Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.
Materials and methods
The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.
Results
In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).
Conclusions
We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis. 相似文献
Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained. This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately. 相似文献
ObjectiveBorderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS.Materials and methodsPatients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes.Results85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate.ConclusionsConservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT. 相似文献
目的:探讨40岁以上高龄女性体外受精-胚胎移植(IVF-ET)的妊娠结局,旨在为高龄女性提供生育咨询以及为改善高龄女性个体化辅助生殖治疗结局提供临床依据。方法:选择我院生殖中心2015年1月—2017年12月女方年龄≥40岁且使用自身卵子行体外受精的共2 467个治疗周期资料,对各项临床数据进行回顾性分析。结果:40岁及以上行辅助生殖治疗的患者,随着女性年龄增加获卵数明显减少(40~48岁女性平均获卵数分别为2.97、 2.69、2.17、2.01、1.77、1.61、1.68、1.29和1.00,44~48岁与40~43岁依次组间比较均P<0.05),尤其是44岁以上女性胚胎发育潜能明显降低(40~48岁囊胚形成率分别为48.90%、43.72%、33.67%、34.29%、24.39%、21.14%、26.32%、16.67%和0%,44~48岁与40~43岁组间依次比较均P<0.05)。共有518个周期行新鲜胚胎移植,结果显示,随女性年龄增加,临床妊娠率(40~48岁临床妊娠率分别为26.92%、21.15%、20.79%、10.96%、18.87%、11.11%、5.88%、0%和0%,43~48岁与40~42岁组间依次比较均P<0.05)、种植率(40~48岁种植率分别为23.65%、19.51%、17.70%、8.54%、7.49%、10.81%、5.56%、0%和0%,43~48岁与40~42岁组间依次比较均P<0.05)和活产率均显著降低(40~46岁活产率分别为18.46%、10.58%、9.90%、5.48%、5.66%、2.78%和5.88%,43~46岁与40~42岁组间依次比较均P<0.05),43岁以上者结局更差。44岁以上女性自然流产率明显增高(40~45岁流产率分别为31.43%、50.00%、52.38%、50.00%、70.00%和75.00%,44~45岁与40~43岁组间依次比较均P<0.05)。46岁女性仅1例妊娠并分娩,47岁和48岁女性均无成功妊娠。与抗苗勒管激素(AMH)>1.0 ng/mL组相比,AMH≤1.0 ng/mL组妊娠率、种植率及活产率均显著下降(27.04% vs. 14.74%,22.99% vs. 13.50%,15.88% vs. 7.37%;均P<0.05),流产率明显升高(41.27% vs. 50.00%,P<0.05)。结论:≥40岁高龄女性随年龄增长生育力逐渐降低。40~43岁年龄段女性助孕仍有一定的价值,尤其是卵巢仍有一定储备者(AMH>1.0 ng/mL),但44岁以上女性原则上不再建议ART助孕,对于46岁以上卵巢功能衰竭的女性强烈建议卵子捐赠或收养。 相似文献