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Association of Pathologic Residual Cancer Burden and Event-Free Survival After Neoadjuvant Treatment for High-Risk Breast Cancer


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In an analysis from the I-SPY2 trial reported in JAMA Oncology, W. Fraser Symmans, MD, and colleagues found that increasing residual cancer burden after neoadjuvant treatment for high-risk breast cancer was associated with poorer event-free survival.

Study Details

In I-SPY2, investigational agents in combination with chemotherapy are compared with chemotherapy alone in women with different subtypes of stage II/III breast cancer who are at high risk of early disease recurrence. Investigational treatments graduate in a prespecified subtype if there is ≥ 85% predicted probability of a higher rate of pathologic complete response in a confirmatory 300-patient 1:1 randomized neoadjuvant trial in that subtype.

W. Fraser Symmans, MD

W. Fraser Symmans, MD

The current analysis assessed the association of pathological residual cancer burden with event-free survival in women who had received neoadjuvant paclitaxel with or without 1 of 10 investigational agents for 12 weeks followed by 12 weeks of cyclophosphamide/doxorubicin and surgery. Residual cancer burden was graded on a unit scale from 0 to 5, with 0 equaling pathologic complete response and higher units indicating greater residual cancer burden.

Key Findings

The analysis included 938 women, with a median follow-up of 52 months.

Each unit increase in residual cancer burden was associated with significantly poorer event-free survival among 357 women with hormone receptor (HR)-positive/HER2-negative disease (hazard ratio [HR] = 1.75, 95% confidence interval [CI] = 1.45–2.16), 173 with HR-positive/HER2-positive disease (HR = 1.55, 95% CI = 1.18–2.05), 88 with HR-negative/HER2-positive disease (HR = 2.39, 95% CI = 1.64–3.49), and 320 with HR-negative/HER2-negative disease (HR = 1.99, 95% CI = 1.71–2.31).

Increasing residual cancer burden was significantly associated with poorer event-free survival among 254 women receiving investigational treatments that graduated (HR = 2.00, 95% CI = 1.57–2.55), 486 receiving those that did not graduate (HR = 1.87, 95% CI = 1.61–2.17), and 198 who received control treatment (HR = 1.79, 95% CI = 1.42–2.26).

In an exploratory analysis, receipt of investigational treatments that significantly reduced residual cancer burden compared with control treatment (including all graduated and nongraduated treatments in HR-negative/HER2-negative patients and graduated treatments in HER2-positive patients) was associated with significantly improved event-free survival after adjustment for HR and HER2 status (HR = 0.61, 95% CI = 0.41–0.93).

The investigators concluded, “In this randomized clinical trial, the prognostic significance of residual cancer burden was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of residual cancer burden in addition to increasing [pathologic complete response] rate and appeared to improve event-free survival. Using a standardized quantitative method to measure response advances the interpretation of efficacy.”

Laura J. Esserman, MD, MBA, of the University of California, San Francisco, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the Quantum Leap Healthcare Collaborative, Foundation for the National Institutes of Health, National Cancer Institute, and others. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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