Advancing Precision Breast Cancer Care Through Molecular Diagnostics

Recent key publications

Liquid Biopsies for Cancer: A Translational Science Review. 
JAMA. 2026 Sep 15;336(11):960-968. doi: 10.1001/jama.2026.13898. Mezzanotte-Sharpe J, Piemonte K, Park BH. 

 Link to full article: https://pubmed.ncbi.nlm.nih.gov/42574031/

Circulating tumour DNA (ctDNA) testing lets clinicians track tumour evolution from a simple blood draw. The authors review the key trial evidence. In DYNAMIC, ctDNA-guided management spared many patients adjuvant chemotherapy without compromising recurrence-free survival, while IMvigor011 showed that serial ctDNA testing can distinguish patients who need adjuvant treatment from those who don’t. Resistance variants such as ESR1 and KRAS G12C now inform the choice of targeted agents. Several companion diagnostics have FDA approval.

Problems are not completely resolved. Tumours can shed DNA unevenly, so sensitivity varies by cancer type. The optimal testing interval is unknown, and costs are substantial. We need to weigh these limitations against emerging uses, including multicancer early detection, and ascertain where evidence is lacking. For clinicians and investigators, this is a critical assessment of what liquid biopsy can and cannot yet deliver.

Comprehensive Liquid Biopsy Testing in Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer Patients: First Results from Routine Clinical Practice. 
Breast Care (Basel). 2026 May 22. doi: 10.1159/000552643. Warwas KM, Volckmar AL, Kazdal D, et al.

 Link to full articlehttps://pubmed.ncbi.nlm.nih.gov/42499691/

Few real-world data show how circulating tumour DNA (ctDNA) testing transforms care in hormone receptor-positive metastatic breast cancer. This retrospective study of 162 patients at a German academic centre examined routine plasma sequencing with a hybrid-capture NGS panel. Results came back in about nine days. ESR1 mutations were detected in 28.4% of patients, and 43.5% of them went on to receive elacestrant, the oral selective oestrogen receptor degrader approved on the basis of EMERALD. PIK3CA, PTEN, and AKT1 alterations often co-occurred. In some cases they shifted treatment to alpelisib or capivasertib. Drawing on SERENA-6 and PADA-1, the authors make the case for panel testing early in the treatment sequence, before options run out. They also point out some of the challenges, reimbursement hurdles and the risk of misinterpreting a negative result.

Standardized Analytical Verification of ctDNA ESR1 Mutation Testing in Metastatic HR+/HER2- Breast Cancer: A European Multicentre Study Using dPCR and NGS-Based Liquid Biopsy. 
Mol Diagn Ther. 2026 Sep;30(5):807-820. doi: 10.1007/s40291-026-00850-9. Rojo F, Guarneri V, Fusco N, et al.

 Link to full article:https://pubmed.ncbi.nlm.nih.gov/42307899/

Plasma ESR1 testing has not been well standardised across Europe, partly because regulators allow locally validated assays instead of requiring a single companion diagnostic. In this multicentre study the authors collected verification data from six referral laboratories, all using the same reference materials for the hotspot variants p.Y537S and p.D538G. Limits of detection with digital PCR ranged from 0.01% to 0.07% variant allele frequency. For next-generation sequencing the range was 0.01% to 0.1%. Limits of blank remained low. Sensitivity, the authors note, depends on cfDNA input, assay design, and preanalytical handling together, not on any one factor alone. They propose practical verification criteria based on CLSI EP17-A2. With elacestrant now approved in Europe and molecular pathology largely decentralised, laboratories introducing ESR1 testing need exactly this kind of guidance. The same framework could also serve future liquid biopsy biomarkers.

Circulating tumour DNA and its clinical relevance in predicting progression-free survival and overall survival in patients with advanced breast cancer: a systematic review and meta-analysis. 
Breast Cancer Res Treat. 2026 Sep 28;219(3):23. doi: 10.1007/s10549-026-08087-0. Ottosen C, Kragelund E, Pedersen MA, et al.

 Link to full articlehttps://pubmed.ncbi.nlm.nih.gov/42804029/ 

The authors aimed to answer an important question: can circulating tumour DNA (ctDNA) complement imaging in advanced breast cancer? A uniform consensus is lacking, and ASCO guidelines still do not endorse it for routine response monitoring. This systematic review and meta-analysis pooled 64 studies, making it the largest synthesis so far of ctDNA's prognostic value in this setting. High baseline ctDNA predicted shorter progression-free survival (pooled HR 2.0) and overall survival (pooled HR 2.7). Unfavourable changes during treatment also indicated worse outcomes. ESR1, PIK3CA, and TP53 alterations were generally linked to poorer prognosis, although results varied between cohorts. The authors discuss the considerable heterogeneity, the risk of bias, and the lack of standardised response criteria. They put forward ctDNA-RECIST as a framework that now needs prospective validation.

Switching to camizestrant at ESR1 mutation emergence before disease progression during first-line treatment of hormone receptor-positive advanced breast cancer (SERENA-6): extended analysis of a double-blind, placebo-controlled, randomised, phase 3 trial. 
Lancet Oncol. 2026 Aug;27(8):941-958. doi: 10.1016/S1470-2045(26)00287-1. Turner NC, Mayer EL, Park YH, et al.

 Link to full article:https://pubmed.ncbi.nlm.nih.gov/42442380/

SERENA-6 puts ctDNA-guided treatment into practice. Patients with HR-positive, HER2-negative advanced breast cancer underwent blood-based monitoring for emerging ESR1 mutations while receiving first-line aromatase inhibitor plus a CDK4/6 inhibitor. When an ESR1 mutation was detected before disease progression, patients were randomised either to switch to camizestrant or continue their aromatase inhibitor, while maintaining CDK4/6 inhibition. Median progression-free survival was 16.0 months with the camizestrant switch compared with 9.2 months in the control group. These results provide direct evidence that detecting molecular resistance through ctDNA can inform an earlier change in treatment, rather than waiting for radiological progression.

Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. 
Lancet Oncol. 2022 Nov;23(11):1367-1377. doi: 10.1016/S1470-2045(22)00555-1. Bidard FC, Hardy-Bessard AC, Dalenc F, et al.

 Link to full article: https://pubmed.ncbi.nlm.nih.gov/36183733/

PADA-1 is the first randomised trial to show that acting on a resistance mutation before radiographic progression improved outcomes. In 83 French centres, 1,017 patients on first-line aromatase inhibitor plus palbociclib had their plasma monitored by droplet digital PCR. Of the 279 who developed a rising ESR1 mutation without concurrent progression, 172 were randomised either to stay on treatment or to switch to fulvestrant while continuing palbociclib. The switch almost doubled progression-free survival after randomisation (11.9 vs 5.7 months; stratified HR 0.61). No new safety signals emerged. Patients who crossed over to fulvestrant only at progression gained just 3.5 months, illustrating the importance of timing, not only the choice of drug, as a driver of efficacy. These results shaped the design of SERENA-6. They also move ctDNA from a prognostic marker to a trigger for treatment decisions.

Longitudinal transcriptomic profiling identifies predictors of response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer: results from the NeoTRIPaPDL1 trial. 
Ann Oncol. 2026 Sep;37(9):1278-1292. doi: 10.1016/j.annonc.2026.05.694. Dugo M, Huang CS, Egle D, et al.

 Link to full article: https://pubmed.ncbi.nlm.nih.gov/42162664/

A biopsy taken during therapy may provide more information than one taken before treatment. This analysis of the randomised NeoTRIPaPDL1 trial examined whether early molecular changes could predict response in triple-negative breast cancer. All 280 patients received carboplatin plus nab-paclitaxel, with or without atezolizumab. RNA sequencing was performed on tumour biopsies taken at baseline and on day one of the second treatment cycle. Early tumour clearance strongly reflected pathologic complete response, occurring in 33.6% of patients receiving chemoimmunotherapy and 16.8% receiving chemotherapy alone. Timing mattered. Baseline proliferation and stromal programmes predicted response in the combination arm, while immune activation during treatment became the dominant correlate. The findings support response-adapted neoadjuvant strategies, in which treatment is intensified or scaled back based on early biological response. This approach is being tested in the I-SPY 2.2 platform.