Key Points
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Neoadjuvant therapy is the standard of care for patients with locally advanced breast cancer and can improve operability of breast cancer
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For patients with HER2-positive breast cancer, the long-term outcomes of neoadjuvant treatment with the anti-HER2 agent trastuzumab should be considered equivalent to those of adjuvant therapy with this drug
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Despite the success of some neoadjuvant trials of dual-agent HER2 therapy for HER2-positive breast cancer, additional overall survival benefits of this approach over single-agent trastuzumab have not been documented in adjuvant trials
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Differences in clinical-trial designs, patient characteristics, breast-cancer biology, and the sequence and schedule of drug administration might have influenced the results of neoadjuvant trials and the contrasting results seen in adjuvant trials
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Prospective neoadjuvant trials with treatment informed by biomarkers and administration of matched experimental drug regimens should address the biological heterogeneity observed within breast-cancer subtypes
Abstract
Neoadjuvant therapy has been established as an effective therapeutic approach for patients with locally advanced breast cancer. Similar outcomes between neoadjuvant and adjuvant chemotherapy have been demonstrated in several trials. Nevertheless, neoadjuvant therapy has some advantages over adjuvant therapy, including tumour downstaging, in vivo assessment of therapeutic efficacy, reduced treatment durations, and the need to enrol fewer patients for clinical trials to reach their preplanned objectives. The number of neoadjuvant trials in patients with breast cancer has increased substantially in the past 5 years, particularly in the context of HER2-positive disease. Substantial improvements in the pathological complete response rate to anti-HER2 therapy, a proposed surrogate end point for long-term clinical benefit, have been observed with neoadjuvant dual-agent HER2 blockade. Thus, it was hypothesized that this approach would provide additional survival benefits over standard-of-care therapy with the anti-HER2 antibody trastuzumab in the adjuvant setting. Emerging data, however, are calling this notion into question. We discuss potential reasons why results of neoadjuvant trials of targeted therapies have not been mirrored in the adjuvant setting, and other than inherent differences in clinical-trial designs and statistical power, we consider how the biology of the disease, patient characteristics, and drug administration and schedule might influence the results.
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De Mattos-Arruda, L., Shen, R., Reis-Filho, J. et al. Translating neoadjuvant therapy into survival benefits: one size does not fit all. Nat Rev Clin Oncol 13, 566–579 (2016). https://doi.org/10.1038/nrclinonc.2016.35
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