# Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer

Source: https://onco.cc/key-papers/paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020/  
OnCo record `paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In 62 women with metastatic triple-negative cancer treated with immunotherapy, high mutation burden (18%) went with a year of progression-free time versus under four months, while PTEN loss (29%) went with almost no responses.

## Summary

62 patients with metastatic TNBC who consented to targeted DNA sequencing and were treated with anti-PD-1/L1 therapy on trials at Dana-Farber (2014 to 2019) alone (23%), with targeted therapy (19%) or chemotherapy (58%). High TMB (10 or more nonsynonymous mutations/Mb; 18%) was associated with longer progression-free survival (12.5 versus 3.7 months; P 0.04); PTEN alterations (nonsynonymous mutation or one- or two-copy deletion; 29%) with lower objective response (6% versus 48%), shorter PFS (2.3 versus 6.1 months) and shorter overall survival (9.7 versus 20.5 months), independent of performance status, prior lines, regimen, visceral disease and PD-L1, and not seen in chemotherapy-treated (90) or non-immunotherapy (169) cohorts.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Clinical Cancer Research
- Year: 2020
- DOI: 10.1158/1078-0432.CCR-19-3507
- Authors: Barroso-Sousa R, Keenan TE, Pernas S, et al.
- Findings: High TMB in 18%: PFS 12.5 versus 3.7 months.; PTEN alterations in 29%: response 6% versus 48%, overall survival 9.7 versus 20.5 months.; Associations independent of PD-L1 and absent in non-immunotherapy cohorts.
- What it means: PTEN loss, the most common PI3K-pathway lesion in TNBC, may mark primary immunotherapy resistance, and TMB may add to PD-L1 in choosing who gets checkpoint blockade.
- Caveats: 62 patients across heterogeneous trials; hypothesis-generating.; Panel-derived TMB.

## Sources

- Barroso-Sousa et al., Clin Cancer Res 2020: TMB and PTEN alterations and checkpoint response in 62 metastatic TNBC patients: https://doi.org/10.1158/1078-0432.CCR-19-3507
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32019858/

## Connected records

- biomarkers: [PTEN alteration (sequencing) and PTEN loss (IHC)](https://onco.cc/biomarkers/pten-alteration/), [TMB-high (tumour mutational burden >= 10 mutations per megabase)](https://onco.cc/biomarkers/tmb-high/)
- cancers: [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/), [PTEN](https://onco.cc/targets/pten/)
- institutions: [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/)
- terms: [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- people: [Nancy U. Lin](https://onco.cc/people/nancy-lin/), [Sara M. Tolaney](https://onco.cc/people/sara-tolaney/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)

---
JSON: https://onco.cc/api/v1/entities/paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020.json