JNCI Cancer Spectrum最新文献

Menopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.4 or higher, where 0.4 was equivalent to a 50-year-old woman with 1 parent diagnosed with either breast cancer or CRC at 55 years of age. Of 24 486 women assessed, 1243 and 405 were diagnosed with incident breast cancer and CRC, respectively. For breast cancer, menopausal HRT ever use versus never use hazard ratios were 1.27 (95% CI = 1.11 to 1.45) for a breast cancer familial risk score below 0.4 and 1.01 (95% CI = 0.82 to 1.25) for a breast cancer familial risk score of 0.4 or higher (Pdifference = .08). For CRC, menopausal HRT hazard ratios were 0.63 (95% CI = 0.50 to 0.78) for a CRC familial risk score below 0.4 and 1.21 (95% CI = 0.73 to 2.00) for a CRC familial risk score of 0.4 or higher (Pdifference = .03). Associations with menopausal HRT use that apply to the general population may not hold for women at moderate or strong familial risk of these cancers.

Background: Undifferentiated carcinoma (UC) is a rare subtype of pancreatic cancer distinguished from UC with osteoclast-like giant cells (UC-OGC) in 2019, affecting interpretation of literature that does not distinguish these subtypes. We sought to identify translationally relevant differences between these 2 variants and compared with pancreatic ductal adenocarcinoma.

Methods: We characterized clinical and multiomic differences between UC (n = 32) and UC-OGC (n = 15) using DNA sequencing, RNA sequencing, and multiplex immunofluorescence and compared these findings with pancreatic ductal adenocarcinoma.

Results: Characteristics at diagnosis were similar between UC and UC-OGC, though the latter was more resectable (P = .009). Across all stages, median overall survival was shorter for UC than for UC-OGC (0.4 years vs 10.8 years, respectively; P = .003). This shorter survival was retained after stratification by resection, albeit without statistical significance (1.8 years vs 11.9 years, respectively; P = .08). In a subset of patients with available tissue, the genomic landscape was similar among UC (n = 9), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 159). Bulk RNA sequencing was deconvoluted and, along with multiplex immunofluorescence in UC (n = 13), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 16), demonstrated statistically significantly increased antigen-presenting cells, including M2 macrophages and natural killer cells, and decreased cytotoxic and regulatory T cells in UC and UC-OGC vs pancreatic ductal adenocarcinoma. Findings were similar between UC and UC-OGC , except for decreased regulatory T cells in UC-OGC (P = .04).

Conclusions: In this series, UC was more aggressive than UC-OGC, with these variants having more antigen-presenting cells and fewer regulatory T cells than pancreatic ductal adenocarcinoma, suggesting potential for immune-modulating therapies in the treatment of these pancreatic cancer subtypes.

Background: Benign breast disease (BBD) increases breast cancer (BC) risk progressively for women diagnosed with nonproliferative change, proliferative disease without atypia (PDWA), and atypical hyperplasia (AH). Leveraging data from 18 704 women in the Mayo BBD Cohort (1967-2013), we evaluated temporal trends in BBD diagnoses and how they have influenced associated BC risk over 4 decades.

Methods: BC risk trends associated with BBD were evaluated using standardized incidence ratios (SIRs) and age-period-cohort modeling across 4 eras-premammogram (1967-1981), precore needle biopsy (CNB) (1982-1992), transition to CNB (1993-2001), and CNB era (2002-2013).

Results: With a median follow-up of 15.8 years, 9.9% of women were diagnosed with BC (invasive and/or DCIS). From the premammogram era to the CNB era, we observed a significant increase in BC risk, rising from an SIR of 1.61 to 1.99. The proportion of proliferative BBD diagnoses (PDWA or AH) increased markedly over time (28.1%-49.7%), as did the proportion of DCIS events (11%-28%; χ2  P < .001). Within specific BBD categories, the risk of invasive BC increased modestly.

Conclusions: Absolute risk of BC within BBD categories remained stable, but the relative risk of BC after BBD increased over time due to notable increases in higher risk BBD lesions, specifically PDWA and AH. These findings illustrate how evolving screening practices have changed the risk profile of BBD and should inform management strategies for patients with BBD in modern clinical settings.

Background: Factors associated with cancer survivors' preventive health behaviors are understudied. We hypothesized that socioeconomic and health-care access factors may be associated with adherence to recommended cancer screenings.

Methods: We conducted a cross-sectional analysis using the 2020 Behavioral Risk Factor Surveillance System. Cancer survivors eligible for United States Preventive Services Task Force-recommended breast, cervical, prostate, and colorectal screenings were included. Multivariable logistic regression models were used to identify socioeconomic factors significantly associated with screening adherence.

Results: Overall, 64 958 (weighted national estimate = 29 066 143) cancer survivors were included. Adherence rates varied across cancer types: 80.9% for breast, 88.9% for cervical, 54.1% for prostate, and 84.7% for colorectal cancer. Key predictors of low adherence included lower income (breast: adjusted odds ratio [aOR] = 0.56, 95% confidence interval [CI] = 0.43 to 0.74; cervical: aOR = 0.38, 95% CI = 0.24 to 0.59; prostate: aOR = 0.36, 95% CI = 0.24 to 0.52; colorectal: aOR = 0.74, 95% CI = 0.57 to 0.96), lack of health-care coverage for colorectal cancer (aOR = 0.51, 95% CI = 0.36 to 0.73), time since last checkup between 1 and 2 years prior for breast (aOR = 0.58, 95% CI = 0.45 to 0.75), prostate (aOR = 0.66, 95% CI = 0.47 to 0.91), and colorectal (aOR = 0.69, 95% CI = 0.56 to 0.86) cancer, and no health-care provider for breast (aOR = 0.68, 95% CI = 0.47 to 0.98), prostate (aOR = 0.45, 95% CI = 0.31 to 0.65), and colorectal (aOR = 0.51, 95% CI = 0.40 to 0.66) cancer.

Conclusion: Cancer survivors' adherence to screening is associated with factors including lack of health-care coverage, lower income, time since the last exam, and having a personal provider. Targeted interventions accounting for such factors may help mitigate these disparities.

Background: Despite advances in understanding genetic susceptibility to cancer, much of cancer heritability remains unidentified. At the same time, the makeup of industrial chemicals in our environment only grows more complex. This gap in knowledge on cancer risk has prompted calls to expand cancer research to the comprehensive, discovery-based study of nongenetic environmental influences, conceptualized as the "exposome."

Methods: Our scoping review aimed to describe the exposome and its application to cancer epidemiology and to study design limitations, challenges in analytical methods, and major unmet opportunities in advanced exposome profiling methods that allow the quantification of complex chemical exposure profiles in biological matrices. To evaluate progress on incorporating measurements of the exposome into cancer research, we performed a review of such "cancer exposome" studies published through August 2023.

Results: We found that only 1 study leveraged untargeted chemical profiling of the exposome as a method to measure tens of thousands of environmental chemicals and identify prospective associations with future cancer risk. The other 13 studies used hypothesis-driven exposome approaches that targeted a set of preselected lifestyle, occupational, air quality, social determinant, or other external risk factors. Many of the included studies could only leverage sample sizes with less than 400 cancer cases (67% of nonecologic studies) and exposures experienced after diagnosis (29% of studies). Six cancer types were covered, most commonly blood (43%), lung (21%), or breast (14%) cancer.

Conclusion: The exposome is underutilized in cancer research, despite its potential to unravel complex relationships between environmental exposures and cancer and to inform primary prevention.

Background: In metastatic colorectal cancer (mCRC), improvements in survival from combining leucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) with bevacizumab have come at the risk of increased rates of high-grade toxicities. Trilaciclib is indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients receiving standard-of-care chemotherapy for extensive-stage small cell lung cancer.

Methods: Patients with untreated mCRC were randomly assigned 1:1 to trilaciclib (n = 164) or placebo (n = 162) prior to FOLFOXIRI/bevacizumab for up to 12 cycles (induction), followed by trilaciclib or placebo prior to fluorouracil/leucovorin/bevacizumab (maintenance). Co-primary endpoints were duration of severe (grade 4) neutropenia (DSN) in cycles 1-4 and occurrence of severe neutropenia (SN) during induction. Secondary endpoints included antitumor efficacy, survival, and safety.

Results: The study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI/bevacizumab resulted in significant reductions in DSN in cycles 1-4 vs placebo (mean, 0.1 vs 1.3 days; P < .001) and occurrence of SN during induction (1.3% vs 19.7%; adjusted relative risk [96% CI] = 0.07 [0.0 to 0.3]; P < .001). Grade 3/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib vs placebo (64.8% vs 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays and with reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs 57.1%; P = .009) and median progression-free survival (10.3 vs 13.1 months; P < .001) were significantly lower with trilaciclib vs placebo.

Conclusions: Administering trilaciclib prior to FOLFOXIRI/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo.

Trial registration: ClinicalTrials.gov: NCT04607668.

Background: Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail.

Methods: The Pathways Study is a prospective cohort study of 4504 women diagnosed with invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their physical activities during the previous 6 months, which were dichotomized as meeting the Centers for Disease Control and Prevention's Physical Activity Guidelines for Americans (≥150 minutes of moderate-intensity or ≥75 minutes of vigorous-intensity activity per week) vs not. Incident CVD events (heart failure, cardiomyopathy, cardiac arrest, ischemic heart disease, stroke) occurring between enrollment and December 2021 were identified from electronic health records. Covariate-adjusted, competing-risks Cox regression models estimated associations between meeting physical activity guidelines and CVD risk.

Results: Compared with women who did not meet physical activity guidelines at their diagnosis, those who did had a 25% lower risk of CVD (HR = 0.75, 95% CI = 0.60 to 0.94). Among the individual CVD outcomes, meeting physical activity guidelines was protective against incident cardiomyopathy (hazard ratio [HR] = 0.54, 95% CI = 0.31 to 0.95), heart failure (HR = 0.66, 95% CI = 0.50 to 0.87), and cardiac arrest (HR = 0.68, 95% CI = 0.49 to 0.99).

Conclusions: Meeting physical activity guidelines at breast cancer diagnosis was associated with lower risk of CVD after diagnosis. Studies investigating changes in physical activity after a breast cancer diagnosis and CVD risk are warranted.

Background: Black women have a 40% higher breast cancer (BC) mortality rate than White women and are at a higher risk of acquiring cardiovascular disease. Proton therapy (PT) can be used to mitigate cardiac radiation exposure; however, PT remains a scarce resource in the United States. We report on the cardiovascular profiles of patients undergoing PT to determine the potential benefit of PT for Black women when compared to non-Black patients.

Methods: We retrospectively analyzed 599 BC patients who received PT from June 2016 to December 2021 at the Maryland Proton Treatment Center. A variety of sociodemographic, disease, and treatment variables were analyzed using descriptive statistics.

Results: With a median follow-up of 26 months (range: 0.47-90 months), Black patients comprised 31.6% of the population and presented with higher rates of hypertension (p < .001), cardiopulmonary conditions (p < .001), and a larger median BMI (p = .015) when compared to the other cohort, a trend that persisted at time of post-PT follow-up. Black women had higher rates of triple negative disease (p < .001) with subsequent greater receipt of neoadjuvant chemotherapy (p = .039). Pulmonary events were 2.6-times more likely to occur in Black patients vs the non-Black cohort after PT (OR : 2.60; CI: 1.39-4.88; p = .003).

Conclusions: Black women presenting for PT had higher baseline risks of cardiovascular co-morbidities combined with more aggressive BC biology and a subsequent 2.6-fold increased risk of pulmonary events after PT. Our findings support the use of advanced radiation techniques as means to spare important organs-at-risk, especially in historically marginalized populations.