Pitfalls and controversies in pathology impacting breast cancer management

ABSTRACT

Introduction: Breast cancer is a heterogeneous disease, at morphological, molecular, and clinical levels and this has significant implications for the diagnosis and management of the disease. The introduction of breast screening, and the use of small tissue sampling for diagnosis, the recognition of new morphological and molecular subtypes, and the increasing use of neoadjuvant therapies have created challenges in pathological diagnosis and classification.

Areas covered: Areas of potential difficulty include columnar cell lesions, particularly flat epithelial atypia, atypical ductal hyperplasia, lobular neoplasia and its variants, and a range of papillary lesions. Fibroepithelial, sclerosing, mucinous, and apocrine lesions are also considered. Established and newer prognostic and predictive markers, such as immune infiltrates, PD-1 and PD-L1 and gene expression assays are evaluated. The unique challenges of pathology assessment post-neoadjuvant systemic therapy are also explored.

Expert opinion: Controversies in clinical management arise due to incomplete and sometimes conflicting data on clinicopathological associations, prognosis, and outcome. The review will address some of these challenges.

KEYWORDS:

• Breast Cancer
• preinvasive
• breast Screening
• biomarkers
• neoadjuvant treatment

Article highlights

• There are many challenges in both the diagnosis and classification of breast carcinomas, particularly with the small sample size of core needle biopsies, often taken from asymptomatic women in the screening setting

• These diagnostic limitations also apply to proliferative and pre-invasive lesions of the breast such as columnar cell lesions, atypical hyperplasia, papillary and sclerosing lesions, and while diagnosis is often aided by immunohistochemistry, this is not helpful in all situations

• The assessment of histological grade and its prognostic significance is less well defined for some of the rarer histological subtypes of carcinoma

• Immune infiltrates and immune checkpoint inhibitors in breast cancers can be usefully assessed in the context of clinical trials; however, the criteria by which they are evaluated are insufficiently well established for routine clinical practice

• In the post-neoadjuvant setting, the response of a tumor to treatment may be regarded as a predictive factor and there are a number of techniques employed to score this; it is less clear whether it is appropriate to use conventional methods of determining histological grade in the post-neoadjuvant setting

• While the potential conversion of receptor status between a primary tumor and its metastases is now acknowledged, the value of testing receptors at multiple metastatic sites and the implication for treatment modification if the receptor status does change, are less well characterized

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

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Funding

This paper received no funding.