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Episode 393: Antibody–Drug Conjugates in Metastatic Breast Cancer

The ONS Podcast

Release Date: 12/12/2025

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“I’ll go back to the backpack analogy. When your kids come home with a backpack, all of a sudden their homework is not on the desk where it’s supposed to be. It’s in the kitchen; it kind of spreads all over the place, but it’s still in the house. When we give antibody–drug conjugates (ADCs), the chemotherapy does go in, but then it can kind of permeate out of the cell membrane and something right next to it—another cancer cell that might not look exactly like the cancer cell that the chemotherapy was delivered into—is affected and the chemotherapy goes over to that cancer cell and kills it,” ONS member Marisha Pasteris, OCN®, office practice nurse in the breast medicine service at Memorial Sloan Kettering Cancer Center in New York, NY, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about ADCs in metastatic breast cancer.

Music Credit: “Fireflies and Stardust” by Kevin MacLeod

Licensed under Creative Commons by Attribution 3.0 

This podcast is sponsored by Gilead and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. 

Episode Notes 

To discuss the information in this episode with other oncology nurses, visit the ONS Communities. 

To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library.

To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.

Highlights From This Episode

“What an ADC is doing is taking the antibody and linking it to a cytotoxic chemotherapy with the idea of delivering it directly into the cell. How I explain this to new nurses or patients is a backpack analogy. If we think of it as a HER2 molecule wearing a chemo backpack, it’s going to find the HER2 receptor attached to it and then drop the chemotherapy into the cell via the backpack. Similar to how we come home from work, we open the key to our door, we’re carrying all of our items, and then we drop our own personal items in our house.” TS 2:30

“The reason that so many patients with metastatic breast cancer are able to receive ADC therapy is because they are targeting two very common antibodies that we see in breast cancer. One is HER2 and the other is trophoblast cell surface antigen 2 (TROP2). These are seen across the board. We see these on triple-negative breast cancers, hormone receptor–positive cancers, and HER2-positive breast cancers. And now we have a new way to talk about HER2, which is a HER2-low. ... Recently, we have found that patients who express low levels of HER2 are able to receive ADC therapy, specifically fam-trastuzumab deruxtecan.” TS 4:21

“Another [ADC] that has just been approved is datopotamab deruxtecan. This is another ADC that targets the TROP2 receptor on a cancer cell. This one carries a lot of side effects. I mentioned earlier that you need an ophthalmology clearance because there is a lot of ocular toxicity around this one. We see a lot of blepharitis, conjunctivitis, there can be blurred vision. Another thing we monitor on this one is mucositis. In the package insert, there’s a recommendation for using ice chips while receiving the treatment. ... Then in the HER2-positive and HER2-low space is the big one, which is fam-trastuzumab deruxtecan. This was approved in 2019 for the HER2-positive patients, then more recently in the HER2-low [patients]. The big [side effect] with this one is interstitial lung disease.” TS 10:11

“Interstitial lung disease is an inflammation or a little bit of fibrosis within the lung that causes an impaired exchange between the oxygen and carbon dioxide. This was seen in the clinical trials, specifically around fam-trastuzumab deruxtecan. During the trials, they had a very small percentage, I think it was 1%, that died due to interstitial lung disease. So, this is a very important side effect for us as nurses to be aware of. It typically presents in patients like a dyspnea. A lot of times, it’s like, ‘Well, I used to be able to walk my kid to the bus stop, but now when I walk there, I feel really short of breath.’ Or ‘I’ve had this dry cough for the past couple weeks and I’ve tried medications, but haven’t had that relieved.’ So, we really need to be aware of that because early intervention in interstitial lung disease is key.” TS 12:57

“ADCs are toxic drugs. They have the benefit of being targeted, but we know that they carry a lot of side effects. ... Their specificity makes them so wonderful and we’ve seen amazing responses to these drugs. But also, we want patients to be safe. We want to give these drugs safely. So, we have to assess our patients and make sure that this is an appropriate patient to give this therapy to. I think that’s an open conversation that clinicians need to have with patients regarding these drugs.” TS 18:08