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The relationship between achievement of a pathologic complete response (pCR) and favorable long-term outcome varies among breast cancer subtypes. We aimed to highlight which neoadjuvant treatment strategy could be most successful in each breast cancer subtype. A recent FDA meta-analysis on randomized neoadjuvant breast cancer trials suggests that the survival differences of patients with or without a pCR were less pronounced in luminal A-like tumors, despite the overall favorable prognosis of these patients. Moreover, even though the strong prognostic effect of pCR in HER2 positive and TNBC, the NOAH study was the only trial which showed a trend in surrogacy of pCR for long-term outcome in HER2-positive subtype. Results from GeparTrio study suggest that patients with hormone-positive tumors might need a response-guided approach, with either an intensification of treatment in case of an early response or a change to other chemotherapy in case of no early response. Furthermore, data from German neoadjuvant trials confirm that an increasing number of chemotherapy cycles is associated with a higher pCR rate, especially in patients with HER2-positive/hormone-positive tumors. In line with these suggestions, Tryphaena study showed a pCR rate that exceeding the 60% threshold, the highest pCR results presented in a large multicenter study. In TNBC, the highest pCR rate in the German neoadjuvant studies was obtained with the simultaneous application of docetaxel, doxorubicin and cyclophosphamide for 6 cycles. However, as shown in GaparQuinto and NSABP 40 trials, treatment effect in TNBC might be further maximized by adding bevacizumab, and two randomized neoadjuvant trials are expected this year to report data on the efficacy of carboplatin.
Neoadjuvant systemic chemotherapy is a possible therapeutic approach for the treatment of locally advanced operable, primarily non-operable or inflammatory breast cancer. Neoadjuvant systemic chemotherapy is an option for breast cancer patients who would require adjuvant chemotherapy otherwise based on clinical and histological examination and imaging. The use of neoadjuvant systemic therapy in operable breast cancer is currently increasing because of its advantages that include higher rates of breast conserving surgery and the possibility of measuring early in-vivo response to systemic treatment. The timing of axillary sentinel lymph node diagnosis (i.e. before or after neoadjuvant chemotherapy) is critical in that it may influence the likelihood of axillary preservation. It is not yet clear if neoadjuvant therapy might improve outcomes in certain subgroups of breast cancer patients. Neoadjuvant treatment modalities require a close collaboration between oncology professionals, including surgeons, gynecologists, medical oncologists, radiation oncologists, radiologists and pathologists. The most important parameter for treatment success and improved overall survival is the achievement of a pathologic complete response (pCR), although the role of pCR in patients with luminal A like tumours might be less informative. Identification of patient subgroups with high pCR rates may allow less invasive surgical or radiological interventions. Patients not achieving a pCR may be candidates for postoperative clinical trials exploring novel systemic treatments.