RESUMO
PURPOSE: Ki-67 is recommended by international/national guidelines for risk stratification in early breast cancer (EBC), particularly for defining "intermediate risk," despite inter-laboratory/inter-observer variability and cutoff uncertainty. We investigated Ki-67 (> 10%- < 40%, determined locally) as a prognostic marker for intermediate/high risk in EBC, pN0-1 patients. METHODS: This prospective, non-interventional, real-world study included females ≥ 18 years, with pN0/pN1mi/pN1, HR+ , HER2-negative EBC, and locally determined Ki-67 ranging 10%-40%. The primary outcome was changes in treatment recommendations after disclosing the Oncotype DX Breast Recurrence Score®(RS) assay result. RESULTS: The analysis included 567 patients (median age, 57 [range, 29-83] years; 70%/1%/29%/ with pN0/pN1mi/pN1 disease; 81% and 19% with RS results 0-25 and 26-100, respectively). The correlations between local and central Ki-67, local Ki-67, and the RS, and central Ki-67 and the RS results were weak (r = 0.35, r = 0.3, and r = 0.46, respectively), and discrepancies were noted in both directions (e.g., local Ki-67 was lower or higher than central Ki-67). After disclosing the RS, treatment recommendations changed for 190 patients (34%). Changes were observed in pN0 and pN1mi/pN1 patients and in patients with centrally determined Ki-67 ≤ 10% and > 10%. Treatment changes were aligned with RS results (adding chemotherapy for patients with higher RS results, omitting it for lower RS results), and their net result was 8% reduction in adjuvant chemotherapy use (from 32% pre-RS results to 24% post-RS results). CONCLUSION: The Oncotype DX® assay is a tool for individualizing treatments that adds to classic treatment decision factors. The RS result and Ki-67 are not interchangeable, and Ki-67, as well as nodal status, should not be used as gatekeepers for testing eligibility, to avoid under and overtreatment.
RESUMO
Uterus transplantation may become the surgical therapeutic modality of choice for uterine factor infertility. However, this procedure still faces technical, therapeutic, and immunologic challenges that limit its success and clinical application. Experimental studies are therefore still needed to address various challenges in the field of uterus transplantation. Among various laboratory animals, small animals are ideal models for the purpose of experimental uterus transplant. However, clinical success in small animal models is not generalizable to clinical application and treatment for uterine factor infertility in humans. Large animal models are necessary because their uterine anatomy and reproductive physiology closely resemble those of humans. In the literature, in general with small or large animal models, the same striking characteristic has been previous regular menstruation. Anesthesia was usually induced through inhalation and/or intraperitoneal injection in small models and intravenous injection in large models. Systemic heparinization was usually performed after preparation of uterus and vessels and before crossclamping of the vessels. Flushing of the graft was performed through the interior iliac artery or aorta. A grafted segment was frequently selected only from one horn of the uterus. The uterine artery, internal iliac artery, and aorta have been frequently used for arterial revascularization into the recipient's external iliac artery or abdominal aorta. The uterine vein, internal iliac vein, and inferior vena cava have been used for venous drainage into the recipient's inferior vena cava, external iliac vein, or uteroovarian vein. In most models, the native uterus was resected to reconstruct the grafted uterus continuity. Other models have left the native uterus in the recipient's abdomen, and stomas have been used for end of the grafted uterus.
