The guidelines and data on mammography are as confusing as ever. The second in our series of cancer roundtables.

Mammography is one of the oldest and most widely used tools in breast cancer screening. In the US alone, close to 40 million mammograms are performed annually[1] and about two thirds of women over the age of 40 have had one in the past two years.[2]

Mammography has evolved rapidly since the 1970s, when radiologists performed the tests using X-ray tubes and no mammary compression. Digital mammography, which provides improved quality images with improved tissue contrast, is now the standard in most practices, with more recent advances including three-dimensional mammography (digital breast tomosynthesis), computer-aided detection and magnetic resonance imaging.

Figure 1. Medio Lateral MammogramOne might think that after all this time we would have uniform screening guidelines that help women make an informed decision regarding preventative health, but consensus is sorely lacking on how early and how often women should be tested, and whether the tool has improved survival rates for certain categories of women. Both the American Cancer Society and the American College of Radiology (ACR)recommend yearly mammograms for all women starting at age 40. For high-risk women, including the carriers of BReast Cancer (BRCA) gene mutations and their untested relatives, the ACR recommends annual screening by age 25.

In contrast, European Commission guidelines recommend only biannual mammograms and only for women ages 50-69. The Canadian Task Force on Preventive Health Care recommends mammograms every two to three years for women 50-69. And the US Preventive Services Task Force, a panel convened by the US Department of Health and Human Services, recommends biannual screenings for average-risk women ages 50-74, but says the decision should be individualized for women ages 40-49.

One recently published study by Toronto researchers seems to be stoking much of the debate over the effectiveness of mammography. A 25-year follow-up of the Canadian National Breast Screening Study, which was initiated in 1980 and has been following women ages 40-59, concluded that annual mammography did not reduce mortality beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available, and that 22% of screen-detected invasive breast cancers were over-diagnosed.[3]

Other randomized controlled studies in the US and elsewhere, however, have associated mammography with a 15%-20% relative reduction in breast cancer-specific mortality among women ages 40-74.

On the heels of the Canadian findings, the Swiss Medical Board, which had already undertaken an extensive review of mammography screening in its own country, recommended that no new systematic mammography screening programs be introduced and that a time limit be placed on Switzerland’s existing programs.[4]

Meanwhile, a Boston-based review of 50 years worth of studies dealing with the benefits and harms of mammography screening found that the benefits had been overestimated and the risks underestimated. The two researchers from Harvard Medical School and Brigham and Women’s Hospital who published the 2014 review[5] suggest that decisions should be individualized based upon a patient’s risk profiles and preferences.

With so many conflicting guidelines and data circling the benefits of routine mammography, it’s no wonder so many women, myself included, are confused about what to do. I have dense breasts, which can make breast cancer screening more difficult and may increase the risk of breast cancer, some studies suggest. I have had almost yearly mammograms since I was 40, and even weathered a few scares that, paradoxically made me ponder the merits of a “mammography holiday.”

Clearly women need some clarity and it’s in our best interests to have a thorough discussion with our doctors as the stakes are high. Breast cancer is the most common cancer in women worldwide —the most recent yearly estimate was 1.7 million new cases. It’s also deadly. In just the US alone, breast cancer will claim an estimated 40,000 women this year.

For some perspective on the recent discourse circling mammography screening I talked with Emily Hickey (EH), corporate senior vice president of Discovery at Charles River.

Figure 2. Digital MammogramIn her professional life, Hickey is committed to reducing the prevalence of breast cancer through the efforts of our internal work and external partnerships. But she also has a deep familial connection with breast cancer. Her mother, Fran, survived two bouts of breast cancer—the first during her 30s and the second during her 40s. And Hickey’s grandmother and three great-aunts succumbed to the disease. Given her family history, Hickey’s mother thought she might have inherited mutations in one or both of the BRCA genes that have been shown to be correlated with a dramatic increase in the risk of breast cancer, but the tests came back negative. As this was a brief relief, Hickey understands there are many other markers to be studied relative to this disease.

How was your mother initially diagnosed?

EH: She felt a lump. This was before the era of widespread routine mammography and ultrasound. We were living on an Army base in Hawaii and her doctor initially told her not to worry about it, that he didn’t think it was worth doing any more evaluation. It kept growing and spreading and when she went back they had to do a full radical mastectomy along with the removal of all the muscle and lymph nodes under her right arm. This was a very invasive, yet routine surgery at that time.

What has been your position on yearly screenings?

EH: From the age of 25, my sister Anne and I have undergone yearly mammograms and MRIs. Both of us have had tumors [detected], and both have been benign so I am a firm believer in routine screening, given our family history. For other women, it might not, because they might have zero-history of breast cancer and therefore [less frequent screenings] might be enough. […] I think we need to look at all these risk categories [family history, BRCA mutations, age] and determine the value and risk-benefit ratio of mammography screening so women can make that informed decision themselves, with the added help of recommendations from their physician.

Is there a way to sort out these conflicting studies and guidelines?

EH: I think the industry needs to conduct a good, solid retrospective review and continue to collect data to refine the guidelines. Accordingly, the industry is already starting to do that.

What factors can affect the accuracy or quality of the mammogram?

EH: There are a lot of timing challenges. If you perform screenings during a certain part of the menstrual cycle—in or around your period—it can cause a false positive because hormonal changes may cause temporary changes in the density of the breast tissue. Using underarm deodorants or lotions on your breasts [the day of the exam] can cause shadows and make images harder to read.

What breast cancers might trigger a false-negative result?

EH: The areolae and nipple is one region where tumors often are not identified. The tissue is different, bulkier, than the rest of the breast so it’s harder to get a good view. Tumors that seed along the chest wall can also be challenging because they are outside the range of the breast tissue that gets imaged. A third category is inflammatory breast cancer. In these cases, [detection] is all about seeing and feeling changes in the breast. A mammogram is unlikely to pick that up.

Are there next-generation tools on the horizon that might reduce reliance on mammography?

EH: Circulating tumor cells. These are cells that are shed by tumors and get circulated throughout the body. We know that tissue biopsies do not help us fully understand metastatic risk, disease progression or treatment effectiveness. Although CTCs are rare, they reveal metastasis in action, helping physicians understand the patient’s current disease status. There remains a strong debate around the use of these cells to monitor disease progression over time. The good news is that it is fairly non-invasive to draw blood for this evaluation relative to taking a piece of tumor. Ideally, the information gained from this evaluation will help the physician modify the patient’s treatment and give insight to their prognosis.

Citations

  1. Food and Drug Administration, MQSA National Statistics, http://www.fda.gov/Radiation-EmittingProducts/MammographyQualityStandardsActandProgram/FacilityScorecard/ucm113858.htm, 2015, website 
  2. US Centers for Disease Control and Prevention, Health, United States, 2014,http://www.cdc.gov/nchs/data/hus/hus14.pdf#076, DHHS Publication No. 2015-1232;245 
  3. Miller, A., et al., Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial, BMJ, 2014;348:g366, doi:10.1136/bmj.g366 
  4. Biller-Andorno, N., Jüni, P., Abolishing Mammography Screening Programs? A View from the Swiss Medical Board,N Engl J Med, 2014;1965;370, doi:10.1056/NEJMp1401875 
  5. Pace, L., Keating, N., A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions, JAMA, 2014;311(13):1327, doi:10.1001/jama.2014.1398

 

How to cite:

McEnery, Regina. Making Sense of Mammography. Eureka blog. Oct 8, 2015. Available: http://eureka.criver.com/making-sense-of-mammography/