Abstract
In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2-) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2- BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.
Highlights
Neoadjuvant chemotherapy (NCT) confers the highest advantages in human epidermal growth factor 2 (HER2) positive and TN breast cancer patients, for whom pathologic complete response (pCR) can be obtained in 50–60% [7,8,9] of cases, while the inherent rates are lower in luminal cancer, where pCR is achieved on average in 10–20% of patients [6,7,8,9]
The body of knowledge on neoadjuvant endocrine therapy has dramatically grown in recent years
A promising therapeutic strategy is represented by the combination of an aromatase inhibitors (AI) and a target agent such as CDK4/6 inhibitors or PI3K–AKT–mTOR pathway inhibitors, further studies are needed to confirm preliminary data
Summary
In triple-negative (TN) breast cancers, none of the prior targets are identifiable or adequately represented to be exploited for therapeutic purposes This latter distinction into subgroups is of key importance due to the relevant differences in terms of prognosis and therapeutic weapons in current use [2,3]. ER-positive tumors are generally considered to be less sensitive to chemotherapy with respect to other subtypes [10] In this subset of patients, a reasonable alternative or integrating strategy to cytotoxic chemotherapy can be represented by neoadjuvant endocrine therapy (NET). In recent years, there has been a renewed interest in NET, mainly due to an increasingly high number of trials testing new drugs in combination with endocrine agents in ER-positive breast cancer patients.
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