Drs. Aline Talhouk (left) and Anna Tinker (right) are recipients of the UBC Faculty of Medicine 2021/2022 Precision Health Catalyst Grant award for their project titled “Risk evaluation and omics screening for targeting prevention in endometrial cancer”.
Read a summary of the project here.
“We are investigating precision health tools to help guide screening and prevention interventions, in an effort to reduce the incidence of endometrial cancer and to promote early detection.”
Can you tell us about the precision health research work in endometrial cancer you’re collaborating on?
This year an estimated 8000 Canadian women+** will be diagnosed with endometrial cancer, and about 1,400 will die from it. Endometrial cancer (EC) is the most common gynecological cancer in the developed world and unlike most cancers, both incidence and mortality rates of EC are increasing1–3, due in part to increasing rates of obesity, a common risk factor3. EC is associated with significant inequity and disproportionately affects vulnerable populations, including ethnic minorities, those with lower socio-economic factors, as well as those with obesity.
EC can be cured by hysterectomy if detected while still confined to the uterus. Patients diagnosed at an early stage can expect an excellent 5-year survival rate of 96%4. On the other hand, only 20% of patients survive an advanced staged diagnosis4. Moreover, EC is preventable in 25-50% of cases with hormone therapy and lifestyle changes. Despite this, there are currently no general screening measures for EC in the general population, due to the low prevalence of disease. Risk modeling can help identify individuals who may benefit from screening for early detection and risk reducing weight loss interventions.
As part of a feasibility and acceptability trial, we are investigating precision health tools to help guide screening and prevention interventions, in an effort to reduce the incidence of EC and to promote early detection. We are using a muti-screening approach to identify post-menopausal women+ from the general population who are at high-risk for EC but who currently do not exhibit any cancer associated symptoms and who would be candidates for prevention.
* We use Women+ to denote all those assigned female at birth irrespective of their gender identity
Can you describe the study protocol and methods/techniques used?
The first part of the study uses an online questionnaire to collect risk factor information to feed into an epidemiological risk model17. Participants at increased risk are invited to the second phase of the study where they will undergo a second screening through the progesterone challenge test (PCT), a hormonal test that involves a 10-day course of low-dose oral progestin followed by the observation of withdrawal bleeding which would trigger referral to gynecologist where they will be counseled per clinical standards, including an endometrial biopsy to rule out cancer. Depending on the results of the biopsy, participants would be recommended surveillance, hormonal therapy or potentially a hysterectomy. Everyone who experiences withdrawal bleeding will be directed to the third phase of the study to participate in a diet and exercise program, the Small Steps for Big Changes7, to help reduce their risk for cancer.
The feasibility of this pilot will be determined based on adherence and acceptability of the proposed protocols, including the acceptability of endometrial biopsy, the current gold standard to rule out endometrial cancer. We believe that ruling out an underlying cancer with less invasive testing than an endometrial biopsy may be better accepted. In a small preliminary study, our team demonstrated that molecular information from DNA and microbiome obtained through self-sampling could replace the need for an endometrial biopsy to rule out cancer. As part of this study, we will obtain self-collected vaginal specimen from all participants before and after the PCT to investigate whether self-sampling can help forego the need for an endometrial biopsy, helping make the study more acceptable in the future.
What results have you seen so far?
We have made significant progress in our study thus far. To date, we have completed all the study protocols and set up which include survey setup, the deployment of a Smartphone application to track specimen collection and to follow participants in the study. We have also successfully enrolled 102 participants who have completed the risk questionnaire in part A. Among these participants, 78 met the eligibility criteria to participate in part B of the study. After thorough evaluation, only 4 individuals to date were deemed to have a high enough risk level to proceed to the next phase with the progesterone challenge. We initiated contact with individuals who met the high-risk criteria and we are beginning part B of the study imminently. This progress marks an important milestone for our study, and we are enthusiastic about the contributions and outcomes that lie ahead.
From your perspective, what do you think is exciting about the future direction of precision health?
Through this study, we aim to gain comprehensive insights into the factors influencing endometrial cancer risk, with the ultimate goal of identifying effective preventive measures. In part A, we will learn more about risk models and risk factors to prospectively validate risk prediction models in a Canadian population. We will also learn about the rate of withdrawal bleeding following a progesterone test, as well as know what risk factors are most associated with withdrawal bleeding. Importantly, we will determine whether less invasive approaches to endometrial biopsy can be used to rule out a pre-existing asymptomatic cancer, this would have the highest impact on acceptability and the design of a future trial geared towards determining the effectiveness of screening.
We deeply appreciate the participation of all individuals involved in every phase of the study. Their involvement is invaluable in our collective effort to advance our understanding of endometrial cancer risk factors and find effective ways to reverse the current alarming trend. By actively participating, these individuals contribute to the development of tools and strategies that aim to make our interventions equitable and accessible to everyone at risk. We recognize the importance of their contributions in providing us with essential data that guides our research and informs future studies.
About Dr. Aline Talhouk
Dr. Aline Talhouk is an early career researcher and assistant professor in the Department of Obstetrics and Gynecology at the University of British Columbia, with associate membership in the Departments of Computer Science, Bioinformatics, and Women+ and Children’s Health. Her work primarily focuses on machine learning and data science in the context of gynecologic cancers, aiming to advance precision medicine. Dr. Talhouk applies statistical and machine learning (ML) approaches to develop predictive models for gynecologic cancers. Her research has received recognition for its meticulous methodology and impact, which has led to significant contributions in endometrial and ovarian cancer research, prompting changes in clinical practices. An important focus of Dr. Talhouk’s research is to improve predictive models to guide screening, by better understanding the impact of genetic, environmental, and lifestyle factors on the development and progression of cancer and cancer precursors.
Since joining the faculty in 2019, Dr. Talhouk has been awarded a Michael Smith BC Health Research Scholar award. She has also received over $7 million dollars in peer reviewed research funding from Canadian Institute for Health Research, the Canadian Cancer Society, the Terry Fox Research Institute, and the Canadian Foundation for Innovation, among others to establish a unique and innovative research program focused on risk prediction modeling for precision prevention, early detection, diagnosis, and treatment decision-making for gynecologic cancers, with the ultimate goal of improving patient outcomes.
About Dr. Anna Tinker
Dr. Anna Tinker is a Medical Oncologist with clinical expertise in the treatment of women with gynecologic malignancies. Her research interests include cancer clinical trials and translational research. She is the Co-Chair of the Ovarian Cancer Working Group for the Canadian Cancer Trials Group, and leads the Gynecologic Cancer Clinical Trials Unit at Vancouver Centre. Her research projects have examined immunotherapy and radiation as cancer therapy, the evaluation of prognostic and predictive biomarkers, and DNA-based cancer detection strategies. Her goals are to provide trials opportunities to patients, and to help women live better and healthier lives.
References:
1. Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer Statistics, 2021. Clin. Cancer J. 71, 7–33 (2021).
2. Lortet-Tieulent, J., Ferlay, J., Bray, F. & Jemal, A. International Patterns and Trends in Endometrial Cancer Incidence, 1978–2013. JNCI J. Natl. Cancer Inst. 110, 354–361 (2018).
3. Smrz, S. A., Calo, C., Fisher, J. L. & Salani, R. An ecological evaluation of the increasing incidence of endometrial cancer and the obesity epidemic. Am. J. Obstet. Gynecol. 224, 506.e1-506.e8 (2021).
4. Survival Rates for Endometrial Cancer. American Cancer Society (2022).
5. Pfeiffer, R. M. et al. Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies. PLoS Med. 10, e1001492 (2013).
6. Hüsing, A. et al. An epidemiological model for prediction of endometrial cancer risk in Europe. Eur. J. Epidemiol. 31, 51–60 (2016).
7. Locke, S. et al. Can small steps result in big changes? Preliminary effectiveness of a community-based diabetes prevention program. J. Exerc. Movement, Sport (SCAPPS Ref. Abstr. Repos. 51, 217–217 (2019).