Breast cancer screening recs

The American College of Physicians just released their screening guidelines for breast cancer in average risk women (see breast ca screening AIM2019 in dropbox, or doi:10.7326/M18-2147).

Details:

-- this new guideline is based on a review and assessment of existing international guidelines

-- they generally found that the methodology differed substantially in the different guidelines, per the AGREE II instrument (Appraisal of Guidelines for Research and Evaluation II):

    -- highest scoring: American Cancer Society, Canadian Task Force on Preventive Health Care, US Preventive Services Task Force, and the World Health Organization

    -- lowest scoring: American College of Obstetricians and Gynecologists, American College of Radiology, and National Comprehensive Cancer Network; typically because they did not articulate well the benefits, harms, and strength of evidence, and how these link to the recommendations

Results:

--Mammography:

    -- when to initiate screening discussion: pretty variable, with recommendations at age 40, 45, and 50

    -- screening average-risk women: most recommendations endorse between ages of 50-74, though two guidelines recommend 50-69.

    -- screening interval: most support biennial, though the ACS suggests starting biennial at age greater than 55, and the Canadian Task Force recommends every 2 to 3 years

    -- when to stop screening: more suggest stopping at age 75, though the ACS suggests stopping once life expectancy is less than 10 years (one study found that it took almost 11 years before one death from breast cancer was prevented for 1000 women screened)

        -- a useful rule-of-thumb: women age 70 and 75 with no comorbid conditions have a life expectancy of 19 and 15 years respectively; however those women with serious comorbid conditions average a life expectancy of 11 and 9 years respectively

    -- screening between 40 and 50 years old: most conclude that there is a close balance between screening benefits and harms in women between 40 and 50; all studies show that screening this age group has the lowest absolute benefit in terms of deaths prevented, and only two found statistically significant benefits from screening

    -- harms of screening:

        -- overdiagnosis (treatment of a cancer that would not have negatively affected a woman’s health in her lifetime) in 22%, higher in those 40 to 49-year-old (range 23% to 41%) than in those 50 to 59 years old (range 16% to 25%)

        -- false positives, by biopsy: 10% to 42% in those with biennial screen over 10 years, higher with annual screening

        -- false negatives: 10 to 13 per 10,000 women

    -- lots of psychological harms resulting from the need for additional follow-up

    -- lifetime radiation exposure: increases with the number of mammographies. By modeling studies, annual screening of women from age 40 to 74 is associated with a lifetime attributable risk of radiation-induced breast cancer of 125 cases per 100,000 women (see blogs cited below)

-- clinical breast exam (CBE):

    -- a full clinical breast exam takes on average 5 to 10 minutes per breast to do correctly

    -- the organizations basically come out against it because there is no clear evidence of clinical benefit

    -- limited trials do suggest that there may be a 2% to 5% false positive result by CBE, with its attendant related harms.

    -- So, given the lack of supportive evidence, the feeling was that those extra minutes spent on CBE could be used for other primary care interventions

-- Other screening modalities: in general, the various guidelines do not feel that women’s self-examination, magnetic resonance imaging, tomosynthesis, or ultrasound can be justified by the studies done

Formal recommendations:

1. 1. In average-risk women aged 40 to 49 years, clinician should discuss whether to screen for breast cancer with mammography before age 50. Discussions should include the potential benefits and harms, and a woman’s preferences. The potential harms outweigh the benefits in most women aged 40 to 49
2. In average-risk women aged 50 to 74 years, clinician should offer screening for breast cancer with biennial mammography
3. In average-risk women aged 75 years or older or in women with a life expectancy of 10 years or less, clinician should discontinue screening for breast cancer.
4. In average-risk women of all ages, clinician should not use clinical breast examination to screen for breast cancer

Commentary:

-- average-risk women are defined as those with no personal history of breast cancer or previous high risk breast lesion, do not have high-risk genetic mutations or other familial breast cancer syndromes, and were not exposed to radiation therapy to the chest in childhood. In general guidelines do not consider other risk factors in their determination of high-risk, such as early menarche, late menopause, oral contraceptives or postmenopausal hormonal therapy, increased breast density in mammography, or family members with a history of postmenopausal breast cancer.
-- One issue here is that there are a plethora of guidelines on the same subject, typically with somewhat different recommendations. Some of this may relate to which primary studies they select to include in their analysis, how they evaluate/rank the methodology of those studies, what their inherent biases are (ranging from guidelines from specialty societies that have self-interest in promoting a recommendation, some of these guideline committees are dominated by researchers with drug company support; and on the other end of the spectrum, some are biased only towards well-documented randomized controlled trials, limiting their ability to make recommendations on many issues, and, besides, many RCTs are designed by drug companies in ways most likely to promote their products)
    -- and, as per a recent blog, the vast majority of guideline recommendations are “expert opinion” and not based on solid data: see http://gmodestmedblogs.blogspot.com/2019/04/guidelines-lacking-evidence-based.html
    -- it is not so surprising, for example, that the American College of Radiology suggest starting mammography screening at age 40, with annual screening, with no specified age to stop screening
-- so, it is useful to see a thoughtful combination of diverse recommendations. But, in essence, this is still a meta-analysis of meta-analyses. It therefore compounds the potential for inaccuracies inherent in each meta-analysis and obscures some of the differences, since the assumptions and methodology of the initial guidelines/systematic reviews/meta-analyses is no longer transparent (this Am College of Physicians study, however, does try to give some of the granular information from the different guidelines).

-- as a perspective here, mammography is really not so great in the first place, leading to mortality benefit at best in a few women per 1000, yet breast cancer is such a devastating large-scale killer of women. this presents the real issue: primary prevention of most breast cancers by decreasing environmental exposures to phytoestrogens/carcinogens/radiation.  some prior blogs of note:

    -- http://gmodestmedblogs.blogspot.com/2018/06/low-dose-radiation-and-subsequent.html : a study in patients with congenital heart disease, showing that low-dose radiation is associated with cancers, esp breast cancer in women

    -- http://gmodestmedblogs.blogspot.com/2017/01/is-mammography-useful.html: questioning the efficacy of mammography at all, finding lots of cancer pick-up but no change in 10 year mortality; and a 17-year Danish program also finding lots of overdiagnosis but no reduction in incidence of advanced cancers

    -- http://gmodestmedblogs.blogspot.com/2016/10/radiologist-variability-in-mammography.html : showing the quite remarkable variability in radiologist reading of mammograms

    -- http://gmodestmedblogs.blogspot.com/2014/01/mammography-concerns-update.html : showing that the harms of screening may well overwhelm the benefits

So, this Am College of Physicians assessment is probably a reasonable approach overall. a few comments:

--clearly, in the course of discussions with women, they will have different perspectives and sensitivities, and some are likely to want more aggressive testing at a younger age. 

--And, though the 10 year life-expectancy cutpoint noted above may be clinically appropriate, some women prefer to continue screening after that, perhaps appropriately (ie we are wrong in our assessment of 10-year mortality) or perhaps the individual is not ready to accept their limited life-expectancy

--I have personally been reasonably effective in promoting biennial screening from age 50 to 75, pointing out both that more frequent mammograms increase the likelihood of false positives as well as potentially creating radiation-induced carcinoma. Though, lacking data, it still make sense to me to continue that screening in healthy women over age 75, given both that the absolute risk reduction of breast cancer mortality seems to increase with age, and that many women will live 15 to 20+ more years. 

geoff

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