Adrian Lee, PhD, director of the UPMC-Pitt Institute of Precision Medicine and Professor at the UPMC Hillman Cancer Center discusses de-escalation of breast cancer treatments.
Interview conducted by Ivanhoe Broadcast News in September 2022.
Can you describe what is a de-escalation of treatment? What is standard, and what were you looking to find out?
LEE: We’ve made great progress in the treatment of breast cancer. There’s been a 40% reduction in death from breast cancer over the last 30 years. Through those advances, we’re doing better with outcomes. But now, we’re trying to make sure that we get the right treatment to the right patient. In some of those cases, it means giving less therapy, trying to give the right therapy to those aggressive cancers and for those indolent cancers giving less therapy. We call this de-escalation or de-implementation.
Could you give some examples of some treatments that at one time were automatic across the board that maybe you could look at backing off on?
LEE: A good example was the use of chemotherapy in early breast cancer. This was was given to the majority of breast cancer cases in the early 2000s. But then, a test came out called OncotypeDx which allowed the physician to decide whether to give chemotherapy or not, and that test reduced the use of chemotherapy by about 30%. Importantly, some women and men were receiving the chemotherapy with little benefit but getting the toxicity, but it is clear that they now don’t need to receive this treatment.
What else are researchers looking at in terms of de-escalation?
LEE: Now we’re looking at different surgical type techniques. For example, looking at the sentinel lymph node biopsy (SLNB), which is a surgery to look how far the breast cancer has spread. We’re looking to see whether we can reduce the use of SLNB. Then, also radiation therapy. There are now trials showing that we can reduce the use of radiation therapy in certain types of breast cancer and thus reduce the toxicity.
What’s the benefit to patients if you’re able to reduce the amount and types of treatments?
LEE: Both of those treatments have quite significant toxicities. With sentinel lymph node biopsy, you have a risk of lymphedema, which many men and women suffer from with swollen arms when you’ve removed those lymph nodes. Radiation therapy obviously is not an indolent treatment, that has many toxicities. So, if we can safely reduce use and in cancers where we know that they’re unlikely to recur, then that’s good for everyone.
What did you find in the 70 and over population when you studied those women?
LEE: In early-stage breast cancers in the elderly, the risk of the breast cancer recurring is very small. That’s what we found in our data set. When you do sentinel lymph node biopsy or radiation therapy, it doesn’t change that risk very much. So, you’ve given someone this toxic therapy, yet it’s had very little effect on their outcomes, so, we are now trying to better define for which of those elderly patients we do not need to use these therapies.
You are also taking steps to study women younger than 70, in the 50 to 70 range. Can you talk about why this range and why is that important?
LEE: We’re trying to understand, is there something unique about those elderly breast cancers, the ones in the older 70s? Is there something about the age, the environment of the person which it developed in that makes it different for therapy? But given our success in identifying those, maybe we can find a similar subset in younger patients. Can we reduce therapy in them, too?
How are you and your colleagues going about the study and how are you looking at all of that data?
LEE: We look at real-world data or real-world evidence. This is data that’s collected just in standard clinical care through our large health care system. We now have electronic medical records and we can sift through that with computers. These computers go and search using something called natural language processing. They search for certain text features that say this is an elderly patient who did or not receive that type of therapy and did or not have this type of outcome. And we have a very large database to do this. We’re essentially learning from the patients we treated. This is called a learning health system.
How long will you study that 50- to 70-year-old data set? When do you anticipate that you would have some kind of findings or some kind of suggestions as where to go next?
LEE: So, the beauty of it, these computers sift through this data pretty fast. We can process the data relatively fast to find these patients, and we’ve already done that, and are now looking at their outcomes. Sometimes, you have to go back and spot check the data as some of the language is quite hard to understand. But we hope relatively soon to know whether we can identify those subsets that don’t require therapy.
What are the implications of having this information?
LEE: We can extend this work to other areas. There are many other areas – for instance, immunotherapy. Most patients receive immunotherapy for their lifetime once they’ve been given it. But we have other trials now trying to de-escalate the use of immunotherapy, i.e., if someone has had an excellent response after one year, do we need to continue therapy forever or can we stop? If this works, it would be good for the patient – they don’t have to take that therapy forever – and it’s good for the health care system because these are wasted dollars on those treatments.
How difficult is it to strike that balance for each individual patient knowing how much is just the right amount and not too much and not too little, where you run the risk of that cancer coming back?
LEE: Every case is unique; each treatment plan is very personalized between the patient and the physician. Understanding how to reduce treatment is difficult research as physicians and patients would like to do the most to reduce the risk of recurrence. And we certainly don’t want to reduce therapy and cause harm. That’s one of our immediate and central goals. However, we don’t want to give aggressive therapy to everyone. We know that in certain cases we’ve been over treating breast cancer. The idea is just how do we make sure everyone is aware, both the physician and the patients, that there are some indications where it’s not required. We do that through education, for example. We try to educate about the risks of recurrence and the benefits of each of the treatments associated with those associated toxicities.
Is there anything you would like to add about your research and de-escalating therapy?
LEE: I think it should be clear that we’re trying to right-size therapy. All patients have standard therapy, it is just ensuring that it is the right amount of therapy. They’re going to have surgery. They’re going to have other therapies. We’re trying to just give the right size of the therapy and the right type of therapy. We’re trying to make it more precise for the patient who’s being treated.
END OF INTERVIEW
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