Predictive and Prognostic Biomarkers for Response to Neoadjuvant Chemotherapy-with and without HER2-Targeting Therapy

Dear Colleagues,

Breast cancer (BC) is the most commonly occurring cancer in women, with nearly 2.26 million cases diagnosed each year.  BC is currently considered a heterogeneous group of tumours with regard to its clinical presentation, epidemiology, histology, radiology, gene expression, prognosis, and response to treatment. Subsequently, BC management remains a significant clinical challenge, hindered by the inability of these tumours to respond to targeted therapeutic agents, and the fact that the population of women with BC is more diverse than expected.

Preoperative neoadjuvant cytotoxic chemotherapy (NACT) is a standard treatment option for the triple negative and HER2+ BC subtypes, in addition to HER2-targeting agents, as it reduces the tumour size prior to loco-regional treatment with surgery and radiotherapy, enables the patient to undergo an in vivo chemo-sensitivity test, and enables the deployment of more intensive adjuvant chemotherapy and the consideration of novel adjuvant treatment for chemo-resistant tumours. The tumour size reduction is monitored in each treatment cycle, which allows doctors to swap to a different chemotherapy regimen should the standard drugs elicit no response, or to fast-track the patient to immediate surgery. However, this treatment option relies on inaccurate clinical examination. With the current patient selection criteria and the cycle-based response monitoring for NACT, only 30–50% of BC patients achieve a pCR (i.e., the microscopic absence of a tumour at surgery), which is generally associated with an excellent prognosis. Meanwhile, the remaining 50–70% of patients with no pCR (i.e., patients with residual disease) experience a wide range of responses to NACT, from near-pCR to complete resistance, and have diverse clinical outcomes (e.g., survival rate); this poses a challenge for BC planning and management. Moreover, there is no reliable and efficient clinical pipeline for accurately stratifying patients before, during, and after NACT based on the likelihood of the treatment’s response and effectiveness.

Therefore, there is an urgent need to identify new prognostic and predictive features that could accurately sub-stratify BC patients, monitor and grade their responses to chemotherapy, and provide tailored and guided treatment to individual patients to avoid serious toxicities and economic burden resulting from unnecessary and ineffective therapies.

Dr. Tarek M.A. Abdel-Fatah
Guest Editor

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• breast cancer
• predictive and prognostic biomarkers
• neoadjuvant chemotherapy
• HER2-targeting agents
• complete pathological response