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.

Triple negative breast cancers are increased in black women regardless of age or body mass index

More on Triple Negative Breast Cancer amongst Black Women - OF ANY AGE
Triple negative breast cancers are increased in black women regardless of age or body mass index
Lesley Stead, Timothy L Lash, Jerome Sobieraj, Dorcas Chi, Jennifer Westrup, Marjory Charlot, Rita Blanchard, John-cho Lee, Thomas King, Carol L Rosenberg

Breast Cancer Research 2009, 11:R18doi:10.1186/bcr2242

Reported online, on the breast cancer research website. black women are three times more likely than other women to develop an aggressive form of breast cancer characterised by "triple negative tumours. The findings held true even when other risk factors such as lifestyle, age and weight were taken into account. In the United States, where the study was conducted, the overall incidence of breast cancer is lower in black women than in white women. But when black women do get breast cancer, it tends to be more advanced when diagnosed, has a higher risk of recurring, and a less favourable outcome.

Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI.

Researchers led by Carol Rosenberg of Boston University analysed 415 breast cancer cases and noted the number of "triple negative" tumours, so called because three critical proteins -- estrogen and progesterone receptors, and the HER2 gene -- malfunction.

"The odds of having a triple-negative tumour were three times higher for black women than for non-black women," said Rosenberg

It had been known that pre-menopausal black women were disproportionately affected by this deadly form of cancer, but the new study showed that these tumours were just as common in black women diagnosed before or after age 50, obese or not.

The higher prevalence of triple negative breast tumours in black women in all age and weight categories likely contributes to black women's unfavourable breast cancer prognosis

Early detection of second breast cancers improves prognosis in breast cancer survivors

Early detection of second breast cancers improves prognosis in breast cancer survivors
N. Houssami, S. Ciatto, F. Martinelli, R. Bonardi, and S. W. Duffy
Advanced access to the publication of this paper, published online March 19, 2009
The impact of early detection of second breast cancers in women who have survived a primary breast cancer is unknown.
The researchers looked at information on 1,044 women who were seen at a medical center in Florence, Italy, between 1980 and 2005 and who had developed a second breast cancer -- 455 with cancer in the same breast (ipsilateral) and 589 with cancer in the opposite breast (contralateral). Of the second breast cancers, 67 percent were asymptomatic, and 33 percent were symptomatic.

The study found that chances of survival improved between 27 percent and 47 percent if the second breast cancer was detected in the early, asymptomatic stage rather than at a later stage when women started to experience symptoms.

The researchers also found that mammography
was more sensitive than clinical examination for detecting second breast cancers -- 86 percent vs. 57 percent. However, 14 percent of the cancers were detected only by clinical examination.

Asymptomatic cancers were smaller than symptomatic cancers, and early-stage cancers were more common in asymptomatic women (58 percent) than in symptomatic women (23 percent). Fewer women with asymptomatic than symptomatic contralateral cancer had node metastases, an indication the cancer may have spread.

Take home message:
Early detection of second breast cancers can reduce the risk of death by as much as half

First Report of a Necrotising Fasciitis of the Breast Following a Core Needle Biopsy

The first report of the aggressive infection, necrotising fasciitis following core biopsy of the breast has been reported by researchers in France.

In a paper published in The Breast Journal this month, the department of OB/GYN in Montpelier, France, describe the case of a 50 year old woman one week after a 14g stereotactic core biopsy for a BIRADS 4 - suspicious lesion.

This is an aggressive infection with a beta-hemolytic streptococcus, which requires aggressive surgery to clear (debride) the infected tissue. Previously only described following mastectomy or breast reduction, this has now occurred following a simple routine core biopsy.

When consenting a patient for a core biopsy, we routinely describe the complication of infection, along with bruising and non-removal of the target lesion. Based on this case, our management should not change, but it remains a salutary lesson, that the most aggressive type of infection can occur in patients attending for a routine biopsy.

Continued attention to hand hygiene, and an aseptic field during biopsy remain important. Interestingly, the staff performing the biopsy did not have their skin tested for whether they were carriers of the B-Hemolytic strep, so we wil never know whether this was a factor

Moderate Alcohol Intake and Cancer Incidence in Women

Published this week in the Journal of the National Cancer Institute, and available to members on the RCRBG website, is the revelation from the Million Women Study, that any alcohol is 'bad' alcohol, as regards breast cancer risk.

Valerie Beral's team at Oxford demonstrated that increasing but moderate alcohol consumption in women was determined to be associated with an increased risk of cancers of the oral cavity and pharynx, esophagus, larynx, rectum, breast, and liver, and with a decreased risk for thyroid cancer, non–Hodgkin lymphoma, and renal cell carcinoma. No differences in cancer risks were observed between drinkers of wine only and other consumers of alcohol

As ever, this could be seen as a scare story, but has to be taken in context with some of the other proven beneficial effects - eg a glass of red wine and its protective effects against heart disease.
If you are a woman who is at increased risk already from family history or a prior biopsy of atypia, maybe you are the one who needs to be aware of this finding and consider modifying your lifestyle.

In the greater scheme of things, everything has risks and benefits - look at HRT use itself, which was the original target of this research

RECIST criteria for tumour volume measurement for trials

The first, formal revision of specific guidelines, known as RECIST (Response Evaluation Criteria in Solid Tumours), used by clinicians to measure tumour size and response to treatment, has been published January 20 in a special issue of the European Journal of Cancer
European Journal of Cancer
Volume 45, Issue 2, January 2009

The only proven way of measuring tumour response is by measuring size on imaging. This of course is subject to measurement error, and so criteria have been published that allow measurement of response in even small tumours (5mm)

When it comes to clinical trials of therapeutic agents, tumour shrinkage (objective response) and time to the development of disease progression are both important endpoints in trials, and, increasingly in recent years, trials have been using time to progression (or progression-free survival) as their main endpoint on which to base conclusions about the efficacy of a drug.

The new RECIST (RECIST 1.1 to distinguish them from the original RECIST) answer some of the questions and issues that have arisen since 2000 as a result of changing methodologies and available treatments

Key changes in RECIST 1.1 that will simplify, optimise and standardise the assessment of tumour burden in clinical trials are as follows:

1. A reduction in the number of lesions to be assessed for response from a maximum of ten to five, and from five to a maximum of two per organ
2. New guidance on making robust measurements of lymph node involvement
3. Confirmation of response is required for trials with objective response as a primary endpoint, but is no longer required for randomised studies, since the control arm of these studies provides appropriate means for interpreting results of the experimental arm
4. The definition of disease progression has been refined so that it not only includes a 20% increase in the size of the lesion, but also a 5 mm absolute increase as well, so that changes of just a few mms in very small tumours, which may be within the range of measurement error, are not unnecessarily described as disease progression
5. Guidance on imaging, including its use in the detection of new lesions and the interpretation of FDG-PET scan assessment

Rising incidence of cancer in survivors

Rising incidence of breast cancer among female cancer survivors: implications for surveillance
Paper in this months British Journal of Cancer, British Journal of Cancer (2009) 100, 77 – 81 from the Netherlands, showing a marked rise in breast cancer incidence among female cancer survivors.

There are certainly questions raised from this study, in contradistinction to recent papers suggesting that most patients who are not in trials or undergoing adjuvant therapy can be discharged after surgery.

What implications will it have on your Cancer Centre's policy?