Lessons from the neoadjuvant setting on how best to choose adjuvant therapies.

Aims: To review the recent literature on neoadjuvant treatment of breast cancer with respect to insights that might be used for better using systemic treatment in early breast cancer.

Results: Much more insight was gained during recent years on how to use information on pathologic complete response (pCR). pCR appears to be a valid surrogate for long-term survival mainly in triple-negative and HER2-positive disease. Patient with breast cancer of these subtypes can be relieved from poor prognosis if they achieve a pCR after neoadjuvant treatment. It can even be speculated that the extent of local and post-surgical systemic treatment can be further reduced. Patients without pCR show a high risk of early recurrence and are at high need for new treatment options. These advantages lead to the recommendation that use of neoadjuvant treatment should not be indicated by tumor size but far more by tumor subtype. As pCR appears to be more sensitive to detect treatment effects than disease-free survival, the neoadjuvant approach identifies easier promising treatments and can even discriminate optimal approaches for biologically defined subgroups. A recent meta-analysis examining pattern of neoadjuvant chemotherapy suggests that luminal-B type tumors require longer duration of treatment, triple-negative tumors require dose-intensified anthracycline-taxane-based treatment of only short duration, and HER2-positive tumors require longer duration (if hormone-receptor positive) and an optimal dose of taxanes. As biomarkers can be easily assessed on tumor tissue before, during, and after treatment, there is increasing data available on markers that e.g. potentially predict resistance to anti-HER2 treatment, predict response to anti-angiogenic drugs as well as efficacy of PARP inhibitors. Validation of these candidate markers remains a challenging task, as patients cohort are usually small and finding studies are compromised by multiple testing.

Conclusion: With the acquired new knowledge from neoadjuvant studies will help to individualize treatment based on biological behavior of breast cancer subtypes.