Clinical trial · Observational
Mechanisms of Response and Resistance to Innovative Treatments in Patients With Locally Advanced or Metastatic Breast Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
Ample evidence has highlighted the significant clinical benefit of novel therapies for many patients with advanced breast cancer (aBC). The use of CDK inhibitors, antibody-drug conjugates (ADCs), immune checkpoint inhibitors (ICIs), and PARP inhibitors as first-line or subsequent treatments has improved progression-free survival (PFS) rates compared to conventional therapies. In selected cases, these treatments have also increased overall survival (OS), reshaping the therapeutic landscape for advanced breast cancer. However, several key questions remain unanswered. For example, what should be the first-line treatment when multiple effective options are available? Determining the optimal sequence of drugs in successive lines of therapy is another major challenge. Furthermore, the development of resistance to treatment and the occurrence of severe adverse events that may lead to early discontinuation or fatal outcomes are pressing concerns. That said, identifying robust predictive biomarkers of response or resistance is crucial for ensuring that patients receive the most effective treatment while avoiding unnecessary exposure to therapies that could cause harm without benefit. Additionally, when multiple effective options exist, selecting the optimal treatment algorithm for each patient based on clinical, pathological, and molecular biomarkers is essential. We herein, aim at employing high throughput methodologies, such as Whole Exome Sequencing, circulating tumour DNA (ctDNA) analysis, digital pathology and radiomics analyses, as well as real-world data obtained both from patients records for the training of a ML-based algorithm that can predict response or resistance to a specific treatment, based on the genetic make-up of the patient and the molecular profile of the tumour.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Breast Cancer | Malignant Breast Neoplasm | CURATED_BROADER | 0.78 |
Interventions
Interventions (0)
Data not yet available
Design
Arms and outcomes
Arms (3)
- label
- ADCs
- description
- Patients receiving treatment with an Antibody-Drug conjugate (e.g Trastuzumab-Deruxtecan, Sacituzumab-Govitecan)
- label
- ICIs
- description
- Patients receiving treatment with an immune checkpoint inhibitor (ICI) (e.g pembrolizumab)
- label
- PARPi
- description
- Patients receiving treatment with a PARP inhibitor (e.g Olaparib)
Primary outcomes (3)
- measure
- Progression-free survival (PFS)
- timeFrame
- Through study completion, 5 years
- description
- Correlation of genetic and molecular/circulating biomarkers with PFS, with PFS defined as the time from enrollment to disease progression or death
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Eligible patients will be 18 years of age and older * Histologically confirmed, advanced breast cancer. * Diagnosis of i) hormone receptor positive and/or ii) HER2-positive or -low or iii) triple negative breast cancer (TNBC). * Patients will be included in the analysis after receiving at least one treatment cycle. Exclusion Criteria: * Diagnosis of early breast cancer at time of enrollment * Unwillingness to provide informed consent * Unwillingness to provide biological specimen * Lack of comprehensive clinical data
References
Publications (12)
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- BACKGROUNDGuidi L, Pellizzari G, Tarantino P, Valenza C, Curigliano G. Resistance to Antibody-Drug Conjugates Targeting HER2 in Breast Cancer: Molecular Landscape and Future Challenges. Cancers (Basel). 2023 Feb 10;15(4):1130. doi: 10.3390/cancers15041130. PMID 36831473
- BACKGROUNDFenton MA, Tarantino P, Graff SL. Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles. Curr Oncol. 2023 Nov 29;30(12):10211-10223. doi: 10.3390/curroncol30120743. PMID 38132377
- BACKGROUNDLitton JK, Rugo HS, Ettl J, Hurvitz SA, Goncalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roche H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. doi: 10.1056/NEJMoa1802905. Epub 2018 Aug 15. PMID 30110579
- BACKGROUNDRobson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4. PMID 28578601
- BACKGROUNDSchmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018 Nov 29;379(22):2108-2121. doi: 10.1056/NEJMoa1809615. Epub 2018 Oct 20.