Advanced Approaches to Breast Cancer Classification and Diagnosis

Abstract

The International Agency for Research on Cancer (IARC) has recently reported a 66% increase in the global number of cancer deaths since 1960. In the US alone, about one in eight women is expected to develop invasive breast cancer(s) (breast cancer) at some point in their lifetime. Traditionally, a BC diagnosis includes mammography, ultrasound, and some high-end molecular bioimaging. Unfortunately, these techniques detect BC at a later stage. So early and advanced molecular diagnostic tools are still in demand. In the past decade, various histological and immuno-molecular studies have demonstrated that BC is highly heterogeneous in nature. Its growth pattern, cytological features, and expression of key biomarkers in BC cells including hormonal receptor markers can be utilized to develop advanced diagnostic and therapeutic tools. A cancer cell's progression to malignancy exhibits various vital biomarkers, many of which are still underrepresented in BC diagnosis and treatment. Advances in genetics have also enabled the development of multigene assays to detect genetic heterogeneity in BC. However, thus far, the FDA has approved only four such biomarkers-cancer antigens (CA); CA 15-3, CA 27-29, Human epidermal growth factor receptor 2 (HER2), and circulating tumor cells (CTC) in assessing BC in body fluids. An adequately structured portable-biosensor with its non-invasive and inexpensive point-of-care analysis can quickly detect such biomarkers without significantly compromising its specificity and selectivity. Such advanced techniques are likely to discriminate between BC and a healthy patient by accurately measuring the cell shape, structure, depth, intracellular and extracellular environment, and lipid membrane compositions. Presently, BC treatments include surgery and systemic chemo- and targeted radiation therapy. A biopsied sample is then subjected to various multigene assays to predict the heterogeneity and recurrence score, thus guiding a specific treatment by providing complete information on the BC subtype involved. Thus far, we have seven prognostic multigene signature tests for BC providing a risk profile that can avoid unnecessary treatments in low-risk patients. Many comparative studies on multigene analysis projected the importance of integrating clinicopathological information with genomic-imprint analysis. Current cohort studies such as MINDACT, TAILORx, Trans-aTTOM, and many more, are likely to provide positive impact on long-term patient outcome. This review offers consolidated information on currently available BC diagnosis and treatment options. It further describes advanced biomarkers for the development of state-of-the-art early screening and diagnostic technologies.

Keywords: biosensors; breast cancer; early diagnosis; heterogeneity; multigene assays; novel biomarkers.

FIGURE 1

A comparative analysis of the number of articles published in the last decade, limiting the search to keywords: “Breast Cancer Diagnosis” and “Early Breast Cancer Detection.” NCBI database was searched as on Nov 1, 2020, to acquire the respective number of publications shown.

FIGURE 2

Classification of breast cancer (BC) based on: (A) The histopatholgical stratification. (B) The molecular stratification, relative grading, therapy requirement, and prognosis. The BC hormone expression reflects an inverse proportion to the tumor grade and cellular proliferation. Luminal A subtype exhibits a better prognosis with a positive response to endocrine therapy. In contrast, TNBC shows no hormonal expression, higher staged and nuclear grade tumor with intense mitotic activity, and poor prognosis. ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor, and TNBC, triple negative breast cancer.

FIGURE 3

Established and promising breast cancer biomarkers for prognosis and diagnosis.

FIGURE 4

A schematic representation of a simple biosensor in detecting specific biomolecules such as cancer-specific biomarkers, shed-off extracellular domains, circulating tumor cells, etc., extracted from different body fluids.

FIGURE 5

Venn diagram showing a shared number of genes/proteins between different multigene tests. BCI: breast cancer index, EP: endopredict, IHC4: immunohistochemical4.