Because women’s health starts with research – the WISDOM trial
- “It’s important for women to have confidence in good scientific research” – WisdomStudy.org
- Women make a series of decisions based on the information provided from their screening. Wouldn’t you want to know what the best option is?
- If you haven’t done so already, learn more about the impact this important research will have on women in our community.
In support of the WISDOM (Women Informed to Screen Depending On Measures of risk) trial, The Doris A. Howell Foundation celebrated its Health and Happiness Series in June with the presentation “Improving Benefits and Reducing Harms from Breast Cancer Screening: The WISDOM Trial,” hosting three renowned specialists in the areas of oncology, epidemiology and genetic testing. Led by UC San Diego Health, UC Davis Health, UCSF, UCLA Health, UC Irvine, and Sanford Health, the mammography screening research trial is searching to determine which strategy produces the most benefit and least harm for women.
The objective was to inform the San Diego community about the latest research being conducted regarding breast cancer screening guidelines, their efficacy, and the steps required to provide women with accurate, personalized prevention processes that effectively diagnose and treat breast cancer ON AN INDIVIDUALIZED basis. If you haven’t done so already, take a look at www.wisdomstudy.org to learn more about the impact this important research will have on women in our community.
When discussing breast cancer, the conclusion tends to be unanimous: early detection saves lives. Whereas research shows that overall mortality rates have gone down, one needs to dig in deeper to understand all the moving parts in breast cancer screening:
- Technology – which has certainly improved
- The development of new ways to treat the different stages of breast cancer
- And most importantly, the personal circumstances, propensity to risk factors, and age
The latest statistics in breast cancer are the following:
- 1 in 8 women will develop breast cancer.
- Breast cancer comprises about 15% of all cancer cases in the US and is the second leading cause of cancer-related death in women, behind lung cancer.
- Overall estimated 5-year survival in female breast cancer patients is around 90% but differs significantly across different stages of breast cancer; 99% when localized to the breast, 85% when localized to the breast and armpit, and 27% if spread to other parts of the body at diagnosis.
- Common risk factors include family history, aging, obesity, alcohol consumption, delayed or no childbearing, high dose of radiation (for treating lymphomas) and menopausal hormone therapy.
|Barbara A. Parker, MD|
Dr. Barbara Parker discussed breast cancer Precision Medicine, breast cancer incidence and death rates, and treatment advances for early and advanced breast cancer.
“Precision Medicine” was defined by the National Cancer Institute in 2015 and focuses on prevention and treatment strategies that take patients’ individual characteristics into account. “A one-size fits all approach to prevention and early detection of breast cancer is not optimal for women,” comments Dr. Parker.
The WISDOM trial provides the opportunity to determine breast cancer risk at the point of screening, and to assign breast cancer screening frequency based upon risk:
- Individualizing care based upon genes, environment, and prognosis; that is, individualizing care based upon family history and inherited genes, reproductive history and environmental exposures, and the prognosis of the cancer based on the tumor characteristics.
- Targeting therapies to specific patients, tumors, and pathways based on the understanding of the risk factors , the subtype of breast cancer, and the molecular profile of some tumors.
- Targeting screening and intervention strategies to patients at highest risk.
|Andrea Z. LaCroix, PhD|
“There are many different guidelines by different organizations, and this adds a lot of confusion for women regarding their own health”, comments Dr. LaCroix, speaker at the event. “The trial is comparing yearly screening to a personalized screening approach. The personalized screening will provide a mammogram timeline based on a participant’s individual risk factors (age, personal and family history, genetic tests for gene mutations and variations) linked to the development of breast cancer,”she concludes.
Dr. LaCroix’s participation in the WISDOM Trial is focused on determining how screening can be improved. She presented the two sides of the breast-health screening coin. Whereas research shows that overall mortality rates have gone down, one needs to dig in deeper to understand all the moving parts in breast screening: technology – which has certainly improved — the development of new ways to treat the different stages of breast cancer, and ultimately, personal circumstances, propensity to risk factors, and age.
In presenting the controversy surrounding breast cancer screening, Dr. LaCroix mentioned that other countries in Europe — France, the Netherlands and Denmark– have just done away with any type of guideline; whereas in the UK, women between the ages of 50 and 70 can get screened as often as desired. This is just a sample of how the breast cancer screening controversy has the potential of affecting women.
In an era where treating breast cancer is pretty much “processed” – meaning same detection and treatment across the board — Dr. LaCroix suggests a change in paradigm. “We clearly need to realize that no cancer is the same, just as breast cancer is not just a single disease”.
Citing Dr. Karsten Jorgensen, “We shouldn’t treat all cancers the same way because they are not the same. Our knowledge of cancer biology tells us that breast cancer represents a spectrum of really different cases of cancer that behave in very different ways. And sadly, screening is not good at picking up those cancers that we really want to pick up.”
Women around the country make decisions based on the information from their screening. If the study can provide a comprehensive picture when dealing with an already difficult illness, decisions like a double mastectomy based on an abundance of caution can save patients the consequences of unnecessary surgery, for example. The Wisdom Study guiding principles are:
- No woman will be screened less aggressively than existing recommendations from major professional societies
- Minimize false positives
- Minimize interval cancers
- Minimize incidence of Stage IIB and higher disease
- Women with known deleterious mutations in hereditary breast cancer genes will be screened according to National Comprehensive Cancer Network (NCCN) guidelines
- Screening recommendations will be practical and scalable
|Lisa Madlensky, Ph.D|
The Wisdom Trial seeks to broaden the understanding of the role risk factors play in the development of breast cancer coupled with the information provided by women, to then provide the individualized screening strategy. “The personalized screening arm takes advantage of all of the advances that have been made in understanding the risk factors and protective factors that each of us may have that relate to our future risk of getting breast cancer”, comments Dr. Madlensky.
Genetic testing is one of the aspects that gets the most questions in the Trial. The Wisdom Study is structured around three main genetic components that allow the creation of a comprehensive panel of genes upon which screening recommendations will be provided:
1. “Traditional” BRCA1 & BRCA2 testing will help determine the propensity for a breast cancer diagnosis. Considering that one in 400 to 800 women have a gene mutation under this classification, having it doesn’t necessarily mean a 100% risk of breast cancer. For women whose family history is unknown, who may be adopted or whose family risk of cancer might be passed down through males, BRCA 1 & BRCA2 will definitely provide a solid foundation in risk assessment and personalization.
2. Women in the Trial additionally get tested for a second set of genes that are extremely rare but are related to an elevated risk of breast cancer (TP53, PTEN, STK11, CDH1, ATM, PALB2, and CHEK2). All women found to have a significant mutation in any of the nine genes listed above will be referred for genetic counseling.
3. A unique score included in the study is the Single Nucleotide Polymorphism (SNP) score. Women have millions of them as it is a normal variation in our genomes. They are unique in the sense that they do not behave the same way in individuals who come from different backgrounds as a general genetic variability would. They are technically easy to assess.
The Study includes a panel of 200+ SNPs. This determines a “risk score”, and depending on that, women with higher scores will be recommended to get their screening mammograms more often
The Wisdom Study is unique because:
- It’s a pragmatic trial: looks at screening in the “real world” – getting women to do what researchers need them to do to follow up on their information is a challenge. By looking at the screening process in a “real world setting” researchers can take concrete actions to guarantee the collection of meaningful information for the study.
- It’s Dynamic: Life happens, and as it does, so the changes in risk factors – for example, aging. Whereas a woman might be considered low risk at 50, once she turns 60, her chances of getting diagnosed with breast cancer increase.
- It’s preference-tolerant: Women who have a strong preference or are averse to randomization can choose randomization or observation arms.
- It’s adaptive: As we learn more about assessing breast cancer risk, our risk assignment processes will be adjusted. Risk assignments will depend on personal information gathered throughout the trial.