# Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial

Source: https://onco.cc/key-papers/paper-hahnen-geparsixto-germline-brca-jama-oncol-2017/  
OnCo record `paper-hahnen-geparsixto-germline-brca-jama-oncol-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In GeparSixto, 17% of triple-negative patients carried a germline BRCA1 or BRCA2 mutation; they responded well to chemotherapy whether or not carboplatin was added, while it was the non-carriers whose complete response rate rose from 36% to 55% with carboplatin.

## Summary

Archived DNA from 291 of 315 TNBC patients in GeparSixto (NCT01426880) was analysed for germline mutations in BRCA1, BRCA2 and 16 other predisposition genes. Pathological complete response (ypT0/is ypN0) was 56.8% with carboplatin and 41.4% without (OR 1.87). Pathogenic BRCA1/2 germline mutations were present in 50 patients (17.2%). Without carboplatin, pCR was 66.7% in carriers versus 36.4% in non-carriers (OR 3.50); carboplatin did not raise the carriers' rate further (65.4%) but raised non-carriers' from 36.4% to 55% (OR 2.14), and non-carriers gained disease-free survival with carboplatin (85.3% versus 73.5%; HR 0.53).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: JAMA Oncology
- Year: 2017
- DOI: 10.1001/jamaoncol.2017.1007
- Authors: Hahnen E, Lederer B, Hauke J, et al.
- Findings: Germline BRCA1/2 in 50 of 291 TNBC patients, 17.2%.; Carriers: pCR 66.7% without and 65.4% with carboplatin; non-carriers: 36.4% rising to 55%.; Non-carriers gained disease-free survival with carboplatin (HR 0.53).
- What it means: Germline status changes the reading of the platinum question: in early TNBC the carboplatin benefit was seen in non-carriers, so a BRCA result argues for testing everyone rather than reserving platinum for carriers.
- Caveats: Secondary analysis of a non-standard regimen with bevacizumab and liposomal doxorubicin.; Small carrier subgroups (24 and 26 patients).

## Sources

- Hahnen et al., JAMA Oncol 2017: germline status and response in 291 GeparSixto TNBC patients: https://doi.org/10.1001/jamaoncol.2017.1007
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28715532/

## Connected records

- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/)
- companies: [German Breast Group (GBG)](https://onco.cc/companies/gbg/)
- terms: [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- trials: [GeparSixto](https://onco.cc/trials/geparsixto/)
- people: [Carsten Denkert](https://onco.cc/people/carsten-denkert/), [Rita Schmutzler](https://onco.cc/people/rita-schmutzler/), [Sibylle Loibl](https://onco.cc/people/sibylle-loibl/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)
- biomarkers: [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/)

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