Pathology of neoadjuvant therapy and immunotherapy testing for breast cancer.
Elena ProvenzanoAbeer M ShaabanPublished in: Histopathology (2022)
Neoadjuvant chemotherapy (NACT) has become the standard of care for high-risk breast cancer, including triple-negative (TNBC) and HER2-positive disease. As a result, handling and reporting of breast specimens post-NACT is part of routine practice, and it is important for pathologists to recognise the changes in tumour cells, tumour-associated stroma and background breast tissue induced by NACT. Familiarity with characteristic stromal features enables identification of the pre-treatment tumour site and allows confident diagnosis of pathological complete response (pCR) which is important for decisions concerning adjuvant therapy. Neoadjuvant endocrine therapy (NAET) is used less frequently than NACT; however, the SARS-COVID-19 pandemic has changed practice, with increased use as bridging therapy if surgery is delayed. NAET also induces characteristic changes in the tumour and stroma. Changes in the tumour microenvironment following NACT and NAET are also described. Immunotherapy is approved for use in advanced TNBC, and there are several trials exploring its role in early TNBC in the neoadjuvant setting. The current biomarker to determine eligibility for treatment with immune checkpoint inhibitors is programmed death ligand-1 (PD-L1) immunohistochemistry; however, this is complicated by lack of standardisation with different drugs linked to tests using different antibodies with different scoring systems. The situation in the neoadjuvant setting is further complicated by improved pCR rates for PD-L1-positive tumours in both immune therapy and placebo arms. Alternative biomarkers are urgently needed to identify which patients will derive benefit from immunotherapy and key candidates are discussed.
Keyphrases
- locally advanced
- neoadjuvant chemotherapy
- rectal cancer
- lymph node
- healthcare
- primary care
- minimally invasive
- end stage renal disease
- stem cells
- squamous cell carcinoma
- palliative care
- newly diagnosed
- bone marrow
- ejection fraction
- clinical trial
- peritoneal dialysis
- quality improvement
- combination therapy
- mesenchymal stem cells
- cell death
- cell cycle arrest
- coronary artery bypass
- prognostic factors
- acute coronary syndrome
- young adults
- replacement therapy
- patient reported outcomes
- pain management