JNCI Journal of the National Cancer Institute最新文献

Background: Women diagnosed with breast cancer at young ages (younger than 40 years) generally have lower survival than their older counterparts. With its young population structure, sub-Saharan Africa provides an informative setting to examine survival among young patients with breast cancer, including consideration of the extended reproductive lives and HIV comorbidities.

Methods: We established a prospective cohort of women aged 18 years and older newly diagnosed with breast cancer in five sub-Saharan African countries during 2014-2017, who were actively followed for up to 7 years. Overall survival, net survival, and Cox model hazard ratios (HRs) were used to assess the association between age at diagnosis and all-cause mortality.

Results: Among 2093 women, 459 (21.9%) were diagnosed under age 40 years ("young" women). Five-year net survival was 36% (95% confidence interval [CI] = 31% to 40%) in these young women, which was 8-14 percentage points lower than that for those diagnosed in their 40s, 50s, 60s, and 70s or older, being 43%, 45%, 47%, and 50%, respectively. Compared with women diagnosed at age 40-59 years, young women had 1.17-fold (95% CI = 1.02 to 1.35) higher mortality rates, unexplained by triple-negative breast cancer and HIV which were both less prevalent in young women than in those aged 40-59 years. Adjustment for sociodemographic, clinical, and treatment factors hardly altered results, except for adjustment for having had a pregnancy within the past 3 years (HR = 1.09, 95% CI = 0.93 to 1.28).

Conclusion: Early onset breast cancer in sub-Saharan Africa was associated with lower survival compared with women aged 40-59 years. This excess mortality was restricted to young women whose breast cancer was diagnosed within 3 years postpartum, thus identifying a patient group with specific early detection, treatment support and research needs.

Background: Fecal immunochemical test (FIT) performance for colorectal cancer screening varies by age and sex, yet most FIT-based screening programs use uniform positivity thresholds. This study assessed the potential benefits of stratifying FIT thresholds based on age and sex.

Methods: We conducted a meta-analysis of FIT sensitivity and specificity at various positivity thresholds by age and sex. We then used these estimates in 2 microsimulation models of colorectal cancer and projected lifetime clinical outcomes, incremental costs, and quality-adjusted life-years (QALYs) gained from age- and sex-stratified FIT strategies. FIT thresholds ranged from 10 to 50 µg hemoglobin per gram of feces.

Results: For current uniform FIT screening (20 µg hemoglobin/gram of feces), models projected 85.67 to 122.15 QALYs gained at incremental costs of ‒$982 to $504 per 1000 individuals compared with no screening. At equivalent costs to current uniform screening, only 1 model found stratified FIT approaches cost-effective, yielding a marginal increase of 1.04 and 1.10 QALYs gained/1000 female and male individuals, respectively. At a willingness-to-pay threshold of $100 000/QALYs gained, both models found stratified FIT cutoffs to be the best strategy, with cutoffs being equal to or higher for males and lowest at older ages (70-75 years). Uniform strategies showed comparable effectiveness, falling within 1 quality-adjusted life-day per person of efficient strategies at up to $112 more per person. Results were sensitive to FIT test performance characteristics and 1-time setup costs.

Conclusion: Stratifying FIT thresholds by age and sex may be cost-effective compared to current screening. The gain in expected health benefits with stratified FIT screening, however, is likely small.

Self-identified race and ethnicity (SIRE) and genetic ancestry are potentially associated with disparities in health outcomes; however, independent effects of SIRE and genetic ancestry on mortality in cancer survivors including when adjusting for multiple risk factors are understudied. Among 23 445 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Screening Trial, SIRE was associated with mortality among prostate, colorectal, lung, ovarian, and breast cancer survivors; genetic ancestry was associated with mortality among prostate, colorectal, and breast cancer survivors. Associations were strong when adjusting for age at cancer diagnosis, sex, and tumor characteristics but attenuated when adjusting for individual-level factors and population-level socioeconomic status. For example, mortality risk was higher among Black vs White prostate cancer survivors and African genetic ancestry vs European genetic ancestry, but associations were attenuated after multilevel adjustment. Results suggest that SIRE and genetic ancestry do not solely reflect biologic variation; rather, social factors may drive mortality differences by SIRE and genetic ancestry.

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent, widespread environmental contaminants, and some are endocrine disrupting. Studies of gynecologic cancers are limited; we evaluated ovarian cancer, a rare, often fatal malignancy.

Methods: This nested case-control study included 318 ovarian cancer cases and 472 individually matched female controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 10 US study centers (1993-2001). We looked at cases through 2016 and quantitated 8 PFAS in prediagnostic serum samples. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for continuous (log2-transformed) and categorized PFAS concentrations by using conditional logistic regression models, implicitly adjusting for matching factors (age, center, year of random assignment, year of blood draw, race and ethnicity) and adjusting for smoking, body mass index, family history of cancer, menopausal hormone therapy and oral contraceptive use, parity, and number of freeze-thaw cycles.

Results: We found a positive association with ovarian cancer for a doubling in 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) concentrations (OR for log2 = 1.24, 95% CI = 1.03 to 1.49) and 62% greater risk among those in the highest quartile (OR for quartile 4 vs quartile 1 = 1.62, 95% CI = 1.03 to 2.54; P for trend = .02). Perfluorooctane sulfonic acid (PFOS) was associated with increased risk (OR for log2 = 1.47, 95% CI = 1.05 to 2.06), with no quartile trend (P for trend = .79). Associations with perfluorononanoic acid (OR for log2 = 1.36, 95% CI = 0.95 to 1.95) and perfluorodecanoic acid (OR for log2 = 1.35, 95% CI = 0.94 to 1.95) were suggested, with nonmonotonic quartile trends (P for trend = .12 to .21). The MeFOSAA associations were strongest in women aged 55-59 years (OR for log 2 = 1.60, 95% CI = 1.13 to 2.27), more moderate in women aged 60-64 years (OR for log2 = 1.31, 95% CI = 0.90 to 1.90), and null among women 65 years of age and older (OR for log2 = 1.02, 95% CI = 0.73 to 1.43; P for heterogeneity = .22). Associations persisted in cases diagnosed 8 years or more after blood collection.

Conclusions: These findings offer novel evidence for PFAS as ovarian cancer risk factors, particularly PFOS and MeFOSAA, a PFOS precursor.