# Exceptional responder

Source: https://onco.cc/terms/exceptional-responder/  
OnCo record `exceptional-responder` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An exceptional responder is a patient whose cancer shrinks or stays controlled far longer than expected on a treatment that helps few people. The US National Cancer Institute defined the term for a study that sequenced such patients' tumours to learn why, and found a plausible molecular reason in about a quarter of them.

## Summary

The National Cancer Institute's Exceptional Responders Initiative defined an exceptional response as a partial or complete response to a systemic treatment whose population response rate is under 10 percent, or an unusually long response, for example lasting more than three times the published median. Of 520 cases proposed by clinicians, 476 were accepted for review, 222 met the definition, clinical data were obtained for 168, tumour tissue for 130, and 109 were successfully analysed by whole exome sequencing and, where possible, targeted deep sequencing, RNA sequencing, methylation arrays and immunohistochemistry; six patients had potentially actionable germline mutations, and the authors concluded that retrospective identification and sequencing of archived pretreatment tissue is feasible (Conley 2021). Integrative analysis of 111 exceptional responders uncovered plausible mechanisms in nearly a quarter, assigned to four categories, DNA damage response, intracellular signalling, immune engagement and genetic alterations characteristic of favourable prognosis, with many tumours in more than one, revealing synthetic lethal relationships and rare lesions that favour therapeutic success (Wheeler 2021). In triple-negative breast cancer the label is applied to the minority of patients with metastatic disease whose responses to immunotherapy or ADCs last for years, and the roadmap on this site tracks the studies that try to explain them; the term is a definition of an outcome, not a biomarker, and a single case cannot establish that a drug works.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: Exceptional response; Exceptional Responders Initiative; Outlier responder; Super-responder; Long-term responder
- Tags: breast; tnbc

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Clinical_endpoint
- Conley, JNCI 2021: the Exceptional Responders Initiative, feasibility of an NCI pilot study: https://doi.org/10.1093/jnci/djaa061
- Wheeler, Cancer Cell 2021: molecular features of cancers exhibiting exceptional responses to treatment: https://doi.org/10.1016/j.ccell.2020.10.015

## Connected records

- cancers: [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- terms: [Homologous recombination deficiency (HRD) in breast cancer](https://onco.cc/terms/hrd-in-breast-cancer/), [PD-L1 combined positive score 10 in triple-negative breast cancer](https://onco.cc/terms/pd-l1-cps-10-tnbc/)

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