Neoadjuvant approach as a platform for treatment personalization: focus on HER2-positive and triple-negative breast cancer

Abstract

The neoadjuvant setting provides unquestionable clinical benefits for high-risk breast cancer (BC) patients, mainly in terms of expansion of locoregional treatment options and prognostic stratification. Additionally, it is also emerging as a strategical tool in the research field. In the present review, by focusing on HER2-positive and triple-negative subtypes, we examined the role of the neoadjuvant setting as a research platform to facilitate and rationalize the placement of escalation strategies, promote the adoption of biomarker-driven approaches for the investigation of de-escalated treatments, and foster the conduction of comprehensive translational analyses, thus ultimately aiming at pursuing treatment personalization. The solid prognostic role of pathologic complete response after neoadjuvant therapy, and its use as a surrogate endpoint to accelerate the drug approval process were discussed. In this context, available data on escalated treatment strategies capable of enhancing pathologic complete response (pCR) rate or improving prognosis of patients with residual disease (RD) after neoadjuvant treatment, were comprehensively reviewed. We also summarized evidence regarding the possibility of obtaining pCR with de-escalated strategies, with particular emphasis on the role of biomarker-driven approaches for patient selection. Pitfalls of the dichotomy of pCR/RD were also deepened, and data on alternative/complementary biomarkers with a possible clinical relevance in this regard were reviewed.

HER2-low-positive breast cancer: evolution from primary tumor to residual disease after neoadjuvant treatment

“…Neoadjuvant treatment currently represents a widely adopted strategy for patients with early breast cancer given the well-acknowledged benefits in terms of expansion of locoregional treatment options, in-vivo evaluation of treatment sensitivity and the possibility to tailor post-neoadjuvant approach based on the pathological response after neoadjuvant treatment 9 , 10 . In this particular context, FDA has recently endorsed to select high-risk patients to be enrolled in adjuvant escalation trials based on the presence of residual disease after neoadjuvant therapy 11 .…”

Physical Therapies for Psychosomatic Symptoms and Quality of Life Induced by Aromatase Inhibitors in Breast Cancer Patients: A Systematic Review and Meta-Analysis

“…The notably improved clinical outcomes in breast cancer juxtaposed with significant treatment-related morbidity and mortality has led to interest in the development of de-escalated therapeutic strategies with the goal of maintaining or further improving oncologic outcomes while reducing short- and long‐term toxicity and treatment-related distress ( 47 ). Currently explored strategies include replacing, reducing, or omitting cytotoxic chemotherapy; reducing dose or volume of radiotherapy; incorporation of less-invasive surgical approaches; and adjuvant therapies ( 48 ). Several clinical trials have provided treatments for AIA, among which are alternative approaches, such as physical exercise, herbal remedies, acupuncture, and yoga, though most evidence are of low quality.…”

Gene-expression signatures to inform neoadjuvant treatment decision in HR+/HER2− breast cancer: Available evidence and clinical implications

“…Initially implemented in clinical practice for the treatment of locally advanced breast cancer (BC) patients, the use of neoadjuvant treatment has progressively increased over the last decades and is nowadays considered the standard of care for many early BC patients as well [1,2]. In this context, neoadjuvant chemotherapy (NCT) is widely used to downstage initially operable BCs, increasing the rates of conservative surgery [3]; however, it is well-known that the magnitude of response to NCT varies significantly according to breast cancer subtype.…”