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33 Years in the Making

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Today (July 28, 2026) marks the first scientific article (includes data analysis) that pairs breast density with a blood test for breast cancer. To be clear, I’m not talking about the circulating tumor DNA blood test (ctDNA), advertised for 50+ types of cancer, but generating unacceptable results for breast cancer. No, I’m talking about a blood test based on 15 or so RNA products from immune-type cells that “turn on” whenever cancer is present somewhere in the body (in this case, with specific patterns for breast cancer).

This blood test is the product of original research emanating from Syantra, Inc (Calgary, Alberta, Canada), and I’m pleased to be part of the team. Today’s report is focused on cost-effectiveness, and the next project will focus more on performance characteristics of the blood test. This current paper is a tough read, but even with skimming you might be able to see why it took our Syantra team (plus experts in health economics) 2 years to analyze results, write the paper, and then get it published. I have previously written articles that link breast density to blood testing, but these have been editorializing with “thought experiments,” rather than actual data. To my knowledge, this is the first time breast density and blood testing have been merged with real data.

Here’s a link to today’s article: 10.1016/j.clbc.2026.07.029

Or, if you just want the title and authors:

ORIGINAL ARTICLE, in Press July 25, 2026, CLINICAL BREAST CANCER

Cost-effectiveness of biennial breast screening in women with dense breasts: exploratory analysis of pathways incorporating an emerging blood RNA test.

Jacie T. Cooper ∙ Alan Hollingsworth ∙ Randy D. Moore ∙ … ∙ John Schneider ∙
Kristina D. Rinker ∙ Eldon Spackman et al

My interest in this topic is documented heavily, both in formal and informal settings….just check out my recent posts on this web site. I make the claim, true or not, that I was the first clinician in the U.S. to promote blood testing as a potentially better way to select patients for MRI screening in addition to mammography. (Note that there were basic scientists at work on this issue, but no clinicians to my knowledge).

Here is the sequence, so if anyone reading this can come close to 1993 in establishing this particular agenda, please contact me, and I’ll quite making the claim. 8 YEARS BEFORE THE FIRST NCI GRANT was issued to develop a blood test for early breast cancer, I started drawing up protocols for a blood test to detect early breast cancer as the BEST WAY to select patients for MRI screening. Such a study is remarkably simple in its design: If screening mammograms are negative, then blood test positive, move on to additional imaging — bilateral breast ultrasound, or better yet, breast MRI. It must have been its simplicity that made it hard to understand because the feedback I received for decades was, “Why? We already have mammography. And it’s 90% accurate.”

And if 90% accuracy were true, we wouldn’t need anything else. So, the first step in trying to convince clinicians of the radical need for improvement was presenting the actual data for mammography, something that could NOT be done at first when mammograms were the only imaging modality (How do you make a comparison if there is only one option?) But once US and MRI hit the scene…wow….turns out we had been missing many more breast cancers than formerly believed.

So how did I get in the game so early?…through a bizarre sequence of events that began in 1993. I attended one of the early breast cancer conferences in Dallas where Dr. Steve Harms (father of breast MRI) was showing his results, using 2 projectors for his 35mm slides even though clinical introduction of MRI was still 10 years away. But what he showed, case after case, was: “Here’s the negative mammogram on the left, then on the right, you see the obvious cancer with MRI.”

I left that conference troubled that the technology was available, but only at research sites where the pre-clinical testing was underway (plus a second form of MRI being tested in Europe). I knew this was going to revolutionize breast imaging, but I also knew that the extraordinary expense, false positives, etc., was going to create a significant downside for MRI. And, it was totally impractical to screen the entire population of women with breast MRI.

Only a few DAYS later, I walked into my Friday morning research conference where I had organized the PhDs on campus at the University of Oklahoma who were interested in doing research on early breast cancer. We met each Friday for many years, but at first, the meeting was to share and cross-educate among the different disciplines (with my interest being early breast cancer). Later, the actual research began to flow. And once a year, I invited myself to present our goals at another meeting — the weekly noon presentation for the entire staff of the Oklahoma Medical Research Foundation (OMRF), my intent being to recruit more members to our Friday morning group. In the end, our study group was about 15 strong. But on this occasion, days after Dallas, one of our senior members, Dr. Paul MdKay, walked in waving a journal article, saying, “Hey, is there a possible use for a blood test to detect early breast cancer?”

And there it was. It would be enough work to last the rest of my career. Through Dr. McKay prompting OMRF to help fund a visit to OKC by the blood test scientist, and an equally dedicated army of OKC women who wanted to see top-notch breast cancer research in Oklahoma, the two groups brought the author of the paper, Dr. Chaya Moroz, to OKC from Israel. I served as her host for several days, as we discussed implementation of her blood test for breast cancer into clinical trials. Negative mammos, positive blood test, then perform MRI. But because there was no MRI available to us yet, we focused on background preparations, clinical trial designs, funding, “thought experiments,” and the possible use of ultrasound. The collaboration with Dr. Moroz did not pan out, but I had written volumes, so to speak, on the implementation of blood testing and MRI. (We are still in the mid-1990s here.)

If I ever get around to writing the full story, I’ll expand. but here it is in brief — OMRF was not the first visit to the U.S. to promote her blood test for breast cancer. Dr. Moroz was already connected to the largest Intellectual Property Law Firm in the U.S. — Penny and Edmonds (NYC — where 100-plus attorneys held advanced degrees in science and engineering). And the point person with whom I would be dealing, in addition to Dr. Moroz, was Leslie Misrock, the top name on the list of partners found on company stationery.

When I flew to Manhattan for my first meeting at the firm, I was swept away by limo (not all that common back then) and escorted to the top floor of a skyscraper (Penny & Edmonds resided on multiple floors). I was met by Leslie Misrock who introduced me to about 15 attorneys sitting around a table. There was only one other doctor present — Chairman of the American College of Radiology Task Force on Breast Cancer — Gerald Dodd, MD. (Also, he was the first Chairman of Diagnostic Radiology at MD Anderson.) And while Dr. Dodd was not directly responsible for the introduction of mammography in the U.S., he strongly supported its use and aided his radiologist-colleague at MD Anderson who helped make it all happen — Robert Egan, MD.

I was still learning breast cancer basics at the time (self-teaching biology, screening epidemiology, pathology, breast imaging, etc.), but I was surprised when it came time to explain how a blood test would work in the current algorithms. I seemed to be the only one in the room who had given it thought, including Dr. Dodd. (Notably, my opinion is unchanged 33 years later.) I made several more trips to NYC and collected enough correspondence from various venture capital groups to fill my files. Yet, in the end, after 5 years, no clinical trials were accomplished and not a single sample of blood was drawn.

Skip ahead to that first patient in OKC who had her blood drawn at the same time she had her screening MRI. That was in 2003, and it would continue through nearly 2,500 volunteers over the course of the next 17 years, until the sponsoring hospital egregiously shut down my entire research foundation, and gave me and my staff our walking papers. During that 17 years, however, we shipped over 10,000 specimens to 13 different research groups, including 3 formal clinical trials. Syantra, Inc. was the 13th, and my association with them was serendipitous.

I had been working with my 12th company when the results of their formal clinical trial proved disappointing, not accurate enough to proceed to commercialization. Starting to wear down from the hefty time commitment (it’s a huge burden on the staff, too), I figured it was time to give it up. The years were passing quickly, and it was clear any new association would take several years to see whether or not their blood test worked. It was probably time to close it down.

When I got back to my office, there was a message for me to call a biotech company in Canada — Syantra, Inc. — that was working on a blood test for early detection of breast cancer. They told me over the phone that when they Googled “early breast cancer detection” that my name kept popping up no matter what key words were used. And thus began my work with Company #13, only DAYS after the failure of #12. That was in late 2016, so it’s been roughly 10 years working with Syantra, the first 4 that included shipping samples from the women at OKC, where we possibly stood to be one of the Principal Investigators of the definitive trial. But after the wrecking ball hit from our sponsoring hospital, we could no longer participate by sending samples and data. As it turned out, however, I had accumulated decades of experience from devoting so much of my time to this goal. It ended up that Syantra leadership asked me to stay on as a clinical consultant, even though I no longer had access to specimens.

So here we are. 2026. The door has been opened, and someday soon we will see a place for blood test early detection in breast cancer. Imagine the following clinical trial design….so simple: A cohort of women with dense breasts (about half the female population) and negative mammograms are enrolled. Even though they are “normal” we know from the MRI studies that there will be about 20 women out of 1,000 who will have cancer detected on the first MRI. That’s 20 cancers missed by mammography! Today, one would have to perform MRI on all 1,000 to find the 20 with cancer. But if a blood test is used, then MRI is performed only when the blood test is positive. The number of negative MRIs and false positive MRIs is drastically reduced, while most of the missed breast cancers are now identified.

For 33 years, it’s been on hold, but now, the change will gradually begin. Instead of using risk factors to select patients for MRI (when most women who get breast cancer don’t have major risks) or instead of overutilization of MRI for women with dense breasts, we have an economically sound way to approach those cancers currently being missed on mamography.

END

Thanks are due Rebecca S. Clinton, MD who headed up the breast MRI program at our hospital and took on the challening role of becoming an expert at breast MRI.

Also, thanks to Dr. Steven Harms, “father of breast MRI,” who helped us in many ways by giving our clinic early access to new technologies that were added to the Aurora Breast MRI system, plus paving our way onto speakers’ panels, group projects and serving as collaborators for many projects over the years.

Syantra, Inc. works to improve early cancer detection, starting with breast cancer as the lead product. Under the direction of Kristina Rinker, PhD, Bob Shepherd, PhD, Randy Moore, MD, and a host of others, it has been a pleasure for me to serve as a link between basic science and clinical outcomes. Visit Syantra at: http://www.syantra.com

25 Years Earlier

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Have you noticed on TV the new way of handling flashbacks? No subtleties. No confusion. Rather, an announcement — 3 days earlier, 7 months earlier, 10 years earlier, 5 seconds earlier, and so on. Although too many flashbacks can be annoying, especially if it’s a flashback occurring within a flashback, I still think the definitive times plastered on the screen are helpful.

Recently, I had a “double flashback,” that is, 2 simultaneous events, unrelated except by the clock, each with its flashback best described as “25 Years Earlier.” Let me explain. During the first week of April 2026, I had two 25-year anniversaries.

The first flashback related to medical history made in April 2001 with the drawing of a blood sample on a patient at high-risk for breast cancer who was undergoing a breast MRI for screening purposes. Breast MRI was new at the time, used primarily for diagnostic problems, although asymptomatic screening was being tested (no official guidelines until 2007). But what we did at Breast MRI of Oklahoma, LLC, was unique. Under Institutional Review Board approval, my team started drawing blood on patients undergoing MRI, with a focus on the asymptomatic screener. I felt “risk assessment” to determine who gets an MRI was only half the solution to more efficient use of the expensive test. It took two decades before the radiologic community realized that breast density would be just as good a predictor of MRI benefit as risk levels. Indeed, we drew up a screening score based on both risk level and breast density wherein we found double the number of cancers than had we simply followed the new American Cancer Society guidelines. And, we varied the screening interval from 1 to 3 years, a move that would be validated in a large study in The Netherlands 10 years after our implementation. And, yes, we published this, yet our well-conceived point system fell by the wayside. Bottom line: even using risk and density together end up prompting many extra MRIs and false-positive biopsies.

So…from the beginning (before MRI was available), I promoted the idea of a blood test for screeners that would take us beyond risk, beyond density, and toward performing MRIs only if the mammograms were negative but blood test positive. I got the jump on this idea in 1993 when we invited Dr. Chaya Moroz to OKC to present her data supporting a screening blood test for breast cancer. With mammograms as the only available screening instrument at the time, the need for a blood test was not recognized as there was nothing else that could be done (ultrasound screening was still a few years away). But I recognized the potential immediately, having recently seen Dr. Steven Harms’ presentation in Dallas about the startling findings of what is REALLY in the breast with MRI. The future “father of Breast MRI” made it clear a revolution was on the way, but it would encounter major obstacles due to cost and false-positives.

I saw the answer as being a blood test to accompany mammograms, and if the mammos were negative, but blood test positive, then perform MRI. That simple concept drives most everything I’ve done in my career. So, it was 1993 when I merged the concepts of a blood test and MRI, but actual research could not begin until we had MRI in place (2001). And as soon as our unit was installed, we began the blood drawing research project. I recall that first patient in 2001 (a personal friend) who underwent that first screening MRI and having her blood drawn on the same visit. My reasoning was simple — how can you develop a blood test that is sensitive enough to detect early breast cancer if your gold standard reference of “normal” is mammography? We are trying to IMPROVE mammography, so the blood samples ought to be based on MRI results, that is, what’s REALLY in the breast.

By gradually accumulating quiality samples and creating a comprehensive database, we ended up as the largest collection of MRI-based samples in the world. When word spread of my unique biobank in OKC, we had researchers from all over the US and internationally accessing our supply. Over 2,000 women participated, and with multiple samples generated out of single blood tubes, we were able to distribute well over 10,000 samples to researchers around the world. (Most of the time, the researchers would be attending the mammoth symposium in San Antonio each year, then they would travel to OKC on the way home to validate what we had in cold storage.) The largest shipment was over 3,000 samples to the University of Nottingham where the principal investigator there would ask me every year at the San Antonio meeting: “Have they made a movie of Flatbellies yet?”

When the dust settled, my team had shipped samples to 13 research entities, and had collaborated with shared knowledge in most of these, culminating in formal clinical trials in 3 of them. Relationships were short-lived when the trials failed, but the company I work with now (Syantra, Inc) uses a novel approach, focused on the immune cells of the body rather than the cancer cells. Those companies now claiming success with circulating tumor DNA are not transparent when it comes to early breast cancer where it just doesn’t seem to work. My last several posts have elaborated on why this is the case, but the main point is that the performance characteristics are represented in such a tricky fashion, few clinicians can sort it out. And, heaven help the lay person.

The most popular of the multi-cancer blood tests (up to 100 cancer types at once!) was recently put to the test in a cohort where all 14 early breast cancers found on mammography were missed by the blood test. That’s a zero detection rate that you won’t find in the company brochures. (Some cancer types, did in fact, have helpful results). Another company based on the same science, includes breast cancer in their mutlti-gene profile, but there is a small asterisk — and if you look at the bottom of the page, the asterisk is explained: “Not indicated to screen for breast or prostate cancer.” Wow! The nerve!

Originally, my role for Syantra was generating those blood samples tied to MRI results in patients being screened, that is, doing what I’d done for many years. This meant clinical input as well. As plans were made for extending the clinical trial, the suggestion on the table was that I would serve as principal investigator for the United States (it’s an international trial), but it was not to be. My sponsoring hospital administration was always critical of our work (in spite of $250K generated from the samples), and when COVID hit, they took the opportunity to close down all the non-critical programs, which includes medical research.

My risk assessment/genetics program that included a longitudinal high-risk clinic, was streamlined more than any similar center in the country as far as I knew, including academia where “streamline” rarely exists. I worked with a board-certified medical geneticist, boarded genetic counselor, nurse practitioner/navigator, administrative assistant, and a research breast imaging tech with a lifetime of experience. The entire group was given their tickets home, not allowed to contact our patients to explain what was happening (leaving hundreds of high-risk women out in the cold). And when COVID was essentially over, the phone didn’t ring to call us back, and my far-reaching program, what was once called the “star in the crown” at my hospital, was tossed away — all gone, with hundreds of blood samples left in the freezer.

My consulting work with Syantra, Inc. is, by far, the longest association I’ve had, among the 13 research entities I’ve worked with in the past. A large clinical trial supports the use of the blood test, including my long-term indication for women with dense breasts and negative mammograms. It’s been 25 years since that first patient held out her arm for venipuncture, writing herself into the history books, sort of a silent partner in the war against breast cancer.

Switching Gears – what about the OTHER 25-year flashback? The very same week that Patient #1 donated her blood in 2001, my first novel — Flatbellies — was released by a small sports publisher, with a rapid rise to the top on Amazon Sports, generating such widespread enthusiasm that the novel was picked up by WW Norton & Co (New York/London), and it ended up with a review in USA Today while also named as a Barnes & Noble Hot Book For the Summer. So, why this new 25th anniversay version of Flatbellies?

One of the many surprises that both publisher and author had was the wide demographic net that was cast by the book. Golfer or not. Male or Female. Young or old. It transcended all groupings, and was at one point, placed next to the cash register of every Barnes & Noble in the world. The book was optioned for film on several occasions, each time with total assurance that the story would make it to the silver screen. But the reality was something different. Unexpected issues arose at every turn, and all options were finally allowed to lapse about 10 years ago.

Book clubs, social clubs, student groups, even “industry” groups, all seemed to have the same questions about Flatbellies. And people wanted answers, as if this were a true story. Were these real characters? Did the grain elevator scene really happen? How about the fireworks scene? Is Neander T a real person? And so forth. Another development was the original hardcover publisher going out of business years later, as this put an end to any royalties. But the looming issue was always TV/film, and two screenwriters worked without pay for these same years, trying to make the film happen. But the 2-hour screenplay wasn’t enough to capture the book, as so many things had to be left out. The same two individuals have started working now on an 8-episode teleplay that we hope will help resurrect the plans for a movie.

With all things considered, I decided that a 25th anniversary version should be published, this time anticipating the questions that so many readers have in a 30-page addendum, “The Story of Flatbellies.” The novel remains the same, but inside scoops, backstory, and photographs are added in this high-quality collector’s volume, titled, “the 25th Anniversary Edition of Flatbellies.“

So, if you look at the two unrelated pathways above, I’m standing now near the end of both careers, but still working along both pathways as before, as long as health holds out. And if someone were to ask me, “What did you accomplish during your career?” I’d have to answer: “Which one?” because 25 Years Earlier, I didn’t take the path less traveled….I took both paths.

Blood Tests for Cancer — it’s harder than you think!

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In my July 2022 blogatorial, I covered the GRAIL blood test (for 50 types of cancer) that had been promoted locally by Mercy Hospital OKC as well as the entire Mercy system. The implication was strong — “We now offer….” which might have meant they had arranged a discount with bulk orders, but it was NOT a statement of exclusivity. Any physician could order the test. In fact, within a 20-mile radius of Mercy Hospital, there were 22 providers signed up to be GRAIL users.

The GRAIL test is a juggernaut backed by Bill Gates, Jeff Bezos, etc., to the tune of billions of dollars (read that July 2022 piece for details). Problem is, it is very difficult to prove a test like this when there are 5 performance characteristics to be applied to 50 cancers, giving 250 data points to evaluate. But when the Big Announcement came, the numbers floating about were not good — that is, the most important characteristic of Sensitivity (percentage of cancers detected) was mediocre at best, while for some cancers (like breast) the results were terrible (all while heavy promotion was underway).

What the circulating tumorDNA (ctDNA) could do quite well was Specificity (fewer false positives) but that’s not what saves lives. Specificity allows for test feasibility, and their number was near 100% for most of the cancer types. Great! Fewer false-positives, more efficient, patient-friendly. But the raw data presented way back in 2022 revealed a twisting of reality that made the test look better than it really was. First of all, much of the reporting was done with advanced stage disease (that’s NOT screening). Take away the Stage III and IV cases, and the Sensitivity for most cancer types plummets. So, rather than admit the poor Sensitivity, the marketing department loaded up using a performance characteristic of “Accuracy” which, in testing parlance does NOT mean Accuracy like you’d think. It’s a formula that blends Sensitivity and Specificity. So, if you have an excellent Specificity of 100% and a bad Sensitivity of 50%, you can blend the two parameters and come up with 75% Accuracy, which is OK, but not great. Much of the marketing material about GRAIL does just that, i.e., rely on Accuracy. But when it comes to measuring saved lives, Sensitivity dominates as the key parameter. If a cohort of patient has 100 cancers, and your test under study can detect 90 of them, then great! 90% Sensitivity! (though you still have to prove fewer breast cancer deaths). Bottom line: it was suspicious in 2022 that GRAIL was not getting spectacular results, and the question was “Does it have any role in patient care today? Specifically, will it save lives, or at least lower the number of advanced cancers?”

Sure enough, when put to the test by the NHS of the United Kingdom, the GRAIL test did not save lives overall, at least when judged by “fewer advanced cases of cancer.” This is a surrogate for saved lives. Now, after the company stock crashed, they went to work and they’ve identified trends of efficacy, noting a core group of 12 cancer types where there might be benefit (the official results, though, are a failure to meet the original primary endpoints). So, by focusing on great Specificity and hiding lackluster Sensitivity, the company shot itself in the foot (though I suspect the test will get better and better over time….especially in those cancers where there are no other proven screening methods).

But what about breast cancer? For some reason, circulating tDNA does not allow reliable early detection of breast cancer. This should be headline news in the breast cancer community, but it’s hardly mentioned. Some companies using this ctDNA approach have dropped breast cancer from their lists of detectable cancers. Oddly enough, Cologuard lists breast cancer in their overview of cancers detected, but with a subtle asterisk denoting “not indicated.” Go figure. Breast cancer and prostate cancer are the only cancer types that are market by the asterisk.

In the PATHFINDER study (35,878 women), one has to go to the online supplements and use a magnifying lens to find out what happened in the 14 cases of breast cancer that were all discovered by mammography. Using GRAIL, NOT A SINGLE BREAST CANCER WAS IDENTIFIED by the blood test. All 14 were found by mammography. Incidentally, please note that the blood test research where I’ve been involved since 1993 is aimed at finding breast cancer EARLIER than mammography, detectable by Ultrasound or more certainly, by MRI. The very purpose of blood test research, in my view, has always been to use blood test results in tandem with mammography, and if the mammograms are negative (esp. if dense tissue), then a positive blood test should prompt Ultrasound at a minimum, and preferably MRI. GRAIL (and other companies using the same ctDNA) doesn’t have a chance in breast cancer — it can’t even find the cancers found on mammography, while our goal is to improve detection beyond mammography.

I’ve spent a lot of time on this topic lately (July 2022 and January 2026), as clinicians are perplexed about this form of testing, and many are confused by the 5 performance characteristics I discussed in detail in the January 2026 blog. Bottom line — by focusing on a single cancer type (like PSA for prostate cancer), we generate tons of data that has to be analyzed closely. Over the years, I’ve submitted 10,000 samples to researchers who are focused on Sensitivity using completely different approaches than GRAIL et al. The company I’ve worked with since 2017 as a clinical consultant is Syantra, Inc. (Calgary, Alberta) where scientists are looking at changes in biomarkers that are NOT directly from cancer cells, but are the changes that occur in immune cells…in response to the breast cancer cells. It’s a different approach, but getting far better Sensitivity than GRAIL. If you are interested, here’s a PR piece that was written recently about the company:

Syantra’s breast cancer blood test isn’t looking for cancer at all

The Toughest Writing Assignment I Ever Had

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Dr. Steven Narod holds many academic titles that demonstrate his consuming interest in breast cancer prevention and screening. Thus, academic positions such as Professor in the Dalla Lana School of Public Health and the Department of Medicine at the University of Toronto indicate interest in both the epidemiology of breast cancer, as well as treatment strategies.

Importantly, he is a detective when it comes to Big Data, and has pulled out some remarkable findings, culminating in “landmark” publications. He has written more than 550 peer-reviewed articles, while the importance of those papers is reflected by an “h-index” of 85, making him the most widely cited breast cancer researcher in the world.

The h-index is generated by computer searching of nearly all the major medical journals to see how often one is cited by others. Cranking out a large number of papers is relatively easy, but how important are those papers? The h-index reveals how often one’s peers quote the author’s published papers. (I devoted a chapter to the h-index in my book, “Best of the Breast Cancer Blogatorials.”)

10 years ago, Dr. Narod et al published shocking results for women with ductal carcinoma in situ (DCIS) that were so difficult to believe, many breast specialists simply chose to ignore the inexplicable findings. By analyzing a well-known database (SEER), he studied 108,196 women with DCIS, focusing on the 956 who later died of breast cancer. OK so far. But then, he found that 517 of the 956 were never diagnosed with invasive disease. They apparently went from DCIS to metastatic breast cancer in one jump. His conclusion was that the overarching biology of breast cancer is different than what we’ve been saying, and that (my words follow) counseling patients with phrases like, “DCIS is not really cancer” or “DCIS is 100% curable” or “DCIS is noninvasive cancer that is no threat to your health” is terribly misguided.

As harsh as those numbers appear at first glance, the study was addressing a very small portion of the total. Less than 1% of DCIS patients died, and it didn’t matter if patients had a mastectomy or breast conservation originally. The implications, though, were huge due to the fact it indicated DCIS could metastasize without evidence of invasion. That is, malignant cells usually trapped inside the duct could squeeze through the basement membrane and travel elsewhere.

An explanation for the bizarre findings prompted me to email Dr. Narod to let him know of our experience in patients with DCIS, studied with pre-op breast MRI under the direction of Dr. Rebecca S. Clinton. We had just published what was then the largest series of pre-op MRI in patients with DCIS. MRI revealed invasive cancers separate from the known DCIS site. The most dramatic finding was when those “unknown” invasive cancers occurred in the opposite breast from the known DCIS as it meant the invasive cancer would be left untreated (unless the patient underwent bilateral mastectomies). While “opposite side invasion” only happened 2% of the time, it still was/is concerning because it meant surgeons were, in effect, operating on the wrong side for DCIS every 50 patients. For a busy breast surgeon this “wrong side” surgery would occur every 2-3 months and could possibly impact survival. Thus, our answer to the Narod data was to perform pre-op MRI on all newly diagnosed patients with DCIS.

The email conversations with Dr. Narod continued (I never met him face-to-face). In our email chats, he plotted out why “elsewhere invasion seen on MRI” was not enough to explain his findings. We went back and forth for a while, then the conversations ended. Even if the conclusion were valid, however, no one was going to deliver chemotherapy to patients with DCIS when the mortality chances were less than 1%. The best we can do is make sure there is no “elsewhere” invasion using MRI, at least in my opinion.

A few years later, I received an email from Marc Lippman, MD, one of the pre-eminent breast medical oncologists in the world, and at that time, he was Editor-in-Chief of the prestigious journal, “Breast Cancer Research and Treatment. I did not know Dr. Lippman, and I had to consider the possibility that I was reading spam.

Dr. Lippman informed me that Dr. Narod had taken his findings from 2 years earlier and had formulated a new theory of breast cancer biology. Overarching biology of breast cancer is of critical importance in screening research as tumors must be vulnerable to early detection. At the time of screening, however, we don’t have any information about the tumors to be found, so we base recommendations on breast cancer as an “overarching” whole (this is the mirror image to “precision or personalized medicine” where a great deal of information is generated AFTER the diagnosis).

Dr. Lippman informed me that Dr. Narod had requested that I write the Commentary to Narod’s paper. In this article, he was proposing a new way of looking at the biology of breast cancer, called the “parallel model.” When it comes to invasive breast cancer, whether surgeons know it or not, a “lumpectomy” is based on Fisher Theory. But even Bernie Fisher admitted his work applied only to invasive breast cancer. “There is no paradigm for DCIS,” I heard him say once circa 1992. But now, Dr. Narod was attempting to correct that deficit with a “new biology” that included DCIS.

In our conversations two years earlier, I’m sure he picked up on the fact that I had studied every discipline as related to DCIS and was fluent in pathology, surgery, radiology, molecular biology, screening epidemiology, risk stratification, and genetic testing. And when a major article is about to be released, journal editors will often publish a “response” or “commentary” from someone in the same field.

And that’s where I came in — a writing assignment given to me by Marc Lippman, MD at the request of Steven Narod, MD. I was in the private sector at the time, my academic credentials long gone. Admittedly, however, my interest in writing (both medicine and novels) had paved the way for many opportunities, so my actual practice was decidedly academic.

Though only 4 pages long, I’ve never spent so much time and effort in a medical-related article. I drew upon electron microscopy studies that had been done 50 years ago yet subsequently forgotten. I drew from the published vagaries of pathologic sectioning of DCIS where inadequate sampling misses the invasive component. I pulled out everything I had read for the past 30 years. This was NOT done to negate the new theory proposed by Dr. Narod, rather, to offer other explanations.

This scrutinizing approach is in keeping with the research philosophy of Dr. Richard Feynman, a Nobel Laureate in Physics (but known more for his wit and wisdom), who said something like this many years ago: “When you’ve completed your experiment and you got the exact results you were expecting, then stop and try to think of every other possible explanation for your findings other than your own hypothesis.

So, my approach was amicable, yet decidedly slanted toward a multi-factorial origin for the findings. My commentary takes the form a published article in its own right (see attachment), complete with references, etc., and it “counts” as a published paper. Yet, everything in print is in response to Dr. Narod’s paper.

I submitted the article to Dr. Marc Lippman, having no idea what to expect. I had been writing commentaries and editorials my entire career, mostly on breast MRI for screening and pre-op staging, so I anticipated many corrections to be made, outlined in the response. Remarkably, Dr. Lippman’s response was so laudatory that I even showed it to my oft-skeptical wife since it would be hard for anyone to believe — “…wonderful job…excellent…in fact, beautiful….” then onward with praise for the multidisciplinary approach of merging so many disciplines into a single polemic. (Beautiful is not an adjective I’ve seen used in cancer literature.)

Enough bragging. Dr. Narod’s landmark article was the “cover story” for that issue of Breast Cancer Research and Treatment, with my paper following. I retired two years later and never heard another thing about the controversy.

Fast forward 7 years, and I’m now retired from patient care, though still collaborating on a blood test for screening (where DCIS results are closely monitored). I still attend the annual San Antonio conference where 12,000 researchers and oncologists meet every December. Since my collaborators are based at the University of Alberta, it’s a good place for us to meet face-to-face. (most of the attendees from 100 countries are doing the same thing)

This past year (December 2025), I was attending one of the small break-out groups (small is measured in the hundreds), that was addressing the “dormant cell theory” as if that were something new (Bernie Fisher demonstrated the phenomenon in rats in the 1950s, helping to solidify his now-famous theory of breast cancer biology).

As I was sitting there waiting for the presentation to begin, I saw a middle-aged man (nowadays I call this,”young”) walking briskly toward me, eyes fixed as if expecting recognition on my part. I had never seen the guy before in my life, but I could tell he was getting ready to engage me. I flipped through the memory banks but could not come up with anything. He looked a bit like Tracy Letts, Pulitzer Prize winner, playwright and actor from Oklahoma (and the son of Billie Letts).

As the man got closer, he barely smiled, but he stuck out his hand in preparation to shake. I stood up. He spoke first.

“Well…here’s someone I should know.”

I glanced at his name tag, but couldn’t read it. Now we were shaking hands.

“Steven Narod,” he announced.

I had to chuckle at the thought of our 10-year history without ever having met. After a bit of small talk, he said, “When I make my presentations, I include your comments and your position, but I also point out that while you are 10% correct, I am 90% correct.

The lights went out, the speaker began, and we took our seats. Dr. Narod left before the talk was over.

50+ Cancer Types from One Blood Sample (the Pathfinder Study)

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When I’m asked my opinion about tests like Galleri from the company Grail (a spin-off from Illumina), I look at my watch to determine if there’s enough time left in the day. These tests are generically referred to as MCED (multicancer early detection tests) or “liquid biopsy” or ctDNA (circulating tumor DNA). The science is sound. Understanding the test is another thing entirely.

On the surface, it looks great. A single blood sample can detect more than 50 types of cancer, hopefully at an early stage. Already, we’re in trouble. There’s a huge amount of data for each of the 50+ cancers. We are accustomed to using at least 7 “performance characteristics” as we discuss screening tests one cancer type at a time. But blood test performance is different for each type of cancer. Multiply 7 performance characteristics by 50 cancer types, and we have about 350 data points to start the review if we want to know how good the test is for each type of cancer. Calling it a “major challenge” doesn’t do it justice.

What do we know so far? At this point, a “large” prospective study, called PATHFINDER, enrolled a little over 6,500 patients, not nearly enough to get a handle on this new approach to screening. The REACH trial is underway, aiming for 50,000 patients, and a UK trial is aiming to enroll 100,000 patients. This should provide some clarity, but numerous controversies will be generated. Consider the patient with a cancer signal that indicates a positive test, but no cancer can be found after multiple radiologic procedures. That patient will be called a “false-positive.” But what if, 12 months later, that patient develops a cancer that fits the original blood test results. In reality, that patient is a “true positive,” we just didn’t have the means to confirm the diagnosis with the first blood sample. But where do you place that patient in your statistical analysis? She or he has should be registered as a “false negative” since the original results indicated “no further action needed.” (btw — this scenario is already occurring).

Consider the fact that mammographic screening is a single test, and the “performance characteristics” are still hotly debated. Now, we shoot for 50 cancer types, and the troubles have already come in the form of class action suits for — in brief summary — due to over-hype followed by a false-positive or false-negative.

The PATHFINDER STUDY was conducted at 7 major health care facilities using one of the MCED tests (Galleri) to screen prospectively for 50+ cancer types. The results? It would take a book filled with data to explain everything. In fact, the authors gave us Supplementary Data online (15 Tables and 5 Figures) because there wasn’t enough room in the main body of the article.

One thing we already know from past articles in the development of Galleri (and other similar tests) — it DOES NOT WORK WELL FOR BREAST CANCER. For some reason, breast cancer cells don’t shed detectable ctDNA as reliably as other types of cancer (more on this later). And, for full disclosure, I’ve been in the breast cancer blood test business for 30 years, so I’m looking at the ctDNA approach with a bias that indicates we should stick with one type of cancer unless future developments indicate otherwise.

Where the test has its most promising role is for those cancer types where screening is not routinely performed or recommended. Take pancreatic cancer, for instance. Finding pancreatic cancer earlier does not automatically save a life. The biology is aggressive and might not lend itself to early detection. Then again, it might prove to be the answer for pancreatic cancer as well as other cancer types not being screened. However, the data is being presented to clinicians in a confusing way that puts a spin on the test that is optimistic beyond reality. The marketing department is not fabricating the facts, rather they are simply molding the perspective (see Addendum at the END on “performance characteristics.”)

For instance, we are told that Specificity (one of the “performance characteristics”) is 99% for multiple types of cancer. That’s great, but what does that mean?….that the test will find 99% of cancers? No, not by a long shot. Specificity says, “Given no cancers in a population, what are the chances that the test will be positive (a.k.a. “false-positive”). Because only a small percentage of patients are carrying occult cancer, the large number of “negatives” in a study dilute the formula and make Specificity look really, really good at 99% (only 1% chance of a false-positive if you undergo the test). In the PATHFINDER study, there were over 6,500+ patients, and that large number is part of both the numerator and denominator of the Specificity formula, generating the tiny 1%.

But ask the question differently, and in a more clinically relevant fashion — “If I get a POSITIVE result on the Galleri test, what are the odds that I’ll actually have one of the 50 types of cancer?” This is a different performance characteristic called Positive Predictive Value (PPV), and it is this number that is critical for a good, informed consent when discussing the test with laymen and health care providers. Here, the large number of 6,500 patients is not part of the PPV formula, so one might get a PPV of 43%, leaving a 57% chance of the test being a false-positive. The false-positives are reasonable with Galleri, but their focus is on the 99% Specificity. Potential users must understand the 99% means that,prior to testing, there is only a 1% chance of a false-positive. Yet, given a positive test, there is a 43% chance of some type of cancer being present upon further investigation, usually radiologic studies, yet ending up with a 57% false-positive rate. At this point in performance, the overall false-positive rate is higher than the true positive rate.

Now, each cancer type has its own Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). (The NPV is hugely diluted by the 6,500 negatives, so it’s not very helpful here). Additional performance characteristics are mentioned below. Then, it gets more complicated as, depending on the cancer type, some cancers are not early at all. So, when divided into stages, one can get frustrated when told “we find 60% of a certain type of cancer,” only to learn that half of them are advanced stage where screening doesn’t help. Leaving the larger numbers for advanced stage in place, however, can lead to easier acceptance of the test.

Even when a test is finding early (smaller) cancers reliably, eventually it will be necessary to document a mortality reduction or one of the surrogates for mortality reduction (fewer interval cancers, stage shift, fewer advanced cancers). We might think we’ve solved the problem of aggressive cancers by finding them smaller, but they could prove to be just as deadly. That’s why a mortality reduction, or surrogate, must eventually be confirmed.

Hang on…here’s the punchline. I’ve not mentioned the most important performance characteristic of all — SENSITIVITY. This is the percentage of cancers that will be detected by a screening test. Stated alternatively, given a certain number of cancers in a cohort, it’s the percentage that will be found by the screening test. Sensitivity is how we generate our mortality reductions. This is where lives are saved, finding more cancers earlier. It is the first characteristic on everyone’s mind when a new screening test is introduced. Specificity is very important when it comes to the feasibility factors, but it doesn’t save lives. To save lives, one has to detect as many cancers as possible, as small as possible, and this is entirely through Sensitivity. The other way to state Sensitivity is through a “false-negative rate.” If mammography is detecting 70% of breast cancers, then its Sensitivity is 70% and its false-negative rate is 30% (false-negative = mammo negative, but cancer present).

For those of us working on a blood test that “specializes” in one cancer type — breast cancer — Sensitivity vastly exceeds what is being seen in the MCED tests. Scientists are approaching 80% to 90% Sensitivity with breast-only blood testing using different methodologies. And this is where it turns bizarre when it comes to breast cancer, which is only one test of 50+ in the Galleri test. In nearly all the MCED studies, the Sensitivity for breast cancer early detection is low. Instead of acknowledging an issue here, amazingly, SENSITIVITY is barely mentioned. I can calculate overall sensitivity for all cancer types from an algorithm in Figure S3 — 21%. FYI…21% is terrible (only finding 21% of cancers), and that’s all types of cancer, and all stages. Limited to smaller Stage I & 2, the number would be even lower. This explains why the company focus is on cancer types for which there is no routine screening.

When it comes to breast cancer and MCED testing, the shocking point is not simply that Sensitivity is left out of the Discussion, but that the breast cancer data is only published deep in the Supplementary materials. There, one is surprised to find14 breast cancers identified through routine screening (exam and mammography) and ZERO were identified with the MCED blood test. Repeat: 14 breast cancers were identified per the usual screening methodology, and not a single one of the 14 had a positive Galleri blood test. There were 5 breast cancer recurrences detected, but that’s not what a screening blood test is for. The medical oncologists might be able to use the information gleaned from recurrences, but I’m totally focused on asymptomatic screening. We’ve lost our way when marketing departments tell us that MCED testing has 99% Specificity (technically true), yet the practical ability of the test to find early, occult cancer was ZERO in the PATHFINDER STUDY.

I’ve barely scratched the surface here, but try to imagine explaining all of the above to a patient or clinician. I didn’t even get into the other performance characteristics (added as Addendum) — 1) Accuracy (a combo of specificity and sensitivity), 2) Cancer Detection Rate (CDRs), or 3) Number Needed to Screen to Save One Life (NNS). Multiply the 7 items by 50 to get 350 data points from which to draw an informed consent. If you’re trying to tackle undiagnosed cancer, the Galleri test (and other MCEDs) are going to help more in those cancers that are not routinely screened. As for breast cancer, it’s not going to help at all unless major improvements are made.

“One Ring to Rule Them All” is a famous phrase from JRR Tolkein and his fantasty world. But when it comes to breast cancer, that’s what we need — a single test that generates Sensitivity of 80-90%, with Specificity of 90%, and good results in the remaining performance characteristics.

So, here’s a breast cancer screening approach for the future:

3D mammography, and if 3D is negative, proceed to a blood test designed for breast cancer. If the blood test is positive, then proceed to contrast-enhance mammography, breast MRI, or molecular imaging. A positive blood test turns screening into a diagnostic work up. The most logical place to begin blood test screening is with women who have dense breast tissue since the miss rate is much higher for them. And, so far, the blood tests being developed are not affected by density levels.

When used primarily for women with dense tissue on negative mammography, then we are talking about a cohort of women in whom, by definition, have already demonstrated ZERO Sensitivity (mammos negative), yet we know that if we proceed with MRI, we will find 10 to 20 occult cancers in the general population. With this knowledge, one could move directly to MRI or the other contrast-enhanced technologies. But this is where the blood test comes in — sparing many from having an MRI et al while still finding most of the hidden cancers.

You can see now why I look at my watch whenever I’m asked what I think about MCED blood testing. The Powerpoint version lasts an hour.

END (almost)

A streamlined view of performance characteristics, as pertains to cancer screening:

The BUILDING BLOCKS for performance are true-positives (TP), false-positives (FP), true-negatives (TN), and false-negatives (FN). These 4 outcomes (expressed in numbers) are then inserted to 4 basic formulas that each have a specific message for the clinician. In lay terms for blood testing (rather than confusing formulas), these 4 primary performance characteristics are:

SENSITIVITY — Given a population with cancers, sensitivity is the percentage of those cancers that will be identified by the screening test in question.

SPECIFICITY — Given a population that includes patients without cancer, what is the percentage that will be correctly identified as negative.

NEGATIVE PREDICTIVE VALUE (NPV) — Given a negative result on the test in question, what is the probability that cancer is absent in such a patient.

POSITIVE PREDICTIVE VALUE (PPV) — Given a positive result on the test in question, what is the probability that cancer will be identified.

Note: in the top 2 characteristics, it is the patients, some of whom harbor cancer, who make up the premise. And, in the bottom 2 characteristics (NPV and PPV), it is the test result that forms the premise. Without going into too much detail, there are some relationships among the Big 4. For instance, a very high Sensitivity will render a test to have a very good NPV, helping to rule out cancer. And, high Specificity will render a test with a good PPV helping to “rule in” cancer.

Ideally, we want all 4 characteristics to be good, or even excellent. That said, there is frequently a teeter-totter relationship between Sensitivity and Specificity. As one tweaks the experimental method to elevate Sensitivity, ground will be lost by worsening Specificity. Or, vice versa. So, in the article reviewed above, you can understand my concern that Sensitivity seems to be neglected except for the online Tables and Figures where one can do their own math.

We’re not done yet. There are also “DERIVATIVE performance characteristics” that are unique expressions dependent upon the Big 4 above. Far and away, the most confusing is “ACCURACY.” You’d think Accuracy meant Accuracy, but it doesn’t. This favorite number is much beloved by the marketing departments where great weaknesses can be hidden. Accuracy, to the research clinician, is a formula that gives equal weight to both Sensitivity and Specificity, combining them into one number. Just for kicks, here’s the formula: TP + TN, divided by TP + TN + FP + FN. When expressed as a graph instead of a number, it is called the Area Under the ROC Curve, often expressed as AUC.

The MCED tests are perfect to demonstrate how bad results can be hidden. If Specificity is 99%, and Sensitivity is an unacceptable 50%, then Accuracy is 75%. Specificity is dragged down, Sensitivity is inflated, but hey, 75% looks fairly good in detecting cancer. But this example doesn’t detect cancer at a 75% rate…it detects it at a 50% rate. Accuracy is not the same as the ability to detect cancer (Sensitivity is the key for detecting cancer). But those who read an article with Accuracy as an endpoint might fail to realize that Sensitivity could be good, bad, or ugly, you don’t know unless Sensitivity has been calculated separately. Sensitivity plus Specificity equals Accuracy. While Accuracy might be helpful in comparing two or more different tests, it has huge abuse potential when it comes to the promotional literature for the MCED tests. In other words, the 99% Specificity is so powerful it easily covers low Sensitivity levels that are quite concerning. This confusion about “performance characteristics” is one of the many reasons that class action suits have arisen with the MCED tests as being “over-hyped” and “over-promoted.”

Another DERIVATIVE performance characteristic based entirely on Sensitivity is the CDR — the CANCER DETECTION RATE. By convention, this is expressed in terms of cancers identified per 1,000 screened patients. There are many variables here, from risk status, to age, to the screening interval, to the modality used for screening. But it is very helpful in comparing different cohorts of patients or comparing different technologies.

Although there are many DERIVATIVE characteristics used to judge the effect of screening, the last one I’ll mention here is “NUMBER NEEDED TO SCREEN to save one life” (NNS). For example, NNS might be 1,500 for screening mammograms in the general population, though NNS will be paradoxically lower for high-risk patients (Example: NNS = “only” 900 mammograms rather than 1,500), and higher for low-risk women (NNS = 2,000 mammograms, rather than 1,500). This derivative is subject to manipulation of the data, as it is not always clear as to when a life has been saved through early detection.

The Big 4 plus derivatives are an integral part of medical practice, from screening to diagnosis to treatment. Yet, without a working knowledge, “industry” can pull the wool over the clinician’s eyes. Even after all these years, in the collaborative group where I work, we sometimes obsess over the various published numbers in a conference setting trying to make sure things are in order. It’s not for the faint of heart.

In conclusion, would I ever order a MCED test like Galleri (there are several), right now as the technology stands? Yes. There are certain germline mutations (born with DNA variants that are present in every cell in the body) that elevate cancer risk throughout the body, many cancer types. The most powerful of the multi-cancer genes is TP53, known as Li Fraumeni Syndrome. The cancers in these families can occur anywhere, in any organ, and the current guidelines include “total body MRI.” But not all patients can have an MRI, or they might have trouble getting insurance to pay for frequent MRIs, or might want assurance more frequently than current guidelines. The same goes for families who test negative on their germline mutations, but the families are loaded with all types of cancer. In other words, they are undiagnosed even though we suspect germline mutations that might only pertain to the one family. For these patients, I think serial MCED testing will prove helpful.

We’re going to be hearing a lot about MCED testing or “liquid biopsy” or ctDNA over the next decade, and additional confusion will be encountered as the tests are potentially useful for reasons other than screening (identifying recurrent disease, guiding therapy, long-term follow-up, etc.) Medical oncologists will be following the events from their standpoint, but I wonder which specialty will take charge of these many options when used for screening?

END

How Did the Month of Halloween Become Breast Cancer Awareness Month?

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(Originally posted October 31, 2019, then yearly in October)

Date for this post: Oct 31, 2025

Mammography schedules are jammed in October. It’s hard to work in the callbacks and biopsies. Everyone is pressured to get it done before the looming Holiday Season. And if we find cancer, it spoils that festive stretch from Thanksgiving to Christmas, Hanukkah, or whatever, through New Years…not to mention the fact that deductibles were met at the time of the mammographic screening, but then in January, it starts over again as cancer care continues. Ugh! How did we ever get here?

Prior to 1980, there were no pink ribbons, no races, no walks. There was very little awareness and breast cancer was not discussed in polite society. The fact that Shirley Temple Black (breast cancer in 1972), Betty Ford (1974) and Happy Rockefeller (diagnosed 2 weeks after Ford in 1974) made their diagnoses public was shocking (and trailblazing). And when the Susan Komen Foundation was established in 1982, newspapers resisted using the words “breast cancer.” As late as 1993 when we opened our doors at the University of Oklahoma Institute for Breast Health, there were complaints about our signage with its “irreverent” word BREAST plastered right there in public.

Let’s go back to the 1940s when Susan and Nancy Goodman were sisters growing up in a well-to-do Jewish family in Peoria, Illinois. Who could have conceived of the notion that both girls carried a mutation in BRCA-1 that would lead to breast cancer in the both of them? After all, it would be more than 50 years before the launch of commercial testing of BRCA-1 and BRCA-2.

susan komen and nancy brinker

(Susan Komen on the left; sister Nancy Brinker on the right)

Susan grew up to be the “darling of Peoria,” a beauty queen and local model. She would enter a disastrous first marriage (groom collapsed at the wedding for starters), followed by a second marriage to Stan Komen who would run a liquor store – Stan’s Wine and Spirits – in Peoria until his retirement in 2014.

At age 33, Susan felt a breast lump. Not a good thing in 1977, on the eve of a revolution about to occur in the management of breast cancer. 1977 was, however, the peak time of enthusiasm for “subcutaneous mastectomies” with the newfangled breast implants for reconstruction…sometimes patient-driven, sometimes surgeon-driven and sometimes both. Pain, cysts, “fibrocystic disease,” you name it, then cough up the money, and surgeons would perform the “scoop out” procedure with implant reconstruction. Some women were very happy with their result. Many were not. And for some, considerable amounts of breast tissue remained in place. Nevertheless, no one at the time conceived of using the procedure for treating cancer — except for Susan’s surgeon who had been recommended by her family physician in Peoria.

After performing subcutaneous mastectomy for Susan’s cancer, the surgeon pronounced her cancer-free, a tad premature since she developed positive nodes shortly thereafter and systemic metastases as well. After treatment at both the Mayo Clinic and M. D. Anderson, she was still left with chest wall recurrences and died 3 years later in 1980 at the age of 36. Given the aggressiveness of this tumor, it is hard to lay blame on the unusual subcutaneous approach used for local control, but it is noteworthy nonetheless.

Meanwhile, younger sister Nancy had moved to Dallas where she became a buyer for Neiman Marcus, and then, in 1981, she became the bride of Norman Brinker, the restaurant magnate who founded Steak and Ale, et al, (now Brinker International) and is credited with the development of that omnipresent dining staple – the salad bar. With her new financial stature and a deathbed promise to her sister Susan, Nancy Brinker founded the Susan G. Komen Breast Cancer Foundation in 1982, a mere 2 years after Susan’s death. The foundation became intimately linked to Dallas as a result of Nancy’s new home, not Susan’s home in Peoria (although Peoria did become a site for a “Komen Breast Center,” a nationwide network concept of screening centers that never happened.)

The first Race for the Cure took place in Dallas, Texas with 800 participants in 1983. The rest is history. I attended the first race in Oklahoma City (1989, as I recall) where participants raced around the track at Remington Park. Pink ribbons were not introduced until 1991, and though several groups lay claim to the pink revolution, I’m pretty sure it was a Komen innovation.

One year after that first Race for the Cure, Nancy Brinker was diagnosed with breast cancer. She underwent unilateral mastectomy and later contralateral prevention, even though her BRCA-1 mutation was not confirmed until 2006.

Initially, the sole agenda for Komen was to flood the country with high quality screening mammography. This drew some objections, including one prominent breast surgeon, the late Susan Love, who broke ranks with the movement by clarifying that mammography is not a “cure,” and that we needed to be thinking more about a true cure and a “post-mammographic era.” Eventually, Komen expanded its scope to all types of breast cancer research.

Nevertheless, the growth of the Race for the Cure was phenomenal, taking place in a parallel fashion to the breast cancer diagnosis and treatment revolution that was well underway. It is estimated that, today, over 1.5 million participants raise money through one of several outreach programs sponsored by Susan G. Komen (several name changes of the foundation have occurred over the years, but Susan’s name is always there). Politics, of course, wormed its way into the activities of Susan G. Komen and eventually Nancy Brinker resigned as CEO.

Back to Breast Cancer Awareness in the spooky month of October. Around 1985 or 1986, the American Cancer Society teamed up with a pharmaceutical company that later became Zeneca, then AstraZeneca, announcing October as National Breast Cancer Awareness month. Zeneca was criticized for self-serving interest since they manufactured pharmaceuticals used for breast cancer. But they had, in fact, done their own internal audit on employees, showing that it was cheaper to screen with mammograms for an early diagnosis than to do nothing and pay for treatment of more advanced disease.

At this same time, the famous (or infamous) Breast Cancer Detection Demonstration Project was reporting results indicating that massive screening of the general population in the U.S. was both feasible and effective. The BCDDP was sponsored by the American Cancer Society and the National Cancer Institute, both organizations riding the waves of the War on Cancer legislation signed by President Nixon in 1971. So, by the mid-80s, the policy makers were wildly enthusiastic about general population screening with mammography, and it was a case of “full steam ahead.”

Still…why October?

I’ve not been able to nail down the exact details surrounding October as Breast Cancer Awareness Month, but I have a theory — a link between the rapid rise of the Susan G. Komen Foundation and the proclamation about October made by the American Cancer Society. I think the answer might be found by looking at Susan Goodman Komen’s birthday – she was born on October 31, 1943. She would have been 82 this Halloween.

More on Prognosis Guarded

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PROGNOSIS GUARDED book contest results:

1981 — National Writers Club Manuscript Competition — 7th prize (with a “perfect 10” score) from several hundred entries

2025 — Independent Press Association — Distinguished Favorite in medical thriller genre

2025 — International Impact Book Award — “Winner” (Top Ten Books from 120 submissions) in suspense/thriller genre

2025 — Eric Hoffer Book Award Finalist (Top 10%) in suspense/thriller genre

Currently, at 4.6 Stars, Prognosis Guarded — The Breakthrough Novel of 1977 That Tried to Break Me — has the highest Amazon ranking of the 9 books by Alan B Hollingsworth/John Albedo

Book Contests For Better or For Worse

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I might be the only author in history to have received a book award for an unpublished novel, then 44 years later, win additional awards for the same novel. One of the oldest clubs for authors is the National Writers Association, founded in 1937, supporting authors both published and unpublished. When I joined in 1980 (then called the National Writers Club), the governing council included Clive Cussler and Jerzy Kosinski. In 1981, I entered the club’s annual book contest for unpublished manuscripts. Genres were the basic dichotomy back then — fiction and non-fiction — whereas today, with so many self-published books on the market, it’s not unusual for genres to be divided into 20 or 30 sub-genres in book contests. To complicate things, some book awards hand out “honorable mentions” to all participants, then pitch an expensive marketing campaign. But even the legitimate contests have proliferated as they aim to help published authors rise toward a major publisher for their future works. And in spite of everything gone ‘internet’ in publishing, the transition to a major literary agent and/or major publisher is usually based on sales figures from the most recent book.

If you read Part One of PROGNOSIS GUARDED (PG), you learned that OU Professor Jack Bickham read my 1977 draft of that book, and anointed it with this: “I don’t know how in the hell you wrote such a nice novel the first time out. I’ve never seen a first book half this good.” After the stars were wiped from my eyes with the publication of COMA by Robin Cook (same story as mine), I began to work on changing the storyline as much as possible to get away from the COMA label. By 1981, I had the version that I recently published in softcover. So, readers today are not reading the COMA look-a-like of 1977, but the revised version of 1981 that was still intriguing enough to warrant a well-known Hollywood agent (Harold Greene) and a NY publisher (St Martins Press). Then, all that stuff fell through as well. This is why the cover of PROGNOSIS GUARDED is the famous Hollywood sign fading into a cemetery (while Part Two relates to Hollywood and literal cemeteries).

When I finally gave up on PROGNOSIS GUARDED, it was the 1981 version that got stuffed in the attic, and I moved on to FLATBELLIES and the beginning of a nice writing career. In fact, I’ve said on many occasions that PROGNOSIS GUARDED is the origin story for FLATBELLIES, the latter being a completely different genre born of my transition away from medical thrillers.

When I uncovered the PROGNOSIS GUARDED manuscript decades later, in 2024, I decided to publish it, along with an explanation as to the bizarre travels the manuscript had taken. I had no idea if it would resonate with today’s readers or not. Certainly, the 1981 version preserved enough of the key elements of a medical thriller (COMA was the first one) that should carry the formula like any good murder mystery.

As a point of interest in this attic discovery, in addition to the only known copy of the manuscript, there was a copy of my results from the entry I had made to the National Writers Club “Book Manuscript Competition.” Oddly enough, the congratulatory letter was accompanied by the score sheet the judge had used. The first paragraph congratulated me on 7th Prize (out of “hundreds”), but it was the score sheet descriptors that would have made Jack Bickham’s original comment seem weak in comparison.

Ten criteria were judged (theme, plot, characterization, descriptions, dialogue, etc), and all 10 had typed comments, all in the superlative. Scoring for each of the 10 criteria could range from any numerical fraction above 0 to 1.0. And with a maximum additive score of 10, my score was….well….a 10. Now don’t ask me why I didn’t win 1st Prize, but I suspect there were at least 6 others who also got 10s, and we were then ranked. Doesn’t matter. What did matter was the P.S. at the bottom of the critique sheet, not part of the official score, where the judge added this: “You may want to find a good agent to handle this since it could have movie or TV possibilities.”

And this was four years after COMA. With regard to that mega-hit, the judge wrote this about my 1981 version of PG: “Your idea, while kin to COMA, is enough different and creative to fly.” (And yet, even with my persistence in pitching PG, rejections would continue another 12 years before I would stick PG in the attic.)

I knew friends wouldn’t believe everything that was happening at this time, so I placed 2 of the key documents in the book, PROGNOSIS GUARDED, Part One — 1) my contract with Hollywood agent Harold Greene, and 2) the letter from Jack Bickham. I chose not to place additional documentation, but if I had, the 3rd document would have been the judge’s scoring sheet from the 1981 competition.

Fast forward from 1981. Same manuscript, only now in October 2024. This time, as a published manuscript, I would enter PG in book contests to see if the same sort of reaction would emerge as had been the case 44 years ago. Much to my surprise, the feedback has been strong, with frantic page-turning near the end as described by readers. Customer reviews on Amazon have been remarkably complimentary, especially noting those reviewers I do NOT know personally. Then, the results from book contests started being announced in 2025, and the reviews that accompanied my awards were quite the surprise. It was like I’d written the book yesterday. The ending seems to grab readers like it did decades ago, and it’s nice to know that my characters are — to quote Paul Simon — are “Still crazy after all these years.”

PROGNOSIS GUARDED book contest results:

1981 — National Writers Club Manuscript Competition — 7th prize (“perfect 10” score) from “hundreds” of entries

2025 — Independent Press Association — Distinguished Favorite in medical thriller genre

2025 — International Impact Book Award — “Winner” (Top Ten Books from 120 submissions) in suspense/thriller genre

2025 — Eric Hoffer Book Award Finalist (Top 10%) in suspense/thriller genre

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Questions (so far) about PROGNOSIS: GUARDED

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Is PROGNOSIS: GUARDED (PG) a prequel to FLATBELLIES?

No. Although PG was written much earlier (first draft 1977) than FLATBELLIES, the story in PG is unrelated to FLATBELLIES, published in 2001. That said, Part One in this “new” PG is the true story of a 17-year effort to get PG published, to no avail. Ordinarily, such an account would be ho-hum, as literary rejection is far more common than literary acceptance. But there’s a difference here — the original PG was pegged as a literary blockbuster “soon to be a major motion picture.” The story of what happened after that first draft in 1977 was a life-changing experience for the 29 y/o author (me). And, the collapse of the original PG led to a major switch in genres on my part, dropping the medical thriller plans and adopting coming-of-age fiction. Thus, Part One of the “new” PG is an “origin story,” explaining the emergence of FLATBELLIES. Part Two is the medical thriller that caused all the controversy and confusion, in print for the first time.

What is the book’s cover trying to show?

The famous Hollywood sign is disappearing, and at the base of the sign is a cemetery. The cover is representing both Part One and Part Two. Part One of PG is the death of a Hollywood dream. Part Two of PG is the novel that deals with orchestrated medical murders of the rich and famous of Hollywood. (In some of the printings, the cemetery at the base of the Hollywood sign is dark and hard to see.)

Is the story of PROGNOSIS: GUARDED pure fiction?

Yes. It’s the only one of my six novels that did not borrow from actual events.

Why isn’t PROGNOSIS: GUARDED available at my local bookstore?

Long story, but I felt that combining Part One and Part Two into a single book (one non-fiction and the other fiction) was going to make traditional publishers squeamish. So, I went the route of publishing through an Amazon resource that gave me full editorial control, but also requires sales to come through Amazon. Depending on how it goes, I might make arrangements with booksellers in OKC to sell PG, as we are ramping up for a 25th anniversary edition of FLATBELLIES, and PG is the start of that process by telling the origin story first. So, if we release the special edition of FLATBELLIES next year, it would likely be sold side by side with PG at bookstores.

What’s best way to purchase the book then?

Online purchase of softcover print ($17): https://store.bookbaby.com/book/prognosis-guarded1

Kindle purchase per Amazon, or however you are accustomed to buying ebooks.

Do you still speak at book clubs?

Yes. I attend any book club within a 2-3 hour driving radius of OKC. Anything beyond that, I do online. Also, some clubs are not specifically book clubs (social clubs, study clubs, etc.), yet they will ask me to speak about writing and publishing in general, or to discuss one of my novels from the past (see http://www.johnalbedo.com). Or, there is great interest in my one true crime story covering the 1923 murder of my grandfather (see http://www.killingalbertberch.com). Contact me through Facebook Messaging to schedule. Or, email alanhollingsworth@cox.net.

I read COMA when it first came out, and now that I’ve read PROGNOSIS: GUARDED, I don’t think the two books are that much alike. What gives?

Recall from Part One that I don’t have a copy of the original 1977 manuscript, which was virtually identical to COMA, complete with suspended human bodies. Several New York publishers (most notably St. Martins Press) asked me to change my version as much as possible to allow publication as an original story. The 1980-81 version I found in the attic (the published version) was the end product of that effort, taking away the science fiction component and transferring the genre to a medical murder mystery. I thought the changes were adequate, but publishers still ruled it “too much like COMA.” This was likely due to the fact that the “medical thriller” was still a new concept, so my revised version was compared to the only other successful thriller at the time — COMA. Had there been 100 medical thrillers on the market, I think PG would have had no trouble falling into that pool. (Remember this from Part One — when Random House rejected my book as “too much like COMA,” the Senior Editor called PROGNOSIS: GUARDED a “hospital intrigue story.”)

Gift Ideas: Books by Alan B. Hollingsworth that have nothing to do with Christmas

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NEW (limited) RELEASE

Online purchases only

PROGNOSIS GUARDED – The Breakthrough Novel of 1977 that Tried to Break Me

Part One – The Bizarre Story Behind the Novel (49 pages)

Part Two – The Novel  (267 pages)                                                                        

ONLINE PURCHASES ONLY:

SOFTCOVER (direct from publisher, allow 7 days for delivery) https://store.bookbaby.com/book/prognosis-guarded1

KINDLE     https://amzn.to/3Nuoyza

NOTE: December 18th is the official launch by Amazon. Softcover can be ordered from the same page as Kindle (above), but delivery won’t be until after December 18.