Breast Cancer Screening Guidelines Changing again

Furore in the colleges and societies, as the US preventive services task force releases it's new breast cancer screening guidelines, following the release of a paper in the Annals of Internal Medicine today

Their recommendations for starting screening at 50 (for women without a family history of breast cancer) with mammograms every 2 years, and ending at 74 years, more closely mimics the recommendations for screening in European countries, and broadly similar to the UK NHSBSP.

The task force is an independent panel of experts in prevention and primary care appointed by the federal Department of Health and Human Services.

The guidelines were published in today's (Nov 16, 2009) edition of the Annals of Internal Medicine

In order to formulate its guidelines, the task force used new data from mammography studies in England and Sweden and also commissioned six groups to make statistical models to analyze the aggregate data. The models were the only way to answer questions like how much extra benefit do women get if they are screened every year

Dr. Karla Kerlikowske, a professor in the department of medicine, epidemiology and biostatistics at the University of California, San Francisco said "The message for most women is to forgo routine mammograms if they are in their 40s.

Starting at age 50, Dr. Kerlikowske said, “the message is to get 10 mammograms in a lifetime, one every two years.” That way they get the most benefit and the least harm from the test. If women are healthy, she added, they might consider having mammograms every two years until age 74.

Nearly two-thirds of all women in their 40s had mammograms within the last two years, as did 72 percent of women age 50 to 65, according to an editorial by Dr. Kerlikowske that accompanies the report.

The Society of Breast Imaging and the American College of Radiology, the American Cancer Society, and many other respected professional organizations, have voiced strong opposition to the changes proposed in the articles.

It is the opinion of the SBI leadership that adopting these guidelines would result in a major step backward in women's healthcare and increased deaths from breast cancer.

Immediately, they provided a number of guidance documents and statements as follows (which is a model for speedy response to crises) -


STATEMENT FROM THE AMERICAN COLLEGE OF RADIOLOGY AND THE SOCIETY OF BREAST IMAGING:
USPSTF Mammography Recommendations Will Result in Unnecessary Breast Cancer Deaths Each Year

Talking Points in response to USPSTF Statement

Detailed ACR Statement on Ill Advised and Dangerous USPSTF Mammography Recommendations: Mammography Screening References

American Cancer Society Statement

Komen Screening Statement 11-16-09

NCI Statement

Rethinking strategies for breast and prostate cancer screening

Twenty years of screening for breast and prostate cancer—the most diagnosed cancers for women and men—have not brought the anticipated decline in deaths from these diseases, argue experts in an opinion piece published Wednesday in the Journal of the American Medical Association

In an article published yesterday (Oct 21, 2009) in JAMA, Laura Esserman et al, one of our UCSF breast surgeons, and leader of the ATHENA project in the University of California, discuss whether we should be reconsidering looking at our screening tools for both breast and prostate cancer, and be more intelligent in their use.


"Screening does provide some benefit, but the problem is that the benefit is not nearly as much as we hoped and comes at the cost of over-diagnosis and over-treatment," said Laura Esserman, MD, professor of surgery and radiology, director of the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center.

We acknowledge that screening is not perfect, as there are a proportion of women who are screened but would never die of the disease (lead time bias). Also there are the group of women who present as interval cancers due to their very different biology. These women still get their mammograms at the proscribed times, but tend to develop cancer between their screening tests.

"We need to focus on developing new tools to identify men and women at risk for the most aggressive cancers, to identify at the time of diagnosis those who have indolent or 'idle' tumors that are not life-threatening,"

Periodic screening may find some tumors early, but patients may not be screened often enough for lethal tumors to be detected in time to prevent death, leading the authors to conclude: "Without the ability to distinguish cancers that pose minimal risk from those posing substantial risk and with highly sensitive screening tests, there is an increased risk that the population will be over-treated."

The authors suggested that to improve screening, "a new focus is recommended for research and care to identify markers that discriminate minimal-risk from high-risk disease (and) identify less aggressive interventions for minimal-risk disease to reduce treatment burden for patients and society."

The authors made the following recommendations for early cancer detection and prevention:

• Develop tests to distinguish between low-risk and lethal cancers.
• Reduce treatment for low-risk disease. “Diagnosing cancers that don't kill the patient has led to treatment that may do more harm than good,” they wrote.
• Develop tools for physicians and patients to help them make informed decisions about prevention, screening, biopsy and treatment.
• Offer treatments individually tailored to a patient's tumor.
• Work to identify the people at highest risk for cancer and use proven preventive interventions.

As part of the ATHENA project we are looking at these aspects across the whole of the University of California medical centers (UCSF, UCLA, UC Irvine, UC Davis and UC San Diego).
This is a mix of researcher and clinicians who are trying to put research to clinical use (bench to bedside medicine)

Targeting screening tests to the at risk population may give better outcomes with fewer so called "false positives" from screening, thereby benefiting the screened women the most. It will also save us from overtreating some of the lower risk/indolent cancers that occur.

NCI commentary is available in their bulletin

CAD and Screening Mammography: ready for prime time?

In this months RADIOLOGY, Robyn Birdwell and Liane Philpotts share their different viewpoints on CAD and screening mammography. Both are well known mammographers in the North East, with Robyn being a guest of the RCR Breast Group at November's Annual Scientific Meeting

In the first of the two articles, Robyn Birdwell talks about the various CAD studies, and how the proponderance of data supports the use of CAD in screening mammography, and that "Having a system to aid the human eye that does nottake vacations, is not vulnerable to fatigue or environmental distractions, is without, emotion, and is designed specifically to assist the very human eye to "look over here" seems like a good idea"
The Preponderance of Evidence Supports Computer-aided Detection for Screening Mammography
Robyn L. Birdwell
Radiology 2009;253 9-16
http://radiology.rsna.org/cgi/content/full/253/1/9?etoc

In the second editorial article, Liane Philpotts points out that recalling patients from screening is sometimes more of an art than a science, and I am sure that many experienced radiologists would share her view.

One of the main issues with CAD is the necessary high false-positive rate of CAD prompts which subsequently means that the specificity is low, and we have the distracting factor of many false calls, while also knowing that not all cancers are picked up by CAD

Understanding of the limitations of computer-aided detection is important for those interpreting mammograms; this cautious approach to the use of computer-aided detection should help optimize this presently imperfect system and minimize the possible detrimental effects

Can Computer-aided Detection Be Detrimental to Mammographic Interpretation?
Liane E. Philpotts
Radiology 2009;253 17-22
http://radiology.rsna.org/cgi/content/full/253/1/17?etoc

Informing patients about breast cancer screening - risks of overdiagnosis

A recent posting on the NHS National Prescribing Centre website blog addresses the issues of possible overdiagnosis of inconsequential cancers found as part of routine screening.

Blog link here

It is estimated that approximately 30% of breast cancers found at screening are of low grade and metastatic potential (low oncotype score) which may never kill the patient, and are therefore counted as being overdiagnosis.

Various tools are available to help primary care providers and others wishing to assist women to make informed decisions about whether to have screening or not.

Patient decision aids may help to guide women make the decision alongside the literature from the NHSBSP

Breast Cancer Risk in Female Survivors of Hodgkin's Lymphoma: Lower Risk After Smaller Radiation Volumes

Breast Cancer Risk in Female Survivors of Hodgkin's Lymphoma: Lower Risk After Smaller Radiation Volumes
Marie L. De Bruin, Judith Sparidans, Mars B. van't Veer, Evert M. Noordijk, Marieke W.J. Louwman, Josée M. Zijlstra, Hendrik van den Berg, Nicola S. Russell, Annegien Broeks, Margreet H.A. Baaijens, Berthe M.P. Aleman, and Flora E. van Leeuwen
Journal of Clinical Oncology, Vol 27, No 26 (September 10), 2009: pp. 4239-4246

Link to Journal

Some good signs for the future in this article from the Netherlands on the breast cancer risk reduction following the reduction in radiation volumes for Hodgkin's disease sufferers.

Reduction of radiation volume appears to decrease the risk for Breast Cancer after Hodgkin's Lymphoma. In addition, shorter duration of intact ovarian function after irradiation is associated with a significant reduction of the risk for Breast Cancer

Image display contrast variation negates consistent mammo readings

So it seems that much of the effects found by the DMIST Study were due to image contrast, inherent with digital imaging.................

A report in Radiology from the DMIST investigators in the August edition -
Radiology August 2009 252:348-357

Link to Journal

Readers most frequently attributed differences in DMIST cancer visibility to variations in image contrast—not differences in positioning or compression—between digital and screen-film mammography.

For women with both fatty and dense breasts, the most frequent reason given for the difference in visibility between film-screen and digital mammography was contrast differences between the two modalities. For women with dense breasts, contrast differences accounted for 70 of the 378 reasons given by the readers for better visibility. Positioning, compression, and technique differences accounted for only 37 of the reasons given for improved visibility

The odds of a cancer being more visible on a digital mammogram—rather than being equally visible on digital and screen-film mammograms—were significantly greater for women with dense breasts than for women with non-dense breasts, even with the data adjusted for patient age, lesion type, and mammography system (odds ratio, 2.28; P < .0001).

The odds of a cancer being more visible at digital mammography—rather than being equally visible at digital and screen-film mammography—were significantly greater for lesions imaged with the General Electric digital mammography system than for lesions imaged with the Fischer (P = .0070) and Fuji (P = .0070) devices. No comment was made about Hologic

The significantly better diagnostic accuracy of digital mammography, as compared with screen-film mammography, in women with dense breasts demonstrated in the DMIST was most likely attributable to differences in image contrast, which were most likely due to the inherent system performance improvements that are available with digital mammography. The authors conclude that the DMIST results were attributable primarily to differences in the display and acquisition characteristics of the mammography devices rather than to reader variability.

JNCI response to latest attack on screening by Grotzche et al

JNCI response to latest attack on screening by Grotzche et al

In a very balanced editorial in today's JNCI, Liz Savage writes about the recent letter to The Times of London, and the claim that up to 50% of cancers are diagnosed unnecessarily by the NHS Breast Screening Programme (NHS BSP), but primarily the attack was again on the content of invitation leaflets sent to women at each invitation. These were changed or amended after their last attack in the media a few years ago.

Although some of their criticism remains valid, their wild claims that 50% of cancers detected by screening would never kill women remains unsubstantiated.
While it is clear, that some women have an exceptionally good prognosis, and probably would never have had disease that would have killed them, the majority (or even if it was just the 50%) would definitely have been helped.

Newer genomic typing of tumors may assist at an early stage of diagnosis (perhaps at initial core biopsy) which group of risk she is in, then if low, she may not need any treatment, or just hormone therapy instead of the current more invasive procedures.

Typing, such as that used by mammaprint (nl), may be able to distinguish between three separate groups, with minimal overlap. Laura Vantveer, on sabatical with UCSF from Holland is developing this technique on all our cancers treated at UCSF. The middle group of women with less aggressive subtyping and the ones most likely to be helped by screening, the high risk women showed marked aggressivity at any size, and appear to need everything (including the kitched sink) thrown at them, to get a response (CPR - complete pathological response)

Women with the least aggressive subtype, may be represented by this group who never progress to a 'killer' cancer, and may be overtreated by being offered chemotherapy, radiotherapy or even surgery. If these cancers NEVER kill anyone, maybe a different term - other than carcinoma - may need to be used to indicate that these are a different disease compared with the real cancers.

These are interesting times, and allow us to start thinking more intelligently about screening, and the outcomes from screening. In the meanwhile.... let's get back to ensuring that women are adequately informed about the benefits and risks at their invitation.