Breast Cancer Management: Monitoring Patients for ILD

Mark D. Pegram, MD: Interstitial lung disease [ILD] is a diagnosis of exclusion. It’s seen with numerous drugs that we use in breast cancer, such as CDK4/6 inhibitors, everolimus, and trastuzumab deruxtecan. So we are constantly screening for this condition, first by taking a careful history. The review of pulmonary history becomes critical in an era where we have drugs that can cause interstitial lung disease. Consequently, we have much more focus now on the review of systems for any even subtle signs or symptoms of pulmonary dysfunctions. That would be cough, shortness of breath, hemoptysis, chest pain, dyspnea with exertion—all these things now are a critical part of the history just on a routine follow-up visit if patients are on any of these drug classes that can be associated with ILD. Moreover, for patients on these types of drugs, when we’re restaging the tumors to see if they’re responding, and if so, how long they’re responding to their current treatment, that’s an opportunity for us to look at the lungs critically using CT imaging of the thorax. That’s also very important, and it’s key to stay on schedule with those staging intervals in patients who are on drugs that can lead to ILD so that you don’t miss a window by skipping a set of scans, for example. For certain drugs, it’s really not a good idea to spread out staging intervals, whereas for more indolent disease treated with let’s say, endocrine therapy alone, sometimes you can have a long remission where you can spread staging intervals out and get fewer scans and therefore, less radiation, less expense, and so forth. But for drugs like trastuzumab deruxtecan, that’s just not possible because we really need to get an imaging look on a periodic basis to look closely at the lungs for any signs or radiographic evidence of ILD, even if it’s subclinical.

We don’t often get pulmonary function tests until after we have, let’s say, a suspected case. It has not yet been shown whether there’s any advantage to routine pulmonary function testing. Things like the FEV1 [forced expiratory volume in the first second of expiration] and vital capacity, those probably aren’t going to change until fairly late In the course of an ILD. So as a screening tool, I don’t think that would be very effective. The diffusion of carbon monoxide might be an interesting measure to look at if you could do it serially as a screening tool. But that work is still underway at various centers studying ILD to see whether DLCO [diffusing capacity of the lungs for carbon monoxide], for example, might be an earlier clue to interstitial lung changes. Finally, whenever we get vital signs in the clinic, it’s routine for us to get a pulse oximeter reading, at least in our clinic. But again, that’s probably going to be a late finding of ILD because of the shape of the oxygen hemoglobin, the saturation curve being a sigmoidal-shaped curve, you have to have pretty profound hypoxia before you’ll start to notice it with a hemoglobin saturation by pulse oximeter. So the pulse oximeter probably won’t be good as a screening tool, but it can be maybe useful to monitor an existing ILD, for example.

Joyce A. O’Shaughnessy, MD: The agents that can cause ILD generally do not cause it frequently. In my practice, I don’t do any particular monitoring for ILD. Some practices are getting O2 [oxygen] saturations every time a patient comes in as part of their vital signs. We’re not doing that. We are usually getting baseline scans, usually a chest CT scan will be a part of the baseline staging evaluation, so we’ll have that. Sometimes patients have antecedent pulmonary disease. They already have their pulmonologist, and so that’s very useful if they have significant COPD [chronic obstructive pulmonary disease]. Here, in Texas, there are a lot of allergies, so there’ll be a lot of asthma and bronchospasm. But basically, we just talk to the patient. We usually rely on history quite a bit for any type of shortness of breath, fevers, and cough. We are always asking that for these agents that can cause ILD. Then we’ll get routine restaging studies. I usually won’t repeat the chest CT scan, unless they have pulmonary disease. If they have liver disease, I’ll get abdominal CT scans. I won’t get chest CT scans. Sometimes however, you’ll see either on the chest or even in the abdominal CT, the lung bases. You can see some ground glass appearance, with patients totally asymptomatic. Then I will probably go ahead and get a full chest CT.

When I see any changes in an asymptomatic patient or a symptomatic patient that are potentially compatible with ILD, I’ll get the pulmonologist involved. It’s complicated because patients experience reflux quite a bit when they’re on these therapies. There’s a lot of acid reflux. There’s some aspiration. The patient is unaware; they’re doing fine. That can cause this low-grade inflammatory ground glass appearance. We have a lot of people with allergies. They can get bronchiolitic changes, and so forth. Also in Texas, we have a lot of histoplasmosis. There’s a lot of old granulomatous disease as well. It’s not easy, but if a patient is symptomatic, if they go to being short of breath or coughing, that’s a different matter. We get them right away to the pulmonologist. But in general, we’re erring on the side of getting pulmonary specialists involved to try to differentiate between any type of a drug-related ILD or just other interstitial changes or parenchymal changes for other reasons. They’ll go ahead and do a bronchoscopy oftentimes and biopsy. If you get a biopsy, you are able to really tell if it’s ILD. The pulmonologist will do that. Or they’ll just watch the patient; they’re not concerned, they will just watch the patient, they won’t think it’s ILD. They’ll just keep a careful eye on patients.

Charles A. Powell, MD, MBA: There are some treatments associated with a risk of interstitial lung disease, and as the treatment options are being reviewed it’s important to know what a patient’s individual risk may be for developing interstitial lung disease, or for having significant respiratory compromise if they do develop interstitial lung disease. One of the first questions that needs to be asked is, does the patient have a prior history of interstitial lung disease? Related to that, does the patient have abnormal lung function at baseline, and does the patient have abnormal chest imaging at baseline? If the answer to all those questions is no, then it’s useful information that would then not necessarily require any intervention or evaluation by a pulmonologist before moving on to treatment. If the answer to those questions is yes, then there probably will be value to a more in-depth assessment of the nature of the potential underlying lung disease that a patient may have to inform the clinical decision-making among the choice of anticancer therapies that may be helpful for the patient’s tumor.

Transcript Edited for Clarity