A Prospective Randomized Comparative Effectiveness Trial to Examine Mammogram Recall Rates after Women Stop Hormone Therapy
Diana S.M. Buist, PhD, MPH
Group Health Research Institute
What's the problem?
Mammography is the only available screening method that has been shown to reduce breast cancer mortality. Yet, like any screening test, it is not perfect - there are missed cancers (false negatives) and false positives. False positives - the suggestion of cancer when it is not present - are a problem in mammography because of their impact on women. False-positive mammograms account for 25 percent of the overall costs of the screening in the US, but more importantly, they may lead to increased anxiety and unnecessary biopsies and treatments
Breast density is an important factor influencing the number of false positives and false negatives of mammographic interpretation. As density increases, the number of false negatives increase and the number of false positives increases. However, breast density is not a static characteristic. It changes with age and in response to internal and external factors, such as pregnancy and hormone therapy. Abnormal screening mammograms, which require additional confirmatory imaging (recalls), are more common in women with dense breasts and in women using hormone therapy.
Despite the findings that hormone therapy is associated with increased risk of breast cancer, some women suffer enough at the onset of menopause that they choose to take hormones. Finding ways to decrease the number of recalls for additional imaging among women with dense breasts without compromising sensitivity is critical for sustaining breast cancer detection in the US in those women who choose to use hormone therapy. Previous research has shown that discontinuing hormone therapy can reduce breast density and the likelihood of having recalls, and some providers suggest that their patients on hormone therapy suspend the therapy for a short time before having a screening mammogram. However, population-based evidence to support this approach in general clinical practice had been lacking.
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How has this research addressed the problem?
In 2008 Dr. Buist and her colleagues at the Group Health Research Institute, at the University of Washington, completed a 5-year randomized clinical trial to determine whether stopping hormone therapy for 1 or 2 months before screening mammography would reduce breast density and the number of recalls in women aged 45 to 80 years. The research team also wanted to assess study participants' tolerance for stopping the therapy for a short time, determine how many women would start therapy again after stopping, and examine rates of adverse events.
The study was set within a healthcare system and was integrated into the course of clinical practice, meaning that the trial was a prospective comparative effectiveness trial. The Radiological Evaluation and Breast Density (READ) study recruited women participating in Group Health's Breast Cancer Screening Program. Group Health is an integrated health plan in western Washington State with 550,000 members. The study participants were all due to receive a screening mammogram and all had had a prior screening exam at Group Health. All eligible women were taking hormones at their previous mammogram and were still using hormones when randomly divided into three groups: continued hormone therapy before the mammogram, no hormone therapy for 1 month before, and no hormone therapy for 2 months before. The women filled out a baseline questionnaire 1 to 2 months before their mammogram and a second questionnaire at the time of their mammogram. Questions dealt with participant demographics, use of and attitudes toward hormone therapy, menopause symptoms and tolerance for stopping hormones (for women randomized to stop). An expert radiologist read the mammograms and recalled those patients who needed additional imaging or evaluation.
Dr. Buist's team found that stopping hormone therapy decreased breast density by small amounts but did not affect recall. Women in the groups that stopped therapy also experienced an increase in their menopause symptoms.
Another important finding was that many - 54 percent - of the women who were invited to join the study declined to participate because they were unwilling to stop hormone therapy for a short time. This was true even knowing that the goal of the study was to improve mammographic accuracy and that they could restart therapy any time they wished. Very few differences distinguished those who refused to participate from those who did join the trial, suggesting that resistance to stopping hormone therapy is strong among users, even when an immediate personal benefit is possible.
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Significance of the study & results
This study has made important contributions to our understanding of the role of breast density in influencing recall rates. For investigators conducting effectiveness research, the READ trial also provided important lessons learned:
- Recognize the line between research and clinical care, not only for providers but for insurers. Because the study was set within a clinical system and within the course of clinical practice, women's mammograms were interpreted by the study radiologist and also by the clinical radiologist. These experts didn't always agree. Who is responsible for working up positive findings from study experts?
- Design a study that will provide information about the obstacles for translating findings into clinical practice. An intervention can work, but if no one is willing to participate, there is no point in spending considerable resources trying to implement the findings in clinical practice.
- Recognize the need to interact with clinic personnel. This is a critical component of CER. It takes time and study resources to interact with service provides in the clinics. CER trials need to ensure sufficient support of clinical leaders and that the research study can be effectively integrated into the flow of the clinic.
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Recent related publications of interest
Buist DS, Anderson ML, Reed SD, Bowles EJA, Fitzgibbons ED, Gandara J, Seger D, Newton KM. Short-term hormone therapy suspension and mammography recall: A randomized trial. Annals of Internal Medicine 2009;150(11):752-765. [View Abstract]
Reed SD, Buist DS, Anderson ML, Bowles EJA, Fitzgibbons ED, Seger D, Newton KM. Short-term (1-2mo) hormone therapy cessation before mammography. Menopause 2009;16(6):1125-1131. [View Abstract]
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