Multi-institutional analysis of incidence and risks for late-onset immune toxicity in breast cancer
Immune checkpoint inhibitors (ICI) improve survival in triple-negative breast cancer (TNBC) but cause late-onset toxicity, with unknown incidence in breast cancer. This retrospective study included 700 patients (61%, n = 424 early-stage; 39%, n = 276 metastatic; 77% TNBC) from four NCI-designated centers treated with ICI between 2014-2021. Chart review identified immune toxicities, defined as ICI-related, as noted by the oncology provider or steroid-treated. 61% (n = 430) had toxicity: 37% (n = 257) early (≤90 days after ICI start), 34% (n = 240) delayed (>90 days), 10% (n = 67) both. Of the delayed, 144 (60%) were on-treatment, 56 (23%) off-treatment, 40 (17%) both. Twenty-two (9.2%) had off-treatment toxicity >1 year post-ICI. Median onset: 138 days (range 90-1380) on-treatment; 76 days (21-1144) off-treatment. Risk increased with more ICI cycles, especially >4 (early OR 1.104; metastatic OR 1.06; p < 0.0001) and higher baseline eosinophils (OR 3.46, p = 0.0484). Metastatic disease (OR 0.18, p < 0.0001) and early toxicity (OR 0.53, p = 0.0008) reduced risk. Findings support the need for high clinical suspicion for late toxicity.
Authors
- Michelle Melisko (ORCID: https://orcid.org/0000-0002-8729-4667)
- Saliha Chaudhry
- Joanne Mortimer (ORCID: https://orcid.org/0000-0002-2935-1934)
- Nikita V. Baclig (ORCID: https://orcid.org/0000-0001-5001-9699)
- Laura A. Huppert (ORCID: https://orcid.org/0000-0002-8512-5608)
- Zoe Quandt (ORCID: https://orcid.org/0000-0002-4568-4368)
- Damé Idossa (ORCID: https://orcid.org/0000-0003-1861-3553)
- Laura Quintal
- Anne Hudson Blaes (ORCID: https://orcid.org/0000-0002-5433-4810)
- A. Jo Chien (ORCID: https://orcid.org/0000-0003-2978-6249)
- Samantha Fisch
- Kelly McCann (ORCID: https://orcid.org/0000-0001-8233-6242)
- Ashraf Tawfik Soliman (ORCID: https://orcid.org/0000-0002-9585-9461)
- Alexis LeVee (ORCID: https://orcid.org/0000-0001-9821-8144)
- Saya Jacob (ORCID: https://orcid.org/0000-0002-9311-5303)
- Kelly Blum
- Hope S. Rugo (ORCID: https://orcid.org/0000-0001-6710-4814)
- Carolyne Face
- Mi‐Ok Kim (ORCID: https://orcid.org/0000-0002-7712-3653)
- Madhuri Chengappa
Institutions
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- City of Hope (US)
- University of Minnesota Medical Center (US)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1038/s41523-025-00849-1
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Roche
- Sanofi
- Gilead Sciences
- F. Hoffmann-La Roche
- Novartis Pharmaceuticals Corporation
- Seagen
- Genentech
- University of California, San Francisco
- Chugai Pharmaceutical
- Daiichi Sankyo Europe