Patients with breast cancer have benefited enormously from the introduction of antibody-drug conjugates and immunotherapies. These treatments have also affected adverse event burdens.

According to research presented at the San Antonio Breast Cancer Symposium 2025, patients with early-stage, high-risk breast cancer who experienced certain adverse events in their first few cycles of therapy were more likely to achieve pathologic complete responses (pCRs). 

Amrita Basu, PhD, associate professor of surgery at the University of California, San Francisco, and colleagues wrote that adverse events can worsen quality of life but may offer insights into cancer treatment response. 

In a study of 288 patients with stage II or III high-risk breast cancer, Basu and colleagues measured 33 patient-reported adverse events using the NCI’s Patient Reported Outcomes - Common Terminology Criteria for Adverse Events system. They evaluated the frequency, severity, and interference of each event and calculated the odds ratios of pCR for each. All patients were previously enrolled in the I-SPY2 trial, during which they received immunotherapy and neoadjuvant antibody-drug conjugates, with or without paclitaxel. 

Patients had a median age of 48 years (range, 20-78). The population was 70.5% White, 11.5% Black or African American, 12.2% Hispanic, and 5.9% Asian. 

The overall pCR rate was 29%. Patients who had specific moderate-to-severe symptoms during cycles 1-3 had higher odds of achieving a pCR. These symptoms were:

• Mouth or throat sores
• Headache
• Joint pain
• Muscle pain 

When Basu and colleagues evaluated associations with the severity of these events, they found that there was an association between the maximum severity of symptoms occurring in weeks 1-3 and pCR.

Compared with patients who had less ideal outcomes, those who achieved pCR experienced more higher-grade heart palpitations and higher-grade muscle pain. However, patients who achieved pCR had less severe tingling and numbness. 

The frequency, severity, and interference of leg or arm swelling was significantly correlated with reduced tumor volume during weeks 1-3. Associations became weak or insignificant after the 6-week mark. 

“Our study utilizes a computational framework that defined sentinel symptoms such as muscle and joint pain, mouth/throat sores, headache, and swelling, as early as weeks 1-3 that were associated with a favorable tumor response. This may suggest an early immune reaction in patients that eventually respond favorably to treatment, and prioritization to continue these patients on treatment may be warranted. Our work can help provide earlier proactive monitoring to mitigate toxicities, to enhance treatment response, and a potential symptom-based early understanding to personalize treatment efficacy.”

─ Amrita Basu, PhD, associate professor of surgery at the University of California, San Francisco, and colleagues

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By Andrew John

References: https://www.abstractsonline.com/pp8/#!/21392/presentation/121

Disclosures: Basu declared no financial ties to drugmakers. Some authors declared financial ties to drugmakers. See full abstract for details.

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