Background and objective: In recent years, the field of breast cancer diagnosis and therapy has witnessed rapid technological advances. Concurrently, the emergence of molecular biology and novel detection methodologies has facilitated the transition of breast cancer management into the precision medicine era. The primary objective of this review is to discuss the transformation in the research and development paradigm for breast cancer therapies and strategies.
Methods: We systematically searched PubMed, EMBASE and Cochrane databases for relevant studies published over the past 20 years using keywords including "breast cancer", "clinical trial", "seamless", "master protocol", "umbrella", "basket", "platform", and "precision medicine". Articles were screened for eligibility and key data extracted. The search was limited to English-language publications.
Key content and findings: The review identifies three core innovations in breast cancer trial methodology: (I) in terms of research speed, the traditional three-stage drug development models are being substituted by "seamless designs" as exemplified by the immunotherapy combination study NCT0328056. (II) Addressing research breadth, "master protocols" such as basket trials (IMMU-132-01), umbrella trials (FUTURE), and platform trials (I-SPY 2) have been introduced, allowing the simultaneous assessment of multiple treatments or disease subtypes within a singular framework. (III) Pertaining to research precision, newer designs utilize biomarkers such as "enrichment" (seen in EMBRACA and OlympiA trials) and "marker stratification" (as in the SOLAR-1 trial), enabling the identification of appropriate patient subgroups and the provision of tailored therapy strategies, a stark contrast to traditional histopathology-based evaluations.
Conclusions: Clinical trial design in breast cancer research has been revolutionized, moving towards more efficient and targeted strategies. Despite the presence of ethical, logistical, and data complexities, it is anticipated that ongoing technological and regulatory enhancements will pave the way for even more refined research approaches, subsequently influencing future research, clinical practices, and policymaking in breast cancer care.
Keywords: Precision medicine; enrichment design; marker stratification design; master protocol; seamless design.
2023 Translational Breast Cancer Research. All rights reserved.