Aim 2: Develop Novel Approaches for Primary and Secondary Prevention

Our research in Aim 2: Develop novel approaches for primary and secondary prevention, emphasizes:

  • Chemoprevention, tobacco cessation, human papillomavirus and obesity
  • Behavioral and communication interventions
  • Cancer screening and early detection

Major ongoing research efforts related to Aim 2 include:

  • A study to define a set of parenchymal complexity phenotypes on breast imaging that may better discriminate risk of invasive breast cancer, including interval cancers missed by screening, and to extend this work to digital tomosynthesis, which is emerging as an important tool in screening (R01 CA207084; Celine M. Vachon, Ph.D., and other principal investigators).

  • Development of a low-cost, noninvasive ultrasound-based tool (label-free ultrasound angio-morphometry analysis) to visualize and quantify microvasculature morphology for detection of breast cancer, with the goal of reducing the number of unnecessary breast biopsies, improving the detection rate and better assessing response to preoperative chemotherapy in patients with breast cancer (R01 CA239548; Azra Alizad, M.D., Mostafa Fatemi, Ph.D., and other principal investigators).

  • Research to assess important psychological and behavioral outcomes of mandates that women undergoing screening mammography be informed of their breast density and to evaluate whether educational enhancement of breast density notification to Latina women is beneficial (R01 MD009682; Celine M. Vachon, Ph.D., principal investigator).

  • To improve cancer prevention in women with atypical hyperplasia, who have an increased risk of breast cancer, a collaborative research study with Mayo Clinic Comprehensive Cancer Center's Women's Cancer Program is identifying biomarkers from breast biopsy tissues that will improve individualized risk prediction and help determine which women will personally benefit from tamoxifen (R01 CA237607; Derek C. Radisky, Ph.D., and other principal investigators).

  • A study that tests interventions targeting factors related to the health care system, providers and patients to improve the population uptake of the human papillomavirus vaccine in adolescents (R01 CA217889; Lila J. Rutten, Ph.D., Robert M. Jacobson, M.D., and other principal investigators).

  • A multilevel, mixed-methods randomized controlled trial through the Alaska Native Tribal Health Consortium to investigate the effectiveness of a new at-home multitarget stool DNA test (MT-sDNA; Cologuard) to improve colorectal cancer screening rates among Alaska Native people living in rural and remote communities (R01 CA247642; Lila J. Rutten, Ph.D., principal investigator).

  • Research to develop a promising bladder cancer diagnostic assay for translation into a test with proven clinical utility to detect and monitor bladder cancer noninvasively through urine analysis (R01 CA206584; Steven Goodison, Ph.D., principal investigator).

  • Studies of early detection of pancreatic cancer that include development of novel blood-based biomarkers and validation through accrual of prospective high-risk cohorts of individuals at genetic or familial risk, or with pancreatic cysts, or with new-onset diabetes. (U01 CA210138; R01 and U01 DK108288, Gloria M. Petersen, Ph.D., principal investigator).

Recently published highlights related to Aim 2 include:

  • Smoking-cessation programs double the chance of achieving abstinence, which translates into improved survival, reduced symptoms, reduced treatment-related side effects, improved surgical outcomes and better quality of life. Despite the recognized importance of smoking cessation among cancer survivors, fewer than 40% of oncologists report that they treat or refer patients for smoking cessation programs, which has prompted exploration of opt-out approaches for tobacco-cessation treatment. However, these strategies raise critical ethical issues. Mayo Clinic investigators published a seminal commentary on the ethical dimensions of opt-out referral. (Ohde, et al. Presumed Consent With Opt-Out: An Ethical Consent Approach to Automatically Refer Patients With Cancer to Tobacco Treatment Services. J Clin Oncol. 2021 Mar 10;39(8):876-880. doi:10.1200/JCO.20.03180. Epub 2021 Jan 13.)

  • Developing policies and planning for low-dose CT scanning for lung cancer screening requires knowledge of eligible populations, especially vulnerable subgroups. Using data from the 2015 National Health Interview Survey, eligibility rates and eligibility-to-incidence ratios were estimated using guidelines, including those from the Centers for Medicare & Medicaid Services, National Comprehensive Cancer Network and U.S. Preventive Services Task Force. Depending on guidelines applied, 8.3 million to 13.3 million people in the United States may be eligible for lung cancer screening, representing 8.3% to 13.4% of the U.S. population 50 to 80 years old. Up to 17.5 million adults may be eligible if expanded criteria are applied. (Pinsky, et al. Potential Disparities by Sex and Race or Ethnicity in Lung Cancer Screening Eligibility Rates. Chest. 2021 Jul;160(1):341-350. doi:10.1016/j.chest.2021.01.070. Epub 2021 Feb 3.)

  • A post hoc analysis of treatment-related adverse events to smoking cessation was performed in the multinational, multicenter EAGLES study, a phase 4, randomized, double-blind placebo-controlled trial that enrolled 8,144 participants. Therapies included varenicline (1 mg twice daily), bupropion sustained-release (150 mg twice daily) and nicotine patch (21 mg once daily with tapering). Adverse events reported by >5% of participants overall and that were reported more frequently in the treated groups versus placebo controls included nausea, insomnia, abnormal dreams, anxiety, irritability, dry mouth, fatigue and application site pruritus. Frequencies vary by specific treatment. Severe adverse events were noted in 1.5% of participants and discontinuation of therapy in 3%. The analysis demonstrates that treatments were well tolerated and manageable. (Ebbert, et al. Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial. Mayo Clin Proc. 2021 Jul;96(7):1801-1811. doi:10.1016/j.mayocp.2020.10.046. Epub 2021 Jun 8.)

  • More than 1 million women undergo a breast biopsy annually in the United States, but only 20% of biopsies are malignant, suggesting a need to reduce unnecessary biopsies through improved radiological characterization of lesions. Individualized-thresholding of Shear Wave Elastography (SWE), a measure of breast stiffness, and clinical factors were evaluated among 644 consecutive women referred for ultrasound examinations, including assessment of 659 masses of which 265 (40.2%) were malignant. Using specified cutpoints for Shear Wave Elastography, one for lesions >10 mm and <5 mm depth and a second cutpoint for other masses, achieved sensitivity of 96.8%, specificity of 92.6%, positive predictive value of 88.8%, and negative predictive value of 91.3%. Combining Shear Wave Elastography with age and BI-RADS density achieved an area under the Receiver Operator Characteristics curve of 0.954 (95% CI: 0.938-0.969). (Gu, et al. Individualized-Thresholding Shear Wave Elastography Combined With Clinical Factors Improves Specificity in Discriminating Breast Masses. Breast. 2020 Dec;54:248-255. doi:10.1016/j.breast.2020.10.013. Epub 2020 Nov 4.)

  • Endometrial cancer incidence and mortality are rising in conjunction with the obesity epidemic. These cancers represent an important source of racial disparities, with disproportionately poor outcomes among Black women. Increasing awareness of symptoms of endometrial cancer and developing improved means of detection are important because 90% of affected patients seek care for abnormal uterine bleeding, but less than 10% of women with this symptom have cancer. Six community-based focus groups with 57 white and Black women in Jacksonville, Florida, were conducted to assess knowledge of endometrial cancer and the acceptability of collecting vaginal fluid for use in a promising molecular endometrial cancer test developed at Mayo Clinic in partnership with Exact Sciences. The study concluded that increased endometrial cancer awareness, self-efficacy and familiarization with tampons could improve prospects for implementing an at-home sample collection approach for endometrial cancer testing. (Ridgeway, et al. Development of Novel Home-Based Tampon Sampling for Endometrial Cancer: Findings from Community-Based Focus Groups With Black and White Women. J Clin Transl Sci. 2021 May 5;5(1):e125. doi:10.1017/cts.2021.787. eCollection 2021.)

  • A diagnostic performance study is an important step toward a blood test for early detection of pancreatic cancer based on identified tissue methylated DNA markers (MDMs) and CA19-9. Thirteen MDMs were optimized in plasma from 170 patients with pancreatic cancer and 170 control participants with a target enrichment long-probe quantitative amplified signal method. In addition, 120 patients in advanced stages and 120 healthy control participants were used to train a prediction algorithm at 97.5% specificity using random forest modeling, followed by an independent blinded test set of 50 patients with early-stage PDAC and 50 control participants. All 340 patients were combined and cross-validated, showing sensitivity of the marker panel of 92%. This study was conducted in collaboration with Exact Sciences. (Majumder S, et al. High Detection Rates of Pancreatic Cancer Across Stages by Plasma Assay of Novel Methylated DNA Markers and CA19-9. Clin Cancer Res. 2021 May 1;27(9):2523-2532. doi:10.1158/1078-0432.CCR-20-0235. Epub 2021 Feb 16.)