Gynecologic oncology最新文献

HER2-targeting therapies are well-described in breast, gastric, and lung cancers, however accumulating data supports a role for HER2-targeted therapies in gynecologic cancers. Despite varied methodologies for HER2 testing, evidence supports that a substantial proportion of endometrial, ovarian, cervical, and vulvar cancers overexpress HER2. This underscores the rationale for HER2-targeted therapies in these malignancies, including the use of HER2-directed tyrosine kinase inhibitors, antibody-drug conjugates, and immune-stimulating antibody conjugates. Understanding mechanisms of resistance to HER2-targeted therapies will inform possible combinatorial strategies.

Objective: To develop and validate an ovarian cancer risk assessment tool for first-degree relatives of patients in the Chinese population.

Methods: A bidirectional multicenter cohort was established, including 529 probands and 3141 first-degree relatives. Cancer incidence was analyzed using the standardized incidence ratio (SIR). Significant variables were identified through Cox regression analyses and visualized via a nomogram. Model performance was evaluated using the C-index, with first-degree relatives stratified into high- and low-risk groups based on a 10 % cancer risk threshold.

Results: Among 1596 first-degree female relatives, 57 ovarian cancer cases were identified, demonstrating a significant increase in SIR (SIR = 9.19; 95 % CI, 7.03-11.83; p < 0.001). In 980 relatives with germline mutations, elevated SIRs were observed for ovarian cancer (SIR = 23.33; 95 % CI, 16.51-32.09; p < 0.001) and breast cancer (SIR = 3.56; 95 % CI, 2.46-5.00; p < 0.001). Cox regression analyses identified key risk factors, including the proband's age of onset, tumor histology, gene mutation status, family history of breast cancer, and relationship to the proband. The nomogram demonstrated good predictive accuracy, with C-indices of 0.75 (training set), 0.75 (internal validation), and 0.71 (external validation). Calibration plots and Kaplan-Meier curves confirmed strong agreement and significant differences between high- and low-risk groups (cut-off value = 2.1).

Conclusions: This study develops and preliminarily validates a risk assessment tool for first-degree relatives of ovarian cancer patients in China, utilizing accessible clinical and familial data to enable early identification of high-risk individuals.

Objective: We describe a tertiary referral center's experience with anaplastic ovarian carcinoma and characterize the genetic landscape of these rare tumors.

Methods: Anaplastic ovarian carcinomas were retrospectively identified from institutional databases from 2013 to 2023. Clinical data and survival outcomes were abstracted from the electronic medical record. Molecular data were obtained from clinical tumor-normal panel sequencing.

Results: Thirteen tumors were identified; 12 (92 %) were associated with or arose from a mucinous carcinoma, and 6 (46 %) were found in a mural nodule. Median age at diagnosis was 39 years (range, 19-77); 6 patients had stage I disease (3 stage IA), 1 had stage II, 5 had stage III, and 1 had stage IV. All patients underwent surgery. First-line postoperative therapy included carboplatin-paclitaxel doublet (n = 8), a 5-fluorouracil-oxaliplatin-based regimen (FOLFOX, n = 1; XELOX, n = 2), and ifosfamide/paclitaxel (n = 1). Two patients did not receive adjuvant chemotherapy for early-stage disease. Six patients had progression or recurrence; 5 had platinum-refractory disease and 1 had an initial progression-free interval of 6.8 months. For the 7 patients without recurrence, median follow-up was 79.7 months. Median overall survival for all patients was 28.1 months (range, 7.8-139.2). Five patients died of their disease. Ten patients had clinical panel sequencing, revealing recurrent somatic KRAS G12D/V hotspot mutations (8 of 10, 80 %) and genetic alterations affecting cell cycle-related genes, including TP53 (6 of 10, 60 %) and CDKN2A (6 of 10, 60 %).

Conclusions: Anaplastic ovarian carcinoma is characterized by KRAS, TP53, and CKDN2A alterations. Novel treatment approaches are needed due to the high rate of platinum-refractory disease.