ABSTRACT
BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.
Subject(s)
Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Complementary Therapies , Letrozole/adverse effects , Musculoskeletal Pain/chemically induced , Aged , Arthralgia/chemically induced , Female , Germany/epidemiology , Humans , Middle Aged , Myalgia/chemically induced , PostmenopauseABSTRACT
BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Breast Neoplasms/drug therapy , Sirolimus/analogs & derivatives , Adult , Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Drug Therapy, Combination , Everolimus , Female , Humans , Middle Aged , Receptor, ErbB-2/metabolism , Sirolimus/administration & dosage , Sirolimus/therapeutic use , Survival AnalysisABSTRACT
368 streptococcal strains from udder secretions of cattle (Sc. agalactiae, Sc. dysgalactiae, Sc. uberis) and 191 streptococcal isolates from horse specimens (Sc. equi ssp. zooepidemicus, Sc. equi ssp. equi) originating from different agricultural regions in Germany (Lower Saxony, in particular the region of Weser-Ems, Bavaria, Altmark) were investigated for their sensitivity to 4 beta-lactam antibiotics (benzylpenicillin, ampicillin, oxacillin, cefotaxime). Two different test methods were applied: the agar diffusion test for determination of the diameter of the zone of inhibition and the E-test for determination of the minimal inhibitory concentration (MIC). According to the evaluation code of DIN 58,940, 98% to 100% of the isolates from the cow udder as well as of the Streptococcus strains from horses were sensitive to the four antibiotics tested. Only Sc. uberis was less sensitive to benzylpenicillin (79.7%) and Oxacillin (83.2%). The strains from different agricultural regions did not differ from each other concerning their sensitivity to beta-lactams. The results of the two methods of sensitivity testing were in satisfactory agreement: Compared to the MIC reference values, misclassifications occurred in the agar diffusion test only at an error rate of between 1.62% (for ampicillin) and 5.21% (for benzylpenicillin).
