Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced and inflammatory disease, converting an inoperable to a surgical resectable cancer. In recent years, neoadjuvant therapy has become an accepted treatment option also for lower tumor stages in order to increase the rate of breast conserving therapy and to reduce the extent of surgery. Furthermore, treatment response can be monitored, and therefore, patient compliance may be increased. Neoadjuvant trials, additionally, offer the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials. Compared to the metastatic setting, the issue of acquired resistance and pretreatments, which may distort treatment efficacy, can be avoided. New trial designs like window-of-opportunity trials or postneoadjuvant trials provide the chance to identify tumor sensitivity or to overcome tumor resistance in early tumor stages. In particular, in HER2-positive breast cancer, the neoadjuvant approach yielded great successes. The dual HER2 blockade with trastuzumab and pertuzumab recently showed the highest pCR rates ever reported. Many new drugs are in clinical testing with the aim to further increase pCR rates. Whether this endpoint really represents a surrogate for long-term outcome is not answered yet and will be discussed in this review. 1. Introduction In recent years, there has been a growing interest in the neoadjuvant approach for early breast cancer. Compared to the classical adjuvant treatment, it offers several advantages. First, it provides the opportunity to monitor response during treatment and allows changing or discontinuing treatment in case of nonresponsiveness. Even if an advantage by changing therapy has not yet been proven, toxicity of an ineffective treatment can be avoided. The demonstration of treatment efficacy, conversely, motivates patients to continue therapy despite toxicities. Second, the rate of breast conservation can be increased, and in case of breast conserving therapy (BCT), the extent of surgery can be reduced. Additionally, primarily inoperable tumors can be downsized allowing a curative intervention. Third, the residual cancer burden (RCB) is a powerful prognostic marker, sometimes changing the initial prognostic profile in either way. Forth, in neoadjuvant trials predictive markers, tumor biology, mechanisms of resistance, and new treatment approaches can be investigated more rapidly and with fewer patients than in adjuvant studies. In the following sections, we give an overview of the historical
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