ABSTRACT
INTRODUCTION: Precision medicine has revolutionized oncology, providing more personalized diagnosis, treatment, and monitoring for patients with cancer. In the context of female-specific tumors, such as breast, ovarian, endometrial, and cervical cancer, proper tissue collection and handling are essential for obtaining tissue, immunohistochemical (IHC), and molecular data to guide therapeutic decisions. OBJECTIVES: To establish guidelines for the collection and handling of tumor tissue, to enhance the quality of samples for histopathological, IHC, genomic, and molecular analyses. These guidelines are fundamental in informing therapeutic decisions in cancer treatment. METHOD: The guidelines were developed by a multidisciplinary panel of renowned specialists between June 12, 2013 and February 12, 2024. Initially, the panel deliberated on critical and controversial topics related to conducting precision medicine studies focusing on female tumors. Subsequently, 22 pivotal topics were identified within the framework and assigned to groups. These groups reviewed relevant literature and drafted preliminary recommendations. Following this, the recommendations were reviewed by the coordinators and received unanimous approval. Finally, the groups made the final adjustments, classified the level of evidence, and ranked the recommendations. CONCLUSION: The collection of surgical samples requires minimum quality standards to enable histopathological, IHC, genomic, and molecular analyses. These analyses provide crucial data for informing therapeutic decisions, significantly impacting potential survival gains for patients with female tumors.
ABSTRACT
The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li-Fraumeni syndrome (LFS) or Li-Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.
