The Expanding Role of Antibody-Drug Conjugates in Breast Cancer Treatment: Oranus Mohammadi, MD

At a recent Institute for Value-Based Medicine® event, Oranus Mohammadi, MD, a medical oncologist and hematologist at The Oncology Institute in Los Angeles, California, discussed the evolving role of antibody-drug conjugates (ADCs) in breast cancer treatment. Mohammadi highlighted how ADCs such as trastuzumab emtansine (T-DM1; Kadcyla; Genentech), trastuzumab deruxtecan (T-DXd; Enhertu; AstraZeneca and Daiichi Sankyo), and sacituzumab govitecan (Trodelvy; Gilead Sciences Inc) have reshaped the treatment landscape across HER2-positive (HER2+), HER2-low, hormone receptor–positive, and triple-negative breast cancers.

Mohammadi also addressed emerging evidence supporting earlier-line use and combinations with immunotherapies, underscoring the paradigm shift from chemotherapy to ADC-based regimens. In addition, she shared her approach to sequencing high-cost targeted therapies, balancing tumor biology, patient characteristics, payer authorization, and clinical trial evidence to optimize patient outcomes.

This transcript was lightly edited; captions were auto-generated.

Transcript

How has the role of antibody-drug conjugates evolved in the treatment of breast cancer?

ADCs, or antibody-drug conjugates, are a combination of monoclonal antibodies that are more targetable and also the cytotoxic drugs that kills the cancer cells. Basically, we deliver the chemotherapy medication to the cancer cells, so the normal tissues or healthy tissues don't get injured. ADCs, recently, or in the last couple of years, shifted the treatment and the paradigm of treatment in breast cancer. Previously, the backbone of treatment in breast cancer was mostly chemotherapy, and now we see the shift to the ADCs every day.

Initial ADCs were tested mostly in the metastatic setting. I would say the first one was T-DM1 in HER2+ breast cancer. That was initially tested for metastatic setting, and then we found the benefit of it in adjuvant setting or in earlier stage HER2+ breast cancer patients.

After that, we found out about the efficacy of T-DXd and other antibody-drug conjugates in metastatic HER2+ breast cancer patients. Then we found that T-DXd role is not just in the HER2+ breast cancer patients. Now we have a very significant efficacy of this medication in hormone receptor–positive breast cancer with HER2-low or HER2-ultralow, and it changed the paradigm of treatment in breast cancer patients significantly. Now we know this medication has a role in first-line setting. There are lots of investigation or trials in the neoadjuvant and adjuvant setting for patients with HER2+ and hormone receptor–positive breast cancer patients for the use of T-DXd.

Another ADC is a sacituzumab [govitecan] that we found the role of it in triple-negative breast cancer patients. Initially in patients who got treatment initially with the chemotherapy and immunotherapy, so for second line or more lines of treatment. Now we know that sacituzumab has a role in first line, and we can use it in first-line triple-negative breast cancer patients, also in hormone receptor–positive breast cancer patients.

Recently, in the last ASCO 2025, we saw the benefit of sacituzumab with immunotherapy also. We're looking at the role of these ADCs in combination with immunotherapies and other targeted agents. We can move them to the first line and in combination with other treatment or targetable mutations.

I believe that ADCs are currently the backbone of treatment, and then you will find the ADCs instead of chemotherapy in the world of breast cancer.

How do you approach the sequencing of high-cost targeted therapies when multiple options are available, and how does payer coverage impact that process?

Whenever we want to choose a medication in metastatic settings or for different lines of the treatment in breast cancer, the first thing that we look for is the biology to see what type of breast cancer that we have, because each type of breast cancer treatment is totally different. The first thing that I look for is if it’s hormone receptor–positive, is it HER2+, or is it a triple-negative cancer? That's my first thing to go for.

Then I will look at my patients in general. I will look at my patients’ comorbidities, also the functional status and also the patients' wishes to get the treatment. When I find out about these 2 parts, after that, I will look for the actionable mutations that patients have, and the medications that are very well studied or in multiple clinical trials. I will try to pick the medication with less side effects, more efficiency, and also with more clinical trials. As long as authorization by the payers or getting approved by the payers, I will try to document very well about my thought process [around] why I chose this medication, and I will try to put and incorporate the clinical trials that got this medication approved for that patient, so when the insurance or the payer is looking at my note, they know why I picked this medication.