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

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

AGO recommendations for the surgical therapy of the axilla after neoadjuvant chemotherapy: 2021 Update

For many decades, the standard procedure to treat breast cancer included complete dissection of the axillary lymph nodes. The aim was to determine histological node status, which was then used as the basis for adjuvant therapy, and to ensure locoregional tumour control. In addition to the debate on how to optimise the therapeutic strategies of systemic treatment and radiotherapy, the current discussion focuses on improving surgical procedures to treat breast cancer. As neoadjuvant chemotherapy is becoming increasingly important, the surgical procedures used to treat breast cancer, whether they are breast surgery or axillary dissection, are changing. Based on the currently available data, carrying out SLNE prior to neoadjuvant chemotherapy is not recommended. In contrast, surgical axillary management after neoadjuvant chemotherapy is considered the procedure of choice for axillary staging and can range from SLNE to TAD and ALND. To reduce the rate of false negatives during surgical staging of the axilla in pN+(CNB) stage before NACT and ycN0 after NACT, targeted axillary dissection (TAD), the removal of > 2 SLNs (SLNE, no untargeted axillary sampling), immunohistochemistry to detect isolated tumour cells and micro-metastases, and marking positive lymph nodes before NACT should be the standard approach. This most recent update on surgical axillary management describes the significance of isolated tumour cells and micro-metastasis after neoadjuvant chemotherapy and the clinical consequences of low volume residual disease diagnosed using SLNE and TAD and provides an overview of this year's AGO recommendations for surgical management of the axilla during primary surgery and in relation to neoadjuvant chemotherapy

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis