Personalized Screening for Breast Cancer - The WISDOM Study

Update from the 2024 Menopause Society Meeting

Getty Images/Science Photo Library

Many of us have heard about the concept of personalized medicine, instead of broad guidelines for large swaths of the population, recommendations are refined so groups of people who need screening or treatment based on greater risk get screened and/or treated those who don’t need that level of care, well, don’t.

One area where precision medicine is gathering speed is in breast cancer screening, and we heard about this at the 2024 Menopause Society meeting in a lecture entitled, Opportunity to ReImagine Personalization for Breast Cancer Screening Treatment and Prevention, by Dr. Laura Esserman, the director of the UCSF Breast Care Center and a Professor of Surgery and Radiology. The lecture asked us to fundamentally rethink screening for breast cancer, because the current guidelines (and all of them that have come before) are not serving all women well. 

During the lecture, Dr. Esserman explained that the current guidelines for breast cancer screening aren’t sufficient for a couple of reasons. First of all, there are seven different screening guidelines in the United States, but which one is best? And even when guidelines are followed, in 2023, 43,700 women died from breast cancer in the United States despite screening. We also heard about cases where an aggressive tumor can develop in the interval between currently recommended mammograms. Might some of these women be better served with different screening? In contrast, we also heard about many slow growing cancers and cancers that may never even spread beyond the breast possibly being over treated because they were found on mammography. And of course we heard there are many cancers that are appropriately identified with current mammographic screening. 

The current situation is a bit like Goldilocks and the porridge that is too hot, too cold, or the right temperature; for some regular screening is too much, for others not enough, and for some it’s just right. The question then is can personalized medicine offer something better so everyone can have perfect porridge? 

How do we change screening so we are more likely to pick up cancers of consequence and less likely to be tripped up by cancers that are unlikely to ever leave the breast? 

Now this is not meant in any way to suggest women shouldn’t be following the current guidelines. They should, because this is the best available data. But given what we know, it’s a worthy scientific question to ask if we can conduct research so that we can do better?

Enter the WISDOM study, Women Informed to Screen Depending On Measures of risk.

WISDOM is a large-scale randomized trial evaluating personalized breast cancer screening to identify approaches that can both save lives and reduce unnecessary tests. The WISDOM study is evaluating standard breast cancer screening of annual mammograms and comparing it with personalized screening. The personalized screening arm considers several measures of risk for breast cancer: 

• Exposures/Lifestyle

• Breast density

• Breast cancer genes (currently nine are being testing)

• A SNP polygenic risk score. SNP is a single nucleotide polymorphism (typically pronounced “snip”), and it is a tiny genetic variation. All DNA is built of four nucleosides or building blocks: adenine (A), cytosine (C), thymine (T), and guanine (G) and the sequence of these buildings blocks is the genetic code or instructions. With a SNP, a G may be replaced with an C (for example) in a certain stretch of DNA. SNPs are common, and while many are harmless, some cause great harm, and some may cause subtle changes that are only important in certain situations, for example, how we respond to a carcinogen.

The WISDOM study is also collecting information on environmental exposure, to evaluate the relationship between certain environmental exposures and the risk of breast cancer. 

How Does WISDOM Work?

After signing up, women select usual screening or personalized screening, so this isn’t a blinded trial. If you choose usual screening, you will fill out a risk assessment questionnaire and the recommendation will be an annual mammogram. The other option is the personalized screening arm, which also involves completing a questionnaire, sending in your mammogram results, and collecting saliva to test for genes and SNPs that may be important for breast cancer. Everyone in the personalized screening arm will receive genetic testing and a free one on one consultation with a breast health specialist to discuss their results as well as personalized screening recommendations for breast cancer, which could result in one of the following:

• No screening until age 50

• Every other year (biennial) mammograms

• Annual mammograms

• Annual mammograms and annual MRI

My understanding is that WISDOM does not pay for mammograms or MRIs, but some insurance companies have partnered with WISDOM and will cover the recommended screening. 

Here’s the flow process from the website:

Who can Participate in WISDOM?

If you are between the ages of 30 and 74, live in the United States, never had been diagnosed with breast cancer or DCIS (ductal carcinoma in site), and speak English or Spanish, you can participate. If you are between ages 30 and 39 you will be enrolled in the personalized group as there are no guidelines for annual screening below age 40. 

I enrolled because I felt it would be hypocritical of me as a health care provider to moan about the lack of data to help my patients, especially when I am someone with dense breasts who the data doesn’t serve very well at all, and not contribute to fixing the problem when presented with an opportunity that was at such a low personal risk for me. I am not saying that to guilt anyone into the study, remember, I am using a lot of “I words” here. 

What’s Sign Up Like?

It was very easy to sign up. As soon as the lecture was over, I entered my data and selected my study arm. I had the advantage of just having heard several lectures on the topic and the study, so didn’t need to spend much time reading. For everyone else, there is plenty of information that should answer all of your questions on the site (click here to read more).  

I chose the personalized arm in part because I have dense breasts, but I can’t get my insurance to cover an MRI because I am just under the current risk based assessment threshold for an MRI. I am curious if the genetic testing will raise or lower my risk and either make me feel more at ease about my dense breasts, or arm me with data to push for an MRI, or pay for one myself if my insurance declines. 

Another reason I chose to participate in the personalized arm is that I have zero family history of breast cancer, but I also have multiple relatives who have lived very long lives and were also long-time heavy smokers and no one died died from cancer or even had it to my knowledge. I have always wondered if there is genetic testing that might shed some light on this. 

Shortly after signing up, just as promised, I received an email asking for my latest mammogram, which I sent along as a PDF. I just received my genetic test in the mail and I am sending that in tomorrow, and will let you know what happens as it unfolds. 

Are You Interested in the WIDSOM Study?

If you are eligible and interested, or even just curious, head over to the WISDOM study.

 We need more studies looking at personal risk, because breast cancer isn’t just one disease and of course, we’re all unique with different risk factors. In addition, many of the studies we are using for guidelines come from before we understood the genetics of breast cancer. Here’s hoping that WISDOM can help us create a more personalized approach to breast cancer screening.  

And with that, I think I have almost covered the data I wanted to share from the 2024 Menopause Society Meeting, although it’s possible I might have one more post in me. We’ll see! 

In case you missed it, Maria Shriver’s Sunday Paper picked up my coverage of the Menopause Society Meeting. 

And I have some great posts that I am working on and am excited to bring to you later this week. So stay tuned!