells release this kind of cell-free DNA, cancer cells release it too. We can detect that kind of circulating tumor DNA from a cancer cell with these sort of very specialized sensitive sequencing approaches, and by doing that, predict people having their cancer come back.
And they're very, very specific, so if you find the CT DNA, across studies in basically in 100%, if you follow patients long enough and if they haven't received treatment since the the last blood draw, they will have their cancer come back. So, those are really promising. We are working on the opposite, which is if you have a negative test, are you really sure that the cancer is never going to come back? That is less certain right now.
The tests are improving in their sensitivity — they're not there yet. We're trying to do trials right now that are looking at adding treatments for patients who have a positive test, and that's really exciting. There are already ongoing active studies looking at that, and the hope is that — because again, most patients with breast cancer will do so well — we may be able to tailor therapy, both escalating treatment for patients who have a positive test and, potentially, if it's safe, deescalating for patients who have a negative test. We're not there yet, but that's the hope that we can get there.
Healio: What unique challenges exist in preventing breast cancer recurrence and spread as opposed to other types of cancer?
Parsons: The challenge in breast cancer is that even though most patients will do really well, there's still more than 40,000 deaths in the U.S. every year from breast cancer and nearly 700,000 in the world. Figuring out which patients are the patients who need more therapies to help prevent the cancer from coming back is a big challenge, because those studies to figure that out take many thousands of patients.
Because we don't have good tests to figure out who those people with potentially lethal breast cancer are, we take all of them and give them a medicine and then see if it works. But we know that in doing those studies, we're giving medicines to too many people, and we're hopeful that with better tests we could figure out who those patients are and then test the drugs in those patients who really need them.
Healio: What risk factors exist for recurrence of breast cancer, and how has our understanding of that evolved in recent years?
Parsons: We have quite a good understanding of some of the clinical and some of the genomic or molecular predictors of recurrence. Some of those are things that have been around that we've known about for a long time, such as the size of the initial cancer, whether and how many lymph nodes might be involved, whether the cancer has gone beyond the localized lymph nodes and into some sort of next stage lymph nodes, and then other things about the cancer, like grade, how fast growing the cells are.
For some cancers, , we have gene expression tests, such as Oncotype [Exact Sciences] and MammaPrint [Agendia], that can give us a score by measuring gene expression to tell us how likely somebody is to have their cancer come back versus not.
And for the subtypes, triple-negative breast cancer is much more likely to recur. HER2-positive breast cancer without appropriate treatment is much more likely to recur — though with treatment, it's one of the most successful therapies, so patients do really well. And hormone receptor-positive breast cancer, which represents the most breast cancers, can be sort of across the spectrum depending on those other factors that we see.
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