Posts

17 July 2019

There are no standard guidelines for mammographic screening for men who have no symptoms (such as a lump), even if they are considered to be at high risk for developing breast cancer. A study recently published in Breast Cancer Research and Treatment* evaluated the performance of screening mammography in asymptomatic high risk men.

The researchers reviewed a prospective institutional database at the Memorial Sloan Kettering Cancer Center, evaluating cases from 2011 – 2018. 827 men underwent mammography during that time period, but 80% were excluded from evaluation for this study as they underwent imaging due to the presence of a mass or other symptoms. Data from 163 asymptomatic patients, considered high risk due to a family and/ or personal history of breast cancer or the presence of a deleterious genetic mutation, was analyzed. 

Of the 163 men, 77% had personal history of breast cancer and 44% had a family history of breast cancer. 15% had deleterious BRCA mutations. Most of the genetic mutations (83%) were in the BRCA2 gene, as expected.

Over the 7-year time period, 806 screening mammography examinations were performed. The majority (792 studies, 98%) were BIRADS 1 or 2, indicating a normal study or benign findings. 10 (1.2%) were BIRADS 3 indicating a “probably benign” finding. Upon follow up, all of these patients were considered to have benign findings. 4 men had BIRADS 4 or 5 findings indicating suspicious or highly suspicious findings for which biopsy was recommended, and all were diagnosed with invasive ductal breast cancer.

Breast cancers in men are often diagnosed at more advanced stages than in women, and as a result, outcomes may be poorer. The authors noted that while mammographic screening has not been shown to reduce breast cancer mortality rates (the reason screening is performed) in men, the detection rate in this high-risk population (4.96 per 1000 examinations) is comparable to the breast cancer detection rate from screening mammography in average risk women. There were no false-positive (“false alarm”) biopsies in this group. The authors acknowledged one of the primary limitations of their study, the relatively small number of patients, and called for larger studies to confirm their findings. They concluded that their study “suggests that screening mammography should be performed in men at increased risk for breast cancer.”

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

3 May 2019

The American Society of Breast Surgeons (ASBrS) has updated their screening mammography guideline, recommending that women of average risk begin annual screening mammograms at age 40. This update brings the ASBrS guideline more in line with those of the American College of Radiology and the Society of Breast Imaging, and are a departure from their previous guideline, which called for screening to start at age 45. The American Cancer Society recommends annual screening from age 45-54, followed by biennial screening with the opportunity for annual screening. The US Preventative Services Task Force recommends biennial screening starting at age 50.

The updated ASBrS guidelines recommend as a first step that all women undergo a formal risk assessment starting at age 25. Risk assessment involves using any one of a number of models to estimate 5-year and lifetime risk of breast cancer development. These models take into account age, family history, menstrual and pregnancy history as well as history of prior biopsy and racial / ethnic background. Some models take into account body mass index and breast density. The ASBrS guideline has additional recommendations, outlined below, depending on risk level. The recommendations listed for women at high risk of breast cancer are consistent with those of the American Cancer Society and National Comprehensive Cancer Network.

When to start and how often to perform screening mammography has been the subject of much debate over the years. The primary issue is the number of lives saved balanced against the harms of screening mammography. Harms include false negatives (cancer is not detected by the mammogram), false positives (suspicious areas that turn out to be benign) and recommendations for additional imaging (added cost and concerns about the potential effects of cumulative radiation). There have also been concerns raised about over-diagnosis and over-treatment: finding cancers that would never pose a threat to a woman’s health or life – but the patient is exposed to the potential harms of cancer therapy.

The goal of screening is not to detect all cancers – otherwise we would recommend complete body imaging for everyone. The goal of screening is to improve the survival from the cancers that are detected. An ideal screening test is relatively inexpensive and performs equally well in the patient population undergoing the screening. Mammography is acknowledged to be an imperfect screening tool – while relatively inexpensive and safe, it simply does not perform the same in women with breasts of different ages and densities. Approximately 1000 women need to be screened to detect 2 – 7 breast cancers, and mammography performs best in women age 50-74. In younger women, a few cancers will be detected, and there may be a survival benefit. However, because breast cancer is less common in younger women, a larger number of women need to be screened to find a single cancer, increasing the likelihood of a harm. The benefits of screening do not always outweigh the risks – at least for an individual patient.

It is also important to note that some of the new ASBrS recommendations, such as 3D mammography as the preferred type of mammogram, supplemental ultrasound in women with dense breasts, and MRI for all women with a history of breast cancer, are still undergoing investigation and are not always covered by insurance. We know that these studies will find additional cancers, but we do not yet have data on improved outcomes. My patients know that I am fond of saying “the more we look, the more we find, but not everything we find needs to be found.”

Two ongoing studies will hopefully provide additional information regarding 3D mammography and screening interval:

  • The TMIST trial is a national multi-center study assessing the performance of 3D compared to 2D digital mammography. This study will assess rates of cancer detection, callbacks and benign biopsies as well as biology of the tumors detected and outcomes.
  • The WISDOM study is evaluating a risk-based screening approach. After a comprehensive risk assessment, genetic testing, and assessment of risk tolerance, patients are assigned annual versus biennial screening. Women can self-enroll in this study (disclosure – I am not involved with the study team but I am enrolled in the study as a participant) and do not have to change mammography facility.

Until we are at a point when an individual woman’s level of risk can be accurately predicted, there is no definitive “best” screening guideline to follow. Recognizing the potential harms of screening mammography, it is no longer appropriate for physicians to simply hand out an order for an annual screening mammogram for all women starting at age 40. A balanced discussion, taking into account an individual woman’s risk and level of risk tolerance as well as the absolute potential benefits and harms of mammography is indicated. These discussions are nuanced and take time. Various genomic assays are being evaluated and it is hopeful that we will at some point have a test that can accurately predict a woman’s risk of breast cancer – which can then be used to provide more tailored guidance regarding imaging. Until that time (and I hate to end this way…), talk to your physician and medical team about what screening option is right for you.

23 August 2016

A study published in the Annals of Internal Medicine evaluated screening mammography taking into account breast density and breast cancer risk. For women age 50-74, the conclusion of the authors was that for women of average risk with low breast density (fatty or scattered fibroglandular), triennial (every 3 year) mammography screening averted the same number of breast cancer deaths as annual or biennial screening. Women screened every 3 years also had lower rates of biopsy procedures. For women at high risk with high breast density (heterogeneously or extremely dense), annual screening was better. High risk / high density patients accounted for approximately 1% of the study population.

The study was funded by the National Cancer Institute. The authors used simulation modeling which included national breast cancer incidence, breast density, and screening performance data. They did not include patients with genetic abnormalities such as BRCA 1/2 mutations. They also did not take into account the impact of MRI or tomosynthesis / 3D mammography.

Risk assessment involves a calculation (using various models) which takes into account a woman’s age, body mass index, menstrual and reproductive history, family history, prior biopsies, and other factors known to influence the risk of breast cancer development. In the current study, the authors used a risk calculator that takes into account breast density. Breast density is a factor associated with breast cancer, although studies vary regarding the impact of density on risk. Adding to the confusion, breast density rating is subjective – different radiologists may assign different density scores to the same patient. The model used in the current study also takes into account factors such as improved detection using digital mammography, improved treatment effectiveness, and the usual decrease in breast density that is seen with increasing age. It is unclear at this time which is the “best” risk assessment model to use – all have limitations, some significantly over-estimate risk, and none are a “crystal ball”.

So what should women do? The ideal screening test is one that is inexpensive, readily available and safe. It should also find cancers early enough to make a difference. Mammograms are an imperfect tool but they perform reasonably well in a wide variety of settings. The ideal screening program is to tailor the technology and screening frequency to the patient’s risk – one size never fits all. Women should be aware of their family history and risk factors, ask about their breast density, and then discuss these factors as well as their personal preferences regarding breast cancer screening with their physicians. True individualized and personalized risk-based screening is not yet a reality, but by making recommendations based on risk, we are taking steps in the right direction.

17 January 2016

In October 2015, the American Cancer Society (ACS) updated their screening mammography guidelines, raising a lot of questions and concerns as annual mammograms were no longer recommended for all women starting at age 40. The United States Preventative Services Task Force (USPSTF) released new guidelines on screening mammography last week. The new USPSTF guidelines recommend an individualized risk-based approach for women age 40-49, and mammographic screening every other year for women age 50-74. The task force acknowledged that screening mammography reduces the likelihood of dying from breast cancer, but noted that the benefit was the greatest for women age 60-69, and the benefit was small for women age 40-49. For younger women, they noted that screening mammography is associated with higher false positives (false alarms).

The conflicting guidelines published by the USPSTF, ACS, and other organizations have caused much confusion. Many women simply want to know what they should do. The reality is, screening mammography is a one size fits all tool, and as any woman knows, that doesn’t really work. The sensitivity (“effectiveness”) of mammograms will vary depending on a patient’s age, menstrual status, use of hormone therapy, body mass index, breast density, and other factors. It is unrealistic to expect that one test can account for all of those variables, as well as personal risk factors for breast cancer, and personal preferences regarding screening risks and benefits.

To state it very simply:

  • Mammograms may lead to improved survival from breast cancer by detecting some cancers early
  • Some breast cancers are so aggressive that early detection does not lead to improved survival
  • Mammograms are imperfect

It is important to note that the USPSTF and ACS recommendations apply to average risk women. Unfortunately, risk assessment is not routinely performed, and many factors associated with an increased risk, such as heavy alcohol intake and breast density, are not taken into account in the existing models. In an ideal world, we would swab a cheek, obtain some DNA, and then determine whether or not a woman is predisposed to develop breast cancer [I’m thinking beyond BRCA and other genetic testing here]. If we can determine that a 30 year old woman, even without a family of breast cancer, is predisposed to develop the disease, we can make educated screening recommendations (perhaps ultrasound and/or MRI, as mammograms are not very helpful in very young women).  If we can determine that a woman is highly likely to die of a heart attack by age 60, and has no cancer predisposition, she might make the decision to forego screening mammography. Unfortunately we’re not quite there yet, but there are genetic risk tests under development.

I recently spoke with a researcher specializing in cancer risk. We discussed that at the end of the day, multiple organizations will continue to look at the evidence and draw different conclusions, so in his opinion, it wasn’t realistic that we should expect consensus. Physicians, researchers, and organizations are currently spending a lot of time and effort arguing with each other about whether mammography should start at age 40, if mammograms should be performed every versus every other year, and when screening should stop. However, our time and efforts might be better spent by working together to address issues such as disparities in access to screening mammography and lack of access to quality mammography and breast care for many women.

Recognizing the variability of each woman and her breasts, acknowledging the uncertainties regarding the risks and benefits of screening, and focusing on a shared decision making approach might help reduce some of the confusion. In medicine, as in many areas in life, there is often more than one right answer. The same applies to screening mammography. Time to move beyond the one size fits all approach.

Additional Reading:
New York Times: Panel Reasserts Mammogram Advice
JAMA: A Public Health Framework for Screening Mammography: Evidence-Based vs Politically Mandated Care 
New York Times: Insurer Rewards Push Women Towards Mammograms
Forbes: A Turning Point in the Breast Cancer Screening Debate?
NPR Shots: Federal Panel Finalizes Mammogram Advice That Stirred Controversy
OncLive Final USPSTF Guidelines
Cornell Mammogram Decision Aid for Women age 40-49

25 October 2015

The American Cancer Society has issued new guidelines for screening mammography, and they are sparking a lot of discussion. Previous guidelines, which have been in place since 2003, have recommended:

  • Annual mammography beginning at age 40 and continuing for as long as a woman is in good health
  • Clinical breast exam (CBE) [exam by a physician] about every 3 years for women in their 20’s and 30’s, and every year for women 40 and over
  • Women should know how their breasts normally look and feel and report any breast changes to a health care provider right away. Breast self-exam (BSE) is an option for women starting in their 20’s.

The current guidelines recommend:

  • Women should undergo regular screening mammography starting at age 45
  • Women 45 to 54 years of age should be screened annually
  • Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually
  • Women should have the opportunity to begin annual screening between the ages of 40 and 44 years
  • Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer
  • Clinical breast exam is not recommended for breast cancer screening among average risk women of any age

The full study was published in the Journal of the American Medical Association. These guidelines seem to be a drastic change, but they are based on careful evaluation of the available literature. They are also more in line with the US Preventative Services Task Force recommendations for breast cancer screening (which are in the process of being updated). Mammograms certainly are of benefit in terms of early detection. However, as we have gained a better understanding of the importance of tumor biology, the mantra “early detection saves lives” does not hold true for all.

As stated on the American Cancer Society website, “The goal of screening mammograms is to find breast cancer early, when treatment is more likely to be successful. But mammograms aren’t perfect, and they do have risks. Sometimes mammograms find something suspicious that turns out to be harmless, but must be checked out through more tests that also carry risks including pain, anxiety, and other side effects.” I disagree with using anxiety as a reason to limit screening recommendations. While some women do experience significant anxiety related to mammography callbacks, proper pre-mammogram counseling should help alleviate some of the worry. As Dr. Elaine Schattner noted in her piece published in Forbes, “concern about fear or anxiety should not form the basis of any screening recommendations”.

These guidelines apply to “average risk” women. But given that ANY woman (and any man) may develop breast cancer, what does “average risk” mean? The first part of risk assessment should be a careful history, including a careful and detailed family history. While most realize that a having a family history of breast cancer increases their risk, fewer understand that family history of other cancers, including ovarian, colon and pancreatic cancers may be “hereditary red flags”, and genetic counseling and testing might be indicated. There are several risk assessment models which can and should be used by physicians on a routine basis. Newer forms of risk assessment which include evaluations of small variations in an individual’s DNA may provide a more personalized risk assessment. The contribution of breast density as well as lifestyle factors such as weight, level of activity, and alcohol intake need to be considered. The North Shore – LIH Health System and Bright Pink both have helpful risk assessment tools.

Mammography has never been a perfect screening test. It has significant limitations in young women and those with dense breast tissue, and in older women it may find more than it needs to. We have a “one size fits all” test, and women and their breasts are most certainly NOT “one size fits all”. The decision when to begin screening and how often to be screened is now a shared decision, between a patient and her physician. Decision support tools, such as Weill Cornell Medical College’s Breast Screening Decisions program, can help women sort through the conflicting information and make a decision that is right for them.

While guidelines can be helpful in making recommendations for populations, the ideal screening method for the individual remains to be seen. For screening mammography to truly be of benefit, we need to determine who is at risk and then decide what imaging modality is most appropriate for that individual woman. We also need to know which lesions, once detected, can safely be ignored. We know where we need to be. Now the science and technology needs to catch up.

Additional information:
New Guidelines for Breast Cancer Screening in US Women – JAMA Editorial
Science Won’t Settle the Mammogram Debate
Stat News: New Guidelines Urge Later, Less Frequent Mammograms
Mammography Guidelines Revisited – Lori Marx Rubiner

 

20 July 2015

This is not a new question, and I promise there will be many parts to this story. The latest: Breast Cancer Screening, Incidence and Mortality Across US Counties, published in the July 2015 issue of JAMA Internal Medicine. The authors of the study noted that rates of early breast cancer detection have increased with the widespread use of screening mammography, but death rates from breast cancer have not decreased, leading to the conclusion that many breast cancers are “overdiagnosed”.

One would expect that if there were an increase in the number of early breast cancers detected due to screening mammography, fewer women would subsequently die from breast cancer. Isn’t early detection the key to survival? A reasonable question that is raised from this study is “What is the value of screening mammography?”. First, several points:

  1. The authors noted that the rates of early breast cancer, especially DCIS, have increased significantly with the widespread use of screening mammography.
  2. It is well known that some breast cancers have such an indolent biologic behavior that they will never become a threat to a breast or to a life.
  3. The more we screen, the more we find. Not everything needs to be found.
  4. Finding indolent lesions is considered “overdiagnosis”. Treating these lesions with traditional surgery, radiation and other treatments is considered “overtreatment”.
  5. Early detection does not always equal cure. Some breast cancers have a very aggressive behavior, and may prove to be fatal even when diagnosed in early stages.

Before you cancel your upcoming mammogram, appointment, some limitations of the study were pointed out in an accompanying editorial: Effect of Screening Mammography on Cancer Incidence and Mortality. One of the biggest criticisms is how the study was actually conducted, using the “ecological method”, which studies large groups, not individuals. It is not possible to tell if the women who were diagnosed with breast cancer are the same ones that subsequently died due to the disease. Other limitations of this of study are that no information is available on tumor subtypes or adjuvant therapy (chemotherapy, hormonal therapy and radiation). Another limitation of the study is that it evaluated data over a 10 year period, which might not be long enough to have an impact on survival rates. Finally, it was discussed that there was the potential for “confounding bias” – factors associated with an increased risk of breast cancer might also be associated with an increased rate of obtaining screening mammograms. [For a good discussion of the types of bias that may be present in research studies, review this article from HealthKnowledge.]

There is no question that we are finding more early stage breast cancers, including DCIS. There is much debate on whether or not DCIS even represents “cancer”. But the reality is that while we recognize that not all cancers will progress, we do not yet have the ability to predict the behavior of a cancer with certainty for an individual woman. We do not yet have that crystal ball.

So now what? The conclusion always seems to be “ask your doctor”. But physicians do not have all of the answers. What is clear is that the decision to begin or continue screening mammography is no longer automatic – discussion about the benefits of mammography, the potential harms, a woman’s own risk tolerance, and personal beliefs is necessary – this is the essence of shared decision making.

Various online tools have been developed to help women make more informed decisions. One is Weill Cornell Medical College’s Breast Screening Decisions, meant to be used by women in their 40’s. This is a start. We also need to develop that “cancer crystal ball”, which will allow us to more accurately predict who will develop cancer, and the behavior of a cancer that has developed. We’re just not there yet. Stay tuned as this is certainly not the last word on this issue.

17 February 2014

Spoiler alert – this will hardly be the last word on the screening mammography debate…

Last week, the British Medical Journal published a Canadian Study which concluded that mammograms are not effective in reducing breast cancer deaths. The study involved 90,000 women. However, there are some major flaws in the study, and “rapid response” letters to the editor were published within hours of the study release. So while the headlines scream “mammograms are not helpful”, the study is in question and it may not be possible to draw this conclusion.

While previous randomized trials have shown a reduction in breast cancer mortality due to screening mammography, there is no doubt that mammography is far from perfect. We have to screen a large number of women to diagnose one with breast cancer. In doing so, a percentage of women will require additional imaging and/or will undergo a needle biopsy for a benign finding. Mammography is not as helpful in younger women and in those with dense breast tissue. In addition, as technology has improved to allow us to see through the breast with more detail, we are diagnosing cancer (and precancerous conditions) that may never become a threat to a woman’s life.  We are trying to find the balance between early detection which often (but not always) leads to improved survival, versus over diagnosis and over treatment.

Part of the problem is our technology. The results of screening mammography are highly variable depending on the patient’s age, breast density, weight, use of hormone therapy, and other factors. We have a one-size-fits-all test, which as every one knows, is really one-size-fits-none. We are also limited in who we screen. Women younger than 40 without a family history of breast cancer have no routine screening recommendations, and mammography is not very helpful in this age group. Many will use this as an argument for the use of ultrasound or MRI examinations. While these modalities may be extremely helpful in a given patient, they have not been proven to be effective in reducing mortality from breast cancer when applied to a general screening population.

It is important to realize that we have an imperfect technology, and our application of that technology to the individual is also imperfect. More research is needed to determine who is actually at risk, and who will truly benefit from screening. In addition, screening needs to be more individualized – a mammogram is not the right screening tool for all. Dr. Peter Beitsch, Past-President of the American Society of Breast Surgeons, has said on many occasions that “female and 40 is no longer acceptable for screening mammography – we need to risk assess each woman individually and use appropriate breast imaging tailored to them.”

In addition to more individualized screening, research is needed into which cancers even need to be treated. Many breast cancers found on mammography may never become a threat to a woman’s life. However, a hallmark of cancer is cell mutation – the slow-growing cancer today may not behave that way in the future, so at this point we err on the side of over treatment, as we cannot reliably predict future biologic behavior. Dr. Robert Miller, a medical oncologist who the Senior Director, Quality and Guidelines and Medical Director, CancerLinQ, at the American Society of Clinical Oncology, stated that “we simply can’t tell if early breast cancer diagnosed by mammogram will be indolent or not. For the individual patient we can’t say it’s ‘over diagnosis’. ”

And that’s really the bottom line. For an individual patient, we do not always have the right answer – our science and technology are just not there yet. While this is frustrating for many patients as well as for physicians, it is exciting to be practicing in a time when we are making progress (albeit slow) towards more individualized screening and treatment recommendations.