Study: Should biannual MRIs replace annual mammograms in high-risk women?
|At a glance||Questions for your doctor|
|Guidelines||Resources and references|
This study is about:
Whether women at high risk for breast cancer benefit from biannual breast
Why is this study important?
The National Comprehensive Cancer Network and the American Cancer Society recommend a screening breast MRI and a mammogram each year for high-risk women, typically starting at age 30. In studies of annual MRI, the cancer detection rates are quite variable. In most studies of annual MRI, only about half of the women in the study were diagnosed with small tumors (<1 cm) and some were diagnosed with lymph node positive tumors. Both the diagnosis of tumors larger than 1cm and lymph node positive tumors translates into more advanced stage disease.
Is the recommended screening regimen for high-risk women the best screening protocol? Questions remain, and many experts are concerned that the increased sensitivity of MRIs may result in false positives that require follow-up screening or biopsy, and increased psychosocial distress that may negatively impact a women’s quality of life. Three posters presented at the 2017 San Antonio Breast Cancer Symposium addressed these issues.
Between 2004 and 2016, researchers at the University of Chicago recruited high-risk women into a clinical trial to prospectively evaluate semiannual MRI and annual mammography. Eligible participants had a lifetime breast cancer risk greater than 20% and/or an inherited mutation in BRCA1, BRCA2, CDH1, PALB2, CHEK2 or other cancer susceptibility gene. (More than half of the enrolled women had a mutation in a high-risk gene.) The participants’ median age was 44 (ranging from 21-73).
The 295 enrolled women were given a clinical breast exam and an MRI scan every 6 months, and a digital mammogram every 12 months:
- At a median follow-up of 3.3 years (range 0-12 years), 3 cases of DCIS and 13 cases of early-stage invasive breast cancers were detected:
- 14 in women with inherited mutations (11 BRCA1, 2 BRCA2, 1 CDH1).
- Among all subjects, the annual incidence rate was 1.3%, but it was 3.5 % in BRCA1 carriers.
- MRI correctly identified all 13 invasive cancers at a mean size of .61 cm, (about the size of a pea) (range .1-1.0 cm); none of the women had lymph node involvement.
- Semiannual breast MRI demonstrated high sensitivity without substantially increasing recall rates or biopsy rates to an unacceptable value.
- Patients with BRCA1 mutations had the lowest biopsy rates needed to detect one cancer as well as higher cancer detection rates than non-BRCA1 carriers.
- Semiannual breast MRI did not increase anxiety, depression or contribute to a decline in mental health over time.
What does this mean for me?
If you are at high risk for breast cancer, this study suggests that having an MRI every 6 months may more effectively detect early-stage breast cancer than an annual MRI and mammogram. In this study, the MRI cancer detection rates are comparable to previous studies looking at MRI. Where this study is unique and meaningful is that it was able to detect earlier stage cancers that are likely more curable and consequently may lead to improved survival in high-risk women.
This study also suggests that semiannual MRIs do not substantially increase recall or biopsy rates; nor do they increase anxiety or depression. This study also suggests that biannual MRI may be an especially effective screening tool for BRCA1 mutation carriers. The study’s lead author, Olufunmilayo Olopade, MD, professor of medicine and human genetics and director of the University of Chicago's Center for Clinical Cancer Genetics was quoted in the media articles, saying "Mammograms remain important for most women. But for women at high risk who are getting an MRI every six months, annual mammograms could probably be eliminated."
Screening breast MRIs for women are not without controversy. Guidelines recommend that they be given with a contrast agent—an intravenous substance that enhances MRI imaging and makes it easier to identify abnormalities. Most contrast agents used for MRI include gadolinium, a metal-based chemical. Experts have expressed concern about the safety of gadolinium, primarily because it remains in patients’ brains and bodies for months to years. Recently, the FDA required that labels for gadolinium-based contrast agents be updated to include a warning and safety measures that should be followed before the agents are given to patients. Please visit Breast Cancer Screening on the FORCE website for updated information on this new warning.
This article is relevant for:
Women at increased risk for breast cancer due to an inherited mutation
This article is also relevant for:
People with a genetic mutation linked to cancer risk
Breast cancer survivors
Women under 45
Women over 45
Be part of XRAY:
- How often and with what method should I be screened for breast cancer?
- Will my MRI include contrast with a gadolinium-based agent? If so, what health risks are associated with this contrast agent?
- Are there any other health risks associated with getting an MRI every 6 months instead of annually?
- Do I still need an annual mammogram if I have an MRI every 6 months?
- Will my insurance cover more frequent MRI screenings?
The following breast cancer screening clinical trials are currently enrolling participants:
- NCT02620852: Women Informed to Screen Depending on Measures of Risk (WISDOM) study. The goal of this study is to determine if breast cancer screening can be made better by personalizing each woman’s mammogram schedule, compared to the current one-size-fits-all, annual approach.
- NCT03979729: Breast Cancer Screening for Underserved Women: Comparing Outcomes and Lowering Recall Rates With 3D- vs. 2D-mammography is recruiting participants in New Mexico who are over age 40 to improve mammogram utility among underserved women.
- NCT03482557: Contrast Enhanced Spectral Mammography vs. MRI for Breast Cancer Screening is recruiting women 30 years or older who are already getting a breast biopsy. Participants will have a contrast-enhanced mammogram and a breast MRI before the biopsy. Radiologists will compare the images to see if the contrast enhanced mammograms and breast MRI are equally proficient at detecting breast cancer.
- NCT03729115: A Multi-Modality Surveillance Program for Women at High Risk for Breast Cancer is a clinical trial at the University of Chicago that is enrolling women age 21 and older who are BRCA1, BRCA2, PALB2 or TP53 carriers for an MRI and anxiety reduction trial.
- NCT03859492: Screening CEDM in Intermediate and High-Risk Patient Populations is a clinical trial at the Mayo Clinic in Arizona that is testing whether Contrast Enhanced Digital Mammography (CEDM) can improve breast cancer detection among women age 35 years and older who have an intermediate or high risk of breast cancer.
- NCT03233191: Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer. The goal of this randomized phase III trial is to evaluate digital tomosynthesis mammography and digital mammography in screening patients for breast cancer.
- NCT03303846: Combined Breast MRI and Biomarker Strategies in Identifying High-risk Breast Cancer Patients trial. This clinical trial is recruiting participants age 18 and older. Study sites are in California, North Carolina, Ohio and Wisconsin.
Who covered this study?
IN-DEPTH REVIEW OF RESEARCH
Women with a personal or family history of breast cancer or a mutation in BRCA1, BRCA2 or certain other genes have a higher-than-normal risk of breast cancer. An intensified screening regimen—annual MRI and annual mammogram–is currently recommended as an early detection strategy for these high-risk women. However, experts still have questions regarding the type and frequency of screening that is best for high-risk women.
Researchers of this study wanted to know:
Whether women at high risk for breast cancer benefit from biannual breast MRI screening.
Population(s) in the study:
Women enrolled in the study had mutations in one of 11 known breast cancer-related genes, a diagnosis of breast cancer or carcinoma in situ before age 35, or a mother or sister who was diagnosed with breast cancer before age 50 (before age 40 for African Americans). The mean age at participation was 43.3 years.
Participants had semiannual breast MRI and annual mammography. During the study, researchers performed 2,111 MRIs (averaging about 7 per participant) and 1,223 mammograms (4 per participant). Biopsy was recommended when mammography results were categorized as suspicious or highly suspicious. Further imaging was recommended and biopsy was performed if clinically indicated when MRI results were incomplete and mammography was suspicious or highly suspicious. Patients also completed psychosocial assessments when they began the study and at subsequent 6-month visits; psychosocial assessments were completed for 232 of 295 (79%) participants.
All study subjects were tested for inherited mutations in 12 genes that are associated with increased breast cancer risk via panel testing. Women with high-risk mutations who completed 5 years of the study protocol were offered continued screening.
- At a median follow-up of 3.3 years (range 0-12 years), 3 cases of DCIS and 13 cases of early-stage, invasive breast cancers were detected:
- 14 cases were in subjects with inherited mutations (11 BRCA1, 2 BRCA2, 1 CDH1).
- Among all subjects, the annual incidence rate was 1.3%, but it was 3.5 % in BRCA1 carriers.
- None of the 16 diagnosed patients had lymph node involvement.
- 13 invasive cancers were detected (mean size of 0.61 cm, range 0.1-1.0 cm).
- 7 breast cancers were identified by MRI at the 6-month screening interval.
- Semiannual breast MRI did not cause elevated states of anxiety or depression or a decline in mental health over time.
- Participants had no significant demographic differences (age, race, income, mutation, and cancer type or cancer history) or psychosocial factors (baseline anxiety, depression or quality-of-life measures.
- Semiannual breast MRI demonstrated high sensitivity (correctly identified breast cancers) and specificity (correctly identified the absence of breast cancer) without increasing rates of recall (being called back for an additional screening) and biopsy beyond an acceptable threshold.
- MRI sensitivity and specificity was 93.7% and 96.6%, respectively
- mammogram sensitivity and specificity was 50% and 97.7%, respectively
- The recall rate was 4.2% for MRI and 2.6% for mammography.
- 89 women had 106 recalls: 74 from MRI imaging alone, 18 from mammography and 14 from combined MRI and mammography.
- 56 biopsies were performed, resulting in the diagnosis of 3 DCIS and 13 invasive breast cancers.
- On average, MRI caused more recalls and follow-up per diagnosis than mammography: statistically, almost 6 women were recalled with 3.3 biopsies per diagnosis, compared to 4 women recalled with 2.1 biopsies per diagnosis, respectively.
This single-institution research shows bi-annual breast MRIs, radiology reader expertise, careful clinical decision making, and improved MRI technology at the University of Chicago can detect early-stage breast cancer more effectively than an annual MRI and mammogram. Other institutions with different cohorts of women may observe varying rates of success with biannual MRI screening. In addition, this study involved a relatively small sample size: only 295 women. Thus, this innovative screening approach needs to be further evaluated to refine and personalize breast cancer risk assessment and prevention.
In this study, biannual breast MRI accomplished the ultimate goal of breast cancer screening—detecting node-negative, invasive tumors smaller than 1 cm. Semiannual MRI performed especially well in BRCA1 mutation carriers who are at increased risk for the most aggressive subtype of breast cancer. Bi-annual MRI did not cause a significantly elevated state of depression or anxiety or a significant decline in mental health over time, regardless of cancer history or genetic mutation status. Finally, this single institution MRI protocol achieved recall rates lower than those considered acceptable for annual MRI or mammography.
Study co-author, Mary-Claire King, PhD said, "The central goal of our study was to understand the needs of the highest risk women. My concern is that mammography and MRI be used in ways that make sense given a woman's personal genetics. Women with mutations in BRCA1 or BRCA2 have very different needs for surveillance for breast disease than do women with no mutations in these genes. This is particularly true for healthy young women with mutations. It's truly critical to offer intensive surveillance to still-healthy women with BRCA1 or BRCA2 mutations."
Share your thoughts on this XRAYS article by taking our brief survey