Scoping review: (Bio)markers for the prognostication of breast cancer recurrence

Abstract

Background: The aim of this study is to gain a comprehensive understanding of the latest advancements in breast cancer recurrence markers, with the aim of identifying minimally invasive or minimally intrusive markers as necessary approach for screening for breast cancer recurrence.

Methods: We followed PRISMA guidelines, systematically searching Web of Science, Scopus, and PubMed from 2010 to December 2023 for secondary papers on breast cancer markers of recurrence. Keywords used to search the databases include but are not limited to: "breast cancer recurrence", "markers", "radiology", "pathology", "clinical features". Studies focusing solely on outcomes after recurrence, such as survival or treatment response, were excluded to ensure the review targeted markers relevant to early prediction. The search was limited to English language. Selected papers underwent screening process according to inclusion/exclusion criteria, and data extraction included publication details, markers, marker modality, among others.

Results: The number of papers considered for this review was 1,138. After two phases of screening process, a total number of 28 reviews were included in this scoping review. We have categorized markers into radiological, clinical, and histopathological types. Among the most relevant clinical markers correlated with breast cancer (BC) recurrence are clinical stage, carcinoembryogenic antigen (CEA), and cancer antigen 15.3 (CA 15.3). We have also identified that the following radiological markers are the most mentioned markers associated with recurrence: mammographic density (MD), tumor heterogeneity, most enhancing tumor volume (METV), radiomic features, and more. Furthermore, we identified nuclear grade, microenvironment heterogeneity, estrogen receptor (ER), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), Ki-67 antigen, as the most significant histopathological markers of breast cancer recurrence.

Conclusion: This review identified promising markers for breast cancer recurrence in three categories: clinical, radiological and histopathological. General practitioners can leverage these insights for enhanced pre-screening, aiding in earlier detection and intervention, thus improving patient outcomes. Unclear cut-off values and disagreement on their use remain obstacles.

Keywords: Breast cancer recurrence; Clinical markers; Histopathological markers; Minimally invasive markers; Prognostic; Radiological markers; Scoping review.

Fig. 1

PRISMA-ScR flowchart

Fig. 2

Most used imaging techniques for marker extraction. x-axis represents the number of articles mentioning markers extracted by the radiological modality. y-axis represents the modality