#3 YOU CAN’T MAKE THIS STUFF UP:

THE AMERICAN COLLEGE OF PHYSICIANS GUIDANCE ON BREAST CANCER SCREENING WEIGHS TRANSIENT ANXIETY AGAINST SAVING LIVES AND LIVES LOSE!

In an effort to cloud the discussion about breast cancer screening, “analysts” who seek to reduce access to screening combine Ductal Carcinoma In Situ (DCIS) with small invasive cancers calling the combination “early breast cancers” as if they are similar.  By definition, DCIS lesions cannot spread outside of the breast (become metastatic) because they are growing inside a milk duct and have no access to blood vessels or lymphatics as a route to spread to other organs.  It is not until they become invasive or “infiltrating” that they can gain that access.  There are legitimate uncertainties as to how best to “manage” DCIS lesions, but invasive breast cancers are “real”.  In fact, as many as 20% of women die from small invasive breast cancers due to undetectable metastases despite the fact that they are considered “early”.  My comments below are primarily with regard to invasive breast cancers.

BAD ADVICE

On April 8, 2019, the Annals of Internal Medicine published “A Guidance Statement From the Clinical Guidelines Committee of the American College of Physicians (ACP)” entitled “Screening for Breast Cancer in Average-Risk Women”(1) promoting advice to women and their physicians that is, quite frankly, unbelievable and unethical.  The document is packed with misinformation and very dangerous “guidance”.  The very first paragraph states “Breast cancer is the fourth leading cause of cancer death” when, in fact it is the leading cause of non-preventable cancer death among women (lung cancer is the first but many of these would be prevented by not smoking).  And it goes downhill from there.  The bottom line is that the ACP is repeating the misguided and dangerous decision that it made in 2007 (2) and advising women to delay screening until age 50 and to then be screened every two years. 

EVERYONE AGREES THAT THE MOST LIVES ARE SAVED BY ANNUAL SCREENING STARTING AT THE AGE OF 40

What is incredible is that the ACP (3) and all the other major organizations, including the United States Preventive Services Task Force (USPSTF) (4) and the American Cancer Society (ACS) (5), agree, and the scientific evidence supports the fact, that the most lives are saved by screening starting at the age of 40.  The stunning message to women is that the ACP, apparently, does not feel that women, when they are in their forties, can deal with the anxiety of being recalled for a few extra views or an ultrasound.  They are advising women that it is better to die an unnecessary death, that could be avoided by annual screening starting at the age of 40, than to be recalled for a few extra pictures or an ultrasound and, for most recalled women, be told that everything is fine. 

EXPERTS ARE PREVENTED FROM GUIDANCE PANELS

It is important to realize that the ACP Panel were not experts.  In a misguided claim that they were avoiding conflicts of interest, they purposely excluded experts in breast cancer screening.  In fact, no one on the panel even provides care for women with breast cancer.  This would be like having me decide guidelines for neurosurgery.  Obviously, I can review the literature, but you would be outraged that I would claim to be able to provide guidance.  With no experience or expertise, I cannot gauge the validity and applicability of the information.  Clearly the inexpert ACP panel lacked the experience and expertise to understand the data.  An obvious example is their specious claim that “mammography was not associated with a reduction in all-cause mortality”.  In fact, among women with breast cancer, the decline in breast cancer deaths significantly reduced all-cause mortality (6).  It is clear that the panel lacked the expertise to assess the data because they were unaware of the fundamental fact that a screening trial of the general population would require more than 2.5 million participants to show that a decline in breast cancer deaths significantly reduces all-cause mortality in a general population (7).  Their claim was simply false and based on a lack of expertise.

WHAT WAS THE SCALE?

The “Guidance” document ignores the facts by claiming to have weighed the benefits against the “harms” of screening.  The main “benefits” are not dying from breast cancer resulting in major gains in “years of life” as well as allowing for less rigorous treatment when cancers are found earlier, a “harm” they forgot about because they don’t’ provide care for women with breast cancer.  Among the “harms” of screening that they listed are “false positives”, “overdiagnosis” and “overtreatment”.  As noted below, delaying screening will have no effect on “overdiagnosis” and “overtreatment” so that the only “harm” that will be altered by delaying screening are recalls which they pejoratively called “false positives”.  These are not, as the name implies, women who are told that they have breast cancer when they do not, but, rather, are women who are recalled for a few extra pictures or an ultrasound, and, in fact, most are told that everything is fine. 

Fundamentally, the ACP is telling women that they think it better to let them die, unnecessarily, then to have them deal with the transient anxiety associated with being recalled.    It is fairly astonishing that an organization that advises our first line health care physicians would make such a decision!  They “weighed” the “harms” against the benefits, but never provided a clear scale.  How many fewer recalls from screening “balance” allowing one woman to die, unnecessarily, whose life could be saved by annual screening starting at the age of 40?

“DON’T WORRY YOUR PRETTY LITTLE HEAD”

In a decidedly “maternalistic/paternalistic, sexist” fashion, they suggest that women ages 40-49 should have a discussion with their physicians to weigh the “harms” against the benefit in an “evidence based” “informed decision making” process, but not so for older women? When did “informed decision making” suddenly stop at the age of 50?   All of us should be provided with accurate information, regardless of age, so that we can all make “informed decisions”.  Why are they singling out women ages 40-49?

NOTHING HAPPENS AT THE AGE OF 50

The Panel also forgot to inform women and their physicians that there is no scientific reason to use the age of 50 as a threshold for screening.  NONE of the factors associated with screening, change abruptly at the age of 50 or any other age (8).  This includes lives saved.  A 49 year old women is indistinguishable from a 51 year old woman.  The most rigorous scientific evidence, randomized, controlled trials, proved that early detection saves lives for women ages 40-74 PERIOD (9,10).  This has been confirmed by numerous observational studies that have shown marked reductions in breast cancer deaths among women who have access to screening and participate compared to those who don’t (11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26).  A major study from the Harvard hospitals showed that more than 70% of the women who died from breast cancer, despite having access to modern therapies, were among the 20% of women who were not participating in screening (27).  A recent study of tens of thousands of women in Sweden showed that the incidence of deaths was 60% lower at 10 years for women who participated in screening compared to those who did not, and 47% lower at 20 years (28) despite all having access to therapy.  These studies applied to women ages 40 and over.

BREAST CANCER IS NOT A TRIVIAL PROBLEM FOR WOMEN AGES 40-49

The panel suggested that breast cancer is not a major problem for women in their forties.  In fact, more than 30,000 women are diagnosed with breast cancer each year while in their forties.  There are more years of life lost to breast cancer among women ages 40-49 then for women ages 50-59 (29).   

A MAJOR DROP IN BREAST CANCER DEATHS – BUT JUST FOR WOMEN!

In the U.S. the death rate from breast cancer, unchanged for 50 years, began to fall in 1990, soon after the start of screening (30).  It has continued to fall so that there are now over 40% fewer women dying each year from breast cancer.  It has been estimated that over 600,000 lives have been saved since 1990 (31).  At the same time, the death rate for men with breast cancer went up in 1990.  It stayed up for several years and then fell back to 1990 levels where it has remained while deaths have continued to fall for women.  The therapies are the same, but men are not screened.  Therapy has improved, but lives are saved when breast cancer is treated earlier.

THERE IS LITTLE IF ANY RADIATION RISK TO THE BREAST OF WOMEN AGES 40 AND OVER

One of the other “harms” that the ACP Panel cited was “radiation associated breast cancer and breast cancers death”.  This is another example of the lack of expertise among the Panel.  It is astonishing that the ACP raised the issue of radiation risk without dismissing it as have all of the other groups that now recognize that there is little if any radiation risk from mammography. The breast is sensitive to high doses of radiation in teenage women, but the risk drops rapidly with increasing age (32).   The “mature” breast is unaffected by the low doses from mammography.  Radiation from mammograms has no measurable effect in women ages 40 and over.  It has been known for years that even the extrapolated risk is well below even the smallest benefit (33,34).   Women have been receiving hundreds of millions of mammograms for over 40 years and no one has ever been found to have developed a breast cancer related to mammography.  But hundreds of thousands of lives have been saved as a result of mammography screening.  The ACP panel forgot to point out that even the computer analysis that they cited (35) (clearly just to scare people because they left out the benefit) shows that “IF” there is any risk (and there is probably none), 60 lives will be saved by screening for every single (theoretical but unprovable) death due to a radiation induced cancer. This is 16 theoretical (and unprovable) deaths compared to 968 lives saved among 100,000 women.

IF IT EVEN HAPPENS “OVERDIAGNOSIS” IS UNAFFECTED BY DELAYING SCREENING

But it gets worse!  As noted above, the ACP panel cited as the major harms of screening – “overdiagnosis” and “overtreatment”.  “Overdiagnosis” is the claim that there are breast cancers that if left alone, would never harm a woman during her life, and this means that, because pathologists cannot differentiate lethal cancers from indolent cancers, diagnosing them will lead to “overtreatment”.  The Panel implied (they never actually stated) that delaying screening would reduce “overdiagnosis” and “overtreatment”.  What they neglected to point out is that this would only be true if the “overdiagnosed”, “fake” cancers disappeared so that the “fake” cancers among women in their forties would not be there by age 50, and would go away if women delayed the time between screening.  They also forgot to tell you that waiting two years between screens will allow breast cancers to have an extra year to grow and metastasize to other organs.  Their (inexpert) claim is “There is little to no difference in breast cancer mortality for screening every year vs. screening every other year (biennial mammography)” when there are no unbiased data to support this claim and computer models suggest a major decline in deaths with annual screening.   It is the fantasy of the inexperienced to think that breast cancers stop growing if you wait an extra year.

MAMMOGRAPHICALLY DETECTED BREAST CANCERS DO NOT DISAPPEAR ON THEIR OWN!

In fact, the concept of “fake”, mammographically detected breast cancers that will disappear if left undetected by screening is based on scientifically unsupportable analyses (36,37,38).  The fact is that no one has ever seen a mammographically detected breast cancer disappear on its own because it never happens.  In a review of almost 500 breast cancers found by mammography that were not treated, not a single one disappeared or even regressed (39).  This means that if you wait until age 50 and screen every two years, the “fake” (“overdiagnosed”) cancers (if they even exist) will still be there.  Delaying screening will have no effect on “overdiagnosis” and consequently no effect on “overtreatment”.  The only “harm” that will be reduced by delaying screening is the recall rate (pejoratively termed “false positives”) noted earlier where women are recalled for a few extra pictures or an ultrasound and most are told that everything is fine.  Approximately 2% of women will be advised to have an imaging guided needle biopsy using local anesthesia (very safe) and 20-40% will be found to have breast cancer (a high yield) at a time when cure is likely.

REALLY ! — THEY FORGOT TO MENTION THE TENS OF THOUSANDS OF UNNECESSARY DEATHS ?!

What the Panel forgot to tell women and their physicians is that the National Cancer Institute sponsored Cancer Intervention and Surveillance Modeling Network (CISNET), used by the USPSTF among others, has shown that if women now in their thirties, wait until the age of 50 to be screened every two years, as many as 100,000 will die, unnecessarily, whose lives could be saved by annual screening starting at the age of 40 (40).  If you put it all together you realize that the ACP has decided that they are willing to allow (advise) tens of thousands of women to die unnecessarily, just to reduce the “recall” rate and a few, very safe, needle biopsies.   This is fairly astonishing.

ENOUGH IS ENOUGH

The ACP should retract their “guidance” and review the data once again with the help of experts so that they can realize the outrageous consequences of their advice.  Mammography, starting at the age of 40, is the only “evidence based” guideline on which all major U.S. groups agree saves the most lives.  We all should be provided with accurate information about our health care and potential risks. “Informed decision making” doesn’t stop at the age of 50!  Women should be provided with the facts and have access to annual mammography starting at the age of 40.  Certainly a panel of individuals with no expertise should not be deciding access to breast cancer screening. Women should decide for themselves, based on accurate and complete information, whether or not they want to participate. 

REFERENCES

1 Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ; Clinical Guidelines Committee of the American College of Physicians. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med. 2019 Apr 9. doi: 10.7326/M18-2147. Epub ahead of print

2 Armstrong K, Moye E, Williams S, Berlin JA, Reynolds EE. Screening mammography in women 40 to 49 years of age: a systematic review for the American College of Physicians. Ann Intern Med. 2007 Apr 3;146(7):516-26.

3 http://www.acpinternist.org/archives/2012/05/policy.htm    last accessed 4/4/2019

4 Siu AL; U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016 Feb 16;164(4):279-96. doi: 10.7326/M15-2886. Epub 2016 Jan 12. PubMed PMID: 26757170

5 Oeffinger KC, Fontham ET, Etzioni R, Herzig A, Michaelson JS, Shih YC, Walter  LC, Church TR, Flowers CR, LaMonte SJ, Wolf AM, DeSantis C, Lortet-Tieulent J, Andrews K, Manassaram-Baptiste D, Saslow D, Smith RA, Brawley OW, Wender R. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA. 2015 Oct 20;314(15):1599-614.

6 Tabar L, Duffy SW, Yen MF, Warwick J, Vitak B, Chen HH, Smith RA. All-cause mortality among breast cancer patients in a screening trial: support for breast cancer mortality as an end point. J Med Screen. 2002;9(4):159-62.

7 Kopans DB, Halpern E. Re: All-cause mortality in randomized trials of cancer screening. J Natl Cancer Inst. 2002 Jun 5;94(11):863


8 Kopans DB, Moore RH, McCarthy KA, Hall DA, Hulka C, Whitman GJ, Slanetz PJ, Halpern EF.  Biasing the Interpretation of Mammography Screening Data By Age Grouping:  Nothing Changes Abruptly at Age 50.  The Breast Journal 1998;4:139-145.

9 Duffy SW, Tabar L, Smith RA.  The Mammographic Screening Trials:  Commentary on the Recent Work by Olsen and Gotzsche.   CA A Cancer J Clin.  2002;52:68-71

10 Hendrick RE, Smith RA, Rutledge JH, Smart CR. Benefit of screening mammography in women ages 40-49: a new meta- analysis of randomized controlled trials.  Journal of the National Cancer Institute Monograph 22: 87-92, 1997.

11 Tabar L, Vitak B, Tony HH, Yen MF, Duffy SW, Smith RA.  Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality.  Cancer 2001;91:1724-31

12 Duffy SW, Tabar L, Chen H, Holmqvist M, Yen M, Abdsalah S, Epstein B, Frodis Ewa, Ljungberg E, Hedborg-Melander C, Sundbom A, Tholin M, Wiege M, Akerlund A, Wu H, Tung T, Chiu Y, Chiu Chen, Huang C, Smith RA, Rosen M, Stenbeck M, Holmberg L.  The Impact of Organized Mammography Service Screening on Breast Carcinoma Mortality in Seven Swedish Counties.  Cancer 2002;95:458-469.

13 Otto SJ , Fracheboud J, Looman CWN,  Broeders MJM, Boer R, Hendriks JNHCL, Verbeek ALM,  de Koning HJ, and the National Evaluation Team for Breast Cancer Screening*  Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review Lancet 2003;361:411-417.

14 Swedish Organised Service Screening Evaluation Group. Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data. Cancer Epidemiol Biomarkers Prev. 2006;15:45-51

15 Coldman A, Phillips N, Warren L, Kan L. Breast cancer mortality after

screening mammography in British Columbia women. Int J Cancer. 2007 Mar

1;120(5):1076-80.

16 Jonsson H, Bordás P, Wallin H, Nyström L, Lenner P. Service screening with

mammography in Northern Sweden: effects on breast cancer mortality – an update. J

Med Screen. 2007;14(2):87-93.

17. Paap E, Holland R, den Heeten GJ, et al. A remarkable reduction of breast cancer deaths in screened versus unscreened women: a case-referent study. Cancer Causes Control 2010; 21: 1569-1573.

18 Otto SJ, Fracheboud J, Verbeek ALM, Boer R, Reijerink-Verheij JCIY, Otten JDM,. Broeders MJM,  de Koning HJ, and for the National Evaluation Team for Breast Cancer Screening.  Mammography Screening and Risk of Breast Cancer Death: A Population-Based Case–Control Study.   Cancer Epidemiol Biomarkers Prev.  Published OnlineFirst December 6, 2011; doi: 10.1158/1055-9965.EPI-11-0476

19 van Schoor G, Moss SM, Otten JD, Donders R, Paap E, den Heeten GJ, Holland R,

Broeders MJ, Verbeek AL. Increasingly strong reduction in breast cancer mortality

due to screening. Br J Cancer. 2011 Feb 22. Epub ahead of print

20 Mandelblatt JS, Cronin KA, Bailey S, et.al. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Annals of Internal Medicine, 2009; 151: 738-747; see also http://cisnet.cancer.gov, last accessed 16 April 2011.

21 Hellquist BN, Duffy SW, Abdsaleh S, Björneld L, Bordás P, Tabár L, Viták B,

Zackrisson S, Nyström L, Jonsson H. Effectiveness of population-based service

screening with mammography for women ages 40 to 49 years: evaluation of the

Swedish Mammography Screening in Young Women (SCRY) cohort. Cancer. 2011 Feb

15;117(4):714-22.

22 Broeders M, Moss S, Nyström L, Njor S, Jonsson H, Paap E, Massat N, Duffy S,

Lynge E, Paci E; EUROSCREEN Working Group. The impact of mammographic screening

on breast cancer mortality in Europe: a review of observational studies. J Med

Screen. 2012;19 Suppl 1:14-25. Review

23 Hofvind S, Ursin G, Tretli S, Sebuødegård S, Møller B. Breast cancer mortality

in participants of the Norwegian Breast Cancer Screening Program. Cancer. 2013

Sep 1;119(17):3106-12

24 Sigurdsson K, Olafsdóttir EJ. Population-based service mammography screening:

the Icelandic experience. Breast Cancer (Dove Med Press). 2013 May 9;5:17-25

25 Coldman A, Phillips N, Wilson C, Decker K, Chiarelli AM, Brisson J, Zhang B,

Payne J, Doyle G, Ahmad R. Pan-canadian study of mammography screening and

mortality from breast cancer. J Natl Cancer Inst. 2014 Oct 1;106(11).

26 Puliti D, Bucchi L, Mancini S, Paci E, Baracco S, Campari C, Canuti D, Cirilli C, Collina N, Conti GM, Di  Felice E, Falcini F, Michiara M, Negri R, Ravaioli A,  Sassoli De’ Bianchi P, Serafini M, Zorzi M, Caldarella A, Cataliotti L, Zappa M;  IMPACT COHORT Working Group.. Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy. Eur J Cancer. 2017  Feb 18;75:109-116.

27 Webb ML, Cady B, Michaelson JS, Bush DM, Calvillo KZ, Kopans DB, Smith BL. A failure analysis of invasive breast cancer: most deaths from disease occur in women not regularly screened. Cancer. 2014 Sep 15;120(18):2839-46.

28 Tabár L, Dean PB, Chen TH, Yen AM, Chen SL, Fann JC, Chiu SY, Ku MM, Wu WY,

Hsu CY, Chen YC, Beckmann K, Smith RA, Duffy SW. The incidence of fatal breast

cancer measures the increased effectiveness of therapy in women participating in

mammography screening. Cancer. 2019 Feb 15;125(4):515-523.

29 Oeffinger KC, Fontham ET, Etzioni R, Herzig A, Michaelson JS, Shih YC, Walter  LC, Church TR, Flowers CR, LaMonte SJ, Wolf AM, DeSantis C, Lortet-Tieulent J, Andrews K, Manassaram-Baptiste D, Saslow D, Smith RA, Brawley OW, Wender R. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA. 2015 Oct 20;314(15):1599-614.

30 Kopans DB.  Beyond Randomized, Controlled Trials:  Organized Mammographic Screening Substantially Reduces Breast Cancer Mortality.  Cancer 2002;94: 580-581

31 Hendrick RE, Baker JA, Helvie MA. Breast cancer deaths averted over 3 decades. Cancer. 2019 Feb 11. doi: 10.1002/cncr.31954. Epub ahead of print

32 Hancock SL, Tucker MA, Hoppe RT. Breast Cancer After Treatment of Hodgkin’s Disease. J Natl Cancer.  Inst 85:25-31, 1993

33 Mettler FA, Upton AC, Kelsey CA, Rosenberg RD, Linver MN.  Benefits versus Risks from Mammography:  A Critical Assessment.  Cancer 1996;77:903-909.

34 Kopans DB. Just the facts: mammography saves lives with little if any

radiation risk to the mature breast. Health Phys. 2011 Nov;101(5):578-82.

35 Miglioretti DL, Lange J, van den Broek JJ, Lee CI, van Ravesteyn NT, Ritley D, Kerlikowske K, Fenton JJ, Melnikow J, de Koning HJ, Hubbard RA. Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study. Ann Intern Med. 2016 Feb 16;164(4):205-14.

36 Kopans DB. Arguments Against Mammography Screening Continue to be Based on Faulty Science. The Oncologist 2014;19:107–112

37 Helvie MA, Chang JT, Hendrick RE, Banerjee M. Reduction in late-stage breast cancer incidence in the mammography era: Implications for overdiagnosis of invasive cancer. Cancer. 2014 Sep 1;120(17):2649-56

38 Etzioni R, Xia J, Hubbard R, Weiss NS, Gulati R. A reality check for overdiagnosis estimates associated with breast cancer screening. J Natl Cancer Inst. 2014 Oct 31;106(12).

39 Arleo EK, Monticciolo DL, Monsees B, McGinty G, Sickles EA. Persistent untreated screening-detected breast cancer: an argument against delaying screening or increasing the interval between screenings. J Am Coll Radiol 2017; 14:863-867.

40 Hendrick RE, Helvie MA. USPSTF Guidelines on Screening Mammography Recommendations: Science Ignored. Am. J. Roentgenology 2011; 196: W112 – W116.


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.