The MAMMOGRAM Conundrum

To know is to know that you know nothing.That is the meaning of true knowledge - Socrates.

The recent Canadian study posed two questions for breast screening:

1.       Does mammography create over diagnoses?

2.       Does mammography as a screening tool help survival?

The answers gleaned from the study were “Yes” and “No.”

Now my two cents...

Let us look at some facts: The predicate of over diagnosis is based upon the argument that early diagnosis is an over diagnosis. In other words finding and treating a DCIS (Ductal carcinoma in situ) is an over diagnosis. Or so some will have you believe. They cite the SEER data and presume that some DCIS can regress back to normal states. Has anyone seen or documented a DCIS regression back to normal? The answer surprises us with a definitive No. Has anyone determined a DCIS by radiological means and then just followed the regression? The reverse answer however can be answered unequivocally that DCIS lesions have been noted to break through the basement membrane and run amok elsewhere in the body when left untreated over time. Studies in the past have estimated reduced mortality (0.3-3.2/1000 women). So if a woman’s life is saved that is a 100% save rate for that woman. Population data does not reflect the need of an individual. It only shows probabilities.

Another way to look at it is, knowing that 10% of all “abnormal” mammograms represent (true positive) cancer diagnosis and only 8-19% of the screened individuals have cancers detected as DCIS. That means over 80% of the cancers are invasive. Invasion indicates propensity to metastasize thus at least 8% of women will be diagnosed early and potentially saved.

Another remarkable non-statement in the study quotes a 5 year survival rate of 100% but fails to mention the 10 year survival rate for DCIS to be 98%. The 2 percent, loss due to breast cancer related mortality, seem not to fit the paradigm of limited disease in the paper.

So the question that we have to answer then is; does screening save lives? The NSABP-17 trial: Of the 818 women enrolled in the trial, 80% were diagnosed by mammography, and 70% of the patients' lesions were 1 cm or less. At the 12-year actuarial follow-up interval, the overall rate of in-breast tumor recurrence was reduced from 31.7% to 15.7% when radiation therapy was delivered (P< .005). Radiation therapy reduced the occurrence of invasive cancer from 16.8% to 7.7% (P = .001) and recurrent DCIS from 14.6% to 8.0% (P = .001). And the EORTC 10853 study: Similarly, of the 1,010 patients enrolled in the trial, mammography detected lesions in 71% of the women. At a median follow-up of 10.5 years, the overall rate of in-breast tumor recurrence was reduced from 26% to 15% (P < .001) with a similarly effective reduction of invasive (13% to 8%, P = .065) and noninvasive (14% to 7%, P = .001) recurrence rates

  The answer, if we are to follow the population based thinking comes from both cohort studies and randomized studies that show a decline in breast cancer related deaths since 1980s when mammography screening was mass utilized. After the initial significant decline post mass screening, the mortality rate from breast cancer has been steady. These trials were initiated between 1963 and 1982 the Health Insurance Plan study, the Malmo study, the Swedish Two county trial, the Edinburgh trial, the Stockholm trial, the Canadian National Breast Screening studies 1 & 2 and the Gothenburg Breast Screening Trial. All but the National Breast Cancer Screening found mammography to result in significant reductions in breast cancer mortality. . 

The NCI report and the SEER data show an incidence of DCIS has increased over time: 5.8/100,000 in 1975 vs. 32.5/100,000 in 2004 which is partly due to mammography yet remains meager to the 124.3/100,000 for invasive breast cancer. Most trials have shown reduced mortality from mammography. Does that mean we are over diagnosing? Or catching it early with a potential for cure? But even relenting a bit, the overall incidence of invasive breast cancer has declined since 1987 and especially since 2000 partly from the HRT knowledge and from catching the disease early. So, thinking this through further we find, a review commissioned by the AHRQ assessed the effectiveness of needle biopsy. The authors synthesized the evidence from 104 studies and concluded that 24% of tumors with DCIS identified from stereotactic guided automatic gun core needle biopsy were found to have found to have invasive breast cancer upon surgical excision (95% CI 0.18;0.32). Early diagnosis and removal therefore does have a decent payback.

What will happen another decade from now if the current professorial intuit plays out and makes women fearful of screening? Only time will tell.  The tragedy of more than 200,000 women being diagnosed with breast cancer and 40,000 dying from it annually in the United States is a reminder to all the well intentioned souls. 

The answers then might be answered as “No” and “Yes.”

References:

http://www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional/page4

Diagnosis and Management of Ductal Carcinoma in Situ (DCIS)Evidence Reports/Technology Assessments, No. 185.Virnig BA, Shamliyan T, Tuttle TM, et al. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Sep. http://www.ncbi.nlm.nih.gov/books/NBK32570/

Fisher ER, Dignam J, Tan-Chiu E, et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer. 1999 Aug 1;86(3):429–38. 

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Smith BD, Haffty BG, Buchholz TA, et al. Effectiveness of radiation therapy in older women with ductal carcinoma in situ. J Natl Cancer Inst. 2006 Sep 20;98(18):1302–10. 

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Solin LJ, Fourquet A, Vicini FA, et al. Long-term outcome after breast-conservation treatment with radiation for mammographically detected ductal carcinoma in situ of the breast. Cancer. 2005 Mar 15;103(6):1137–46.

Nystrom L, Andersson I, Bjurstam N, et al. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet. 2002 Mar 16;359(9310):909–19

Roberts MM, Alexander FE, Anderson TJ, et al. The Edinburgh randomised trial of screening for breast cancer: description of method. Br J Cancer. 1984 Jul;50(1):1–6.

Frisell J, Lidbrink E, Hellstrom L, et al. Followup after 11 years--update of mortality results in the Stockholm mammographic screening trial. Breast Cancer Res Treat. 1997 Sep;45(3):263–70.

Miller AB, To T, Baines CJ, et al. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50–59 years. J Natl Cancer Inst. 2000 Sep 20;92(18):1490–9.

Miller AB, To T, Baines CJ, et al. The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med. 2002 Sep 3;137(5 Part 1):305–12.

Bjurstam N, Bjorneld L, Warwick J, et al. The Gothenburg Breast Screening Trial. Cancer. 2003 May 15;97(10):2387–96.

Shapiro S. Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan J Natl Cancer Inst Monogr. 1997:27–30.

MOUNTAIN SPORTS AND HEALTH

I admit that I love skiing! But then so do the hundreds of thousands others. And they are probably more avid then I and probably better at it too.

Mountain sports have an inherent fact that most of us ignore as we expectantly run to the ticket windows. Ah for that cold icy fresh air first stoking the warm fire of desire. The chairlift awaits and the gondola beckons but there is something amiss, just ever so slightly that you cannot put your finger to it.

So let me count the ways that, that amiss has some physiological ramifications to it.

I first became aware when my daughter would wake up at a resort in the Colorado Rockies and start heaving up her last night’s dinner. No fun there. I was annoyed (imagine) that she was really not interested in skiing but wanted to veg out in the room. Then it became certain even to the most resistant one (me) that every vacation a similar episode developed. What was happening? Just about then, the resort started offering a canister full of oxygen for purchase. I bought several of them and gave them to everyone in our family. Guess what happened? No more heaving! No more complaints! She was the first one out with her skis and poles.

Okay so what happened? It appears that when a sea-level dude or "dudette" comes over to a 8000 foot elevation without acclimatization the hypoxemia (low oxygen levels) in some generates a gastric regurgitation (upchuck). Additionally I was noting myself a tiny residue of headache and always filtered that through the lens of a difficult work period prior to a vacation (taking care of all the sick ones that required attention immediately for the time period I would be away). But those two to three whiffs from the canister cured that too. No more headaches. Voila, amazing two problems solved with one swing of the bat.

Then I started thinking about other possibilities that might also be at play:

A friend of mine with a labile hypertension controlled with low dose anti-hypertensive medicine ended up in the emergency room after being airlifted due to a hypertensive crisis. His blood pressure was sky high and fear of strokes was a significant consideration. Thankfully it was resolved with additional medication. The next year, he told me that he carried extra blood pressure medicine when he went to more than the mile high resort and lo and behold a similar occurrence was at hand but one he was prepared for (he is a physician). The logic from this suggests that hypoxemia (low oxygen levels) seem to drive the vaso-constrictive mechanisms of the arteriolar system, with an associated rise in the heart rate and respiratory rate as a compensatory mechanism. (You will notice shortness of breath when you walk the mile in your ski boots carrying your skis and poles at that high altitude).

Another visual at the airport one time while returning from our vacation, I observed a young woman in the wheel chair being pushed to the gate for departure. I found out that she had been hospitalized with a blood clot and was returning home from a miserable “vacation.” That was sad in itself, but what of this blood clot? I wondered.

It turns out that similar to the risks of developing a blood clot in the long flight a similar mechanism migh be at play in a mountainous resort for sea level dwellers. The high altitude with its marginalized oxygen levels associated with dry air that saps the moisture from within the body at rest (and more with exercise) and the vaso-constrictive phenomenon, I mentioned earlier can be a doozy for a blood clot in the leg. Add to that potential a mutation of the Factor V Leiden mutation present in 5% of the population and or the less common Prothrombin mutation that are promoters of blood clots the results can be terrifying and hurtful. (I am not going to mention all other risk factors such as age>65, existence of cancer, birth control pills, obesity etc. Suffice it is to say there are many other issues that can predispose a person to developing blood clots)

When all the factors are present, what makes the clot itself? Imagine a blood flow through a smooth blood vessel. The flow is linear. The “stuff” red and white cells and platelets all stay in the middle of the stream while the “liquid” as in plasma surrounds the core. A disruption due to a crossed leg, a injury can impair the linear flow and the platelets “fall-off” to the sides and with the other ingredients mentioned as in dehydration (thickens the blood and slows the flow) hypoxemia (causing compensatory vaso-constriction) and the last hammer (Factor V Leiden mutation) makes factors in the blood including platelets “stickier,” you now have the set up for the disrupted blood flow and piling on of the clotting factors around the nidus of the platelets and ouch, the leg hurts. The higher risk is that one of those clots can run the venous blood stream and end up in the lung with compromised breathing and endanger life. To prevent is simple, Drink plenty of water, invest in a canister of oxygen and use it and take a baby aspirin (81 mg) provided your doctor (not some “provider” but the real critical analytic decision maker) agrees to the use of this medication based on your history.

Oh and I might not have mentioned that skiing is a dangerous sport because there are inherent risks of falls and crashes that can cause broken bones, separated shoulders, ACL (Anterior Cruciate Ligament in the knee joint) tears and other sundry eventualities that twitter friends like @hjulks in the Orthopedic field know all too well and how to manage and fix.

Mitigating risks is easy once you know the hazards.

Skiing/snowboarding without a helmet does not prevent accidents but may save you from a brain injury. Now that you have chosen your "bling" on what to wear and show off, don't forget the "thing" that protects your noggin. Skiing and snowboarding under control can also save you from visiting the orthopedic department, the hematology department and the neurosurgery department.

Enjoy your vacation!

Know the risks!

Prepare in advance!

Have a ball!

ASSUMPTIONS

The gathering storm seems to instill a foreboding in all things living. The dark skies, the billowing clouds, and the quiet of the birds and the first raindrop spell danger. Something this way comes, something, which strikes dissonance into the harmony of human existence.

The storm comes, lashes its collective wrath and moves on and those that survive gather their collective wit and start to live again. It is the existential human drama. Life recouples, survives and redoubles her efforts to keep living.

But there is a new kind of storm that pricks the edges of our understanding. This one carries a darker more sinister purpose. This one is blacker than black. It is not a storm of nature’s doing. It is man-made, conjured up in that 3-pound universe that drives humanity. This storm is called ASSUMPTION.

Assumptions exist in most all things scientific. Theoreticians who conjure up new probabilities and create models that describe the human condition and its existence; live on the ragged cliffs of thought. Let us take the existence of Black Holes, which was the mathematic model created by Stephen Hawking. It was the creation of a fecund mind subsequently visualized in reality.

We see assumptions drive every aspect of society nowadays. Once what was considered the purview of theoreticians is now the domain of the “journalists” and self-proclaimed “experts.”

A short course in today’s expertise is evident in the controversies that surround the scientific world. A review of the scientific literature reveals that 50% of the studies cannot be duplicated. Leave alone the concept of verification and validation of any experiment as the hallmark of rigor, here the initial premise is so false that duplication is well-nigh impossible. The falsity is based on the notion of the many biases that form the prejudice behind the “study.” Biases run the underworld of the false prophets of profit. Biases induce assumptions to satisfy the end result that one is predisposed to at the outset.

Let me explain: If you want to prove that Product X leads to Effect Y then all one has to do is manipulate the question of how to evaluate Effect Y. Or select individuals that are more likely to answer in the affirmative. Or build on the expectation of the Product X using the “Placebo-effect” as the surrogate to arrive at the conclusion. Then use the “intent” to remove those individuals that do not conform to the paradigm of the cause and effect to distill down the argument to obtain the relevant p-value. And voila you have a study that becomes “EVIDENCE” for the rest of. There they go harping the benefits of “Evidence Based…!”

Two recent cases come to mind: The mammogram Canadian study and its fall out in medicine. The “experts” continue to “wing” their way into one or the other camp. Both sides are passionate in their thought but both are prejudiced under the weight of their bias. The other subject of recent hifalutin assumptions is the disappearance of Malaysian Flight #370. The missing aircraft, crew and passengers continue to fuel assumptions. Everyone stokes the flame a bit. “Experts” abound but not one has any idea of what happened. Might it not be prudent to just keep one’s opinion to oneself until facts reveal the truth? But, that does not keep the 24-hour BS cycle of non-news News and the wealthy journalists employed with their million dollar salaries happy. The News must be created. The minds must be cajoled to a certain viewpoint. The paradigm must be polished every day. When one considers that 1 out 4 Americans surveyed do not know that the earth revolves around the sun, what hope is there for that 25% to realize the difference between truth and fiction and for that matter have any scintilla of self-emboldening critical thinking?

I shudder to think.

“I must be cruel only to be kind; Thus bad begins, and worse remains behind.” - Shakespeare