Status of breast cancer detection in young women and potential of liquid biopsy

Abstract

Young onset breast cancer (YOBC) is an increasing demographic with unique biology, limited screening, and poor outcomes. Further, women with postpartum breast cancers (PPBCs), cancers occurring up to 10 years after childbirth, have worse outcomes than other young breast cancer patients matched for tumor stage and subtype. Early-stage detection of YOBC is critical for improving outcomes. However, most young women (under 45) do not meet current age guidelines for routine mammographic screening and are thus an underserved population. Other challenges to early detection in this population include reduced performance of standard of care mammography and reduced awareness. Women often face significant barriers in accessing health care during the postpartum period and disadvantaged communities face compounding barriers due to systemic health care inequities. Blood tests and liquid biopsies targeting early detection may provide an attractive option to help address these challenges. Test development in this area includes understanding of the unique biology involved in YOBC and in particular PPBCs that tend to be more aggressive and deadly. In this review, we will present the status of breast cancer screening and detection in young women, provide a summary of some unique biological features of YOBC, and discuss the potential for blood tests and liquid biopsy platforms to address current shortcomings in timely, equitable detection.

Keywords: breast cancer; early detection; involution; liquid biopsy; molecular diagnostics; postpartum; young women.

Figure 1

Comparison of BI-RADS classification to mammography sensitivity and percent of women under/over 45. The Breast Imaging Reporting and Data System (BI-RADS) uses mammographic density for classification of breasts based on percent of fibroglandular tissue. The four categories are (A) predominantly fatty (≤25%), (B) scattered fibroglandular (26–50%), (C) heterogeneously dense (51–75%), and (D) extremely dense (76–100%). The distribution of mammographic density was adapted from Checka et al. (90) and sensitivity from Lynge et al. (91). The sensitivity of mammography is decreased with dense tissue which is predominantly found in young women (92). The density of breast tissue decreases with age making mammography a suitable option for older women but presents a gap in screening of young women. Mammographic images originally open access published by Pawlak et al. (2023) (93).

Figure 2

Visual representation of differences in the microenvironment of nulliparous YOBC and PrBC or PPBC. The top panel represents full view and ductal view of normal, undifferentiated (nulliparous) mammary gland, prior to pregnancy. As indicated, the basement membrane and basic structure of the duct remains intact, compared to the parous state. In the bottom panel, a full view and ductal view of the parous mammary gland is presented. The mammary gland undergoes cyclical remodeling prior and post-childbirth. Involution is a remodeling process that occurs post-lactation. It involves process such as matrix metalloproteinase (MMP) activation, immune cell recruitment and dysregulation, lymphatic expansion, extracellular matrix (ECM) degradation, epithelial-to-mesenchymal transition (EMT) and other activities that allow breast cancer cells to escape the primary tumor more easily, migrate into circulation and establish secondary sites in other locations.

Figure 3

The potential of liquid biopsy to improve breast cancer screening accessibility through primary, community-based care. The current breast cancer screening guidelines do not have recommendations for several at-risk populations due to lack of diagnostic technology. Implementation of liquid biopsy early detection tests may allow for breast cancer screening to be accessed through a primary physician instead of a specialized clinic. This would address barriers of distance to facility, travel time and transportation. There is still a need for improvement of imaging modalities such as MRI, PET and QT ultrasound to be used complementary to liquid biopsy.