JNCI Cancer Spectrum最新文献

Background: Gene expression assays help personalize adjuvant chemotherapy decisions for hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC). The 70-gene risk of distant-recurrence signature, MammaPrint, demonstrated clinical utility in guiding chemotherapy de-escalation in genomically low risk patients in the MINDACT trial. This study evaluates MammaPrint as a continuous predictor of chemotherapy benefit in HR+HER2- EBC using real-world data (RWD) from the FLEX Registry.

Methods: The study evaluated 1002 patients treated with endocrine therapy (ET) only or ET with chemotherapy (ET+CT) enrolled in FLEX (NCT03053193) with 5-year median follow-up. Propensity-score matching balanced treatment groups by menopausal status, T-stage, and nodal status. The primary endpoint was distant recurrence-free interval (DRFI). Regression and Cox proportional hazards models assessed chemotherapy benefit across MammaPrint Index (MPI) risk.

Results: Most patients were postmenopausal (70.1%), node-negative (70.0%), and had grade 2 tumors (51.2%). The regression models showed that MPI strongly predicted 5-year DRFI in ET only (R2 = 0.99, P < .001) and ET + CT (R2 = 0.90, P < .001) groups, corresponding to an average absolute chemotherapy benefit of 5.6% in High 1 and 10.9% in High 2. Minimal improvement in DRFI with chemotherapy was observed for Low (1.7%) and UltraLow (<1.0%) risk groups. A multivariate Cox model with an MPI-by-treatment interaction term demonstrated that increasing MPI risk was associated with greater chemotherapy benefit on DRFI (HR = 0.15, P = .047). Chemotherapy benefit was significantly associated with premenopausal status, but not age, T-stage, nodal status, or grade.

Conclusions: These RWD from the FLEX Registry demonstrate that MPI is predictive of both DRFI prognosis and chemotherapy benefit in HR+HER2- EBC. (NCT03053193).

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard-of-care for hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib, the first approved CDK4/6i, significantly improved progression-free survival (PFS) in randomized controlled trials (RCTs). However, real-world (RW) outcomes may differ due to broader patient populations. This meta-analysis evaluates the applicability of pivotal RCT findings to RW settings.

Methods: We conducted a systematic review and meta-analysis of RW studies on HR+/HER2- MBC treated with palbociclib+aromatase inhibitors (AI) or fulvestrant, reporting median PFS (mPFS) and/or overall survival (mOS). Pooled mPFS/OS was estimated using the median of medians (MM) and weighted MM (WM). RW estimates were deemed comparable to RCTs if MMPFS/OS or WMPFS/OS fell within RCTs' 95% confidence intervals (CIs). Similar criteria applied to pooled hazard ratios (HRs) of PFS/OS for palbociclib+AI vs AI in visceral/nonvisceral subgroups.

Results: Twelve RW studies were analyzed. First-line palbociclib+AI MMPFS (22.5 months, 95% CI = 19.5 to 31.8) aligned with PALOMA-1/2 pooled mPFS (23.9, 95% CI = 20.2 to 27.6). First-line palbociclib+fulvestrant MMPFS (13.5, 95% CI = 11.6 to 28.5) exceeded PALOMA-3 (11.2, 95% CI = 9.5 to 12.9). Second-line palbociclib+fulvestrant MMPFS (11.5 months, 95% CI = 6.3 to 15.3) was consistent with PALOMA-3. RW first-line mOS (51.2 months, 95% CI = 49.1 to 53.3) surpassed PALOMA-1/2 pooled mOS (45.7, 95% CI = 37.5 to 53.8). WMOS (49.1 months, 95% CI = 49.1 to 53.3) was slightly lower than RCTs (53.7, 95% CI = 37.5 to 53.8). Palbociclib+AI outperformed AI in RW visceral disease, aligning with RCTs, and showed heterogeneous but favorable benefit in nonvisceral disease.

Conclusions: RW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.

Solid organ transplant recipients (SOTRs) in the United States have lower risks for breast and prostate cancers than the general population. To explore whether pretransplant screening explains this observation, we conducted a case-control study of US adults aged 65 years or older using the SEER-Medicare database (2000-2019). We included 252 279 breast cancer cases, 3 855 275 female controls, 316 981 prostate cancer cases, and 2 361 846 male controls. We used Medicare claims to identify solid organ transplant procedures and screening with mammography or prostate-specific antigen testing before case/control selection. SOTRs exhibited reduced risks for breast cancer (adjusted odds ratio = 0.60, 95% CI = 0.45 to 0.80) and prostate cancer (0.84, 95% CI = 0.71 to 1.00). These inverse associations were significant among screened individuals, although a borderline association for breast cancer was suggested in unscreened women. Pretransplant cancer screening probably largely explains the reduced risks of breast and prostate cancer among US SOTRs, but there may also be other protective factors.

Socioeconomically disadvantaged counties exhibit higher cervical cancer incidence and poorer survival. However, the specific impact of the magnitude of persistent poverty on these outcomes remains largely unexamined. Using national cancer registry data, we observed that women living in persistent poverty counties who have experienced extreme poverty (≥40% poverty) have more than 1.5 times higher cervical cancer incidence and twice the mortality rate as women who lived in nonpersistent poverty counties. Furthermore, stage-specific incidence was consistently higher in persistent poverty counties across localized, regional, and distant diagnoses. Five-year mortality for localized cervical cancer diagnoses was nearly twice as high in extreme poverty counties (11% vs 6%, 2-sided P = .03). These findings highlight substantial disparities in cervical cancer outcomes associated with increasing magnitude of persistent poverty and underscore the need for targeted interventions in economically vulnerable communities to reduce disparities and achieve cervical cancer elimination goals.

Background: Obesity is highly prevalent among Hispanic and Latino adults and is an established risk factor for 13 cancers; however, studies focused on Hispanic and Latino adults are limited. We examined 6 anthropometric measures in association with incidence of obesity-related cancers among Hispanic and Latino adults, overall and by sex, age, and heritage.

Methods: We included 16 415 Hispanic and Latino adults from the Hispanic Community Health Study/Study of Latinos. Baseline (2008-2011) anthropometric measures included body mass index (BMI), waist circumference, waist-to-height ratio, waist-to-hip ratio, fat mass index, and percent body fat. The incidence of 13 obesity-related cancers was ascertained through linkages with 4 state cancer registries (n = 330 incident obesity-related cancer diagnosed over a mean follow-up of 10.7 years). Survey-weighted Cox models estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between each anthropometric measure and latent class analysis-derived groups and obesity-related cancer risk.

Results: Hazard ratios were elevated among adults with the highest levels of anthropometric measures and more so among women than among men. For example, a BMI of at least 30 (vs <25) kg/m2 was associated with an adjusted hazard ratio of 1.42 (95% CI = 0.88 to 2.30) overall and adjusted hazard ratios of 2.22 (95% CI = 1.18 to 4.16) in women and 0.46 (95% CI = 0.20 to 1.02) in men. Adjusted hazard ratios also varied by Hispanic and Latino heritage. For example, a 1-standard deviation increase in BMI was associated with a 63% (HR = 1.63, 95% CI = 1.10 to 2.41) increase in obesity-related cancer risk among South American adults but not among Central American adults (HR = 1.03, 95% CI = 0.53 to 2.00).

Conclusions: Multiple anthropometric measures were positively associated with obesity-related cancer risk, particularly among women. Efforts to reduce obesity may be important for cancer prevention in Hispanic and Latino adults.

Background: Political determinants of cancer risk are largely unexplored, conceptually and empirically.

Methods: Observational analysis of associations present in 2017-2021 between 5 state-level political metrics and 4 age-standardized cancer outcomes (regional and distant stage at diagnosis for breast, cervical, and colorectal cancer among screening-age adults and premature cancer mortality), overall and in standardized linear regression models adjusting for state-level poverty and medical uninsurance.

Results: In fully adjusted models (adjusted for state-level poverty and state-level medical uninsurance variables: % working age adults [age 35-64] without medical insurance; number of years of state Medicaid expansion), each 1 SD shift toward a more liberal political ideology (measured by voting record) among elected officials in the US House of Representatives was associated with decreased risk of diagnosis with regional and distant breast and colorectal cancer (respectively: -0.76, 95% confidence interval [CI] = -1.26 to -0.25; -0.75; 95% CI = -1.5 to 0). Risk of premature cancer mortality likewise was lower, in the fully adjusted models, with each 1 SD shift toward more liberal scores for the state electoral college vote (-2.01, 95% CI = -3.68 to -0.33), the state liberalism policy index (-2.51, 95% CI = -4.48 to -0.54), and political ideology of elected officials in the US Senate (-1.93, 95% CI = -3.71 to -0.14).

Conclusion: Our state-level analyses suggest that political metrics are associated with preventable cancer outcomes. Efforts to reduce population burdens of cancer and inequities in these burdens could benefit from analyses of sociopolitical drivers of cancer risk across the cancer continuum.

Background: Prior studies evaluating racial disparities in cancer outcomes used regional measures of deprivation when accounting for socioeconomic status, which lack granularity. We evaluated differences in prostate cancer mortality between Black and White men using individual home prices in addition to regional metrics to understand the impact of individual wealth on prostate cancer outcomes.

Methods: Individuals diagnosed with prostate cancer between January 2004 and December 2016 in the Ohio Cancer Incidence Surveillance System were included. Individual home addresses were linked to the Area Deprivation Indices and home prices using data from an online real estate marketplace. Using inverse probability weighting to balance patient characteristics, we assessed differences in prostate cancer-specific mortality or other-cause mortality between Black and White men after accounting for clinical characteristics and social determinants of health (insurance, area deprivation, and home price).

Results: We identified 70 660 (85%) White and 12 192 (15%) Black men with prostate cancer. Black race was associated with a higher risk of prostate cancer-specific mortality in models that adjusted for age and year at diagnosis (subdistribution hazard ratio = 1.45, 95% CI = 1.45 to 1.57) and with the addition of cancer variables (subdistribution hazard ratio = 1.16, 95% CI = 1.06 to 1.26). In models that incorporate social determinants of health, however, rates of prostate cancer-specific mortality and other-cause mortality were not statistically significantly higher for Black men (subdistribution hazard ratios = 1.10, 95% CI = 0.98 to 1.24, and 1.02, 95% CI = 0.95 to 1.09), respectively.

Conclusions: After accounting for clinical characteristics and social determinants of health at the individual level, Black men were not at increased risk of prostate cancer mortality relative to White men.

Background: Use of a commercial database to obtain residential history information in environmental epidemiologic studies of cancer can lead to information bias if data availability varies by individual sociodemographic factors or case status. Residential data that are not missing at random and data that are discordant with cancer registry or birth record address data can impact subsequent exposure assessments. In our study of childhood cancers, we aimed to determine if the availability of residential history information differs by case status or other potential confounders and if there was agreement with cancer registry and birth records address data.

Methods: We worked with LexisNexis to retrieve residential histories for mothers of 3573 childhood cancer cases and 7160 controls born 2000-2015 in Los Angeles and Orange Counties in Southern California. We used linear regression to determine independent predictors of having residential history returned by LexisNexis. We assessed concordance between maternal address at birth and child's address at diagnosis available from registry data and the LexisNexis residential history by comparing street addresses and geocoded coordinates.

Results: Maternal characteristics (birthplace, race and ethnicity, education, insurance provider) and child's case status were associated with the mother having any address returned by LexisNexis. When comparing geocoded coordinates of cases, less than 10% of LexisNexis addresses during the diagnosis year matched cancer registry addresses. Birth record addresses matched LexisNexis-provided addresses for 47% of mothers.

Conclusion(s): This study elucidates potential implications of using commercial databases such as LexisNexis to reconstruct residential histories and derive exposure measures in cancer case-control studies.