The impact of p53 protein expression on the achievement of complete pathomorphism in neoadjuvant drug therapy for early HER2-positive breast cancer (results of a retrospective single-center study)

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Abstract

Background: Neoadjuvant therapy (NAT) is currently the gold standard for the treatment of early HER2-positive breast cancer (BC). However, only patients who achieve a complete pathological response (pCR) benefit from overall survival and progression-free survival (OS and PFS). The question of which patients should begin treatment with neoadjuvant therapy (NAT) and which should be treated initially with surgery remains a matter of debate.

Objective: Determination of the role of tumor p53 expression in achieving pCR after NAT in patients with early HER2-positive breast cancer by review prepared histological biopsy specimens for p53 expression determination, followed by a logistic regression analysis of the resulting database to calculate the relationship between achieving complete pathological response and the presence of p53 expression.

Materials and methods: A retrospective analysis of the medical records of 50 patients who received combination or comprehensive treatment for early (cT1-3N0-2M0) HER2-positive breast cancer in the General Oncology Department, S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department, over a 4-year period from 2021 to 2024. All patients were assessed for p53 protein expression in preoperative biopsy specimens using immunohistochemistry assay. The presence or absence of p53 protein expression was analyzed and correlated with the achievement of pCR.

Results: The presence of p53 protein expression significantly increases the likelihood of achieving a complete pathological response (pCR=1). OR=9.33 indicates that patients with p53 expression have a 9-fold higher chance of pCR than patients without it. The result is statistically significant (p=0.0024), confirming the role of p53 protein expression as a strong predictor of response to NAT.

Conclusion: p53 protein expression is a significant predictor of achieving a complete pathological response (RCB = 0) after effective NAT.

About the authors

Ivan N. Kuts

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department

Email: vanya-kuts97@yandex.ru
ORCID iD: 0000-0003-1516-6110

Oncologist, Oncosurgical Department No. 71 (General Oncology)

Russian Federation, Moscow

Konstantin S. Titov

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department; Peoples’ Friendship University of Russia named after Patrice Lumumba

Email: vanya-kuts97@yandex.ru
ORCID iD: 0000-0003-4460-9136
SPIN-code: 7795-6512

Dr. Sci. (Med.), Professor, Leading Researcher, Professor, Department of Oncology and Roentgenology named after V.P. Kharchenko

Russian Federation, Moscow; Moscow

Dmitry A. Karseladze

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department

Email: vanya-kuts97@yandex.ru
ORCID iD: 0000-0002-9877-1078

Cand. Sci. (Med.), Research Fellow, Surgeon, Oncosurgical Department No. 71 (General Oncology)

Russian Federation, Moscow

Evgeny I. Zakurdaev

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department

Email: vanya-kuts97@yandex.ru
ORCID iD: 0000-0001-8613-9609

Cand. Sci. (Med.), Pathologist, Pathology Department

Russian Federation, Moscow

Sergey S. Lebedev

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department; Russian Medical Academy of Continuous Professional Education

Email: vanya-kuts97@yandex.ru
ORCID iD: 0000-0001-5366-1281

Dr. Sci. (Med.), Associate Professor, Deputy Chief Physician for Oncology, Leading Researcher

Russian Federation, Moscow; Moscow

Ivan N. Lebedinsky

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department; Russian Medical Academy of Continuous Professional Education

Email: vanya-kuts97@yandex.ru
ORCID iD: 0000-0001-7735-1106

Cand Sci. (Med.), Senior Researcher, Head of Oncosurgical Department No. 71 (General Oncology)

Russian Federation, Moscow; Moscow

Nikita P. Chizhikov

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department; Russian Medical Academy of Continuous Professional Education

Email: vanya-kuts97@yandex.ru
ORCID iD: 0009-0004-0584-8657

Pathologist, Head of the Pathology Department

Russian Federation, Moscow; Moscow

Angelina V. Tatarova

S.P. Botkin Moscow Multidisciplinary Research and Clinical Center of the Moscow Healthcare Department; Russian Medical Academy of Continuous Professional Education

Email: vanya-kuts97@yandex.ru
ORCID iD: 0009-0005-3865-0046

Surgeon, Oncosurgical Department No. 71 (General Oncology)

Russian Federation, Moscow; Moscow

Fedor Yu. Roshchin

Author for correspondence.
Email: vanya-kuts97@yandex.ru
ORCID iD: 0009-0004-0477-7690

Independent Specialist, Statistical Consultant

Russian Federation, Moscow

References

  1. Злокачественные новообразования в России в 2023 году (заболеваемость и смертность). Под ред. А.Д. Каприна и др. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2024. 276 с. илл. [Malignant neoplasms in Russia in 2023 (incidence and mortality). Ed. by A.D. Kaprin et al. Moscow: P.A. Herzen Moscow Oncology Research Institute − branch of the National Medical Research Center of Radiology of the Ministry of Health of the Russian Federation, 2024. 276 p. ill. (In Russ.)].
  2. Жукова Л.Г., Андреева Ю.Ю., Завалишина Л.Э. и др. Клинические рекомендации. Рак молочной железы. 2021. [Zhukova L.G., Andreeva Yu.Yu., Zavalishina L.E. et al. Clinical guidelines. Breast cancer. 2021. (In Russ.)]. URL: https://cr.minzdrav.gov.ru/schema/379_4
  3. Тюляндин С.А., Артамонова Е.В., Жигулев А.Н. и др. Практические рекомендации по лекарственному лечению рака молочной железы. Практические рекомендации RUSSCO, часть 1. Злокачественные опухоли. 2023;13(#3s2):157–200. [Tyulyandin S.A., Artamonova E.V., Zhigulev A.N. et al. Practical guidelines for drug treatment of breast cancer. RUSSCO Practical Guidelines, Part 1. Malignant tumors. 2023;13(#3s2):157–200. (In Russ.)].
  4. Gianni L., Pienkowski T., Im Y.H., et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. https://dx.doi.org/10.1016/S1470-2045(16)00163-7
  5. Schneeweiss A., Chia S., Hickish T., et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278–84. https://dx.doi.org/10.1093/annonc/mdt182
  6. TCGA-Cancer Genome Atlas Network Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.
  7. Kastenhuber E.R. and Lowe S.W. Putting p53 in context. Cell. 2017;170:1062–1078.
  8. Tonnessen-Murray C. et al. The p53 protein: from cell regulation to cancer. In The p53 Protein: From Cell Regulation to Cancer (Lozano G and Levine A.J., eds). Cold Spring Harbor Laboratory Press, 2016. P. 173–186.
  9. Soussi T. TP53 mutations in human cancer: database reassessment and prospects for the next decade. Adv Cancer Res. 2011;110:107–139.
  10. Soussi T., Beroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer. 2001;1:233–240.
  11. Bertheau P., et al. TP53 status and response to chemotherapy in breast cancer. Pathobiology. 2008;75:132–139.
  12. Silwal-Pandit L., et al. TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance. Clin Cancer Res. 2014;20:3569–3580.
  13. Chen M.B., et al. Value of TP53 status for predicting response to neoadjuvant chemotherapy in breast cancer: a meta-analysis. PLoS One. 2012;7:e39655.
  14. Faneyte I.F., Schrama J.G., Peterse J.L., et al. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer. 2003 Feb 10;88(3):406-12. https://dx.doi.org/10.1038/sj.bjc.6600749
  15. Firouzabadi D., Rezvani A., Dehghanian A., Mahmoudi L. Association of ki67 and tumor marker p53 in locally advanced breast cancer patients and evaluation of response to neoadjuvant chemotherapy: a survey in South Iran. Cancer Manag Res. 2019 Jul 11;11:6489-6497. https://dx.doi.org/10.2147/CMAR.S203831
  16. Kandioler-Eckersberger D., Ludwig C., Rudas M., et al. TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. Clin Cancer Res. 2000 Jan;6(1):50-6.
  17. Kim T., Han W., Kim M.K., et al. Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer. J Breast Cancer. 2015 Mar;18(1):16–21. https://dx.doi.org/10.4048/jbc.2015.18.1.16
  18. Shien T., Kinoshita T., Seki K., et al. p53 expression in pretreatment specimen predicts response to neoadjuvant chemotherapy including anthracycline and taxane in patients with primary breast cancer. Acta Med Okayama. 2013;67(3):165-70. https://dx.doi.org/10.18926/AMO/50409
  19. Wang Y., Xu Y., Chen J., et al. TP53 mutations are associated with higher rates of pathologic complete response to anthracycline/cyclophosphamide-based neoadjuvant chemotherapy in operable primary breast cancer. Int J Cancer. 2016 Jan 15;138(2):489-96. https://dx.doi.org/10.1002/ijc.29715
  20. Tewari M., Krishnamurthy A., Shukla H.S. Predictive markers of response to neoadjuvant chemotherapy in breast cancer. Surg Oncol. 2008 Dec;17(4):301-11. https://dx.doi.org/10.1016/j.suronc.2008.03.003
  21. Tiezzi D.G., Andrade J.M., Ribeiro-Silva A., et al. HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination. BMC Cancer. 2007 Feb 26;7:36. https://dx.doi.org/10.1186/1471-2407-7-36
  22. Kariya S., Ogawa Y., Nishioka A., et al. Relationship between hormonal receptors, HER-2, p53 protein, Bcl-2, and MIB-1 status and the antitumor effects of neoadjuvant anthracycline-based chemotherapy in invasive breast cancer patients. Radiat Med. 2005 May;23(3):189-94.
  23. Darb-Esfahani S., Denkert C., Stenzinger A., et al. Role of TP53 mutations in triple negative and HER2-positive breast cancer treated with neoadjuvant anthracycline/taxane-based chemotherapy. Oncotarget. 2016 Oct 18;7(42):67686-67698. https://dx.doi.org/10.18632/oncotarget.11891
  24. Wang M., Wei Z., Kong J., Zhao H. Comprehensive evaluation of the relationship between biomarker profiles and neoadjuvant chemotherapy outcomes for breast cancer patients. Diagn Pathol. 2024 Mar 20;19(1):53. https://dx.doi.org/10.1186/s13000-024-01451-y
  25. Duman B.B., Sahin B., Acikalin A., et al. PTEN, Akt, MAPK, p53 and p95 expression to predict trastuzumab resistance in HER2 positive breast cancer. J BUON. 2013 Jan-Mar;18(1):44-50.
  26. Pons L., Hernandez L., Urbizu A., et al. Molecular Landscape, Genomic Shift, and Prediction in the Neoadjuvant Setting of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. Mod Pathol. 2025 May 6;38(9):100787. https://dx.doi.org/10.1016/j.modpat.2025.100787
  27. Chen M.B., Zhu Y.Q., Xu J.Y., et al. Value of TP53 status for predicting response to neoadjuvant chemotherapy in breast cancer: a meta-analysis. PLoS One. 2012;7(6):e39655. https://dx.doi.org/10.1371/journal.pone.0039655

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