Cancer prevention research (Philadelphia, Pa.)最新文献

The aim was to assess whether subject's participation in early-phase chemoprevention trials was satisfactory and identify features associated with subjects' satisfaction. Thirteen trials that investigated a range of candidate agents from 2006 to 2021 by the Cancer Prevention Network were included. The five-item "Was It Worth It?" (WIWI) questionnaire was administered to all subjects at the end of each trial's intervention or at early termination. Satisfied overall was defined as a participant response of "yes" to the first three questions. Six hundred ninety-one participants from the United States, Canada, Puerto Rico, and Honduras enrolled on a trial. Six hundred fifty-two (94.4%) completed the WIWI questionnaire. Of these, 493 (75.6%) were White, non-Hispanic/Latino; 39 (6.0%) Black, non-Hispanic/Latino; 98 (15.0%) Hispanic/Latino; and 8 (1.2%) of another race/ethnicity. One hundred ninety-three were women (29.6%), 121 (17.5%) were ≥65 years, and 517 (79.3%) participated in a placebo-controlled trial. Eighty-five percent indicated being satisfied overall. Compared with White, non-Hispanic/Latino, the odds of not satisfied overall were 2.96 times higher for Black/Asian/>1 race, non-Hispanic/Latino (P < 0.001) and 0.40 times lower for Hispanic/Latino (P = 0.004). The odds of not satisfied overall was 1.9 times higher when the number of preintervention adverse events experienced was ≥1 (P = 0.012), 1.8 times higher when the percentage of the intervention duration with adverse events was >5% (P = 0.024), and 7.4 times higher for subjects who terminated the intervention early (P < 0.001). These findings can inform the design of future chemoprevention trials and help investigators improve accrual, retention, adherence, and diversity in this underexplored research setting.

Prevention relevance: The five-item "WIWI?" questionnaire, which captures the participant-reported experience of trial participation, gives the subject a voice in the development of new chemopreventative agents. This study in 652 subjects looked at satisfaction with participation in early-phase chemoprevention trials for higher-risk, cancer-free men and women. See related Spotlight, p. 7.

Clinical cancer prevention and interception trials target high-risk populations and require agents with favorable risk-to-benefit ratios. Participant experiences are crucial in trial design, as highlighted in this issue of Cancer Prevention Research by Zahrieh and colleagues, which applied the "Was It Worth It?" questionnaire to evaluate participants' experiences in cancer chemoprevention trials. This study is the first examination of satisfaction in early-phase chemoprevention trials for high-risk individuals. This timely study underscores the need to assess and integrate participant and advocate feedback in completed, ongoing, and future trials. This spotlight commentary emphasizes the importance of participant experiences in enhancing trial designs for cancer prevention and interception. See related article by Zahrieh et al., p. 11.

Although chemoprevention medications, including selective estrogen receptor modulators and aromatase inhibitors, are recommended for women at high risk for breast cancer, their uptake remains low. In contrast, statin use for atherosclerotic cardiovascular disease (ASCVD) risk reduction is widely adopted. We conducted a retrospective cohort study among a population of women aged 40 to 79 who underwent screening mammograms at Columbia University Irving Medical Center (CUIMC) from 2014 to 2016. For each woman, we calculated breast cancer risk using the Breast Cancer Surveillance Consortium version 3 (BCSCv3) risk calculator and ASCVD risk using the American Heart Association (AHA) risk calculator. High risk using the BCSCv3 calculator was defined as ≥5% invasive breast cancer risk at 10 years, and high risk using the AHA calculator was defined as >7.5% ASCVD risk at 10 years. Average 10-year risk of invasive breast cancer was lower than that for ASCVD (2.47% vs. 7.53%, P < 0.001). Based on disease risk, 4.7% and 34.4% of participants met high risk criteria for breast cancer and ASCVD, respectively. Chemoprevention uptake among women at high risk for breast cancer was lower than statin uptake among women at high risk for ASCVD (4.6% vs. 72.9%). Numerous barriers likely contribute to this discrepancy in uptake, including provider familiarity with and knowledge of chemoprevention, patient concerns about medication safety, absence of routine breast cancer risk assessment, and lack of intermediate biomarkers to monitor treatment response. Given the increased acceptance and uptake of statins relative to chemoprevention, there is potential value in putting chemoprevention in the context of statins to promote awareness and uptake.

Prevention relevance: Among women undergoing screening mammograms, for women at high risk for breast cancer and ASCVD, chemoprevention uptake was lower than that of statins. We propose multiple barriers to account for this difference and describe how acceptance of statins could serve as a model for promoting the uptake of chemoprevention medications.

YAP1 is a co-transcription factor that promotes malignant and stem cell properties in cancer. We previously found that YAP1 dysregulation is associated with aging in human mammary epithelia. With increased age, YAP1 expression changes in luminal epithelial cells, the prospective breast cancer cell of origin. Because age is a significant risk factor for breast cancer, we tested if YAP1 dysregulation acted early in cancer progression by conferring cellular states associated with increased cancer susceptibility. Here we find, that with increased age and genetic risk for developing cancer, human breast tissues showed significantly increased YAP1 expression and cultured primary human mammary epithelial cells (HMEC) showed significantly increased expression of both YAP1 and its transcriptional targets. Increased YAP1 expression in cultured HMEC induced gene expression changes associated with increased cancer susceptibility such as genes associated with: stem cell fate, increased telomerase activity, breast cancer progression, and increased age and genetic breast cancer risk. Further, overexpression of YAP1 in post-stasis HMEC- finite lifespan cells which have bypassed a retinoblastoma-mediated senescence barrier- promoted properties related to an increased growth potential. We found that YAP1 dysregulation in finite epithelial cells allows for access to gene programs and functions that are typically thought to be restricted to stem cells. We hypothesize that YAP1 acts early in breast cancer progression, long before development of a tumor, to impose cancer susceptible molecular states.

Lung cancer is the leading cause of cancer-related death. The incidence and mortality rates are higher for Black men than for White men. Protein arginine methyltransferase 6 (PRMT6) is known to be associated with lung cancer tumorigenesis and prognosis, and different levels of PRMT6 expression by race and sex may explain lung cancer disparities among Black men. To examine differences in PRMT6 by neighborhood violence as social stress, we obtained 88 formalin-fixed, paraffin-embedded tissue sections of patients with lung cancer. Using immunohistochemistry, samples were stained and scored [histochemical score (H-score)] for PRMT6 levels. Logistic regression was used to examine the likelihood of having a high H-score (≥ median) by race and sex, controlling for age, smoking status, tumor type, grade, stage at diagnosis, and neighborhood homicide rate. The odds of having a high H-score were higher for Blacks than Whites, but there was no sex difference when controlling for tumor characteristics. High homicide was negatively associated with high H-scores. Controlling for all other variables, the odds ratio (OR) of having a high H-score for Black versus White males was 7.8, and the OR for Black versus White females was 1.8 for the low homicide group. The ORs for both Black versus White males and Black versus White females were more than 3 times higher for the high homicide group. Overexpression of PRMT6 may explain the lung cancer disparity in Black men. Exposure to social stress may contribute to higher levels of PRMT6. Social and biological differences affecting race and sex groups need further investigation.

Prevention relevance: This study explores the impact of living in a high violence neighborhood, which may contribute to the elevated risk of lung cancer and tumor prognosis. Epigenetic modification may be a mechanism linking social exposure and biological changes. Addressing neighborhood-level social stress exposure may improve the prevention and intervention of lung cancer.

Germline and somatic alterations in the epidermal growth factor receptor (EGFR) gene contribute to the pathogenesis and therapeutic response of non-small cell lung cancer (NSCLC). This retrospective single-center study analyzed 507 Azerbaijani patients with NSCLC who were genotyped for EGFR mutations between 2009 and 2024. Real-time PCR identified somatic EGFR mutations in 137 cases (27.0%), whereas next-generation sequencing confirmed germline EGFR T790M variants in 11 patients (2.1%). Among these, nine carried concurrent somatic EGFR alterations, and two harbored only germline variants; the latter are excluded from the present analysis and will be reported separately. All germline carriers had a positive family history of lung cancer. Germline carriers were more often diagnosed at early stages (I-II, 45.5% vs. 18.2% in noncarriers; P = 0.03), and four developed tyrosine kinase inhibitors resistance within 6 to 8 months of treatment. Kaplan-Meier and Cox regression analyses revealed no significant survival difference between hereditary and somatic mutation groups (median overall survival 24.9 vs. 24.0 months; log-rank P = 0.69; hazard ratio = 1.19; 95% confidence interval, 0.52-2.73). These findings indicate that germline EGFR T790M represents a measurable hereditary variant within the South Caucasus population and emphasize the need to integrate germline testing into diagnostic workflows and familial risk assessment strategies for EGFR-driven NSCLC.

Prevention relevance: This study underscores the clinical importance of the rare germline EGFR T790M mutation in lung cancer. Detecting carriers with a family history may allow earlier diagnosis and inform targeted prevention, supporting more precise screening for high-risk individuals.

Lung cancer is the leading cause of cancer-related death. The incidence and mortality rates are higher for Black men than for White men. Protein arginine methyltransferase 6 (PRMT6) is known to be associated with lung cancer tumorigenesis and prognosis, and different levels of PRMT6 expression by race and sex may explain lung cancer disparity among Black men. To examine differences in PRMT6 by neighborhood violence as social stress, we obtained 88 formalin-fixed paraffin-embedded tissue sections of lung cancer patients. Using immunohistochemistry, samples were stained and scored (H-score) for PRMT6 levels. Logistic regression was used to examine the likelihood of having a high H-score (≥ median) by race and sex, controlling for age, smoking status, tumor type, grade, stage at diagnosis, and neighborhood homicide rate. The odds of having a high H-score were higher for Blacks than Whites, but there was no sex difference, controlling for tumor characteristics. High Homicide was negatively associated with high H-scores. Controlling for all other variables, the odds ratio (OR) of having a high H-score for Black vs. White males was 7.8, and the OR for Black vs. White females was 1.8 for the low homicide group. The ORs for both Black vs. White males and Black vs. White females were more than 3 times higher for the high homicide group. Overexpression of PRMT6 may explain lung cancer disparity in Black men. Exposure to social stress may contribute to higher levels of PRMT6. Social and biological differences affecting race and sex groups need further investigation.

Implementation of invitation systems has been shown to increase breast cancer screening rates. However, implementation of active outreach strategies in Latin American programs is limited. We conducted a pragmatic randomized controlled trial-the breast cancer ATICA study-to evaluate the effectiveness and implementation of a digital messaging-based intervention to increase breast cancer screening. A total of 248 Argentinian women ages 50+ years were recruited from 10 health care centers in Santa Fe, Argentina, and randomly assigned (1:1) to the intervention (n = 123) or control group (n = 125). The intervention included up to four Short Message Service (SMS) messages inviting participants to schedule an appointment for mammography through WhatsApp or the usual care control group (n = 125). Effectiveness outcomes were the proportion of women who underwent mammography within 105 or 45 days of enrollment. The reach, effectiveness, adoption, implementation, and maintenance framework was used to evaluate the implementation of the intervention. Our results showed that women in the intervention group (n = 123) were significantly more likely than women in the control group (n = 125) to undergo a mammography within 105 days (23.6% vs. 6.4%, difference 17%, 95% confidence interval, 7.7%-27.0%) and within 45 days (15.4% vs. 3.2%; difference 12%, 95% confidence interval, 4.3%-20.0%; P = 0.02). Our results also showed high acceptability and appropriateness of the intervention. Our study demonstrates that sending consecutive SMS messages, including a WhatsApp number to ask for an appointment, effectively increased breast cancer screening. This mobile health intervention could be an excellent option to improve access to breast cancer screening in low- and middle-resource settings in which active invitation systems are challenging to implement.

Prevention relevance: Breast cancer remains a significant public health concern, and strategies to improve access to screening are urgently needed. This study is one of the first pragmatic randomized controlled trials in Latin America that demonstrate the effectiveness and real-world implementation of an SMS-based intervention to increase participation in breast cancer screening.

In the current landscape of clinical studies, the concept of statistically significant association is often mixed up with the expectation of improved prediction performance. We discuss the two concepts, association and prediction, and present the epidemiologic principles and statistical constructs that underlie the discrepancy between statistically significant associations and the rationale for their lack of impact on improving prediction in terms of discrimination. This issue is illustrated using an existing breast cancer dataset. The concept of statistically significant association should not be mixed up with the expectation of improved discrimination performance. Although some markers may not markedly improve discrimination, they can still have substantial clinical relevance by identifying critical biological pathways that inform novel treatment or prevention strategies. Development of models for both association and prediction assessments should be directly tied to clinical translation to move adoption forward to advance precision medicine.

Prevention relevance: Development of models for both association and prediction assessments should be directly tied to clinical translation to move adoption forward to advance precision medicine.