MD, FRCSC, MPH
Dr. Janice Kwon obtained her medical degree and Obstetrics and Gynecology training at Queen’s University. She completed her fellowship training in Gynecologic Oncology in Toronto, followed by a Masters degree in Public Health from Harvard. She had a 2-year appointment at the University of Texas M.D. Anderson Cancer Center in Houston, Texas prior to her appointment at UBC.
Dr. Kwon is the Associate Head of Research for the UBC Department of Obstetrics and Gynecology. She is the Chair of the Gynecology Surgical Tumour at BC Cancer, acting Chair for the Priority and Evaluations Committee at BC Cancer, and Vice Chair of the Research and Outcomes Evaluation Committee for the BC Cancer Surgeon Network. She is the Chair of the National BRCA Collaborative through the Society of Gynecologic Oncology of Canada, and serves on the Committee on Economic Analysis for the Canadian Cancer Trials Group.
Dr. Kwon’s major area of research interest is in health policy relating to gynecologic cancers and hereditary cancer syndromes, including cost-effectiveness analyses of testing criteria and risk-reducing strategies for women at risk for genetic mutations. She holds a Health Professional Investigator Award from the Michael Smith Foundation for Health Research.
Women who inherit a BRCA gene mutation are at high risk for breast cancer and the most lethal type of ovarian cancer, high-grade serous ovarian carcinoma (HGSC).A woman diagnosed with HGSC has a 20% chance of unknowingly carrying a BRCA mutation, and is eligible for genetic testing in BC, regardless of age, ethnicity, or family history. Getting a blood sample to do genetic testing in this woman is critical, because if she is found to have a BRCA mutation: 1) her relatives (daughters, sisters) can be tested, and HGSC can be PREVENTED in them, and 2) she herself can be treated with PARP inhibitors that can improve survival.
The problem, however, is that the yield of genetic testing is low (test 100 women to find 20 with a BRCA mutation), and only 50% of women with HGSC undergo such genetic testing. This excludes 50% from effective treatment and leaves their family members at high risk. How can BRCA mutations be better identified?One strategy is to begin with testing the HGSC tumour itself. If the tumour has a BRCA mutation, PARP inhibitor treatment can be given. These women can also be targeted for genetic testing, and about 70% of them will have an inherited BRCA mutation. Only those with a BRCA mutation in the tumour would have to be referred to the Hereditary Cancer Program for genetic testing. This would improve the efficiency and yield of genetic testing, by reserving the genetic counselling and testing resources specifically for these women who are at highest risk of carrying a mutation.
Tumour testing of HGSC is not routinely done in BC. We are in the process of conducting a pilot study of tumour testing for BRCA mutations in HGSC, and a cost-effectiveness analysis of its impact on ovarian cancer survival and future cancer prevention, to justify this tumour testing in this patient population.
1. Kwon JS, Daniels MS, Sun CC, Lu KH. “Preventing future cancers by testing women with ovarian cancer for BRCA mutations”. J Clin Oncol 2010;28(4):675-82
This is the first cost-effectiveness analysis to demonstrate that testing women with high-grade serous carcinomas of the ovary for BRCA mutations is cost-effective, regardless of family history. Conventional testing criteria for BRCA in many jurisdictions in Canada and the United States were based on family history. This publication has contributed to a change in policy throughout many centres in North America. This testing is important for women with ovarian cancer, because of the downstream effects on their first-degree relatives who benefit the most from the knowledge of having a genetic mutation that increases their risk for both breast and ovarian cancer. They can undergo risk-reducing interventions such as surgery, which will ultimately reduce the incidence and costs incurred from these cancers.
2. Kwon JS, Gutierrez-Barrera AM, Young, DL, Daniels MS, Sun CC, Lu KH, Arun B. “Expanding the criteria for BRCA mutation testing in breast cancer survivors”. J Clin Oncol 2010;28(27):4214-20
This is the first cost-effectiveness analysis to demonstrate that testing women under age 50 with a triple-negative (estrogen, progesterone, HER2/neu receptor negative) breast cancer for a BRCA mutation is cost-effective, regardless of family history. Prior to this, women were not eligible for BRCA mutation testing unless they had a significant family history of cancer, or a personal history of breast and ovarian cancer, or belonged to a specific ethnic group. Testing women with triple-negative breast cancers is important because these women are still at risk for ovarian cancer, and therefore will benefit from prophylactic oophorectomy, and their first degree relatives can benefit from risk-reducing interventions against both breast and ovarian cancer. Many jurisdictions across Canada have now adopted this into their guidelines for genetic testing.
It is now well recognized that the majority of high-grade serous ovarian cancers (HGSC) originate in the fallopian tube, and not the ovary. In 2010 OVCARE launched an educational campaign of “opportunistic salpingectomy”, encouraging women and their health care providers to consider salpingectomy (removal of the fallopian tubes) at the time of hysterectomy for benign gynecologic conditions or instead of tubal ligation, as a preventive measure against ovarian cancer. It was estimated that this practice could reduce ovarian cancer risk by 20-40% over the next 20 years. Salpingectomy is favourable to salpingo-oophorectomy (removal of fallopian tubes and ovaries) because it does not cause instant menopause, and the short and long term adverse effects associated with removing the ovaries. Our group has demonstrated that opportunistic salpingectomy is a cost-effective cancer prevention strategy, and it is not associated with significant short or long-term side effects. Our group is now in the process of evaluating the costs and benefits of this procedure in terms of long-term benefits (reduction in ovarian cancer risk and mortality).
1. Kwon JS, McAlpine JN, Hanley GE, Finlayson S, Cohen T, Miller D, Gilks CB, Huntsman D. “Costs and benefits of opportunistic salpingectomy as an ovarian cancer prevention strategy”. Obstet Gynecol 2015;152(2):338-45.
2. Hanley GE, Kwon JS , Finlayson SJ, Huntsman DG, Miller DM, McAlpine JN. “Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: A cohort study from British Columbia, Canada”. Am J Obstet Gynecol 2018;219(2):172e1-172.e8.doi: 10.1016/j.ajog.2018.05.019. PMID: 29852159
3. Hanley, GE, Kwon JS , McAlpine JN, Finlayson SJ, Huntsman DG, Miller DM. “Examining indicators of early menopause following opportunistic salpingectomy: A cohort study from British Columbia”. Am J Obstet Gynecol 2020. 2020 Feb 15. pii: S0002-9378(20)30143-5. doi: 10.1016/j.ajog.2020.02.005. PMID: 32067967
The mismatch repair (MMR) system is a DNA repair mechanism that corrects errors in DNA replication. The MMR system is controlled by 4 genes: MLH1, MSH2, MSH6, and PMS2. These genes can be abnormal because of an inherited mutation (passed down through generations), or an acquired mutation (occuring by chance during one’s lifetime). An inherited mutation in one of these MMR genes causes a condition called Lynch Syndrome, which is associated with very high lifetime risks of developing colorectal and endometrial cancer. If a woman has endometrial cancer, her tumour tissue can be tested for the presence of absence of MMR proteins (corresponding to the 4 MMR genes). If one of the proteins is absent (MMR deficiency), she can be referred to the Hereditary Cancer Program for genetic testing to confirm Lynch Syndrome. If the proteins are all present, the genes are functioning properly, which means there is no mutation and she does not need to be tested. Our group was the first to publish a cost-effectivneess analysis of MMR testing in endometrial cancer as a screen for Lynch Syndrome. Subsequently we have demonstrated that MMR deficiency itself (with or without Lynch Syndrome) is an important prognostic and predictive marker. Patients with MMR deficient tumours may be eligible for targeted therapy (immunotherapy). All women with endometrial cancer diagnosed in the Vancouver Coastal Health Authority region are eligible for tumour testing for MMR deficiency. We are in the process of developing a provincial program so that all women in BC diagnosed with endometrial cancer, regardless of region of residence, can having this important testing. It has implications for genetic testing and cancer prevention among relatives, as well as treatment selection for these cancer patients.
1. Kwon JS, Scott JL, Gilks CB, Daniels MS, Sun CC, Lu KH. “Testing women with endometrial cancer to detect Lynch syndrome”. J Clin Oncol 2011;29(16):2247-2252
This is the first cost-effectiveness analysis to demonstrate that using immunohistochemistry to screen women with endometrial cancer for Lynch Syndrome is more effective and less costly than traditional Amsterdam II criteria. Prior to this, women could not be tested for Lynch Syndrome unless they had a significant family history of cancer (Amsterdam II criteria). Immunohistochemistry can identify those who should be referred for genetic testing. This testing is important for these women because if proven to have a mutation, they are still at high risk for colorectal cancer, and their first-degree relatives can benefit from risk-reducing interventions to prevent colorectal and endometrial cancer. Immunohistochemistry is currently being done on all endometrial cancers in the Vancouver Coastal Health authority region, and is being implemented as part of a provincial program, which will be the first of its kind in Canada.
2. Kim SR, Pina A, Albert A, McAlpine J, Wolber R, Gilks CB, Kwon JS . “Does MMR status in endometrial cancer influence response to adjuvant therapy?” Gynecol Oncol 2018;151:76-81. doi: 10.1016/j.ygyno.2018.08.020. Epub 2018 Aug 29. PMID: 30172479
3. Kim SR, Pina A, Albert A, McAlpine JN, Wolber R, Gilks B, Carey MS, Kwon JS . “Mismatch repair deficiency and prognostic significance in patients with low-risk endometrioid endometrial cancers”. Int J Gynecol Cancer 2020 Jun;30(6):783-788. Doi: 10.1136/ijgc-2019-000910. Epub 2020 Apr 30. PMID: 32354793
4. Lee PWC, Bedard AC, Samimi S, Beard VK, Hong Q, Bedard JEJ, Gilks CB, Schaeffer DF, Wolber R, Kwon JS, Lim HJ, Sun S, Schrader KA. “Evaluating the impact of universal Lynch syndrome screening in a publicly-funded healthcare system”. Cancer Medicine 2020 Jul 23. doi: 10.1002/cam4.3279. PMID: 32700475