Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jun 19

PMID 38892013

Authors

Bruno de Paula

Susanne Crocamo

Carlos Augusto Moreira de Sousa

Priscila Valverde

Fabiana Rezende

Eliana Abdelhay

Affiliations

Soon will be listed here.

Abstract

The intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominantly basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed tumors (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%), and basal-like immune-activated tumors (IHC-BLIA, 10.9%). The pCR rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes, although IHC-BLIA demonstrated a trend toward better survival, and IHC-mesenchymal, worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

Citing Articles

Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine.

Afzal M, Vahdat L J Pers Med. 2024; 14(7).

PMID: 39063972 PMC: 11278458. DOI: 10.3390/jpm14070719.

References

Asleh K, Riaz N, Nielsen T . Heterogeneity of triple negative breast cancer: Current advances in subtyping and treatment implications. J Exp Clin Cancer Res. 2022; 41(1):265. PMC: 9434975. DOI: 10.1186/s13046-022-02476-1. View

Hu H, Tong K, Tsang J, Ko C, Tam F, Loong T . Subtyping of triple-negative breast cancers: its prognostication and implications in diagnosis of breast origin. ESMO Open. 2024; 9(4):102993. PMC: 11024544. DOI: 10.1016/j.esmoop.2024.102993. View

Kumar S, Bal A, Das A, Bhattacharyya S, Laroiya I, Khare S . Molecular Subtyping of Triple Negative Breast Cancer by Surrogate Immunohistochemistry Markers. Appl Immunohistochem Mol Morphol. 2020; 29(4):251-257. DOI: 10.1097/PAI.0000000000000897. View

Jaaskelainen A, Soini Y, Jukkola-Vuorinen A, Auvinen P, Haapasaari K, Karihtala P . High-level cytoplasmic claudin 3 expression is an independent predictor of poor survival in triple-negative breast cancer. BMC Cancer. 2018; 18(1):223. PMC: 6389078. DOI: 10.1186/s12885-018-4141-z. View

Marra A, Trapani D, Viale G, Criscitiello C, Curigliano G . Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies. NPJ Breast Cancer. 2020; 6:54. PMC: 7568552. DOI: 10.1038/s41523-020-00197-2. View

Liu Y, Jiang Y, Xu X, Yu K, Jin X, Hu X . Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer. Breast Cancer Res. 2016; 18(1):33. PMC: 4791797. DOI: 10.1186/s13058-016-0690-8. View

Burstein M, Tsimelzon A, Poage G, Covington K, Contreras A, Fuqua S . Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2014; 21(7):1688-98. PMC: 4362882. DOI: 10.1158/1078-0432.CCR-14-0432. View

Oakman C, Viale G, Di Leo A . Management of triple negative breast cancer. Breast. 2010; 19(5):312-21. DOI: 10.1016/j.breast.2010.03.026. View

Yin L, Duan J, Bian X, Yu S . Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020; 22(1):61. PMC: 7285581. DOI: 10.1186/s13058-020-01296-5. View

10.

Rala de Paula B, Kumar S, Morosini F, Calabria Cardoso D, de Sousa C, Crocamo S . Real-world assessment of the effect of impact of tumor size on pathological complete response rates in triple negative breast cancer after neoadjuvant chemotherapy. Chin Clin Oncol. 2020; 9(6):78. DOI: 10.21037/cco-20-111. View

11.

Mayer I, Zhao F, Arteaga C, Symmans W, Park B, Burnette B . Randomized Phase III Postoperative Trial of Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: ECOG-ACRIN EA1131. J Clin Oncol. 2021; 39(23):2539-2551. PMC: 8577688. DOI: 10.1200/JCO.21.00976. View

12.

Kim S, Moon B, Lim W, Park S, Cho M, Sung S . Feasibility of Classification of Triple Negative Breast Cancer by Immunohistochemical Surrogate Markers. Clin Breast Cancer. 2018; 18(5):e1123-e1132. DOI: 10.1016/j.clbc.2018.03.012. View

13.

Leeha M, Kanokwiroon K, Laohawiriyakamol S, Thongsuksai P . Immunohistochemistry-based molecular subtyping of triple-negative breast cancer and its prognostic significance. Pathol Oncol Res. 2023; 29:1611162. PMC: 10235452. DOI: 10.3389/pore.2023.1611162. View

14.

Lehmann B, Bauer J, Chen X, Sanders M, Chakravarthy A, Shyr Y . Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011; 121(7):2750-67. PMC: 3127435. DOI: 10.1172/JCI45014. View

15.

de Paula B, Kieran R, Koh S, Crocamo S, Abdelhay E, Munoz-Espin D . Targeting Senescence as a Therapeutic Opportunity for Triple-Negative Breast Cancer. Mol Cancer Ther. 2023; 22(5):583-598. PMC: 10157365. DOI: 10.1158/1535-7163.MCT-22-0643. View

16.

Rossi C, Fraticelli S, Fanizza M, Ferrari A, Ferraris E, Messina A . Concordance of immunohistochemistry for predictive and prognostic factors in breast cancer between biopsy and surgical excision: a single-centre experience and review of the literature. Breast Cancer Res Treat. 2023; 198(3):573-582. PMC: 10036406. DOI: 10.1007/s10549-023-06872-9. View

17.

Zhao S, Ma D, Xiao Y, Li X, Ma J, Zhang H . Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance. Oncologist. 2020; 25(10):e1481-e1491. PMC: 7543239. DOI: 10.1634/theoncologist.2019-0982. View

18.

Xu M, Yuan Y, Yan P, Jiang J, Ma P, Niu X . Prognostic Significance of Androgen Receptor Expression in Triple Negative Breast Cancer: A Systematic Review and Meta-Analysis. Clin Breast Cancer. 2020; 20(4):e385-e396. DOI: 10.1016/j.clbc.2020.01.002. View

19.

Bianchini G, De Angelis C, Licata L, Gianni L . Treatment landscape of triple-negative breast cancer - expanded options, evolving needs. Nat Rev Clin Oncol. 2021; 19(2):91-113. DOI: 10.1038/s41571-021-00565-2. View

20.

Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Flechon A . Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022; 399(10336):1695-1707. DOI: 10.1016/S0140-6736(22)00367-1. View