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Article

Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive Mutation Analysis: A Proof-of-Concept Study in BRCA1-Driven Breast Cancer Patients

by
Anna P. Sokolenko
1,2,
Fedor V. Moiseyenko
3,
Aglaya G. Iyevleva
1,2,
Alexandr O. Ivantsov
1,
Georgiy D. Dolmatov
3,
Ksenia V. Shelekhova
3,
Elizaveta V. Gulo
3,
Anastasya X. Topal
3,
Elizaveta V. Artemieva
3,
Nuriniso H. Abduloeva
3,
Nikita A. Rysev
3,
Daria A. Barsova
3,
Natalia V. Levchenko
3,
Nikita M. Volkov
3,
Vitaliy V. Egorenkov
3,
Vladimir M. Moiseyenko
3 and
Evgeny N. Imyanitov
1,2,3,*
1
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 Saint Petersburg, Russia
2
Department of Medical Genetics, St.-Petersburg Pediatric Medical University, 194100 Saint Petersburg, Russia
3
City Cancer Center, 68A Leningradskaya Street, Pesochny, 197758 Saint Petersburg, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(3), 1870; https://doi.org/10.3390/ijms24031870
Submission received: 18 December 2022 / Revised: 6 January 2023 / Accepted: 13 January 2023 / Published: 18 January 2023
(This article belongs to the Special Issue Recent Advances in Breast Cancer Research)
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Abstract

Neoadjuvant chemotherapy (NACT) for breast cancer (BC) often results in pathologic complete response (pCR), i.e., the complete elimination of visible cancer cells. It is unclear whether the use of ultrasensitive genetic methods may still detect residual BC cells in complete responders. Breast carcinomas arising in BRCA1 mutation carriers almost always carry alterations of the TP53 gene thus providing an opportunity to address this question. The analysis of consecutive BC patients treated by NACT revealed a higher pCR rate in BRCA1-driven vs. BRCA1-wildtype BCs (13/24 (54%) vs. 29/192 (15%), p < 0.0001). Twelve pre-/post-NACT tissue pairs obtained from BRCA1 mutation carriers were available for the study. While TP53 mutation was identified in all chemonaive tumors, droplet digital PCR (ddPCR) analysis of the post-NACT tumor bed revealed the persistence of this alteration in all seven pCR-non-responders but in none of five pCR responders. Eleven patients provided to the study post-NACT tissue samples only; next-generation sequencing (NGS) analysis revealed mutated TP53 copies in all six cases without pCR but in none of five instances of pCR. In total, TP53 mutation was present in post-NACT tissues in all 13 cases without pCR, but in none of 10 patients with pCR (p < 0.000001). Therefore, the lack of visible tumor cells in the post-NACT tumor bed is indeed a reliable indicator of the complete elimination of transformed clones. Failure of ultrasensitive methods to identify patients with minimal residual disease among pCR responders suggests that the result of NACT is a categorical rather than continuous variable, where some patients are destined to be cured while others ultimately fail to experience tumor eradication.
Keywords: BRCA1 mutation; breast cancer; neoadjuvant chemotherapy; pathologic complete response; review BRCA1 mutation; breast cancer; neoadjuvant chemotherapy; pathologic complete response; review

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MDPI and ACS Style

Sokolenko, A.P.; Moiseyenko, F.V.; Iyevleva, A.G.; Ivantsov, A.O.; Dolmatov, G.D.; Shelekhova, K.V.; Gulo, E.V.; Topal, A.X.; Artemieva, E.V.; Abduloeva, N.H.; et al. Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive Mutation Analysis: A Proof-of-Concept Study in BRCA1-Driven Breast Cancer Patients. Int. J. Mol. Sci. 2023, 24, 1870. https://doi.org/10.3390/ijms24031870

AMA Style

Sokolenko AP, Moiseyenko FV, Iyevleva AG, Ivantsov AO, Dolmatov GD, Shelekhova KV, Gulo EV, Topal AX, Artemieva EV, Abduloeva NH, et al. Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive Mutation Analysis: A Proof-of-Concept Study in BRCA1-Driven Breast Cancer Patients. International Journal of Molecular Sciences. 2023; 24(3):1870. https://doi.org/10.3390/ijms24031870

Chicago/Turabian Style

Sokolenko, Anna P., Fedor V. Moiseyenko, Aglaya G. Iyevleva, Alexandr O. Ivantsov, Georgiy D. Dolmatov, Ksenia V. Shelekhova, Elizaveta V. Gulo, Anastasya X. Topal, Elizaveta V. Artemieva, Nuriniso H. Abduloeva, and et al. 2023. "Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive Mutation Analysis: A Proof-of-Concept Study in BRCA1-Driven Breast Cancer Patients" International Journal of Molecular Sciences 24, no. 3: 1870. https://doi.org/10.3390/ijms24031870

APA Style

Sokolenko, A. P., Moiseyenko, F. V., Iyevleva, A. G., Ivantsov, A. O., Dolmatov, G. D., Shelekhova, K. V., Gulo, E. V., Topal, A. X., Artemieva, E. V., Abduloeva, N. H., Rysev, N. A., Barsova, D. A., Levchenko, N. V., Volkov, N. M., Egorenkov, V. V., Moiseyenko, V. M., & Imyanitov, E. N. (2023). Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive Mutation Analysis: A Proof-of-Concept Study in BRCA1-Driven Breast Cancer Patients. International Journal of Molecular Sciences, 24(3), 1870. https://doi.org/10.3390/ijms24031870

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