Node-positive breast cancer: Which are the best chemotherapy regimens?

Breast cancer-associated mortality has been significantly reduced since the 1990s, mainly because of early diagnosis and systemic therapeutic interventions. All three therapy components-cytostatic therapy, endocrine therapy and targeted antibody therapy-are at present necessary tools for the curative treatment of primary breast cancer. This article reviews the evidence base for the use of various chemotherapy schedules in patients with primary, node-positive breast cancer, including schedules in combination with targeted HER2/neu therapy

Trastuzumab (Herceptin (R)): Monoclonal antibody in the treatment of HER2/neu-overexpressing breast cancer in the metastatic and (neo)adjuvant situation

Trastuzumab (Herceptin (R)) is a humanized monoclonal antibody that specifically targets HER2/neu (human epidermal growth factor receptor-2) breast cancer cells, which are overexpressed in about 25-30% of breast carcinomas. After phase I and II trials, several phase III studies of trastuzumab alone or in combination with various chemotherapies were conducted. Patients with HER2/neu overexpression levels of 3+ determined by immunohistochemical assay or gene amplification (fluorescence in situ hybridization) derive most clinical benefit from trastuzumab. Taking into consideration efficacy and side effect profile, the combination of trastuzumab and paclitaxel showed an improvement of all clinical parameters, including overall survival, for the first time in the history of palliative breast cancer therapy. The application of trastuzumab has meanwhile become an established part of systemic therapy of metastastic breast cancer, and excellent data of its application in the adjuvant setting now exist (NSABP-B31, NCCTG-N9831, HERA), with significantly better relapse-free survival in the treatment arms with trastuzumab. Ongoing trials investigate the role of trastuzumab in the neoadjuvant setting. Trastuzumab is generally well tolerated. Cardiotoxicity is the main concern, thus monitoring of cardiac function is recommended

Testing chemotherapy efficacy in HER2 negative breast cancer using patient-derived spheroids

Background Targeted anti-HER2 therapy has greatly improved the prognosis for many breast cancer patients. However, treatment for HER2 negative disease is currently still selected from a multitude of untargeted chemotherapeutic treatment options. A predictive test was developed using patient-derived spheroids to identify the most effective therapy for patients with HER2 negative breast cancer of all stages, for clinically relevant subgroups, as well as individual patients. Methods Tumor samples from 120 HER2 negative patients obtained through biopsy or surgical excision were tested in the breast cancer spheroid model using scaffold-free cell culture. Similarly, spheroids were also generated from established HER2 negative breast cancer cell lines T-47D, MCF7, HCC1143, and HCC1937 to compare treatment efficacy of heterogeneous cell populations from patient tumor tissue with homogeneous cell lines. Spheroids were treated in vitro with guideline-recommended compounds. Treatment mediated impact on cell survival was subsequently quantified using an ATP assay. Results Differences were observed in the metabolic activity of the untreated spheroids, whereby cell lines consistently achieved higher values compared to tissue spheroids (p < 0.001). A higher number of cells per spheroid correlated with a higher basal metabolic activity in tissue-derived spheroids (p < 0.01), while the opposite was observed for cell line spheroids (p < 0.01). Recurrent tumors showed a higher mean vitality (p < 0.01) compared to primary tumors. Except for taxanes, treatment efficacy for most tested compounds differed significantly between breast cancer tissue spheroids and breast cancer cell lines. Overall a high variability in treatment response in vitro was seen in the tissue spheroids regardless of the tested substances. A greater response to anthracycline/docetaxel was observed for hormone receptor negative samples (p < 0.01). A higher response to 5-FU (p < 0.01) and anthracycline (p < 0.05) was seen in high grade tumors. Smaller tumor size and negative lymph node status were both associated with a higher treatment efficacy to anthracycline treatment combined with 5-FU (cT1/2 vs cT3/4, p = 0.035, cN+ vs cN−, p < 0.05). Conclusions The tissue spheroid model reflects current guideline treatment recommendations for HER2 negative breast cancer, whereas tested cell lines did not. This model represents a unique diagnostic method to select the most effective therapy out of several equivalent treatment options

Follow-up for breast cancer - the patients' view

Background: International and national guidelines (S3 guideline) for the surveillance of post-treatment breast cancer patients recommend a clinical follow-up including routine history and physical examination and regular mammograms. The practice of a clinical follow-up has been often discussed, but has been proven not to be inferior when compared to an intensified follow-up in randomized trials. Patients and Methods: The present manuscript reports the patients' view on the basis of a survey including 2000 patients with a history of breast cancer. Results: A total of 452 patients (22.6%) answered the questionnaire. The median age was 62 years (range 23-85 years). More than 80% of the patients were disease-free at the time of the survey. The need for surveillance was affirmed by the majority of patients (>95%), and one third stated that there was a need for more technical efforts during follow-up. In contrast to the follow-up guidelines, the results of the present survey indicated that most of the regularly scheduled follow-up visits were expanded using extensive laboratory and imaging procedures. Conclusion: This survey shows that the majority of physicians obviously do not accept the present follow-up guidelines. A new surveillance study investigating the efficacy of an intensified surveillance based on the improved possibilities of modern diagnostics and endocrine, immunotherapeutic, chemotherapeutic and interventional treatment options is warranted

The Reality in the Surveillance of Breast Cancer Survivors—Results of a Patient Survey

Background: International guidelines for the surveillance of breast cancer patients recommend a minimized clinical follow-up including routine history and physical examination and regularly scheduled mammograms. However, the abandonment of scheduled follow-up examinations in breast cancer survivors remains a contradiction to established follow-up guidelines for other solid tumours.Patients and Methods: We report the patients’ view on the basis of a survey performed in two separate geographical areas in Germany. The questionnaires were sent out to 2.658 patients with a history of breast cancer.Results: A total of 801 patients (30.1%) responded to the questionnaire. The results of the survey can be summarized in two major categories: First, necessity for surveillance was affi rmed by a majority (>95%), and 47.8% of the organized patients answered that there was a need for more intensive diagnostic effort during follow-up. The main expectation from an intensified follow-up was the increased feeling of security as expressed by >80% of the women. Second, the present survey indicates that most of the regularly scheduled follow-up visits were expanded using extensive laboratory and imaging procedures exceeding the quantity of examinations recommended in the present follow-up guidelines.Conclusion: Despite the fact that only one third of the patients responded to the questionnaire, the survey indicates that a majority of physicians who treated these patients still do not accept the present follow-up guidelines. To some extent this may be explained by the observation that patients and possibly also their doctors trust that intensified follow-up increases diagnostic security and survival. Since considerable changes in the treatment options of breast cancer have been made during the last decades a new trial of investigations in follow-up is warranted

Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy--the SpheroNEO study

Background Aim of this prospective study was to predict response to neoadjuvant therapy in breast cancer patients using an in vitro breast cancer spheroid model. Methods Three-dimensional spheroids were directly generated from fresh breast tumor biopsies of 78 patients eligible for neoadjuvant therapy. Cell survival was measured after in vitro exposure to the equivalent therapeutic agents in the breast cancer spheroid model. Treatment results in vitro were correlated with pathological complete response (pCR, i.e. ypT0 ypN0) determined at surgery. Results A mean cell survival of 21.8 % was found in the breast cancer spheroid model for 22 patients with pCR versus 63.8 % in 56 patients without pCR (P = .001). The area under the receiver operator characteristic curve to predict pCR was 0.86 (95 % CI: 0.77 to 0.96) for cell survival in vitro compared to 0.80 (95 % CI: 0.70 to 0.90) for a combined model of conventional factors (hormone- and HER2 receptor, and age). A cutoff at 35 % cell survival for the spheroid model was proposed. Out of the 32 patients with values below this threshold, 21 patients (65.6 %) and one patient (2.2 %) with a cell survival greater than 35 % achieved pCR respectively; (sensitivity 95.5 % (95 % CI: 0.86 to 1.00); specificity 80.4 % (95 % CI: 0.70 to 0.91)). Extent of residual disease positively correlated with increased cell survival (P = .021). Conclusion The breast cancer spheroid model proved to be a highly sensitive and specific predictor for pCR after neoadjuvant chemotherapy in breast cancer patients

Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019)

A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynakologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was Estimating the magnitude of clinical benefit. The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient

Long-Term Summertime Investigations of Pelagic and Benthic Realms with Continuous Observations of Vertical Particle Flux in the Fram Strait and the Central Arctic Ocean

Sea ice volume and extent currently experience massive reduction in the Arctic Ocean due to climate change. Our long-term study aims at tracing effects of environmental changes in pelagic and benthic systems and investigate accompanying impacts on the fate of organic matter produced in the upper water column on its way down to the seafloor. Since the start of our observations in 1999, we have already seen some effects and will present selected data sets from the upper water column and benthic data during summer expeditions as well as results from vertical particle flux measurements that were obtained from annually deployed sediment traps at the LTER (Long-Term Ecological Research) observatory HAUSGARTEN in the eastern Fram Strait (79°/4°E) and on fewer occasions in the central Arctic Ocean (CAO). Highest biomass was found in the eastern Fram Strait and lowest in the heavily ice-covered regions in the CAO. Flux rates of POC where at least one order of magnitude lower in the CAO than in the eastern Fram Strait. While in the CAO ice algae dominate the recognizable flux fraction, faecal material prevailed in eastern Fram Strait traps. This points towards different systems of organic matter production and modification and, thus, different mechanisms determine the efficiency of the biological carbon pump. These differences are also reflected in the benthic communities in the CAO and in the eastern Fram Strait. These first results have shown the importance of long-term observations and encouraged the continuation of the Arctic Ocean Observing System FRAM (FRontiers in Arctic marine Monitoring) to record environmental and biological data at high temporal and spatial resolution