Subcutaneous (SC) trastuzumab has long been approved as a cancer treatment for early and advanced HER2-positive (HER2+) breast cancer by both the European Medicines Agency (EMA) and Agência Nacional de Vigilância Sanitária (ANVISA), the Brazilian National Health Surveillance Agency. A pivotal non-inferiority phase III trial, which aimed to provide a more convenient and cost-effective treatment in the HER2+ breast cancer neoadjuvant setting, showed that the SC group met prespecified efficacy endpoints and the SC formulation was considered as safe as the intravenous (IV) formulation. Considering the recent approval of several biosimilars, new SC formulations are also an interesting manufacturer strategy as these drugs can obtain patent protection. Despite being considered non-inferior to the IV formulation of trastuzumab, in clinical development, the SC formulation elicited higher immunogenicity, mainly related to overall anti-drug antibodies (ADAs); however, this finding was classified as clinically non-significant. In this article, we explore different aspects of the benefits and risks of the SC trastuzumab formulation according to published data.
Reducing primary tumor volume is the main role of neoadjuvant chemotherapy for breast cancer. We evaluated the benefit of adding docetaxel to anthracyclin as neoadjuvant therapy. This study is a retrospective cohort analysis comparing the efficacy of neoadjuvant chemotherapy in patients subjected to docetaxel and epirubicin or 5-fluoruracil, epirubicin and cyclophosphamide combinations (DE and FEC group, respectively). The mean number of chemotherapy delivered was similar in both groups (P = 0.8). A total of 316 patients were treated (151 in FEC group and 165 in DE group). Primary endpoint was the clinical and pathological response to therapy. Breast conserving surgery rate was compared. In T1/2 staged patients, the complete clinical response rate was 7.5% in FEC group and 32% in DE group (P = 0.002), and the breast conserving surgery rate was 72 and 73% in FEC and DE groups, respectively (P = 0.9). In the subset of patients staged as T3 and T4a-c, objective response was higher in DE group (P < 0.0001 and P = 0.008, respectively). Breast conserving surgery rate was 38 and 63% in FEC and DE groups, respectively, in T3 staged patients and, 20.5 and 37% in T4a-c staged patients (P = 0.003 and 0.08). Despite the similar number of chemotherapy cycles delivered in both groups, the presence of microscopic axillary lymph node involvement after chemotherapy was less frequent in DE group. Neoadjuvant chemotherapy with DE combination is more effective in terms of clinical and pathological response propitiating higher breast conserving surgery rate than FEC combination in stage II and III breast cancer.
Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMIX30 kg/m 2 ). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLR high (NLR44) was found to be an independent prognostic factor for recurrence and mortality, while the PLR high (PLR4150) group had no impact on survival. A subgroup of patients with NLR high and BMI high had the worst disease-free survival (P=0.046), breast cancer-specific survival (Po0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLR high and BMI high had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.
Microinjection of glycine into the rostral (bilateral) and caudal (midline) commissural nucleus of the solitary tract (NTS) using three guide cannulas implanted in the direction of these sites produced an increase in mean arterial pressure (MAP) and abolished the pressor response to chemoreflex activation [potassium cyanide (n = 7)]. Strychnine, a glycine receptor antagonist, attenuated the increase in MAP, and in this new experimental condition (n = 5) the pressor response to chemoreflex activation was not altered. Considering that the effect of glycine on the attenuation of the pressor response to chemoreflex activation could be secondary to the increase in baseline MAP, in a third group of rats (n = 5) sodium nitroprusside infusion (intravenous) after microinjections of glycine into the NTS normalizes MAP. In this case, the pressor response to chemoreflex activation was similar to the control. These data show that glycine when microinjected bilaterally into the lateral commissural NTS as well as into the medial commissural NTS plays no major inhibitory role in the processing of the neurotransmission of the sympathoexcitatory component of the chemoreflex.
Cancer is a major public health issue worldwide, especially in the developing world where 70% of the cancer-related deaths occur. During the last three decades, with the advent of targeted therapies using monoclonal antibodies, patients' survival and quality of life have dramatically improved. Unfortunately, these great accomplishments came at the expense of high financial costs which most of the population living in low-and middle-income countries cannot afford. Biosimilars (biotherapeutic products that are similar to an already licensed reference biotherapeutic product in terms of quality, safety and efficacy) have been successfully used in Europe and in US with a substantial reduction in price of around 30%. Brazil is about to have trastuzumab as the first biosimilar available to treat cancer patients in the country. Based on strict regulatory legislations, biosimilars are expected to deliver affordable yet effective and safe treatment options all over the world, expanding the access to cancer treatment and reducing inequalities.
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