Molecular Pathology in Breast Disease: Diagnostic, Prognostic, and Therapeutic Tools

Overview

Journal Virchows Arch

Specialties Cell Biology
Molecular Biology
Pathology

Date 2023 Nov 28

PMID 38015260

Authors

Zsuzsanna Varga

Umberto Maccio

Affiliations

Soon will be listed here.

Abstract

Molecular testing in breast cancer gained increasing attention and importance as specific molecular results can tailor not only oncological decisions on systemic adjuvant or neoadjuvant or in metastatic setting, but increasingly serve in diagnostic routine histopathological services to differentiate between morphologically overlapping or ambiguous histological pictures. Diagnostic tools involve in most cases a broad spectrum of immunohistochemical panels, followed by entity-specific in situ hybridization probes and in given cases NGS-based sequencing. Workflow of which methodology is applied and in which order depends on the specific entity resp. on the given differential diagnosis in question. Regarding prognostic/predictive molecular testing, the choice of assay and the workflow are based on clinical algorithms and on the evidence of targeted therapies following the molecular alterations. In this review paper, we aim to address the use of molecular technics in [1] the histological diagnostic setting (such as subtyping of invasive carcinomas/malignant spindle cell tumors and sarcomas and some B3 lesions) and [2] in the context of adjuvant or neoadjuvant or other clinical settings with special focus of targeted therapies.

References

Gennari A, Andre F, Barrios C, Cortes J, de Azambuja E, DeMichele A . ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021; 32(12):1475-1495. DOI: 10.1016/j.annonc.2021.09.019. View

Laetsch T, Dubois S, Mascarenhas L, Turpin B, Federman N, Albert C . Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018; 19(5):705-714. PMC: 5949072. DOI: 10.1016/S1470-2045(18)30119-0. View

Barroso-Sousa R, Pacifico J, Sammons S, Tolaney S . Tumor Mutational Burden in Breast Cancer: Current Evidence, Challenges, and Opportunities. Cancers (Basel). 2023; 15(15). PMC: 10417019. DOI: 10.3390/cancers15153997. View

Cima L, Kaya H, Marchio C, Nishimura R, Wen H, Fabbri V . Triple-negative breast carcinomas of low malignant potential: review on diagnostic criteria and differential diagnoses. Virchows Arch. 2021; 480(1):109-126. PMC: 8983547. DOI: 10.1007/s00428-021-03174-7. View

Varga Z, Sinn P, Seidman A . Summary of head-to-head comparisons of patient risk classifications by the 21-gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer. Int J Cancer. 2019; 145(4):882-893. DOI: 10.1002/ijc.32139. View

Gradishar W, Moran M, Abraham J, Abramson V, Aft R, Agnese D . NCCN Guidelines® Insights: Breast Cancer, Version 4.2023. J Natl Compr Canc Netw. 2023; 21(6):594-608. DOI: 10.6004/jnccn.2023.0031. View

Christgen M, Bartels S, Radner M, Raap M, Rieger L, Christgen H . ERBB2 mutation frequency in lobular breast cancer with pleomorphic histology or high-risk characteristics by molecular expression profiling. Genes Chromosomes Cancer. 2018; 58(3):175-185. DOI: 10.1002/gcc.22716. View

Murase R, Sumida T, Ishikawa A, Murase R, McAllister S, Hamakawa H . Novel therapeutic strategies for malignant salivary gland tumors: lessons learned from breast cancer. Int J Otolaryngol. 2011; 2011:187623. PMC: 3227505. DOI: 10.1155/2011/187623. View

Brett J, Spring L, Bardia A, Wander S . ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021; 23(1):85. PMC: 8365900. DOI: 10.1186/s13058-021-01462-3. View

10.

Euhus D, Timmons C, Tomlinson G . ETV6-NTRK3--Trk-ing the primary event in human secretory breast cancer. Cancer Cell. 2002; 2(5):347-8. DOI: 10.1016/s1535-6108(02)00184-8. View

11.

Geyer F, Pareja F, Weigelt B, Rakha E, Ellis I, Schnitt S . The Spectrum of Triple-Negative Breast Disease: High- and Low-Grade Lesions. Am J Pathol. 2017; 187(10):2139-2151. PMC: 5809519. DOI: 10.1016/j.ajpath.2017.03.016. View

12.

Burstein H, DeMichele A, Somerfield M, Henry N . Testing for Mutations to Guide Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023; 41(18):3423-3425. DOI: 10.1200/JCO.23.00638. View

13.

Cserni G, Quinn C, Foschini M, Bianchi S, Callagy G, Chmielik E . Triple-Negative Breast Cancer Histological Subtypes with a Favourable Prognosis. Cancers (Basel). 2021; 13(22). PMC: 8616217. DOI: 10.3390/cancers13225694. View

14.

Romanucci G, Mercogliano S, Carucci E, Lunardi M, Caneva A, Benassuti C . Low-grade adenosquamous carcinoma of the breast: a review with focus on imaging and management. Acta Radiol Open. 2021; 10(4):20584601211013501. PMC: 8114760. DOI: 10.1177/20584601211013501. View

15.

Rakha E, Brogi E, Castellano I, Quinn C . Spindle cell lesions of the breast: a diagnostic approach. Virchows Arch. 2021; 480(1):127-145. PMC: 8983634. DOI: 10.1007/s00428-021-03162-x. View

16.

Yan M, Gilmore H, Harbhajanka A . Mucoepidermoid Carcinoma of the Breast With Rearrangement: A Case Report and Literature Review. Int J Surg Pathol. 2020; 28(7):787-792. DOI: 10.1177/1066896920916779. View

17.

Haefliger S, Muenst S, Went P, Bihl M, Dellas S, Weber W . Tall cell carcinoma of the breast with reversed polarity (TCCRP) with mutations in the IDH2 and PIK3CA genes: a case report. Mol Biol Rep. 2020; 47(6):4917-4921. DOI: 10.1007/s11033-020-05553-w. View

18.

Salgado R, Peg V, Ruschoff J, Vincent-Salomon A, Castellano I, Perner S . Gene expression signatures for tailoring adjuvant chemotherapy of luminal breast cancer: the pathologists' perspective. Ann Oncol. 2021; 32(11):1316-1321. DOI: 10.1016/j.annonc.2021.08.1993. View

19.

Trihia H, Lampropoulos P, Karelis L, Souka E, Galanopoulos G, Provatas I . Tall cell carcinoma with reversed polarity: A case report of a very rare breast tumor entity and mini-review. Breast J. 2021; 27(4):369-376. DOI: 10.1111/tbj.14165. View

20.

Burstein H, Curigliano G, Thurlimann B, Weber W, Poortmans P, Regan M . Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021; 32(10):1216-1235. PMC: 9906308. DOI: 10.1016/j.annonc.2021.06.023. View