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.

Recent Advances in Pathology: the 2022 Annual Review Issue of The Journal of Pathology

“…Integrating molecular pathology and epidemiology to identify relevant factors such as environmental exposures, host genetics, and lifestyle will be vital to examine the complex relationships with breast cancer risk, requiring comprehensive sets of appropriately annotated patient material within biobank collections. It is hoped that the current progress in studies of cancerisation fields will improve our understanding of breast cancer processes, and lead to improved screening strategies and treatments [15].…”

“…understanding of breast cancer processes, and lead to improved screening strategies and treatments [15].…”

Field Effect Detection by Light Scattering in the Breast Cancer Risk Determination

“…This can be present in the entire organ or parts thereof (prostate), as well as in paired organs (breasts), 16 and in the hematologic and nervous systems; 17 perhaps the whole body can be exposed to cancer development as a result of inherited or acquired genetic defects during embryogenesis (for example, Li-Fraumen syndrome) 18 . Some authors proposes 19 , as a current perspective on the field effect, to broaden the causative agents, including a wide range, in both exogenous and endogenous factors. Exogenous agents include chemicals such as tobacco smoke, physical agents such as ultraviolet radiation, and infectious agents such as Helicobacter pylori, human papillomavirus, and hepatitis B. Endocrine secretions (for example estrogens, testosterone), exocrine secretions (for example gastric acid), and even inherited cancer mutations (BRCA 1,2) constitute the endogenous causal factors of the field effect.…”

Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles

“…Recent advances in molecular, genomic and bulk sequencing techniques have supported the role of field cancerization ( 17 ). In breast cancer, microsatellite markers, epigenetic aberrations, transcriptomic deregulations and hTERT overexpression have been detected in histologically normal mammary tissues ( 18 , 19 ). In head and neck cancer, loss of heterozygosity of chromosome 9p and telomere dysregulation were commonly observed in benign squamous hyperplasia ( 20 , 21 ).…”