“We invite you to participate in the Tapestry study, whose goal is to understand how patient care may be impacted when results from DNA sequencing are in the medical record,” states the message that appears with my downloading e-mail. “The Tapestry study is a screening test. It looks at 11 genes associated with BRCA-related hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolemia. It is not a diagnostic test, nor does it look at all of the genes associated with hereditary ovarian cancer,” continues the dialogue.
Hmmmm…. My attention has been captured. Should I consider a genetic study or is this a really bad idea? I did have ovarian cancer when I was 38 years old. But that was 25 years ago, and nothing has happened since. I am pretty sure I don’t have any genetic mutations for cancer. I have no family history of breast or ovarian cancer. But still . . . I do have a daughter who has become concerned here lately as to her risk of ovarian cancer. If all this testing were to come back negative, it would provide her with peace of mind.
Three days later on October 23, 2020, I respond to the e-mail and join Mayo Clinic’s Health Tapestry Genomic Sequencing in Clinical Practice study. I am sent a kit into which I am to collect a specific amount of sputum. I spit into the collection container and mail it off to the lab in the pre-addressed box. Then I wait. The information given me was that the test results would take up to twelve weeks to be reported. That was simple.
Several months go by and I do receive the fun results for the ancestry and genetic traits part of the study. I am 95% of European ancestry with 5% of Middle Eastern and African heritage. Mixed in there is a 0.8% Ashkenazi Jewish. I find out later this is important as 2% of those of Ashkenazi Jewish descent have a BRCA mutation. The results say I am not lactose intolerant (knew that). I have not adapted to be able to avoid malaria (Oh really!). I do not have the adaptation to be able to thrive in lower-oxygen environments at high altitudes (guess I’ll stay on the plains). I do have a genotype associated with the ability to adapt in cold climates (Brr… doesn’t seem like it some days in this cold MN climate). Along with lots of other useless tidbits, I learn I have brown eyes, tend towards curly hair, am taller, and tend to tan rather than sunburn; all things I have somehow managed to figure out after being on earth for 63 years. But what I really want to know, do I have a gene coding for cancer, is suspended in the health results that only say, “pending.” I think this very strange.
Towards the end of January 2021, my husband is also invited to join this same study. He signs up on February 2, 2021, and submits his saliva sample a few days later. Ten weeks later, on April 19, 2021, his results are flashed to us as “ready.” He is negative for all eleven of the genes they are testing for that code for cancer. Hurrah, at least our daughter has a fighting chance!
Puzzled as to why he has received his results and I have not, I send an e-mail to Helix, the company being used by Mayo for this study, “I signed up for the Helix genetic study back in October 2020. The information originally stated that we would receive results by twelve weeks. It has now been 5 months and there are still no medical results. I did get the basic genetic characteristics results, but I am just curious why I still haven’t gotten my medical results…?” Helix does promptly respond, “Our systems indicate that your sequencing has been sent out for interpretation. At this time, I cannot give you a time frame … Your Health results are taking longer to sequence than previously stated. We are unfortunately back logged due to Covid 19.” I find this all very confusing. Yes, maybe Covid is slowing down their results but that doesn’t explain how someone who signed up after me has already received their results and I haven’t. I am convinced that they have lost my sample and/or my results and are finding it convenient to blame it on Covid. It doesn’t occur to me until later that they are simply not telling me the truth; that they do know the results and because they are positive, they are not ready to tell me. If I could read between the lines, it would say, “Your results were positive. Therefore, we sent them to be confirmed by a second company.”
Three more months go by. I send several more e-mails to this company and each time I am told that my results, “are delayed due to supply chain issues” or “covid testing taking priority.” Finally, on July 26, they report that “it looks like your results are in a recent batch that should be released by Helix any day now.” Coincidently, Mayo sends an email three days later that says “you will receive an email from Helix very soon, with instructions on how to access your results on the Helix website. As a participant in this study, a Mayo Clinic genetic counselor would like to review your results with you over the phone.” This should have been my clue that Mayo has already known the results for some time, and they are not good. Afterall, they never requested to talk to my hubby by phone to discuss his results.
It isn’t until July 31, 2021, 9 months after signing up for this study that I get the results. “You were found to have an actionable* variant in the BRCA2 gene that is associated with a genetic condition called Hereditary Breast and Ovarian Cancer (HBOC). Individuals with HBOC have an increased risk for certain types of cancer, including breast, ovarian, prostate, and others.”
A numbness spreads over me. Why did I think joining this study was a good idea? I would have been better off never knowing. What I had hoped would provide peace of mind to my daughter has opened a yawning pit of anguish and anxiety. I am now 63 years old and have lived 25 years without any cancer reoccurrence. I have no desire to make any “might be possible cancer” a focus of my life. I can’t live that way. But the question remains, should I ignore what was better unknown or try to pursue some interventions, some of which are of a huge magnitude in order attempt to prevent what might happen? The medical community seems to be in a huge rush now to push me down this path towards interventions. No one seemed to care much before, and my cancer diagnosis 25 years ago has pretty much been forgotten. When I think about it later, the whole process of the genetic testing makes me angry. Helix and Mayo have known for at least 6 months but kept trying to pretend they didn’t by blaming other issues and now, it is all a big rush for me to respond.
I take a breath and step back. There is no emergency here. I don’t have cancer. The first intervention I request is to be retested by another reputable company to make sure this is an accurate result and can be used to drive any decisions made going forward and will be accepted by health insurance companies. After being led along for 9 months, I do not trust the results I am being given. And it is not the first time such a test result has been wrong. I decide to give a blood sample this time as it has a higher rate of reliability than saliva and proceed to do so in early August. But if I was hoping for a different result, I will be disappointed. This test confirms the original finding of a “pathogenic variant (mutation) in the BRCA2 gene associated with Hereditary Breast and Ovarian Cancer syndrome.”
So what is the big deal with this genetic mutation and what are it’s implications? BRCA1 and BRCA2 genes code for proteins that work to suppress cancer cells, mostly in breast tissue, and help to repair any DNA damage that occurs in the course of normal life. If they are missing or damaged, the cells cannot repair themselves and they go on to grow unchecked and become cancerous. BRCA2 is found on chromosome 13 while BRCA1 is found on chromosome 17 so they have slightly different cancer type expressions when missing. BRCA2 is associated with a 45 -83% lifetime risk, according to Mayo genetics, of developing breast cancer by age 70 (the average risk for the general population is 12%), a 27% risk of developing ovarian cancer by age 80 (the general population has a 1-2% risk). I think I have that one covered already. BRCA2 mutations also are associated with a higher risk of pancreatic cancers and melanoma than the general population.
Well, if that isn’t all depressing. And how is one even supposed to begin to deal with statistics like that? My first reaction is to have a double mastectomy without reconstruction and get it over with. I don’t want to be thinking about breast cancer every moment for the rest of my life. But after doing significant research on double mastectomies, I realize that they are not benign surgeries either. Many women have chronic pain afterward. Others have numbness and upper body muscle weakness. I am a fairly healthy 64-year-old by now. I run a chainsaw. I lift weights. I’m active. I do not want a life where I am cancer free but simply existing because I am debilitated and in pain constantly. And finally, having my breasts removed will remove any chance of having a meaningful intimate relationship with my husband. I am distressed to say the least about the dismal statistics but can’t decide what I want to do.
In October, I meet with a doctor from the breast clinic at Mayo. We go through my options: 1. Do nothing (that is not encouraged at all) 2. Have a double mastectomy (see reservations above) 3. Start taking aromatase inhibitors to help prevent cancer and/or 4. Monitor with alternating mammograms and breast MRIs every 6 months. I groan at each of them. I hate visiting medical facilities and doctors and have no desire to visit there constantly. Taking aromatase inhibitors sounds interesting but it is mostly a “hit and miss, maybe” approach. No one knows if I will actually get the kind of cancer that is prevented by drugs that block estrogen production and uptake. So there is a chance that I’m taking a toxic drug that is providing no benefit to me personally. I lean heavily away from their use after I read the side effects: hot flashes, night sweats, join pain by 50% of those taking it, muscle pain, and bone loss. I am back to the same issues of decreased quality of life to treat what currently doesn’t exist. I don’t know what to do.
Before I leave my breast appointment, I am offered the opportunity to join another study, “GENetic Risk Estimation of Breast Cancer Prior to decisions on preventative therapy uptake, risk reduction surgery, or intensive imaging surveillance: A study to determine if a polygenic risk score influences the decision-making options among high-risk women.” The polygenic risk score will take into account genetic risk factors, known as single nucleotide polymorphisms (SNPs) for breast cancer. While individually, these SNP risk factors are of little clinical value, when combined as a polygenic risk score (PRS), they yield a strong risk factor for breast cancer and can be used to personalize breast cancer risk. In other words, the polygenic risk score is an analyzing of 30 or more genes that influence whether a person develops cancer and coming up with a projection for any one particular person as to what their personal chances are of developing breast cancer. At first, I reject the idea of joining another study. I am already overwhelmed by all the information and decisions being thrown at me but the more I think about it, I wonder if it could provide me with the information to make a definitive choice as to the direction I should go. And so I sign up for one more genetic study. While I wait for the results, I try to go about life as normally as possible.
This time, I do not have as long to wait. Within 8 weeks, the results are back. “I have good news,” are the first words from the doctor’s mouth when I sit down with her. “You are in the lowest 7th percentile on the polygenic risk scoring. Because you had a hysterectomy at age 38,” she says, “I assess that you have a 9% risk of developing breast cancer in 5 years, an 18% risk in 10 years, and a lifetime risk of 27%.” That figure is still high compared to the general population, but I now know which direction I am going. At least for the present time, I will alternate the mammogram and breast MRI every six months. If any abnormality ever shows up, I will opt immediately for a double mastectomy without reconstruction. Now that I have made this decision, we have to come up with a plan for safely performing the MRI as I am allergic to the gadolinium dye that they use. This will be my biggest roadblock to following through on this decision.
In November of 2021, after loading up on methylprednisolone and Zyrtec, an anti-histamine, I successfully traverse the breast MRI. All findings are negative. I can breathe a sigh of relief, at least for six months. I begin to move on with life and focus on the future. And then, “your Cologuard test is positive.” Is there no end to this craziness? Is this what old age is all about? Waiting for the cancer shoe to drop? I reject that premise. I choose to live my life in freedom from such fear, God willing – to treasure each day for what it is.