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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.

Once Again, It’s Time for Star Search

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My “new” book release is PROGNOSIS: GUARDED, a medical thriller drafted originally in 1977, making the novel nearly a half century old. Of all the author duties that accompany a book launch, the worst is “begging for stars” on Amazon Customer Reviews. Somehow, the star system (under 4 stars, the book does not exist) has bypassed professional reviews, making the Customer Review the most important parameter other than actual sales. So, if you read the book — available in softcover and Kindle, sold only online (see below) — and feel inspired, here’s the link to Customer Reviews: https://amzn.to/3Nuoyza

To help explain the 47-year gap between the first draft and publication, I added an introductory segment, such that our marketing “blurbs” read something like this:

Terror is timeless. This 1977 medical thriller will have you turning pages faster than you can say “Robin Cook” (whose 1977 novel COMA defined a new genre). But what happened to PROGNOSIS: GUARDED between 1977 and 2024? PART ONE takes the reader on a wild ride through the world of publishing and the life-changing impact the book had upon the author whose original draft was a locked and loaded blockbuster (or so everyone thought). PART TWO is the novel itself — PROGNOSIS: GUARDED, still crazy after all these years.

Early Is As Early Does

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“Early detection is the key,” we all say. But is it really that straightforward? In the late 1980s, one of the most influential surgeons in the history of breast cancer management (Bernie Fisher, MD) was at the podium defending his theory of breast cancer biology, in support of lumpectomy, when he said: “I don’t know what early breast cancer really is. There’s no satisfactory definition.” Mammography had hit the scene, prompting the term, “mammographically-detected cancers,” but Dr. Fisher was adamant that his theories that justified lumpectomy were not dependent on the method of tumor detection. Furthermore, just because a cancer was identified through screening mammography did not necessarily mean it was “early.”

(For those who believe that screening mammography was the primary reason behind breast conservation, or that pre-op mammography was part of the “package” tested in the landmark NSABP B-06 trial, you might be surprised to know that accrual to those studies started in the 1970s and did not require that mammograms be performed. Lumpectomy arose from a biologic theory that pre-dated mammography, and would have confirmed the safety of lumpectomy with or without mammography.) That said, if Dr. Fisher didn’t know the definition of “early breast cancer,” then who am I to attempt a definition? And, yes, I remember that it’s the umbrella name of this blog.

  Bernard Fisher, MD

The problem with the term, Dr. Fisher explained, was that small tumors can still be deadly, and large tumors can be indolent, so using tumor size for the definition was not reliable. And if we try to use a measure of time to represent early vs. late, we are equally lost since we really don’t know how long the tumor has been present. He maintained that the outcome (cure vs. no cure) was based on the inherent biology of the tumor and how it interfaced with the “host’s” immune system. Both tumor and host were equally important. Since he came up with that theory from laboratory studies in the 1950s, it’s hard today to call this concept “new.” Yet, given the immense amount of research now being performed, not necessarily on the cancer cells, but on the immune cells that govern the host reaction, one can say that the late Dr. Fisher was a scientific prophet or, at least, remarkably prescient.

I bring this up because I was recently surprised by a “new” use of the term “early.” In fact, within the context I’m going to give you, “early” was used for what I’ve always called “late,” or even “locally advanced.”

Recently, I attended the 46th annual San Antonio Breast Cancer Symposium, a spectacle that every breast specialist should attend at least once (I think this was my 20th time). Over 10,000 attendees from 102 countries, with literally 1000s of posters and presentations over a 5-day period. The conference has always been skewed heavily toward medical oncology and its associated research, now in high speed with the development of countless drugs that alter the immune system to attack cancer cells. And all power to them. But if you’re looking for new developments in breast imaging, surgery, radiation, plastics, prevention, or basic pathology, this is not the conference for you. These topics are relegated to the poster sessions, rather than the podium. Even more than before, it has become a medical oncology event, along with related research. Admittedly, one reason I attend is to meet with international collaborators who have made the trip to San Antonio. In fact, the first 3-4 times I attended, I went to meetings “on the side” and didn’t even enroll in the course itself.

This time around, I had not attended for three years, so you’d think not much had changed. But it has. There is a shifting tide, a subtle sociologic phenomenon, that I can’t find the right words to describe. It’s easier to point out that we were told: “Given physician stress levels of today,” we attendees would have access to massages, yoga, etc. And, “if you need to up your brand,” there was a professional photographer stationed in the event center who would give you the “head shot” of your choice. The line of scientists and clinicians hoping to “up their brand” was long and was populated by attendees who appeared as teen-agers to me. A quiet voice whispered: “This is no country for old men.”

Back to the conference sessions. One by one, researchers and clinicians approached the podium and announced the title of their presentations, many of which contained the phrase “early breast cancer.” For a generic example, “Thank you for that wonderful introduction. I will be presenting today the final results of the XXX trial that administered YYY in combination with ZZZ versus YYY alone in the pre-surgical neoadjuvant therapy of early breast cancer. Over and over, it was early, early, early, while I’m seeing late, late, late. Through societal forces too complex for my blood, in the past 3 years, it had become a conventional norm to apply the word “early” to any patient with breast cancer who did NOT have known metastatic disease. That is, any patient with Stage I, Stage 2, or Stage 3. It seemed the only time “late” would have been used was if study patients had Stage 4 disease.

So, as the researchers would announce life expectancies extended by 3 months, or 5 months, or 8 months, through the use of the new ZZZ compound, I had to think what would have been the results if every participant in each particular trial had been on a long-term program of breast MRI screening at 1-2 year intervals? In fact, we’re only now seeing the “cure rates” for breast cancer when discovered by MRI, but it appears that very few patients would have qualified for the ZZZ trial because their disease would have been “too early.” 

Debate and analysis about the relative benefit of systemic therapy (by medical oncology) vs. screening (by radiologists) has, in the past, called it a tie — that is, both approaches reduce breast cancer specific mortality by the same amount. But that’s mammography, where half the cancers are missed when breast tissue is dense. Screening with MRI is a whole different ballgame, yet it is held in check due to outdated guidelines (that don’t include breast density…yet), and the impracticality and cost of screening the entire population with MRI.

But I digress. My astonishment was in the new definition of “early.” And it speaks to the remarkable confusion imparted by different meanings for the same word or words. Brilliant scientists somehow get comfortable with the ambiguous lexicon used by their particular sub-specialty, while colleagues from different camps are using the same word for something else. Oddly enough, I’ve published an Editorial on this very thing.

In 2015, the Editor-in-Chief of The Breast Journal asked me to write a critique about the lead article, which was going to be published soon. Such an analysis of a lead article is a time-consuming honor, by the way, that counts very little for anything, other than knowing your opinion is respected by at least a few. But when I read the article about to be published (dealing with the implications for surgery and radiation when patients have more than one location of tumor in the breast), I asked if I could use a major deficiency as a springboard for another topic entirely — the power of language (a theme in my novels, too). The authors, all from a prestigious academic center, had used terminology that meant different things to different people. Specifically, no attempt was made to distinguish the varied definitions of “multifocal” vs. “multicentric,” in my view, imparting a great deal of confusion for any reader. Same thing for the term “local recurrence,” which drags around several different definitions as well.

The result was an Editorial titled, “The Beginning of Wisdom is the Definition of Terms,” a phrase I borrowed from Socrates.

Some of my colleagues around the country got a kick out of the tongue-in-cheek editorial and emailed their responses, and that was the end of that. But 2 years later, a notification came through the mystery of the internet, stating that I had been quoted in the Journal of Volcanology and Geothermal Research. Must be a different Alan Hollingsworth, I thought. Nevertheless, I looked it up, and sure enough — I’d made it into the world of volcanos. As it turned out, this article was an appeal for the different sub-specialists to sit down and agree upon the meaning of “overpressure” (a word that sounds pretty important to me). Apparently, reservoir engineers, volcanologists, and structural geologists, were all using the word “overpressure,” but each group used a different definition. The problem, apparently, is widespread. (Must have something to do with that nebulous concept — human nature.)

So, what is the definition of “early breast cancer?” As I noted above, if Bernie Fisher doesn’t know, then I can’t claim enlightenment. Yet, if all breast cancers were discovered at a size 1.0cm or smaller, deaths due to breast cancer would plummet. Mammography is not reliable enough to guarantee this small size, especially when density camouflages the tumor. Yes, some tiny cancers can still metastasize prior to early discovery, and yes, some small cancers might be so slow-growing that “early” detection is not required. But overall, MRI or MBI (molecular breast imaging) or CEM (contrast-enhanced mammography), can identify tumors reliably, with incredible life-saving potential, and we’re now on the brink of confirmation of this dramatic mortality reduction. Yet, due to cost and the cumbersome aspects of using a contrast agent, it has been impractical to screen the general population with these highly accurate tools.

But what if I were to tell you that screening MRI and contrast-enhanced mammography (CEM) can be performed at a cash rate that is only a fraction of the going rate? For my patients who weathered the $4,000 storm of a few years ago, screening MRI can be offered for one-tenth the price patients were asked to pay previously. That’s one-tenth. 

COMMERCIAL BREAK

Premier Breast Health Institute of Oklahoma — http://www.pbhiok.com — Call 405-768-1970 for a risk assessment appointment to see if insurance will cover your screening MRI. Or, check the price of the various imaging studies if insurance does not offer coverage. Whole breast ultrasound adds a lot if you have dense breasts, but CEM or MRI can offer a higher detection rate than mammography and ultrasound combined. 

Primary Staff: Dr. Anna Stidham (breast radiologist), Dr. Stephanie Taylor (breast surgeon), Courtney Carrier, MPH, MSN, APRN, NP-C (certified nurse practitioner genetic counselor)

END COMMERCIAL

As for my personal research dealing with blood testing that would properly identify who should have MRI or CEM, perhaps the purpose makes more sense now. FYI — current blood tests being covered by the media often have low sensitivity for cancer detection, that is, EARLY CANCER (there it is again). These tests might boast an 80% detection rate, for example, but then you read the fine print — that number is applicable to advanced stages only, Stages 3 and 4. Developing a breast cancer blood test has turned out to be remarkably difficult because it has to work in “early” disease. The test that finds 80% of Stage I breast cancers will be something to write home about. But if that same 80% sensitivity holds up for even smaller tumors, and in the face of dense breasts….well, we’re talking about a revolution in screening that would impress even the likes of Dr. Bernie Fisher.

For more off-the-cuff, tongue-in-cheek, cliche-laden musings, get a copy of this collection of essays (blogatorials), available on Amazon.

Breast Cancer Risk Alterations go “White Rabbit”

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“One pill makes you larger, and one pill makes you small…”

Although Jefferson Airplane’s Grace Slick was writing about something else entirely in 1967, we had an unusual coincidence this week when two events were publicized widely regarding breast cancer risk alterations due to pills. One pill raises your risk for breast cancer, while another makes risk smaller.

First, the pill that makes risk larger. Birth control pills (and hormonal-release IUDs). Treated as if this were the first study of its kind, a very small risk for breast cancer was announced in terms that made it sound larger. A “25% risk increase” is a “relative risk” not an absolute risk. I’ve been writing about this “relative risk vs. absolute risk” for exactly 23 years (introduced in the first lay book on risk assessment in 2000). First of all, I would point out that this controversy has already had hundreds of studies published, and there are so many caveats, I won’t even bother to walk through the story. However, some of the studies show no risk at all (depending on the preparation — high progesterone pills or low) or a slight risk. Either way, the risk is so small that it should not alter recommendations to patients beyond awareness. Besides, birth control pills lower the risk of both ovarian and endometrial cancer.

As for the “relative” vs. “absolute,” I won’t bore you with the math. Just know that the media (and the researchers) much prefer to discuss their results in “relative” terms because the number is ALWAYS larger. In this case, the researchers broke ranks and actually took the time to explain how a 25% relative risk increase is a big pill to swallow, and when couched in absolute risk terms, the reality is much much smaller. For practical purposes, it’s not a major issue (unlike postmenopausal hormone replacement risk, which can generate some concerning numbers, albeit far below most other risk factors).

And now, for the pill that makes risk smaller. The big announcement came this week, again presented in relative terms. But in this case, when converting to absolute benefit, it’s a compelling option. The story dealt with the National Health Service in the United Kingdom endorsing the use of anastrozole (Arimidex) to lower the risk of breast cancer “by 50%.” First, let’s convert this to absolutes. If your absolute risk for breast cancer is 20% lifetime, and you cut that in half, there is an absolute chance of 10% for major benefit (the benefit being never developing breast cancer). If your baseline risk is a higher 50% lifetime, then the absolute benefit is a lowering of your personal risk from 50% to 25%. That is, a one-in-four chance that the pill you took for 5 years kept you from getting breast cancer.

Taking a pill to prevent breast cancer is really a remarkable option when you think about it. Here’s how the discovery was made: When tamoxifen was new on the market (1970s), its use was to take the place of hormone-lowering surgeries (oophorectomy, adrenalectomy, even removal of the pituitary), primarily in the treatment of metastatic disease. Then, its indications were expanded to use as an adjunct treatment for breast cancer patients to lower the risk of metastatic disease later on. THEN, someone noticed that when used in the adjunct setting, women who took tamoxifen were not getting breast cancers in the opposite breast as much as would have been calculated. In fact, the chances of getting contralateral cancer later on, were cut in half for those women who completed 5 years of tamoxifen. NEXT STEP — multiple prevention trials internationally were performed in the 1990s confirming that giving tamoxifen to healthy women lowered risk by one-third to one-half.

Most unusual, however, was the fact that the benefit increased over time — that is, AFTER the drug was stopped. One trial failed to reach statistical significance while the women were on tamoxifen, but as the years went on, subsequent to the discontinuation of tamoxifen, statistical significance was reached! Theories abound as to how this is possible, but the point is….if a person decides to partake in risk reduction using a pill, you can calculate the benefit for the next 20 years even though they only take the drug 5 years.

As the design of the “P-1” trial from the NSABP prompted lively discussions, the greatest controversy was the inclusion of premenopausal women (some other trials included postmenopausal women only). Many of us predicted it would not work in this group of younger women. We were wrong. Not only did it work (not quite as well as in postmenopausal women) but it became the risk-reducing drug of choice for younger women as a result of the favorable side effect profile. Older women were faced with an increased risk of blood clots and endometrial cancer when using tamoxifen for prevention, but the premenopausal women did not have to deal with these issues, generating pretty much an ideal drug, considering we’re recommending this for healthy women (recalling “do no harm”).

As an incidental point, the Gail risk assessment model was introduced to the public when it was chosen as the means to calculate risk for entry to the NSABP P-1 tamoxifen prevention trial. It was validated as accurate by the P-1 trial, at least when it comes to predicting the number of breast cancers that would occur in a high-risk cohort. (At the individual level, however, the initial version of the Gail model was only slightly better than flipping a coin.)

To clarify the nature of these drugs: tamoxifen and raloxifene are both SERMS (selective estrogen receptor modulators) working as antiestrogens in some body locations (breast, by blocking estrogen receptors) and as estrogen in other locations (bone). And when it comes to the uterus, there are differences — tamoxifen acts like an estrogen in postmenopausal women while raloxifene is neutral. Thus, the name SERMs which implies, “estrogen-like in some locations, but anti-estrogen in others.”

As for the aromatase inhibitors (there are more than just the 3 we all hear about), they are pure antiestrogens, everywhere. Circulating estrogen is diminished across the board, rather than receptor blockade. Thus, the greatest concern is the lowering of bone density, sometimes requiring treatment. There is also a common side effect of aching joints, or even non-specific aching, of uncertain mechanism.

Fast forward to today’s options for “pharmacologic risk-reduction.” (The original term was “chemoprevention” but that word stuck in patients’ throats, scaring off candidates, so the name was changed.) Tamoxifen remains the drug of choice for premenopausal women. Raloxifene (Evista) is the drug of choice for postmenopausal women (not quite as powerful as tamoxifen, but no endometrial cancer, only a slight risk of blood clots, and beneficial for bone density). And if more risk reduction is warranted than Evista can provide, the aromatase inhibitors can be used for prevention. The story this week was anastrozole (Arimidex), but the others work as well, offering an approximate 50% risk reduction if the patient can take the drug 5 years (yes, there’s some protection with shorter treatments).

Is this new info? No. These studies were completed a long time ago and FDA approval followed for the SERMs. I have many patients who completed their tamoxifen, or their raloxifene, or their aromatase inhibitor, and now have protection (a lower level of risk) for at least 20 years, maybe more.

Now here’s the Kicker, and the reason I became heavily involved in this arena. Analysis of participants in the P-1 trial revealed a subset where the benefit was even greater than those women at high-risk due to a positive family history. The most dramatic result was in the women with “atypical hyperplasia” on a prior biopsy where a 90% risk reduction was realized. This launched an entire industry aimed at “searching for atypical hyperplasia” to identify the best candidates for pharmacologic risk reduction (thus, ductal lavage, nipple aspirate fluid, random FNA cytology, ductoscopy, etc). After all, 90% risk reduction is close to the same benefit as preventive mastectomies.

As the data from subsequent trials emerged and matured, the benefit was adjusted to a 75% risk reduction range, which is still remarkable. Nevertheless, given the large number of candidates for pharmacologic risk reduction, few women opt for the 5-year plan. In fact, the “industry” sort of dried up, not because the science was off, but rather, the lack of patient interest in pharmacologic risk reduction, even from those at high risk, even if submitting to any of the measures to find “atypia.” No point in performing ductal lavage if the patient is going to decline pharmacologic risk reduction. Over 500,000 women take Evista for its other FDA-approved indication — bone density improvement — but try suggesting it for breast cancer risk reduction, and patients balk. The NSABP even launched a study to understand why women didn’t buy into the NSABP’s huge and expensive studies (13,000 women in P-1 and 20,000 in P-2). It largely remains a mystery as to why pharmacologic risk reduction has been underutilized, but it’s still available through “shared decision-making” between the patient and her health care provider.

Maybe the reluctance has something to do with next line of lyrics in “White Rabbit”….. And the ones that mother gives you don’t do anything at all.

END

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

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(Originally posted October 31, 2019, then October 31, 2023)

Date for this post: Oct 1, 2024

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 81 this Halloween.