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Introduction: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years. Here we present 4-year follow-up data for a cohort of 78 patients treated with neoadjuvant TCH. Methods: Between 2009 and 2014 we treated 78 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m²) and carboplatin (AUC 6) every 3 weeks (q3w) and trastuzumab (4 mg/kg loading dose then 2 mg/kg) q1w. Lymph node involvement was verified by sentinel lymph node or core-cut biopsy. Patients were diagnosed at a mean age of 55.5 years; 65.4% had hormone receptor-positive tumors, 34.6% presented with grade 3 disease and 51.3% of patients were node positive. Patients were monitored every 2 cycles by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery, trastuzumab was continued q3w up to 1 year. Results: No grade III/IV toxicities occurred and no case of congestive heart failure was observed. Neither dose modifications nor dose delays were necessary. 34 of the 78 patients (43.6%) achieved a pCR, 27 of the 40 node-positive patients (67.5%) experienced nodal conversion. After a median follow up of 48.5 months the disease-free survival (DFS) was 84.6%, the distant disease-free survival (DDFS) was 87.2% and the overall survival (OS) was 91%. Only T stage and nodal status at baseline were found to be significantly associated with survival estimates. Conclusion: The anthracycline-free regimen TCH is effective and safe in the neoadjuvant therapy of HER2-positive breast cancer, yielding DFS, DDFS and OS probabilities comparable to the results of adjuvant trials. Our data support the use of TCH as a neoadjuvant therapy regimen for patients with HER2-positive breast cancer. They also strongly encourage the use of taxanes and platinum salts as the chemotherapy backbone in studies investigating dual blockade with trastuzumab and pertuzumab in the neoadjuvant setting.

Introduction: In a previous study our group showed a beneficial effect of targeted intraoperative radiotherapy (TARGIT-IORT) as an intraoperative boost on overall survival after neoadjuvant chemotherapy (NACT) compared to an external boost (EBRT). In this study we present the results of a detailed subgroup analysis of the hormone receptor (HR)-positive HER2-negative patients. Methods: In this cohort study involving 46 patients with HR-positive HER2-negative breast cancer after NACT, we compared the outcomes of 21 patients who received an IORT boost to those of 25 patients treated with an EBRT boost. All patients received whole breast radiotherapy. Results: Median follow-up was 49 months. Whereas disease-free-survival and breast cancer-specific mortality were not significantly different between the groups, the 5-year Kaplan-Meier estimate of overall mortality was significantly lower by 21% with IORT, p = 0.028. Non-breast cancer-specific mortality was significantly lower by 16% with IORT, p = 0.047. Conclusion: Although our results have to be interpreted with caution, we have shown that the improved overall survival demonstrated previously could be reproduced in the HR-positive HER2-negative subgroup. These data give further support to the inclusion of such patients in the TARGIT-B (Boost) randomised trial that is testing whether IORT boost is superior to EBRT boost.

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