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Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time. This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails.

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Background: The heterogeneity of metastatic breast cancer (MBC) necessitates novel biomarkers allowing stratification of patients for treatment selection and drug development. We propose to use the prognostic utility of circulating tumor cells (CTCs) for stratification of patients with stage IV disease. Methods: In a retrospective, pooled analysis of individual patient data from 18 cohorts, including 2436 MBC patients, a CTC threshold of 5 cells per 7.5 ml was used for stratification based on molecular subtypes, disease location, and prior treatments. Patients with >= 5 CTCs were classified as Stage IVaggresive, those with < 5 CTCs as Stage IVindolent. Survival was analyzed using Kaplan-Meier curves and the log rank test. Results: For all patients, Stage IVindolent patients had longer median overall survival than those with Stage IVaggresive (36.3 months vs. 16.0 months, P < 0.0001) and similarly for de novo MBC patients (41.4 months Stage IVindolent vs. 18.7 months Stage IVaggresive p < 0.0001). Moreover, patients with Stage IVindolent disease had significantly longer overall survival across all disease subtypes compared to the aggressive cohort: hormone receptor-positive (44 months vs. 17.3 months, P < 0.0001), HER2-positive (36.7 months vs. 20.4 months, P < 0.0001), and triple negative (23.8 months vs. 9.0 months, P < 0.0001). Similar results were obtained regardless of prior treatment or disease location. Conclusions: We confirm the identification of two subgroups of MBC, Stage IVindolent and Stage IVaggresive, independent of clinical and molecular variables. Thus, CTC count should be considered an important tool for staging of advanced disease and for disease stratification in prospective clinical trials.

Einleitung: Die Persistenz von disseminierten Tumorzellen im Knochenmark von Patientinnen mit Brustkrebs ist mit einer schlechten Prognose assoziiert. Vorbereitende Studien lassen erkennen, dass diese Patientinnen von einer gezielten, sekundär-adjuvanten Therapie profitieren können. Das Her-2/neu-Protein wird als eines der vielversprechensten Ziele angesehen. Ziele dieser Studie waren zum einen, den Her-2/neu-Status der disseminierten Tumorzellen im Knochenmark festzustellen, und zum anderen, den Her-2/neu-Status der disseminierten Tumorzellen mit dem des Primärtumors zu vergleichen, um so die Bedeutung einer Her-2/neu-Expression bei disseminierten Tumorzellen hinsichtlich Prognose und Prädiktion beim Mammakarzinom zu zeigen. Methoden: Dazu wurden Knochenmarkaspirate von 137 Patientinnen mit primärem Mammakarzinom gewonnen und mit einer immunhistochemischen Doppelfärbung auf zytokeratin-positive und/oder Her-2/neu-positive Tumorzellen hin untersucht. Der Her-2/neu-Status des Primärtumors wurde mit dem HERCEP-test™ immunhistochemisch an bioptisch und/oder an chirurgisch gewonnenem Untersuchungsmaterial festgestellt. Ergebnisse: Bei 46 (34%) Patientinnen wurden zytokeratin-positive Tumorzellen im Knochenmark gefunden. 20 (43%) dieser Patientinnen hatten Her-2/neu-positive disseminierte Tumorzellen. Bei 7 (41%) von 17 Patientinnen mit mehr als einer zytokeratin-positiven Tumorzelle war die Her-2/neu-Expression der disseminierten Tumorzellen heterogen. Bei 13 der 45 Primärtumoren fand sich eine Her-2/neu-Überexpression (+2/+3). Die Konkordanzrate zwischen Primärtumor und disseminierten Tumorzellen lag bei 62%. Bei 12 der 20 Her-2/neu-negativen Primärtumoren fanden sich Her-2/neu-positive disseminierte Tumorzellen. Schlußfolgerungen 1) Her-2/neu-positive disseminierte Tumorzellen können bei Patientinnen mit Her-2/neu-negativen Primärtumoren gefunden werden. Die Antigenstruktur der disseminierten Tumorzellen sollte daher bei der Therapieplanung in Form einer sekundär Antikörper-assozierten Therapie berücksichtigt werden. 2) Die Her-2/neu-Überexpression bei disseminierten Tumorzellen ist bei einzelnen Patientinnen heterogen. Dies könnte die Effektivität einer nur auf das Her-2/neu-Antigen ausgerichteten Immuntherapie senken. Introduction: The persistence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with poor prognosis. Preliminary studies indicated that these patients may benefit from secondary adjuvant targeted therapy. HER2 protein is suggested as one of the most promising targets. The aims of this study were (1) to determine the HER2 status of DTC in BM of breast cancer patients (2) and to compare the HER2 status of DTC and corresponding primary tumors. Methods: Bone marrow aspirates from 137 primary breast cancer patients were included into the study. A double staining procedure was used for the identification of cytokeratin-positive (CK)/HER2 positive cells. HER2 status of the primary tumor was immunohistochemically assessed by the HERCEP-test™. Results: In 46 of 137 (34%) breast cancer patients CK-positive cells were detectable in bone marrow. Disseminated tumor cells with HER2 positivity were found in 20 (43%) of these patients. The HER2 expression on DTC was heterogeneous in 7 of 17 (41%) patients with more than one cytokeratin-positive cell. HER2 overexpression (+2/+3) was present in 13 of the 45 available primary tumors. Concordance rate between primary tumor and DTC was 62%. In 12 of 20 patients with HER2 negative tumors HER2 positive DTC were detected. Conclusions: (1) HER2 positive DTC can be detected in patients with HER2 negative primary tumors. Therefore, the antigenic profile of DTC may be considered for treatment decision using (secondary) antibody based strategies. (2) However, the HER2 overexpression on DTC is heterogeneous in individual patients which may reduce the efficacy of an immunotherapy based strategy directed against HER2-antigen only.