Tumor mutational burden in non-immunotherapy patients with heavily pretreated metastatic breast cancer: long-term outcomes from a single institution

Abstract

Patients with heavily pretreated (≥3^rd-line treatment) metastatic breast cancer (MBC) had poor outcomes and lack prognostic biomarkers. Tumor mutational burden (TMB) was a prognostic biomarker for immunotherapy, but is not well defined in non-immunotherapy. Forty-nine heavily pretreated MBC not received immunotherapy were enrolled between March 2016 and September 2018. TMB of metastatic tumor tissue was evaluated by targeted next-generation sequencing of a 247-genes panel. CBRs (clinical benefit rates) were 47.7% (9 months), 36.2% (12 months) in high TMB patients, higher than 16.1% (9 months), 8.1% (12 months) in low TMB patients, respectively. After a median follow-up of 38 months, patients with high TMB had a longer mPFS (median progress-free survival) compared to low TMB patients in 3^rd-line treatment group (13.5 versus 7 months, HR 0.32, p = 0.019) but not in >3^rd-line treatment group. Cox regression showed TMB and line of treatment were the two independent prognostic factors for prolonged mPFS in heavily pretreated MBC, with a HR of 0.34 (p = 0.009) for high TMB and 0.37 (p = 0.013) for 3^rd-line treatment. In luminal subtype, mPFS was longer with endocrine therapy (ET) alone than with endocrine therapy + chemotherapy (ET + CT) in high TMB cohort (p = 0.037) but shorter mPFS with ET alone than with ET + CT in low TMB cohort (p = 0.047). High TMB and line of treatment are two independent prognostic factors for prolonged mPFS in heavily pretreated MBC patients. TMB may be a predictive biomarker of efficacy with ET alone or ET + CT in luminal subtype.

Keywords:

• Heavily pretreated
• metastatic breast cancer
• tumor mutational burden (TMB)
• targeted next-generation sequencing
• non-immunotherapy

Acknowledgements

We thank Annoroad Gene Tech. (Beijing) Co., Ltd for help with targeted next-generation sequencing and data analysis.

Disclosure statement

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Authors’ contributions

FW, LLW and JL designed the study. MLC, NNL, XFW, WWH, XHC, KC performed data acquisition. FW carried out the majority of the data analysis work and drafted the manuscript. FW, LLW and JL had full access to all study data and take responsibility for the integrity of the data, the accuracy of the data analysis, and interpretation of data. All authors were responsible for critical revisions, and all authors read and approved the final version of this work.

Data availability statement

All data generated or analyzed during this study are included in this published article and its additional files.

Additional information

Funding

The project was supported by the Fujian Provincial Health Technology Project (Grant number: 2020GGB012), Natural Science Foundation of Fujian Province (Grant number: 2018J01264 and 2018J01265), and Science and Technology Program of Fujian Province (Grant number: 2018Y2003).