Systemic therapy for early-stage breast cancer: learning from the past to build the future

Abstract

The treatment of breast cancer has improved dramatically over the past century, from a strictly surgical approach to a coordinated one, including local and systemic therapies. Systemic therapies for early-stage disease were initially tested against observation or placebo only in adjuvant trials. Subsequent clinical trials focusing on treatment ‘fine-tuning’ had a marked increase in cohort size, duration and costs, leading to a growing interest in the neoadjuvant setting in the past decade. Neoadjuvant trial designs have the advantages of enabling the direct evaluation of treatment effects on tumour diameter and offer unique translational research opportunities through the comparative analysis of tumour biology before, during and after treatment. Current technologies enabling the identification of better predictive biomarkers are shaping the new era of (neo)adjuvant trials. An urgent need exists to reinforce collaboration between the pharmaceutical industry and academia to share data and thus establish large databases of biomarker data coupled with patient outcomes that are easily accessible to the scientific community. In this Review, we summarize the evolution of (neo)adjuvant trials from the pre-genomic to the post-genomic era and provide critical insights into how neoadjuvant studies are currently designed, discussing the need for better end points and treatment strategies that are more personalized, including in the post-neoadjuvant setting.

Development and Assessment of a Novel Core Biopsy-Based Prediction Model for Pathological Complete Response to Neoadjuvant Chemotherapy in Women with Breast Cancer

“…This study examined the predictive factors of NAC per se for pCR in breast cancer. In recent years, with the development of therapeutic agents and advances in breast cancer treatment strategies, more and more treatment options are being used in neoadjuvant therapy, such as neoadjuvant targeted therapy, neoadjuvant endocrine therapy, and neoadjuvant immunotherapy [ 60 ], and more studies are needed to explore the role of these options, alone and in combination, in neoadjuvant therapy.…”

Phenylsulfonimide PPARα Antagonists Enhance Nrf2 Activation and Promote Oxidative Stress-Induced Apoptosis/Pyroptosis in MCF7 Breast Cancer Cells

“…BC is the most common malignancy in women, and one of the three most common cancers worldwide. Although therapy has progressed over the past years and early diagnosed BC is now considered potentially curable, there is still a need for newer targeted therapies which make the prospect of long-term disease control in metastatic BC an increasing reality [ 29 ]. Recently, it has been reported that redox-sensitive molecules such as Nrf2 may play a role in the control of BC progression [ 30 ] and the development of drug resistance and metastasis [ 31 ].…”

Transcriptome Meta-Analysis of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy

“…As we demonstrated in the four-quadrants analysis of NAC response and survival outcomes, integration of both short-term and long-term clinical outcomes is more meaningful in guiding clinical decisions. Residual cancer burden (RCB), which is a continuous index to measure treatment responses based on primary tumor and nodal metastases, is considered the better endpoint to replace pCR for the neoadjuvant treatment responses in clinical trials [ 67 , 68 ].…”