Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive
Anna P Sokolenko1,2, Fedor V Moiseyenko3, Aglaya G Iyevleva1,2
1Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 Saint Petersburg, Russia.
International Journal of Molecular Sciences
|February 11, 2023
Summary
Neoadjuvant chemotherapy (NACT) for breast cancer (BC) effectively eliminates visible cancer cells in most patients. Ultrasensitive genetic testing confirms that a pathologic complete response (pCR) indicates complete eradication, not just minimal residual disease.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Neoadjuvant chemotherapy (NACT) is a standard treatment for breast cancer (BC).
- Pathologic complete response (pCR) signifies the absence of detectable cancer after NACT.
- The presence of minimal residual disease (MRD) in pCR patients remains uncertain.
Purpose of the Study:
- To investigate whether ultrasensitive genetic methods can detect residual breast cancer cells in patients achieving pCR after NACT.
- To leverage TP53 gene alterations in BRCA1-mutated breast cancers to assess treatment efficacy.
Main Methods:
- Analysis of breast cancer patient cohorts treated with NACT.
- Comparison of pCR rates between BRCA1-mutated and BRCA1-wildtype tumors.
- Utilized droplet digital PCR (ddPCR) and next-generation sequencing (NGS) to detect TP53 mutations in pre- and post-NACT tumor tissues.
Main Results:
- BRCA1-mutated breast cancers showed significantly higher pCR rates (54%) compared to BRCA1-wildtype (15%).
- TP53 mutations were detected in all pre-NACT tumors from BRCA1 carriers.
- Post-NACT, TP53 mutations persisted in all non-pCR cases but were absent in all pCR cases, confirmed by ddPCR and NGS.
- TP53 mutation detection in post-NACT tissues was absent in 10/10 pCR patients and present in 13/13 non-pCR patients.
Conclusions:
- Achieving pCR after NACT reliably indicates complete elimination of breast cancer clones, even with ultrasensitive detection methods.
- The study suggests NACT response is a categorical outcome, distinguishing between patients destined for cure and those with ultimate treatment failure.
- TP53 mutation status serves as a robust marker for assessing treatment response in BRCA1-mutated breast cancer.
