Can we tailor neoadjuvant (primary) systemic therapy for breast cancer?

Primary systemic treatment (PST) is currently considered as the standard treatment for locally advanced breast cancer (LABC) and constitutes also a standard option for primary operable disease. PST can render inoperable tumours operable, and improves breast conservation rates. Unfortunately, an increase in the pathologic complete response (pCR) rates with neoadjuvant systemic treatments has not been followed by the improvements in disease free or overall survival. Clinical response is notoriously inaccurate in predicting pathologic complete responses or long term results. Careful monitoring of tumour and nodal response to PST, throughout the course of the treatment, is still mandatory mainly for the identification of progressive disease. Mammography and ultrasound have a reduced accuracy for predicting the size of the residual tumour; magnetic resonance imaging and functional imaging by PET are promising new tools for response assessment. The subgroup of patients who achieve pCR following PST chemotherapy have significantly higher disease free survival (DFS) and overall survival (OS) than the patients with residual disease, but overall, neoadjuvant chemotherapy does not provide a survival benefit when compared with the same regimen administered in the adjuvant setting. Neither the best regimen nor the optimal duration of PST has been definitely established. Several factors demonstrated their value in predicting higher pathologic response rates with neoadjuvant chemotherapy: smaller tumours versus larger tumours, higher grade versus well differentiated tumours, hormone receptor (HR) negative tumours versus those with positive receptors, ductal histology versus lobular, and higher proliferation rate versus slow growing tumours. Despite a large amount of published data, the use of predictive and prognostic factors to guide therapeutic decisions in the clinic still needs refining. Numerous studies are planned, using the preoperative experimental platform, to facilitate drug development and speed up the progress in the field of breast cancer.