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Breast Cancer ADCs
Navigating Treatment With Breast Cancer ADCs Through Expert Case Discussions

Released: October 07, 2025

Kimberly Podsada
Kimberly Podsada, MSN, NP-C, CNS
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Key Takeaways
  • Early recognition and proactive management of ADC-related toxicities are essential to minimize complications and maintain treatment efficacy.
  • Advanced practice providers should prioritize patient education and multidisciplinary collaboration to ensure timely reporting of symptoms, appropriate supportive care, and individualized dose modifications when necessary.

Antibody–drug conjugates (ADCs) have transformed the treatment landscape for patients with breast cancer, but these present unique toxicity profiles that require effective management. Advanced practice providers have a critical role in recognizing, preventing, and addressing adverse events (AEs) associated with ADCs to maintain treatment continuity and optimize patient outcomes. This commentary highlights 4 case scenarios of patients with breast cancer who will be treated with an ADC.

Case Discussion 1
A 58-year-old woman was diagnosed with early-stage estrogen receptor–positive/progesterone receptor–positive/HER2-positive breast cancer in 2019. She completed neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab, followed by mastectomy/sentinel lymph node biopsy, radiation, and adjuvant trastuzumab/pertuzumab with an aromatase inhibitor. Two years after completing surgery, she was hospitalized for headaches and found to have HER2-positive left cerebral metastases. She proceeded with resection and radiation and started the ADC trastuzumab emtansine. After restaging scans revealed systemic and brain disease progression, she completed stereotactic radiosurgery and started trastuzumab deruxtecan (T-DXd) in January 2024. Her nausea was managed with triplet antiemetic prophylaxis with olanzapine, but her fatigue became severe, limiting activities of daily living, and the T-DXd dose was reduced. A routine staging scan revealed increasing small patchy densities mostly in the upper lungs suspicious of pneumonitis. 

What is your management recommendation based on this finding? 

First, I would call the patient to assess symptoms and hold T-DXd. Unfortunately, treatment with T-DXd comes with a risk of interstitial lung disease (ILD) and pneumonitis, including fatal cases. Although most cases are grade 1/2, it is incumbent on us as healthcare professionals to recognize early signs and reduce the risk of progression. When pulmonary imaging suggests suspicious findings, call the patient to discuss symptoms. If asymptomatic, withhold ADC treatment and consider steroids. The patient can resume treatment once grade 1 (asymptomatic) ILD is resolved. If the patient has symptomatic (grade 2) ILD, discontinue treatment and start steroids immediately. 

Case Discussion 2
In May 2018, a 72-year-old woman was diagnosed with recurrent metastatic estrogen receptor–positive/HER2-negative breast cancer with disease in the right axilla. She completed multiple lines of therapy: fulvestrant plus ribociclib, paclitaxel, eribulin, everolimus, capecitabine, T-DXd, fulvestrant, and capivasertib, but discontinued because of a severe skin/Stevens-Johnson–like reaction and stomatitis, and carboplatin/gemcitabine but eventually dropped carboplatin and added pembrolizumab. She is currently receiving sacituzumab govitecan (SG) but experienced disease progression and reports baseline significant fatigue, neuropathy, diarrhea, and a history of stomatitis.

If she is transitioned to Dato-DXd, what prophylactic patient education is essential to help mitigate common and severe AEs of Dato-DXd? 

This patient needs to be properly educated on strategies to mitigate not only her potential nausea but also oral and ocular toxicities. One common AE of ADCs, including datopotamab deruxtecan (Dato-DXd), is nausea. The phase III TROPION-Breast01 trial reported any-grade nausea in approximately 51% of patients, with only 1.4% reporting grade ≥3 nausea. Grade 1/2 nausea may be bothersome and require additional intervention outside of premedications prior to Dato-DXd infusion. Dato-DXd can also cause stomatitis, including mouth ulcers and oral mucositis. Upfront education should include preventive and prophylactic management of stomatitis, such as using ice chips during treatment, a steroid-based mouth rinse 4 times daily, and a soft toothbrush with flossing. Avoidance of abrasive foods that may contribute to oral tissue damage can also be considered. Ocular toxicities, including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision, are also commonly associated with Dato-DXd use. In TROPION-Lung01 and TROPION-Breast01, dry eye was the second most commonly reported ocular surface event, most of which were grade 1/2. I strongly recommend that patients use a preservative-free eye lubricant 4 times daily and as needed. It is preferred that patients follow-up with their eye care provider before starting Dato-DXd and avoid wearing contacts. 

What should you do if this 72-year-old patient starts Dato-DXd and reports shortness of breath and dyspnea on exertion? 

Dato-DXd should be held, and a chest CT should be performed. Dato-DXd, similar to T-DXd, is associated with a risk for ILD/pneumonitis. When any change in pulmonary status is reported, a chest CT is needed to rule out ILD. Since this patient is symptomatic, Dato-DXd can be held until a complete workup is performed. Regardless of other possible baseline health concerns, such as anxiety, panic attacks, or asthma, that may contribute to pulmonary symptoms, any reported new and concerning pulmonary changes while receiving Dato-DXd or T-DXd require an immediate workup and treatment hold, and multidisciplinary intervention should be considered. 

Case Discussion 3
A 75-year-old woman was diagnosed with early-stage triple-negative breast cancer (TNBC) in 2016 and completed neoadjuvant chemotherapy, lumpectomy/axillary lymph node dissection, and radiation. However, in 2020, an incidentally discovered lung nodule, suspicious for metastatic recurrence, was confirmed as metastatic TNBC. After lobectomy, the patient started atezolizumab and nab-paclitaxel (pembrolizumab was not approved at that time) but reported significant fatigue and developed endocrinopathies because of immunotherapy. Her baseline and chronic comorbidities included osteoarthritis, back pain, diabetic neuropathy, cervical stenosis (status post cervical spine fusion in March 2020), and obstructive sleep apnea. Her BMI is 40 kg/m2, and she has a history of migraines. The patient uses an electric wheelchair because of difficulty with ambulation related to a long history of back pain and other joint pain. After 6 months of therapy, staging scans showed disease progression, and she started SG in December 2020, noting increased fatigue as well as new nausea and diarrhea.

What should be the next course of action for managing this patient’s symptoms? 

Performing a thorough patient assessment is key when formulating an appropriate intervention. Assess whether the patient is using interventions that were previously recommended. Loperamide, antiemetics, and dietary changes are recommended as initial steps. The timing of diarrhea is also important for determining whether intravenous atropine (for early onset) or subcutaneous octreotide (for delayed onset) is needed. Diarrhea occurred in 64% of all patients treated with SG, and grade 3/4 diarrhea occurred in 11%. Nausea occurred in 64% of all patients treated with SG, and grade 3/4 nausea occurred in 3%. Premedicate with a 2-drug or 3-drug combination regimen, and add a premedication antiemetic or olanzapine, if needed. If symptoms are severe, rule out infectious causes and consider hydration and electrolyte replacement. 

Case Discussion 4
A 43-year-old woman was diagnosed with de novo metastatic TNBC to bones, confirmed by biopsy. BRCA testing revealed no mutations. The patient received frontline therapy with paclitaxel and pembrolizumab. After subsequent infusions, she reported neuropathy and hypothyroidism, an immune-mediated adverse reaction. She started long-term thyroid hormone replacement, and the paclitaxel dose was reduced. At the time of disease progression, she started carboplatin and gemcitabine. However, the dose was reduced and discontinued on Day 8 because of cytopenias and fatigue. She is getting ready to start SG. 

When educating this patient, are there specific AEs for which you should monitor or assess? 

In this case, the patient should be educated on and monitored for neutropenia. Neutropenia occurred in 64% of patients treated with SG, and grade 3/4 neutropenia occurred in 49%. Encourage patients to notify their healthcare professionals immediately with any fever, chills, or other signs of infection. Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended for all patients at increased risk of febrile neutropenia; these include older patients, patients with previous neutropenia, and those with a poor performance status or multiple comorbidities. Check the patient’s complete blood cell counts before proceeding with Day 1 and Day 8 infusions and, if needed, hold treatment, initiate G-CSF, delay treatment, or reduce dosage. 

Your Thoughts
How do you integrate early recognition of ADC-related AEs such as ILD, stomatitis, and neutropenia into your routine patient assessments, and what multidisciplinary strategies have you found most effective in preventing treatment interruptions? Post a comment to join the discussion.

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