Early Detection- Catching Cancer When It Is Curable

Review of the book "Early Detection" by Bruce Ratner and Adam Bonislawski.

By Gitte Pedersen, CEO of Genomic Expression, and Norman Friedland co-founder, of FullSky Partners.

The message “You’ve got cancer” creates immediate shock and fear. If these words are for your spouse, child, parent, brother, sister, aunt, uncle, cousin, neighbor, best friend, or teammate, the horror can be much greater.

Words of shock fear and sadness are spoken almost 2 million times a year, with increasing trends - especially for a younger population and an underserved demographic.

Early Detection provides the plan, with the potential impact of Rachael Carlson’s Silent Spring to dramatically reduce cancer mortality trajectory.

“We need to flip our decades-long priority of focusing largely on the treatment of advanced cancers–often in stage III or stage IV - and shift the emphasis to early detection of cancerous growth, until now the poor stepchild of the whole process”

The numbers tell the story. Healthcare economist Dr. Tomas Philipson’s research into the economic and patient benefits of early cancer detection is mind-blowing

"The life-years gained from screenings are estimated to be 15.5–21.3 million lives. These benefits translate into a value of $8.2-$11.3 trillion at full potential and $6.5-$8.6 trillion considering current adherence"

Early Detection makes the same point

"By detecting cancer early 90% is curable whereas only 10% of cancers detected late can be treated effectively"

Early Detection begins with the story of Bruce’s brother, Michael, who had access to the world’s leading cancer experts but who nonetheless died within 8 months of his cancer diagnosis. Cancer also killed Bruce’s grandmother, mother, and sister-in-law.

"I write of my family history not because it is unique, but because it is not. This is our shared destiny. For men, there is roughly an on-in two chance of a cancer diagnosis and a one-in-three chance for women"

As Katie Couric said “Why not me” when she was faced with her own cancer diagnosis after losing her husband to cancer years earlier.

Early Detection does not require the reader to have an advanced life science degree to follow the argument for early detection. The narrative is direct and focused. Chapter 7. Death By Zip Code, points out that breast cancer mortality for Black women in Washington DC’s Seventh and Eight Wards is four times the rate for the overall city. Washington DC is not a statistical anomaly, but one data point that reflects heightened mortality in underserved populations.

Linda Goler Blount, President of the Black Women’s Health Imperative notes that the shortcomings of the current screening guideline ignore the fact that “Black women are statistically diagnosed younger and with more aggressive cancers. Our health guidelines must reflect the realities of all women, especially those at heightened risk”

Early Detection’s concluding sentences tell us the goal is within reach:

“Addressing disparities and guaranteeing access to screening can significantly enhance the effectiveness of early-detection protocols, ensuring that all people, no matter their background, benefit from these advances. A comprehensive approach that prioritize patient needs, enhances medical literacy, funds cutting edge research and encourages strategic collaborations will produce the radically lower mortality rates that have so far in the war on cancer, eluded us”

Cancer touches all of us - buy the book on Amazon and share your story.

Why I wrote this review:

I am a biotech entrepreneur developing cancer diagnostics by analyzing RNA thus the following is my own 5 cents and not part of the book.

Our current healthcare systems under-valuate and under-pay for diagnostics and overpay for drugs. We are at a pivotal moment where the way we detect cancer and treat patients must change because the current paradigm is failing and driving up costs without producing better survival data. The latter is very well documented in the book.

Such a change will require a concerted effort/collaboration between all stakeholders from government (funding), payors (cover the cost of testing), regulators (FDA), and the biotech industry as well as investors.

We need diagnostics that:

1) Risk stratify patients for screening to reduce the cost of general screening and the negative impact of false positives which is not just an issue for the new test but also for the older ones eg PSA and Mamograms also produce false positives. In our current system, the only classifier is age. That misses younger people where cancer rates are increasing and it causes invasive biopsies and procedures. Those tests exist to a certain degree and they are underused e.g. a mutation in the gene called BRCA dramatically increases the lifetime risk of breast and ovarian cancer. Having a BRCA mutation means the person has a likelihood of?45% to 85%?of developing breast cancer in their lifetime, along with a 10% to 46% risk of ovarian cancer. The probability of breast cancer among the general population is about 12%. Ovarian cancer is rarer, affecting less than 1% of the general U.S. population. A family history of cancer is not a sufficient risk factor as 50% of people with a faulty BRCA gene don't have a family history of cancer. Lifestyle accounts for more than 70% of all cancers: smoking, drinking alcohol, obesity, and a sedative lifestyle are all things that are easy to determine in a general physician’s office. AI is going to help solve this as demonstrated by researchers from Denmark and Stamford in collaboration. They showed that they could identify people with risk of developing pancreatic cancer 12 month prior to diagnosis based on the existing data in the Electronic Medical Records.

2) Early detection will dramatically decrease costs and increase survival. The new pan-cancer tests are all using DNA sequencing and they can detect cancer early in some high mutation frequency tumors such as lung and skin, basically organs that are exposed to the environment. Internal organs such as breast, ovarian, and prostate are low mutation frequency tumors and can not be detected early by DNA sequencing alone. Therefore we need better screening tests for those cancers. We also need screening tests that can be performed in low-resource settings. Mamograms and X-rays-based lung cancer screenings require scheduling and traveling for individuals who don’t have time and often have no healthcare insurance. We need to solve this by removing friction for everyone to access screening.

3) Treatment navigation. Most of the 300 drugs that the FDA currently has approved in cancer are approved without any biomarker guidance. They are approved based on lengthy and expensive studies that enroll all patients and treat them all the same. That produces bismal response rate of 20-50%. It’s rare to see response rates above 50% unless the patient group has been selected using complex biomarker algorithms that are not simple single biomarker assays. Those cases are examples that proves it is possible with today’s technologies to develop tests that identify a much narrowly defined responder group which will drive up response rates up and reduce cost of care as well as all the collateral damage that comes with any cancer treatment. There are no other product on the planet that can be priced at $500M and only work 50% of the time - example CAR-T treatment which is curable but only for half of the patients’ after 5 years. This needs to change. The way we develop and approve drugs and the way we treat patients. DNA sequence-based tests are available for patients who do not respond or recur. Again they are underutilized, often the patients themselves have to ask for the tests and they work best in high mutation frequency tumors. We need to test before we treat and with tests that a) predict response to current static standard of care treatment to avoid cost and suffering from over-treatment to the current generation of drugs and b) Follow response during treatment with tests that can measure response and relapse between the scans which typically happens every 3-6 month.

Why I started Genomic Expression

I started Genomic Expression with my brother after our parents were diagnosed with cancer. We are both scientists and knew that if they did standard of care, there was zero chance of survival. I call that evidence-based death. My mother’s cancer was detected early and she decided to forgo chemo which at the time was the only available option. We supported her, there was no difference in survival rates. She had 5 years with a high quality of life before it metastasized to her bones. She then enrolled in a clinical study which wasn’t effective. Today she would have had access to tests to identify a clinical study for which there was a better match between her tumor drivers and the drug in development in addition to tests to monitor more closely for recurrence.

My father’s cancer was detected late. He wasn’t treated at all. We knew we only had him for a limited time and we made the best of that time. I still miss him every day.

This experience and several others - family members and friends have propelled us to relentlessly pursue the development of better diagnostics in all the categories above focusing on RNA which is a more powerful biomarker type, especially in low mutation frequency tumors such as breast, ovarian, and prostate and a lot of rare cancers.

My parents developed cancer due to their lifestyle. Western lifestyle need to change to reduce cost of healthcare going through the roof. Today 80% of adults in the USA have a chronic condition and 60% and 40% have two or more. Changing lifestyle is much harder once life is a routine. Therefore this change needs to happen early in life. My suggestion is that we need to teach healthy lifestyles in schools. Great sports are offered in American schools, but no cooking and healthy eating skills. That is such a simple change.

I have done everything in my power to teach my kids healthy lifestyle and eating habits. They are now grown-ups. They both exercise daily, eat healthy and they are both excellent cooks. Because I traveled a lot when they were young, it was frequently my American husband’s duty to cook and feed them. I always called home and asked what they had for dinner and his answer one day was burgers. Well what kind of veggies did they have, I asked and his answer was ketchup.

Awareness of what constitutes a healthy lifestyle is lacking in the general population. Our environment is filled with toxins: forever chemicals, microplastics, food, and cosmetic ingredients that cause cancer and other diseases.

The EPA and the FDA need to step up and regulate the toxins out of the environment and what we eat. As an educated consumer, I am able to read the labels but then I am not the average consumer. Some of the ingredients in ice-cream and skin care products e.g. sunscreen have been banned in Europe for decades, .

More about Early Detection

Bruce Ratner teamed up with Adam Bonislawski, an editor at GenomeWeb. I had the pleasure of meeting Bruce Ratner in New York at a pre-launch of his book at Cornell where he presented for a selected crowd of biotech executives and clinicians. I later attended the official launch of the book in New York on May 6, 2024 where I was given a signed copy of the book. In the following, I review the book which I recommend to anybody that cares about moving the needle to improve the survival of cancer patients.

The book is a testament to the long and thorny process of developing and implementing cancer screening tests e.g. lung cancer low-dose CT scanning for high-risk patients is only used in 5% of the target population. In contrast, breast mammograms, pap smears, and PSA testing are widely used however with significantly lower uptake in low-income settings.

The story of the pap smear is astonishing and started in 1928. It took 10 years to develop, another 10 years to get accepted by the medical community, and 20 years to get fully implemented. That simple test has practically eradicated death from cervical cancer today long before the approval of a vaccine that prevents HPV cancers.

Cancer is asymptomatic in the early stages, therefore it is impossible to detect it early unless we screen for it. Today screening tests have been developed for lung, breast, colon, and cervical cancer representing 50% of all cancer deaths. None of these screening tests are perfect - they miss some cases e.g Mamograms miss 20% and PSA causes overtreatment of slow-growing prostate cancers due to false positives. There is simply an inverse relationship between sensitivity and specificity.

Rare cancers represent 25% of all cancer cases and deaths and there are no screening tests for those. There are several pan-cancer screening tests in development from Grail and Thrive/Exact Sciences and others.

Grail published data from multiple studies that found 1 cancer in 100 people but they also found 1 that is not a real positive which is called a false positive. False positive is an issue due to the increase in cost of care for additional scans and in some cases invasive procedures such as biopsies that put these patients at risk.

(Pan cancer screening may play a role in a smaller subset of high-risk individuals that have eg BRCA mutations which increase lifetime risk of breast and ovarian cancer - as well as other cancers - my opinion).

At the book launch, Bruce Ratner stated that if we take out the reduction of lung cancer resulting from the reduction of smoking we have not dramatically moved the needle in terms of better survival rates - even with some of the most advanced therapies developed in recent years. In other words, the massive investment in developing and treatment with new drugs has not paid off yet.

The National Cancer Institute (NCI) only invests $600M/year in the development of prevention solutions whereas their total budget is $7.3B. Keytruda which only works in some late-stage cancer with average response rates of 20% provides Merck revenue of $30B/year.

The book is a must-read for everybody who cares about cancer. Since 1 out of 2 people die from cancer today we are all touched by this disease.

It is a call to action to everybody from governments to regulators and hospitals to do better and more when it comes to early detection of cancer. The book produces a strong case that it’s possible and will have a positive return on investment as well as improve survival rates for patients in a much shorter timeframe that the +10 years it takes to develop better drugs.

References

1 CDC, Persistent Underutilization of?BRCA?Testing for Breast and Ovarian Cancer in the United States: Implications for Health Disparities, https://blogs.cdc.gov/genomics/2023/07/25/persistent-underutilization/#

2? Susan Komen “Breast Cancer Risk Factors:?BRCA1?and?BRCA2?Inherited Gene Mutations in Women” https://www.komen.org/breast-cancer/risk-factor/gene-mutations-genetic-testing/brca-genes/

3 Weitzel ?JN, Lagos ?VI, Cullinane ?CA, ?et al. ?Limited family structure and?BRCA?gene mutation status in single cases of breast cancer.??JAMA. 2007;297(23):2587-2595

4 Most cancer cases 'caused by lifestyle, environment - not bad luck, Medical News Today https://www.medicalnewstoday.com/articles/304230#

5 Placido, D., Yuan, B., Hjaltelin, J.X.?et al.?A deep learning algorithm to predict risk of pancreatic cancer from disease trajectories.?Nat Med?29, 1113–1122 (2023). https://doi.org/10.1038/s41591-023-02332-5

6 Rectal Cancer Disappears After Experimental Use of Immunotherapy, https://www.mskcc.org/news/rectal-cancer-disappears-after-experimental-use-immunotherapy?

7 Kathryn M. Cappell et al.,?Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy.?JCO?38,?3805-3815(2020). DOI:10.1200/JCO.20.01467

8 Xu H, Li N, Wang G, Cao Y. Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas. Front Immunol. 2023 Mar 27;14:1110028. doi: 10.3389/fimmu.2023.1110028. PMID: 37051246; PMCID: PMC10083339.

9 CDC, Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area https://www.cdc.gov/pcd/issues/2024/23_0267.htm

10 Common US foods that are banned in other countries, https://stacker.com/food-drink/common-us-foods-are-banned-other-countries?

11 9 Beauty Ingredients That Are Banned In Europe (But Legal in the U.S.)? https://www.byrdie.com/banned-ingredients-europe