IN-DEPTH REVIEW OF RESEARCH

Study background:

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.

Study findings: 

• 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.

Limitations:

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.

Conclusions:

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."

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Posted 2/1/18