Field cancerization in breast cancer

Abstract

Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post-surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri-tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter-patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri-tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri-tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords: breast cancer; cancer-adjacent tissues; field cancerization; histologically normal.

Figure 1

Overview of how healthcare records and individual molecular data could be used to guide stratified care. (A) Patients would be referred to hospital, where a subset would be presented with a breast cancer diagnosis. For each patient, the molecular characteristics of the excised tumor and their associated peri‐tumoral tissues would be recorded in their medical records. (B) Information from both electronic health records (e.g. demographics, pathology, imaging, etc.) and molecular assessments of tumor and surrounding histologically normal tissues (e.g. genomics, transcriptomics, etc.) would be available to clinicians. (C) This information would then be used to stratify patients into clinically significant groups, such as risk of recurrence, or used to help guide the clinical management of patients based on pharmacogenomic vulnerabilities within the residing tissues.