How Genetic Testing Guided My Breast Cancer Journey – To Eschewing Beef
Two months ago, I joined a club nobody wants to be a member of – the 1 in 8 women who develop breast cancer at some point in their lifetimes. It turned up on a routine mammogram.
I’m happy it’s okay these days to talk about breast cancer – when my mom first had it in 1988, that wasn’t true. I haven’t thought much yet about marching and holding a sign next October for Breast Cancer Awareness Month. I don’t have the strength to hold up a sign right now, but I’m trying to help by explaining things on the Facebook groups of “pink sisters” I’ve joined recently. Many of their questions concern genetic testing.
The media tends to focus on celebrities like Angelina Jolie undergoing surgery before they have cancer because they’ve inherited a susceptibility mutation. But genetic testing is also critically important for those of us who have already been diagnosed.
After my biopsy confirmed that I had ductal carcinoma in situ (DCIS) – a milk duct filled with cancer cells – I knew I needed genetic testing to tell whether I needed a single or double mastectomy. As a genetic counselor, I’d never sent myself for BRCA testing because my family history didn’t fit the classic profile of several young affected family members. Only my mom had it, and she was older. The guidelines now advise testing for anyone of Ashkenazi heritage.
Next up in this unexpected journey: choosing and meeting my breast surgeon. Before she could say much, I began babbling gene names: BRCA, but also CHK2, ATM, RB1, p53, BARD1. Several dozen genes disrupt natural DNA repair, allowing mutations in oncogenes and tumor suppressor genes to persist. A mutation in any one of them would mean both breasts had to go. I didn’t want to take the risk that cancer would develop in the healthy one and I’d need a second surgery.
As my anxiety escalated, the doc spoke up.
“Ricki. You can’t diagnose yourself. Find another genetic counselor.”
So I did. Bonnie Liebers runs Genetic Counseling Services.com, providing telecounseling and helping patients and their health care providers access the best tests for them. The clock was ticking because my husband Larry and I were about to leave on a trip to Costa Rica planned a year ago. Genetic testing would inform my treatment and also reveal whether my three daughters and my sister needed testing too.
The next day, still stunned, I sat down with Bonnie, a personal friend. She calmly laid out the brochures from six genetic testing labs, comparing the offerings and coverage as if we were ordering takeout. We selected Invitae’s 80-gene panel, a blood test. I’d hear about the most likely suspects first, such as the BRCA genes.
(Things are ramping up fast in the genetics of cancer diagnosis and treatment. My 2015 Angelina Jolie post mentioned Invitae’s test, which then covered 34 genes. And Memorial Sloan Kettering Cancer Center recently announced a 468-gene panel for cancer cells. And that’s just mutations. Gene expression profiling for predicting recurrence is another story.)
A week later, right after we’d traversed the hanging bridges through the cloud forest near the Mount Arenal volcano in Costa Rica and were waiting for our group to catch up, a magical moment of wi-fi revealed my preliminary genetic test results. No mutations in the top tier of genes! A day later another blip of connectivity in the rainforest brought news that I didn’t have mutations in any of the other genes either.
Great news! So I faced a trio of time-based consequences:
Immediate: I’d only need a single mastectomy.
Short term: my daughters and sister were not at elevated risk of having inherited a susceptibility mutation in the genes I was tested for.
Long term: I could now focus on controllable risk factors. Let me explain.
Most Cancers Are NOT Inherited
The public service announcement for breast cancer screening in New York state (Get Screened, No Excuses), featuring a patient proclaiming “but there’s no cancer in my family,” corrects the common misconception that cancer is inherited. It’s most often a genetic disease, but not an inherited one. There’s a difference.
In most breast cancer cases, the mutations are somatic, occurring only in the breast cells and therefore not inherited. The explanation goes back decades to the 2-hit hypothesis of cancer: Most cancers arise from two recessive mutations, or “hits,” in a single body (somatic) cell.
Only 5 to 10 percent of cancers are inherited, with a mutation coming in with the sperm or egg. People who inherit cancer-susceptibility mutations, like Angelina Jolie, present in all of their cells, are already halfway to cancer at conception. All they need is one mutation in a body cell to start the disease, and that’s why some elect prophylactic surgery.
My cancer was not inherited. Instead, it began when a gene whose protein product regulates the cell cycle (frequency of division) in a single cell within a single milk duct mutated. That first glitch was recessive – the normal gene counterpart on the second copy of whatever chromosome it was part of maintained the normal cell cycle. Maybe I was 7 when that initial hit happened, or 27, or 47. Who knows.
But sometime within the past few years, in that very same cell, a second mutation zapped that very same gene, but in the second copy of the chromosome. Having two mutations in the same gene lifted the protection of recessiveness, and that cell now had an advantage: it could divide more frequently than the cells around it.
The cell may have had an advantage, but I didn’t.
Soon the cancer cell divided. Then there were 2, then 4, then 8 cells, and on and on until a little lump jutted from the inner lining of a lone milk duct. The runaway cells had filled the little tube by the time I saw the “suspicious” mammogram mid-November 2017, sparkling with a trail of telltale calcifications bisecting my breast. The sparkles hadn’t been there a year earlier; it was a high-grade growth.
Analyzing My Controllable Risk Factors
Some risk factors are out of our control: being female, menstruating young and/or entering menopause late, being older, inheriting mutations. Learning that I hadn’t inherited the most common breast cancer gene variants enabled me to focus on controllable risk factors. But there was one more uncontrollable circumstance to consider that’s rarely written about: spontaneous mutations.
These just happen, due to a chemical phenomenon (a tautomeric shift) in which any of the four types of DNA bases – A, T, C, and G – are fleetingly in a slightly different form that has to do with the position of hydrogen bonds. If a fork of replicating DNA comes along as a base is caught in this rare form – a little like catching an executive in her jammies – then the rare base can’t pair with its usual partner (A with T and G with C), and an incorrect DNA base pair is inserted. If the change to the encoded protein affects how it controls the cell cycle, cancer can result.
Spontaneous mutations are a fact of life, a consequence of chemistry. But environmental exposures can also trigger mutations, and these are likely behind many “2-hit” cancers.
The first cancer-environment link came from British physician Sir Percival Pott, who in 1770 attributed the high rate of scrotal skin cancer among chimney sweeps in London to their crotch-level exposure to a chemical in soot.
My family is riddled with cancers, but they all began later in life and had environmental explanations – lung and tongue cancers among smokers, lymphoma in a radiologist, skin cancer in a sun worshipper. I suspect that the thyroid cancer I had in 1993 was due to 5 years of orthodontia as a kid, unprotected from the x-rays. My exposure in utero to diethylstilbestrol (DES) upped my breast cancer risk. Pesticides that are estrogen mimics, such as DDT, cause breast cancer too.
I’ve done what I could to lower my risk – nursed 3 babies; exercised every day; avoided cigarettes, alcohol, or estrogen patches or pills; no long-term oral contraceptives; and I spread compost and manure on my garden, not organophosphate pesticides.
But diet is something else I can control and haven’t (other than low-carb), and it ties in with my recent visit to Costa Rica.
No More Beef!
Clearing land to raise cattle is destroying rainforests, as bovine flatulence pours out the greenhouse gas methane. And beef consumption has long been associated with increased cancer risk.
Grilled beef releases heterocyclic aromatic amines (HAAs), which are absorbed into the bloodstream and sent to the liver, where they’re metabolized into mutagens – chemical compounds that raise the risk of certain cancers. Broccoli and Brussels sprouts produce glucosinolates, which activate xenobiotic metabolizing enzymes that take those nasty HAAs down a different, non-mutagenic pathway.
Spewing HAAs on the barbie isn’t the only risk of eating red meat. Absence of an enzyme makes the human immune system react to eating meat from organisms that do make the enzyme. And cattle and pigs make it.
Specifically, the enzyme, CMAH, encodes a cell surface sugar, Neu5Gc, a type of sialic acid. That sugar functions as a “xenoantigen” – when we encounter it, our immune systems crank out antibodies and promote inflammation, raising the risk of arthritis and cancer.
Last month David Alvarez-Ponce’s team at the University of Nevada described, in Genome Biology and Evolution, how muscle tissue (aka meat) safe for human consumption is in birds, reptiles, platypuses, spiny anteaters, and of course other primates. Interestingly, some breeds of dogs and cats make the offending sialic acid and some don’t – but I don’t think anyone is contemplating consuming their pets.
Surviving cancer is all about accepting what is, yet becoming empowered to live with what is while continuing to do whatever possible to lower risks. They persist. Treated cancers can return and new ones appear. Just do the math.
We have 30 trillion cells, all but the red blood cells harboring genomes where the mutation rate is 5 in 100,000 DNA bases per cell division for the youngest, rising to 5 in 20,000 among the oldest. At last count, at least 130 of those genes are oncogenes or tumor suppressor genes. That means that being “cancer-free” is probably impossible, for any of us, and that’s why “no evidence of disease” is a more honest way for oncologists to give good news to patients.
My journey from breast cancer to genetic testing to eliminating beef may have been circuitous, but it may lower the risk of my having to go through surgery again. I wish I’d started sooner, and I hope that this post helps folks.
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As a DES exposed woman, I had cervical cancer in 1981. I was also diagnosed with lupus shortly after that. For unrelated reasons, I stopped eating red meat products. My lupus then went into remission for almost 20 years. Multiple stressors in my life resulted in a return of the lupus symptoms and positive lab work. Fast forward to 2014, after another decade of becoming too disabled to work, a divorce after 26 years that was a long time in the making, I was diagnosed with breast cancer. Your article made so much sense out of this journey I’ve been on. I look forward to reading more of your articles. Thank you
Thanks. It’s hard to believe sometimes that lightning has struck twice — you too. Be well!
You are insane.
Please explain. If I’ve made a factual error, I’m always happy to correct it. I may be a bit under the weather, but insane? I don’t think so.
Wow Ricki- I didn’t know. What a beautiful way you have used this to help others understand. But of course that’s who you are – in the midst of your own angst, you always think of this might help others. Proud to call you friend.
Hi Sue! I didn’t tell many people, because it happened so fast, we were about to leave for Costa Rica, and then the holidays descended and everybody disappeared into their families. I kept it off Facebook because I didn’t think I could handle all the prayers, but being on the FB groups for breast cancer plus postings at other sites showed me why prayers are necessary, vital, for so many to be able to face each day. Quite the learning experience. Major conclusion from thousands of women: this changes you forever. It’s like nothing I’ve ever experienced and you know from our hospice work we’ve seen a lot. I submitted a very different essay on my experience to Modern Love at the NY Times and hope for once they don’t reject me. Thanks for your nice note. Let’s do lunch (in awhile …)!
I am a breast cancer survivor for the second time. I am an African American woman over sixty and a doctoral student. My journey to better health has just started, and is focused on diet and exercise. Giving up the cultural foods that I have lived with is not easy, but I am choosing life over death. My intention is to read some of your literary work, and change my profile one bite at a time.
So nice to meet you! Exercise is so important too. I’m doing ok avoiding red meat, most meat, but my three cats aren’t very happy. They freak out at soy sausages. Stay well!
As usual a well written excellent explanation. And there may be very good reasons to avoiding eating beef vis a vis rainforests and greenhouse gases, or even other health reasons. However the association with breast cancer remains unproven. You might want to look at a recent article in the February 2018 issue of the European Journal of Cancer entitled: “Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis” The reference is: European Journal of Cancer, 2018-02-01, Volume 90, Pages 73-82. Their conclusions: “Consumption of processed meat, but not red meat, may increase the risk of breast cancer. ” In both the UK Biobank cohort study and in their meta-analysis, red meat consumption was not associated with breast cancer. In their cohort study, over a median of 7 years follow-up of participants aged 40–69 years, 4819 of the 262,195 women developed breast cancer. The consumption of processed meat was associated with an increase in the risk of breast cancer in the UK Biobank. Their meta-analysis confirmed the findings of carcinogenic risk of processed meat. However in both the UK Biobank cohort and the meta-analysis, red meat consumption was not associated with breast cancer. Obviously there are limitations to the study but they also comment that a previous meta-analysis based on estimates of incremental intake of red and processed meat conducted by the World Cancer Research Fund reported similar findings to their study. The previous meta-analysis also found that there was no association between red meat intake and breast cancer, whereas the pooled RR for 50 g/day intake of processed meat and post-menopausal breast cancer was 1.13, 95% CI 0.99–1.29. So while the Neu5Gc story is interesting and provocative, the real world clinical significance has yet to be proven. I don’t think you need to feel badly about not giving up eating meat sooner.
Hi Dr. Ludman. Thanks for writing. The study you cite is a meta analysis with no apparent genetic information. Meta means a bit of apples, oranges, lemons, etc. The only stratification I could find was by post and pre menopausal, and within menopausal, whether women had taken ERT or not. No mention of any genes. Therefore, the study is lumping together what may actually be dozens of genetically distinct conditions that we call breast cancer. The ICD code the paper cites doesn’t seem to have genotyping, and the data came from “routine hospital admission” records, cancer registries, and death certificates. I don’t think these sources record germinal mutations — somatic probably wouldn’t be known — and, if so, if a study were stratified by say CHEK2, ATM, p53, BRCA, an association with red meat consumption is possible. This is a great example of how science can disprove but not prove. Outcomes depend on study design. I’d like to see a prospective, blinded study that compares breast cancer patients with different germinal mutations.
Fantastic article. Traditionally there have been so many barriers and obstacles to genetic counseling for too many rare disease patients and families. Improving this accessiblity is so important in also improving genetic diagnosis rates, and helping people reach a diagnosis faster. Online and virtual, direct to consumer genetic counseling options, https://fdna.health/knowledge-base/what-is-genetic-counseling/, and understanding how this tools have the potential to revolutionize genetic analysis and diagnosis, while improving rare disease patient outcomes, is crucial.