Context and Policy Issues
In 2007, there will be an estimated 22,300 Canadian women diagnosed with breast cancer, and approximately 5,300 deaths. The risk factors for breast cancer include reproductive and hormonal factors, lifestyle factors, a family history of breast cancer, and mutation in the tumour suppression genes BRCA1 or BRCA2.
Women at high risk for breast cancer usually develop the disease at a younger age, when breast tissue has a higher density. This high-density breast tissue makes mammography less sensitive. In addition, women with mutations in BRCA1/2 may be more susceptible to DNA damage, so that exposure to the ionizing radiation of mammography may be contraindicated. As a result, magnetic resonance imaging (MRI) is proposed as an alternative screening modality for these women.
While mammography is the most commonly used technology for breast cancer screening, the American Cancer Society recommends annual MRI screening for individuals with BRCA1/2 mutations, those having a first-degree relative with a BRCA1/2 mutation, or those with a lifetime risk for breast cancer of 20% to 25%.
- What is the clinical effectiveness of MRI screening compared to film mammography in women with a high risk of breast cancer?
- What is the cost-effectiveness of MRI screening compared to film mammography in women with a high risk of breast cancer?
- What is the strength of evidence used to support the American Cancer Society’s guidelines regarding MRI screening for woman at high risk of breast cancer?
A limited literature search was conducted on health technology assessment resources, including PubMed, EMBASE, CINAHL, BIOSIS, The Cochrane Library (Issue 3, 2007), the University of York Centre for Reviews and Dissemination (CRD) databases, ECRI’s HTAIS, EuroScan, international HTA agencies, and a focused Internet search. Results include articles published between 2002 and June 2007, and are limited to English-language publications.
Summary of Findings
Evidence on the clinical effectiveness of MRI screening for breast cancer detection in high-risk women contained in systematic reviews, health technology assessments, and observational studies were included in this report. One health technology assessment, two systematic reviews, and 10 observational studies were found. No randomized controlled trials were found.
MRI was reported to be more sensitive than mammography for the detection of breast cancer in high-risk women. The information in the health technology assessment on MRI for breast cancer screening was limited, however, it was suggested that MRI was more sensitive than mammography for the detection of breast cancer in high risk women. One systematic review reported that the sensitivity of MRI for breast cancer screening ranged from 71% to 100%, compared to 13% to 40% for mammography. The sensitivity was reported to be 100% for MRI screening, compared to 33% to 46% for mammography in another systematic review. The specificity was reported to be 91% to 95% for MRI (false-positive rate of 5% to 9%), compared to 93% to 99% for mammography (false-positive rate of 1% to 7%). The evidence was reviewed in a horizon scanning report, which stated that the sensitivity ranged from 96% to 100% for MRI and 33% to 44% for mammography. The specificity was reported to be 91% to 95% for MRI and 92% to 99.5% for mammography.
The included observational studies all reported similar results. The sensitivity of MRI was higher than that for mammography, and the specificity was generally higher for mammography compared to MRI. The sensitivity of MRI was reported in five of the 10 included studies. The sensitivity ranged from 77% to 93.8% compared to 30% to 58.8% for mammography. The specificity of MRI ranged from 81% to 97.2% and that of mammography ranged from 93% to 96.8%.
A limited number of studies (four) that described the costs associated with MRI screening for breast cancer were available. An Italian study found that it cost about €6,000 per MRI-detected breast cancer, which the authors deemed to be cost-effective. A UK study reported the additional cost per cancer detected was ₤28,284 for MRI and mammography combined, compared to mammography alone. The incremental cost per cancer detected was ₤11,731 for BRCA1 carriers and ₤15,302 for BRCA2 carriers. Another UK study found there was an 80% chance that MRI combined with mammography would be cost-effective for 40- to 49-year-old women assuming a ₤20,000 willingness-to-pay threshold. An American study reported a cost per QALY gained of $88,651 for BRCA1 carriers and $188,034 for BRCA2 carriers aged 25 years to 69 years. For women aged 35 to 54 years, the cost per QALY gained was $55,420 and $130,695 for BRCA1 and BRCA2 carriers respectively.
Quality Assessment of American Cancer Society’s Guidelines
Using the AGREE instrument (Appraisal of Guidelines Research and Evaluation), two independent reviewers assessed the quality of the American Cancer Society’s guidelines. The rigour of development was found to be low, because the inclusion and exclusion criteria, the external review process, and the process for updating the guidelines were not reported. The editorial independence from the funding body and the conflicts of interest were not reported, making the editorial independence score zero. The clarity and presentation were well done, because the recommendations were specific and easily identifiable.
Conclusions and Implications for Policy Making
The cost-effectiveness studies suggest that MRI for breast cancer screening could be cost-effective, depending on the willingness to pay and the value attributed to one QALY. Overall, MRI has a higher sensitivity for breast cancer screening compared to mammography. In addition, the number of cancers detected by MRI alone was higher than that detected by mammography alone, although MRI also missed some cancers. These results indicate that some breast cancers would have been missed with mammography screening alone and the addition of MRI resulted in more cancers being detected. High-risk women, such as those with BRCA1/2 mutations, those having a first-degree relative with a mutation, or those with a strong family history of breast cancer, seem to benefit most from the addition of MRI to the screening modality.