br Recently reductions in VTE risk have
Recently, reductions in VTE risk have incidentally been observed with certain medications. Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, are generally used for the treatment of hypercholesterolemia, however multiple studies have demonstrated that statin use is also associated with a reduced risk of VTE in cancer populations [7–10] and in the non-oncologic setting . Similarly, as-pirin, which permanently inhibits cyclooxygenase 1 on Jasplakinolide and ex-erts both anti-inflammatory and anti-thrombotic effects , is also associated with protective effects on cancer-related VTE development [13,14].
Women with endometrial cancer often have multiple medical co-morbidities, and statin and aspirin use seems to be prevalent [15,16]. Nevertheless, the effects of statin and aspirin use on VTE risk have not been examined in the endometrial cancer population. The objective of this study was to examine the association between statin and/or aspirin use and VTE risk in women with endometrial cancer.
2. Materials and methods
This retrospective multicenter study examined consecutive cases of women with endometrial cancer from two U.S. centers and four Japanese centers between 2000 and 2015. Institutional Review Board approval was obtained at each site. Eligible women were those with a histologic diagnosis of endometrial cancer and available information for medication usage at endometrial cancer diagnosis. Exclusion criteria included synchronous secondary primary malignancy, VTE prior to en-dometrial cancer diagnosis, and lack of medication information. Some of the cases were included within the context of our prior study, which examined effects of aspirin on endometrial cancer survival .
2.2. Clinical information
Among eligible cases for the study, salient variables pertaining to VTE risk and cancer diagnosis were abstracted, including patient demo-graphics, medical comorbidities, medications, tumor characteristics, treatment type, and survival events. Patient demographics included age, race/ethnicity, and body habitus. Medical comorbidities at diagno-sis included hypertension, diabetes mellitus, and hypercholesterolemia, and medications included use of statins and aspirin at endometrial can-cer diagnosis. Tumor characteristics included histologic type of endo-metrial cancer, serum cancer antigen 125 (CA-125) level at diagnosis, and cancer stage. Treatment type included use and type of hysterec-tomy and chemotherapy use. Survival information included endome-trial cancer recurrence.
2.3. Study definition
For patient demographics, age was grouped by quartile, and obesity was classified per the CDC criteria (body mass index b30, 30–34.9, 35.0– 39.9, and ≥40 kg/m2) . Cancer stage was re-classified based on the 2009 International Federation of Gynecology and Obstetrics staging
system . Type I endometrial cancer was defined as grade 1–2 endometrioid adenocarcinomas, whereas type II endometrial cancer was defined as other histology types . Information regarding chemotherapy use was collected, as chemo-therapy can be associated with increased risk of VTE . Per the prior criteria for VTE risk in endometrial cancer , cancer stage was grouped as stage I–II versus III–IV and CA-125 levels were grouped as b35 versus ≥35 IU/L. Hysterectomy type was grouped as laparotomy, minimally in-vasive, or no hysterectomy based on a prior study associating hysterec-tomy mode and VTE risk .
VTE events were assessed during follow-up, and the time interval between endometrial cancer diagnosis and VTE was collected. Cases without VTE were censored at last follow-up. Cases lost to follow-up were also censored at the last known visit. The type of VTE was also col-lected (deep vein thrombosis [DVT] alone, pulmonary embolism [PE] alone, or both). In our institutions, diagnosis of VTE was generally made radiographically via Doppler studies, computer tomography, or ventilation-perfusion scans crossopterygians were performed when VTE is clinically suspected, and routine scans to diagnose subclinical VTE are not performed.
2.4. Study population
There were 2527 women with histology-confirmed primary endo-metrial cancer and without a history of VTE or synchronous malignancy who had information regarding medication type available at diagnosis. The median follow-up time was 43.0 months (interquartile range, 24.6–64.4). There were 132 women who were diagnosed with VTE, resulting in a 5-year cumulative risk of 6.1% estimated by a time-dependent life table. The most common VTE type was DVT alone (n
2.5. Study objectives
The primary objective of the study was to examine the association between statin and/or aspirin use and VTE risk in women with endome-trial cancer. The secondary objective of the study was to identify the clinico-pathological factors associated with the benefit of statin and/or aspirin use on VTE risk.