What Oncology Nurses Need to Know About ADCs in Breast Cancer

Antibody-drug conjugates (ADCs) now span early-stage and metastatic breast cancer, and the oncology nurses and advanced practice providers (APPs) who give them carry much of the work of selecting patients, catching toxicities early, and preparing patients for treatment.

Kelly Fischer, MSN, FNP-BC, and Sarah Fischer, NP, both nurse practitioners in the Breast Medical Oncology Clinic at Dana-Farber Cancer Institute in Boston, Massachusetts, presented "Antibody-Drug Conjugates in Breast Cancer" at JADPRO Live 2026, held October 15 to 18 in Minneapolis, Minnesota.¹ In an interview with Oncology Nursing News following the meeting, they described how their team selects patients, approaches sequencing when evidence is still evolving, and monitors for interstitial lung disease (ILD), neuropathy, cytopenias, and cardiac toxicity.

The session's learning objectives covered evidence-based use of ADCs in early-stage and metastatic breast cancer, guideline-informed sequencing and dose modification, patient counseling to support shared decision-making and adherence, and management of ADC-associated toxicities, including ILD, neuropathy, and cytopenias.¹

Which patients are candidates for ADC therapy in breast cancer?

Biomarker status drives the choice of agent. At Dana-Farber, patients who present with metastatic disease typically undergo genomic testing, often with the Guardant360 assay, according to Kelly Fischer. Hormone receptor and HER2 status come first.

For patients whose tumors are traditionally classified as HER2 negative, immunohistochemistry (IHC) scoring determines eligibility for fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu). T-DXd is approved for unresectable or metastatic hormone receptor (HR)–positive, HER2-low or HER2-ultralow breast cancer that has progressed on 1 or more endocrine therapies in the metastatic setting, based on the phase 3 DESTINY-Breast06 trial (NCT04494425), in which median progression-free survival (PFS) was 13.2 months with T-DXd vs 8.1 months with chemotherapy (HR, 0.64; 95% CI, 0.54-0.76).²

"That's a critical factor in determining what the treatment regimen will be for them," Kelly Fischer said of HER2 IHC scoring.

The ADC landscape has also moved earlier in the disease course and into the first line:

• Early-stage HER2-positive disease: On May 15, 2026, the FDA approved T-DXd followed by a taxane, trastuzumab, and pertuzumab (THP) in the neoadjuvant setting for stage II or III disease, and T-DXd as adjuvant therapy for residual invasive disease after neoadjuvant trastuzumab- and taxane-based treatment, as Oncology Nursing News previously reported.^3,4 In DESTINY-Breast11 (NCT05113251; N = 927), the pathologic complete response rate was 67.3% with T-DXd-THP vs 56.3% with dose-dense doxorubicin and cyclophosphamide followed by THP (P = .003). In DESTINY-Breast05 (NCT04622319; N = 1635), 3-year invasive disease-free survival was 92.4% with T-DXd vs 83.7% with trastuzumab emtansine (T-DM1; Kadcyla) (HR, 0.47; 95% CI, 0.34-0.66; P < .0001).³
• First-line HER2-positive metastatic disease: On December 15, 2025, the FDA approved T-DXd plus pertuzumab based on DESTINY-Breast09, in which median PFS was 40.7 months vs 26.9 months with THP (HR, 0.56; 95% CI, 0.44-0.71; P < .0001).⁵
• Triple-negative breast cancer (TNBC): On June 24, 2026, sacituzumab govitecan-hziy (Trodelvy) was approved for first-line metastatic TNBC as monotherapy for patients who are not candidates for PD-1/PD-L1 inhibitors (ASCENT-03; median PFS, 9.7 vs 6.9 months) and in combination with pembrolizumab (Keytruda) for tumors with a PD-L1 combined positive score of 10 or greater (ASCENT-04/KEYNOTE-D19; median PFS, 11.2 vs 7.8 months).⁶ On May 22, 2026, datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) was approved for unresectable or metastatic TNBC in patients who are not candidates for PD-1/PD-L1 inhibitor therapy, based on TROPION-Breast02, in which median overall survival was 23.7 months vs 18.7 months with chemotherapy (HR, 0.79; 95% CI, 0.64-0.98).^7,8

How should APPs approach ADC sequencing?

As more ADCs enter practice, patients may receive more than 1 over the course of metastatic disease, and the optimal order has not been established.

"This is a big question and still being looked at and studied," Sarah Fischer said. "So there's not a clear consensus on the appropriate way to do it, but our providers usually look at the different payloads."

She noted that a patient with TNBC who progresses on sacituzumab govitecan may go on to T-DXd, although, as she noted, both agents carry the same type of payload, a topoisomerase I inhibitor, and that some clinicians use chemotherapy between ADCs. The phase 2, noncomparative TRADE-DXd trial (NCT06533826) is evaluating Dato-DXd or T-DXd in patients with HER2-negative (HER2-low or HER2-0) metastatic breast cancer whose disease progressed on prior ADC therapy, with crossover to the other agent at progression.⁹

Kelly Fischer described a patient enrolled on TRADE-DXd at Dana-Farber whose disease progressed after about 3 cycles of T-DXd. "But she then switched immediately to Dato-DXd and she got about 8-ish months off of Dato, which was interesting," she said. "But we are looking more at sequencing because there's not really a clear consensus of what to do or what to use first or what to use next."

How can nurses catch ILD before it becomes severe?

T-DXd carries a boxed warning for ILD and pneumonitis, and Dato-DXd labeling includes ILD/pneumonitis among its warnings and precautions.^3,7 With T-DXd now used in curative-intent settings, Sarah Fischer emphasized surveillance imaging.

With T-DXd now used more often in the neoadjuvant and adjuvant settings, she said, "screening CT chest scans every 6 weeks [are] crucial because there are a lot of patients that are asymptomatic."

Early detection, she explained, creates the opportunity to hold treatment until ILD resolves and potentially resume the drug, which matters most when a tumor is visibly responding in the neoadjuvant setting. In the metastatic setting, staging scans are supplemented by patient reporting.

"We have the staging scans, but I also tell patients it's always, always report any changes in your breathing," Sarah Fischer said. "So you have to be really on top of any new dry cough, any changes."

Kelly Fischer added that the respiratory assessment requires context. A new, persistent dry cough without other upper respiratory symptoms warrants attention, which can be harder to sort out during influenza and COVID-19 season. Patients with lung metastases may already have dyspnea or cough at baseline.

"So I always say, you know, any change from your baseline respiratory status, please let us know," she said.

What other toxicities require monitoring with ADCs?

Before each cycle, the Dana-Farber team sees patients and reviews laboratory values because ADCs can cause myelosuppression and neutropenia. Mild nausea and fatigue are common across the class, and cytopenias occur most often with sacituzumab govitecan and T-DXd, according to prior Oncology Nursing News coverage of ADC toxicity profiles.¹⁰ Sacituzumab govitecan carries a boxed warning for diarrhea and neutropenia, and Dato-DXd labeling includes ocular adverse reactions and stomatitis/oral mucositis.^6,7

Neuropathy is an assessment point at every visit. "Neuropathy can occur with T-DM1 specifically, with that ADC. So, we do have to ask if they're having any numbness, any tingling," Kelly Fischer said. "That way, we can adjust the dosing because it actually can be a permanent side effect of therapy. So, we really need to intervene quickly and early."

Cardiac monitoring is also part of the workflow because some ADCs can cause left ventricular dysfunction, a warning on the T-DXd label.³ "So usually in the metastatic setting, we'll be getting echocardiograms every 6 to 12 months. And then in earlier stage settings, we will get echocardiograms usually every 3 months on these therapies," Kelly Fischer said.

How can nurses prepare patients for ADC treatment?

Because patients receive a large volume of information before starting treatment, every patient at Dana-Farber is scheduled for a chemotherapy teaching session and receives written materials on the most common adverse effects and the treatment schedule. The team then reviews the information again at the visit before the first infusion.

What are the key takeaways for oncology nurses?

• Confirm the biomarker profile: Hormone receptor status, HER2 status, and HER2 IHC score determine which ADC a patient is eligible for.
• Expect sequencing questions: No consensus defines the order of ADCs; trials such as TRADE-DXd are evaluating sequential use.⁹
• Build in ILD surveillance: The Dana-Farber team uses screening chest CT every 6 weeks with T-DXd in early-stage disease and teaches patients to report any change from baseline breathing.
• Assess neuropathy at every visit: Ask about numbness and tingling so dosing can be adjusted before effects become permanent.
• Track counts and cardiac function: Review laboratory values before each cycle and schedule echocardiograms per the treatment setting.
• Front-load education: A chemotherapy teaching session, written materials, and a review before the first infusion help prepare patients for treatment.
• Use pharmacy partners: Pharmacists can support medication education, prior authorization, and financial assistance.

References

1. Fischer K, Fischer S. Antibody-drug conjugates in breast cancer. Presented at: JADPRO Live 2026; October 15-18, 2026; Minneapolis, MN. Accessed October 23, 2026. https://jadprolive2026.eventscribe.net/index.asp

2. Steinzor P. FDA approves trastuzumab deruxtecan for HER2-low/ultralow breast cancer. AJMC. January 28, 2025. Accessed October 23, 2026. https://www.ajmc.com/view/fda-approves-trastuzumab-deruxtecan-for-her2-low-ultralow-breast-cancer

3. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki for HER2-positive early-stage breast cancer. FDA. May 15, 2026. Updated May 16, 2026. Accessed October 23, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-two-separate-indications-fam-trastuzumab-deruxtecan-nxki-her2-positive-early-stage

4. ONN Staff. FDA grants dual approval for T-DXd in HER2+ early breast cancer. Oncology Nursing News. May 16, 2026. Accessed October 23, 2026. https://www.oncnursingnews.com/view/fda-grants-dual-approval-for-t-dxd-in-her2-early-breast-cancer

5. FDA approves T-DXd plus pertuzumab in metastatic HER2+ breast cancer. CancerNetwork. December 15, 2025. Accessed October 23, 2026. https://www.cancernetwork.com/view/fda-approves-t-dxd-plus-pertuzumab-in-metastatic-her2-breast-cancer

6. FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of TNBC. The ASCO Post. June 2026. Accessed October 23, 2026. https://ascopost.com/news/june-2026/fda-approves-sacituzumab-govitecan-hziy-as-monotherapy-and-in-combination-with-pembrolizumab-for-first-line-treatment-of-tnbc/

7. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic triple-negative breast cancer. FDA. May 22, 2026. Accessed October 23, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-triple-negative-breast-cancer

8. Attobrah Q. Datopotamab deruxtecan improves survival outcomes in advanced triple-negative breast cancer. Oncology Nursing News. April 30, 2026. Accessed October 23, 2026. https://www.oncnursingnews.com/view/datopotamab-deruxtecan-improves-survival-outcomes-in-advanced-triple-negative-breast-cancer

9. TReatment of ADC-refractory breast cancEr with Dato-DXd or T-DXd: TRADE DXd. ClinicalTrials.gov identifier: NCT06533826. Accessed October 23, 2026. https://clinicaltrials.gov/study/NCT06533826

10. Rikal M. What toxicities are common for ADCs approved in breast cancer? Oncology Nursing News. August 19, 2025. Accessed October 23, 2026. https://www.oncnursingnews.com/view/what-toxicities-are-common-for-adcs-approved-in-breast-cancer-