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The Mammography Debate: Now and beyond

Constantine1by Constantine Kaniklidis, Research Director, No Surrender Breast Cancer Foundation (NSBCF)

 

Untangling the Issues: The Good, the Bad, and the Ugly

The mammography debate has been raging heatedly and  sometimes corrosively for decades, reflecting both the passions of partisans on both sides of the debate, as well as the exquisite complexity of the underlying issues. The upshot is that many women continue to hear and read confusing and sometimes contradictory claims, leaving many critical questions undecided: When should I start screening, at 40, or after 50, or even younger? Should I screen annually or every two years (biennially)? At what age should I stop screening? And what are the harms of screening?  These are among the many concerns of screening-eligible women seeking some clarity within the chaos of dueling guidelines and conflicting advice.

The Central Questions

I have engaged these issues and others in two recently published articles (June 2105) in the journal Current Oncology, one an invited editorial and the other a “Perspectives in Oncology” review; important other contributions have also appeared in the journal and elsewhere (see “Further Reading”).  Although we have a reasonable consensus that mammographic screening has significant benefits, the central question becomes: (1) do the benefits outweigh any potential harms? This I take up below, but I add two overlooked questions to this central one: (2) how do mammography decisions play out in the real world, among the women facing screening choices? and (3) given that decades of claims and counterclaims have to date failed to resolve some of the most vital issues in the debate, can we move constructively beyond the limitations of conventional mammography, to leverage new technologies that may to a large extent obsolete many of the outstanding questions and concerns?

 

A Guided Tour of the Benefits

So to begin with the central question, are the benefits of mammographic screening greater than the potential harms? Certainly, a significant reduction in mortality from breast cancer is considered the primary benefit. Omitting technical details, reviews of the most robust data – from the so-called “gold standard” of randomized controlled trials (RCTs) as well as observational data (field data from individuals in a sample) across Europe and Canada – there is an average of 17 – 40% reduction (allowing for variation between studies) reported in deaths for women aged 50 to 69 either invited to or actually attendant at screening (versus non-invited or non-attendant women), which represents a significant saving of lives.

 

But notice even here that much of the debate over mammographic screening is framed far too narrowly, solely around whether survival is ultimately affected. But there are potential benefits beyond just reduction of mortality, and these include: (1) diagnosis at earlier stages, typically with smaller tumors and no spread to lymph nodes; (2) reduced likelihood of aggressive treatments and its associated morbidities; (3) detection of high-risk lesions like DCIS and certain atypias, most being diagnosed in the screened group, which then allows for chemoprevention and/or MRI surveillance; and (4) avoidance of the compromised quality of life (QoL) associated with the diagnosis of advanced disease. Ignoring these very real benefits has compromised the debate and yet advantages like these, even independent of any reduced deaths from breast cancer, are very real and important to women.

 

The Harms, in Perspective

Now what of the claimed harms of mammographic screening? The most cited is overdiagnosis, but the definition of overdiagnosis is somewhat elastic across authors and studies. Minimally, it can denote the detection of a cancer which would never have gained potential lethality and so would not be responsible for the screened individual’s death. Or more broadly, it can be construed as the discovery of a cancer which would simply not have been otherwise diagnosed or become clinically evident (or symptomatic) during the individual’s lifetime if screening had been omitted. But at its heart, the occurrence of overdiagnosis boils down to the case of someone being diagnosed with a disease (here, breast cancer) that will not go on to cause them harm. Regardless of the definition chosen, the claim is that the principle real harm stemming from overdiagnosis is overtreatment, that is, the treatment of cancers not significantly progressing (non-progressive) or highly slow-growing (indolent) and so unlikely if left untreated to cause symptoms or shorten life.

 

But here we should not become – as many partisans in the debate have – excessively focused on only the potential harms of overdiagnosis. We must also acknowledge the real harms of underdiagnosis, which includes a progressive decline in survival for each annual mammography screening a woman omits: we have evidence that women who have missed any of their previous five annual screenings incur more than a doubling of risk for all-cause mortality compared with subjects having no missed screenings, and this also argues against a biennial (every two-year) schedule as the current guidelines in much of North America and Europe are now advising.

 

Still, the question remains, what is the degree of overdiagnosis caused by mammographic screening? If we limit the data to studies with strong methodological controls only – ones that explicitly control for certain critical factors like the incidence of breast cancer during screening, and certain biases (in particular, something called length-time bias) – then those studies collectively show an overdetection rate only ranging between 1 – 10%, which the benefits would significantly outweigh. But what of other claimed harms like negative psychological effects like anxiety experienced from any false positive results received? Although we can grant these may not be trivial, more recent robust data suggests that the magnitude of such anxiety is small and that in any case it appears largely transient, with little potential for longer-term consequences. Moreover, whether there is any clinically relevant level of harm from such angst remains undemonstrated.

 

Finally, many women remain concerned about the cumulative risk of exposure to ionizing x-rays used in mammograms, with hyperbolic reporting sometimes stirring up a sort of “dose hysteria”. But multiple studies have found the risk of radiation-induced breast cancer to be reassuringly extremely low, where the total lifetime risk from screening every year for 40 years (age 40 – 80) ranges between only 0.01 to 0.025%. In addition, other studies have found that patients exposed to mammographic radiation did not in fact have a significantly higher risk of developing other malignancies (thyroid and hematological cancers). Therefore women should not be discouraged from gaining the benefits of regular screening due to fear of radiation-induced breast or other secondary cancers.

 

Lessons Learned

Therefore, balancing the countervailing substantial benefits we have already described above, we are left with the conclusion that the balance sheet remains positive for mammographic screening, with benefits outweighing any claimed harms. And although still intensely debated, data suggests that the weight of the robust evidence does not support an age 50 start point on the low end, but rather argues for benefits of screening for women in their forties, as well as in the elderly, past the arbitrary upper end cutoff of 74. But as always every woman, and every case, is different – for example some women may have high risk factors, or dense breasts – so women should assure a candid discussion with their health professionals to weigh all special and individual factors in order to make the most informed decision.

 

A Healthy Splash of Reality: What Women Really Think

A number of recent studies have found that women overwhelmingly elect annual mammographic screening, and beginning at no later than 40, with additional data decisively confirming that even when informed of potential harms, women show regret-avoidance behavior in preferring the risk of overtreatment to the risk of undertreatment. Thus, by and large, screening-eligible women – the ultimate stakeholders in the mammography debate – pay scant attention to the cacophony of the controversy, accepting overdiagnosis, false positives, and any associated anxiety as acceptable consequences of screening in order to obtain the greater benefits it may confer.

 

“Movin’ Out”: Beyond the Mammography Debate

Given decades of the controversy surrounding mammography, we must finally focus on more constructive efforts to improve breast cancer screening, beyond what’s available from just conventional (2D) mammography. New technologies are beginning to appear: abbreviated breast MRI (ABMRI) and (2) tomosynthesis (aka, “3D” mammography) are the two most important, increasingly adopted and with costs decreasing to potentially make them in the near future near-competitive in cost with traditional mammography.

 

ABMRI is a highly streamlined,  stripped-down-to-its-very-essence, version of the many complex sequences of imaging operations embedded in conventional magnetic resonance imaging (MRI), and when advanced protocols are used (with exotic names like ultraFAST and TWIST), then despite the radical streamlining, there is no compromise to diagnostic accuracy or cancer yield (roughly, the level of malignancies detected). Such streamlined ABMRI protocols can also deliver substantial cost reductions, possibly even allowing for batch MRI screening, and may therefore emerge as the standard for breast screening, avoiding many of the residual debating points surrounding mammography.

 

A second highly promising technology, digital breast tomosynthesis (DBT) or tomosynthesis for short, aka three-dimensional (3D) mammography, was originally invented and developed at Massachusetts General Hospital by Dan Kopans, a leading pro-screening voice in the mammography debate and is even further along, having been approved by Health Canada in 2009 and by the U.S. FDA in 2011 as an adjunct to two-dimensional (2D) mammography. The three-dimensional reconstruction enables viewing through layers of tissue to allow for multiple images of the entire breast from all angles, and the benefits include substantial reduction in recalls (unnecessary biopsies or additional tests) and false positives, for increased cancer detection rates with high accuracy, and for earlier detection of small cancers not captured on mammography and those in dense breast tissues. Collectively, these tip the risk-benefit ratio toward tomosynthesis over current conventional 2D technology.

 

Both these technologies – abbreviated breast MRI (ABMRI) and tomosynthesis – avoid the small potential harms of mammograms, improve on cancer detection, and start to obsolete conventional mammography – and at least some of its associated controversies – going forward. As I concluded in my review:

 

If the new technologies are not “the way out,” they are at least the hint of the way forward, beyond the current cycle of contentions and contentious repartee that often don’t quite intersect, are largely ignored by the women affected, rely on data often corrupted by methodologic[al] limitations, and rarely therefore convincing to other than the faithful.

 


 

 

Further Reading

  1. Kaniklidis C. Beyond the mammography debate: a moderate perspective. Curr Oncol 2015; 22(3):220-9.
  2. Kaniklidis C. Through a glass darkly: the mammography debate. Curr Oncol 2015; 22(3):171-3.
  3. Foulkes WD. Screening mammography: the turning of the tide? Curr Oncol 2014; 21(5):205-7.
  4. Narod SA. Reflections on screening mammography and the early detection of breast cancer: A Countercurrents Series. Curr Oncol 2014; 21(5):210-4.
  5. Kopans DB. Review of papers in current oncology on the CNBSS women ages 40-49. Curr Oncol [Reader Comment. Posted: 14 Jan 2015].
  6. Yaffe MJ. Point: Mammography screening-sticking to the science. Curr Oncol 2015; 22(3):174-6.
  7. Narod SA. Counterpoint re: “Mammography screening-sticking to the science”. Curr Oncol 2015; 22(3):177.
  8. Taylor P. Breast Cancer Screening: Paul Taylor takes stock of the debate between advocates and opponents. London Review of Books. 5 June 2014; 36(11): 30-32.

 


 

 

ConstantineKaniklidisConstantine Kaniklidis is currently Director of Research for the No Surrender Breast Cancer Foundation (NSBCF), a not-for-profit organization providing high-quality critically reviewed and appraised information and guidance to the breast cancer community. His focus is on the most challenging of advanced / metastatic disease, especially triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC). He is also the Editor of Evidence-based Medicine for the Open Directory Project. Research interests include epigenetic reprogramming, optimal treatment of CNS metastases (brain and leptomeningeal), drug interactions and resistance in oncology, and evidence-based integrative oncology. He is also active at the intersection of politics and medicine, as in his widely accessed paper “Cancer, Culture and Cooperation in the Middle East”. 

 


 

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