RESUMO
BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. RESULTS: The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. CONCLUSION: The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.
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BACKGROUND: Currently, there is a lack of prognostic evaluation methods for non-serous epithelial ovarian cancer (EOC). METHOD: We collected patients with non-serous EOC diagnosed between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database into a training cohort (n = 2078) and an internal validation cohort (n = 891). Meanwhile, patients meeting the criteria were screened from the Fujian Provincial Maternal and Child Health Hospital from 2013 to 2022 as an external validation cohort (n = 56). Univariate and multivariable logistic regression were used to determine the independent prognostic factors of cancer-specific survival (CSS) to construct the nomogram. The nomogram was validated by the concordance index (C-index), receiver operating characteristics (ROC) curve and calibration curves. RESULT: Age, laterality, preoperative CA125 status, histologic type, tumor grade, AJCC stage, surgery lesion, number of lymph nodes examined, residual lesion size, and bone metastasis were identified as independent prognostic factors to construct the nomogram. The nomogram showed better predictive ability than FIGO stage through internal and external cohorts validation. The C-index of the nomogram in the training cohort, validation cohort, and external validation cohort were 0.831, 0.835 and 0.944 higher than those of the Federation International of Gynecology and Obstetric (FIGO) stage, P<0.05. The Area Under Curve (AUC) values results indicated great clinical usefulness of the nomogram. The calibration curve indicated good agreement between the nomogram prediction and actual survival. CONCLUSION: We developed a nomogram with high predictive accuracy to predict survival in patients with non-serous EOC.
RESUMO
Identifying BRCA mutations and homologous recombination deficiency (HRD) is the key to choosing patients for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy. At present, a large amount of research focuses on the application of HRD detection in ovarian cancer. However, few studies have discussed the relationship between HRD detection and postoperative survival in patients with epithelial ovarian cancer (EOC). This study included 38 consecutive patients with EOC who underwent cytoreduction surgery. Owing to tissue availability, only 29 patients underwent molecular profiling and survival analysis. Overall, 21 (72.4%) tumors had HRD scores of ≥42. Mutations in BRCA were observed in 5/29 (17.2%) patients. In this cohort, an HRD score of ≥42 was more common in serous ovarian tumors. We found no statistically significant association between homologous recombination repair (HRR) genes and HRD scores except for tumor protein P53 (TP53) mutation. We also found a strong positive association between HRD scores and chromosomal instability (CIN). In the survival analysis, an HRD score of >23 was correlated with better postoperative progression-free survival (pPFS). With increased depth of research, an appropriate HRD score threshold may serve as a prognostic tool and should be assessed in future studies to predict the clinical value of PARPi.