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25 Years Earlier

abhollingsworth Leave a comment

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.

The Toughest Writing Assignment I Ever Had

abhollingsworth Leave a comment

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.