Trasias Mukama

Prospective evaluation of 92 protein biomarkers for early detection of endometrial cancer

Abstract The human epididymis protein 4 (HE4) remains the best available endometrial cancer (EC) biomarker; however, its discrimination between cases and cancer‐free individuals is limited and might be improved when combined with other protein markers. We evaluated the discrimination capacity of 92 proteins as potential early detection biomarkers for EC in nested case–control studies in the European Prospective Investigation into Cancer and Nutrition (EPIC) (63 cases, 123 controls) and Janus (75 cases, 146 controls) cohorts, evaluating blood samples taken ≤2 years prior to diagnosis. Proteins were measured with the Olink Target 96 Oncology II panel assays. Areas under the receiver operating characteristic curves (AUCs) were calculated using logistic regression. The discrimination between cases and controls of top‐performing proteins was modest (EPIC: HE4, CA125, CAIX, and S100A4; Janus: HE4, CA125, FURIN, CXCL13, and IL6; AUC range: 0.65 [S100A4], 0.76 [HE4, EPIC] within 0 to <12 months of blood collection) and decreased as the time between blood draw and cancer diagnosis increased (12–24 months AUC range: 0.49 [S100A4], 0.69 [CA125, Janus]). The combination of these other markers with HE4 did not improve discrimination. HE4 and other candidate proteins had limited discrimination between EC cases and controls and hence do not appear to be useful for early detection of this disease in women at average population risk.

A Prospective Study Consortium for the Discovery and Validation of Early Detection Markers for Ovarian Cancer – Baseline Findings for CA125

Abstract Purpose: Epithelial ovarian cancer (EOC) is a lethal malignancy. Cancer antigen 125 (CA125), the “best” available marker for detecting EOC, has insufficient sensitivity and specificity for earlier-stage disease and is not a meaningful screening tool, motivating the search for further biomarkers. Cancer biomarker discovery is enhanced by “omics” technologies. Discovery studies for EOC biomarkers should be conducted in prediagnosis blood samples from prospective cohorts to maximize the likelihood of identifying markers that can detect disease before usual diagnosis and in earlier disease stage while reducing methodologic biases. Experimental Design: Individual cohorts with prediagnosis blood samples have insufficient sample size for such studies. Thus, we established “Prospective Early Detection Consortium for Ovarian Cancer” (“PREDICT”)—a collaboration of nine prospective studies—to assemble a sufficient number of EOC cases with blood samples collected ≤18 months before diagnosis plus controls. The 457 cases and 1,687 controls have circulating CA125 measured using a clinical assay. Results: The discrimination capacity for single CA125 measurements in samples collected <6 months prior to diagnosis was high (AUC; PREDICT overall = 0.92; range across cohorts of nonpregnant individuals = 0.89–0.98) and declined with extended time between blood collection and diagnosis. Between-cohort variability in CA125 levels and predictive performance was observed. Conclusions: Ongoing investigations in PREDICT are evaluating the early detection potential of tumor-associated autoantibodies and miRNAs using CA125 as a benchmark. PREDICT is a well-characterized resource for identifying and validating detection markers for EOC that may then be used in multimodal screening as a complement to CA125 and combined with imaging.

Risk‐adapted starting age of breast cancer screening in women with a family history of ovarian or other cancers: A nationwide cohort study

BACKGROUNDThere is a lack of evidence‐based recommendations for the age at which women with a family history of cancers other than breast cancer should start breast cancer screening.METHODSUsing Swedish family cancer data sets, the authors conducted a nationwide cohort study including 5,099,172 Swedish women born after 1931 (follow‐up, 1958‐2015). Accounting for calendar time, they calculated the relative risk of breast cancer for women with a family history of a discordant cancer in 1 first‐degree relative. Furthermore, the authors used 10‐year cumulative risk to determine the ages at which women with a family history of discordant cancer reached risk thresholds at which women in the general population were recommended to start breast cancer screening.RESULTSA family history of cancer at 15 sites was associated with an increased risk of breast cancer. Among women younger than 50 years, the highest risk of breast cancer was observed for those with a family history of ovarian cancer (standardized incidence ratio, 1.44; 95% confidence interval, 1.26‐1.64). In these women, the risk of breast cancer associated with a family history at other cancer sites ranged from 1.08‐fold for prostate cancer to 1.18‐fold for liver cancer. When breast cancer screening was recommended to be started at the age of 50 years for the general population, women with 1 first‐degree relative with ovarian cancer attained the threshold risk for screening at the age of 46 years. Women with a family history of other discordant cancers did not reach the risk thresholds for screening at younger ages.CONCLUSIONSMany cancers showed familial associations with breast cancer, but women with a family history of these cancers (except for ovarian cancer) did not reach risk thresholds for screening at younger ages.