1. Aetna considers magnetic resonance imaging (MRI), with or without contrast materials, of the breast medically necessary for members who have had a recent (within the past year) conventional mammogram and/or breast sonogram, in any of the following circumstances where MRI of the breast may affect their clinical management:

   1. To detect implant rupture in symptomatic members; or
   2. To detect local tumor recurrence in breast cancer members who have undergone mastectomy and breast reconstruction with an implant; or
   3. To detect local tumor recurrence in individuals with breast cancer who have radiographically dense breasts or old scar tissue from previous breast surgery that compromises the ability of combined mammography and ultrasonography; or
   4. To assess tumor location, size, and extent before and/or after neoadjuvant chemotherapy in persons with locally advanced breast cancer, for determination of eligibility for breast conservation therapy; or
   5. To detect the extent of residual cancer in the recently postoperative breast with positive pathological margins after incomplete lumpectomy when the member still desires breast conservation and local re-excision is planned; or
   6. To localize the site of primary occult breast cancer in individuals with adeno-carcinoma suggestive of breast cancer discovered as axillary node metastasis or distant metastasis without focal findings on physical examination or on mammography/ultrasonography; or
   7. To guide localization of breast lesions to perform needle biopsy when suspicious lesions exclusively detected by contrast-enhanced MRI cannot be visualized with mammography or ultrasonography; or
   8. One initial breast MRI to evaluate persons with newly diagnosed lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS ); or

   9. To map the extent of primary tumors and identify multicentric disease in persons with localized breast cancer (Stage I or II, T0-1 N0-1 M0) prior to surgery (lumpectomy versus mastectomy).

2. Aetna considers breast MRI a medically necessary adjunct to mammography for screening of women considered to be at high genetic risk of breast cancer because of any of the following:

   1. Confirmed presence of BRCA1 or BRCA2 mutation; or
   2. First degree blood relative with BRCA1 or BRCA2 mutation and are untested; or
   3. Have a lifetime risk of breast cancer of 20-25 percent or more using standard risk assessment models (BRCAPRO, Claus model, Gail model, or Tyrer-Cuzick); or
   4. Carry or have a first-degree relative who carries a genetic mutation in the TP53 or PTEN genes (Li-Fraumeni syndrome and Cowden and Bannayan-Riley-Ruvalcaba syndromes); or

   5. Received radiation treatment to the chest between ages 10 and 30 years, such as for Hodgkin disease.

3. Aetna considers breast MRI medically necessary to detect intracapsular (silent) rupture of silicone gel-filled breast implants. Screening for silent intracapsular rupture more frequently than every two years is not considered medically necessary.

4. Aetna considers breast MRI experimental and investigational for all other indications, including any of the following, because there is insufficient scientific evidence to support its use:

   1. To confirm implant rupture in symptomatic individuals whose ultrasonography shows rupture, especially with implants more than 10 years old (ultrasound sufficient to proceed with removal); or
   2. To screen for breast cancer in members with average risk of breast cancer; or
   3. To evaluate breasts before biopsy in an effort to reduce the number of surgical biopsies for benign lesions; or
   4. To differentiate benign from malignant breast disease, especially clustered microcalcifications; or
   5. To differentiate cysts from solid lesions (ultrasound indicated); or
   6. To provide an early prediction of response to adjuvant breast cancer chemotherapy in guiding choice of chemotherapy regimen.
      
5. Aetna considers computer-aided detection of malignancy with MRI of the breast experimental and investigational because its clinical value has not been established.

See also CPB 584 - Mammography.

Mammography is the only screening test proven to lower breast cancer morbidity and mortality.  Although mammography is an effective screening tool, it does have limitations, especially in women with dense breasts.  New imaging techniques are being developed to overcome these limitations, enhance cancer detection, and improve patient outcome.  Digital mammography, computer-aided detection (CAD), breast ultrasound, and breast magnetic resonance imaging (MRI) are frequently used adjuncts to mammography in today's clinical practice.

An expert panel convened by the American Cancer Society recommended the use of MRI for screening women at a 20 to 25 percent or greater lifetime risk for breast cancer (Saslow, et al., 2007). The panel states that, in addition to mammography, annual screening using MRI is recommended for women who:

• have a BRCA 1 or 2 mutation
• have a first-degree relative with a BRCA 1 or 2 mutation and are untested
• have a lifetime risk of breast cancer of 20-25 percent or more using standard risk assessment models
• received radiation treatment to the chest between ages 10 and 30, such as for Hodgkin Disease
• carry or have a first-degree relative who carries a genetic mutation in the TP53 or PTEN genes (Li-Fraumeni syndrome and Cowden and Bannayan-Riley-Ruvalcaba syndromes).

The ACS guidelines recommend use of MRI in addition to, not in place of, mammography for screening high-risk women (Saslow, et al., 2007). The guidelines explain that all of the clinical trials screened participants with both MRI and mammography at the same time. The guidelines state that there is no evidence to support one approach over the other. "For the majority of women at high risk, it is critical that MRI screening be provided in addition to, not instead of, mammography, as the sensitivity and cancer yield of MRI and mammography combined is greater than for MRI alone."

The guideline provides information about three risk assessment models available for calculating breast cancer risk (BRCAPRO, Claus model, and Tyrer-Cuzick). Software for each model is available online (see Appendix below). The three risk models utilize different combinations of risk factors, are derived from different data sets, and vary in the age to which they calculate cumulative breast cancer risk. As a result, they may generate different risk estimates for a given patient. This variability is an indicator that the risk models provide approximate, rather than precise, estimates of breast cancer risk. According to ACS guidelines, each of the risk models can be used for the purpose of identifying patients who would benefit from breast MRI screening (Saslow, et al., 2007). In additionk, the Gail model is widely used in research studies and clinical counseling to predict a woman's lifetime risk of developing breast cancer. Calculation of a 5-year and lifetime breast cancer risk according to the Gail model can be performed by accessing the National Cancer Institute's website (http://www.nci.nih.gov) and searching for information on breast cancer risk.

The ACS panel also identified several risk subgroups for which the available data are insufficient to recommend either for or against MRI screening (Saslow, et al., 2007). They include women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography.

Although ultrasound is sufficient to confirm rupture of breast implants in women with symptoms, MRI may be necessary to detect intracapsular rupture of silicone gel-filled breast implants in asymptomatic women. The sensitivity of plastic surgeons familiar with implants to diagnose rupture is 30% compared to 89% for MRI (Holmich, et al., 2005). The FDA therefore recommends that women with silicone gel-filled breast implants have regular breast MRIs over their lifetime to screen for silent rupture.  The FDA-approved labeling of silicone gel-filled breast implants recommends that the first MRI be performed 3 years postoperatively, then every 2 years thereafter. The FDA recommends that the MRI have at least a 1.5 Tesla magnet, a dedicated breast coil, and a radiologist experienced with breast implant MRI films for signs of rupture.

Houssami et al (2008) reviewed the evidence on MRI in staging the affected breast to determine its accuracy and impact on treatment. These researchers estimated summary receiver operating characteristic curves, positive predictive value (PPV), true-positive (TP) to false positive (FP) ratio, and examined their variability according to quality criteria. Pooled estimates of the proportion of women whose surgery was altered were calculated. Data from 19 studies showed MRI detects additional disease in 16 % of women with breast cancer (n = 2,610). Magnetic resonance imaging incremental accuracy differed according to the reference standard (RS; p = 0.016) decreasing from 99 % to 86 % as the quality of the RS increased. Positive predictive value was 66 % (95 % CI, 52 % to 77 %) and TP:FP ratio was 1.91 (95 % CI, 1.09 to 3.34). Conversion from wide local excision (WLE) to mastectomy was 8.1 % (95 % CI, 5.9 to 11.3), from WLE to more extensive surgery was 11.3 % in multi-focal/multi-centric disease (95 % CI, 6.8 to 18.3). Due to MRI-detected lesions (in women who did not have additional malignancy on histology) conversion from WLE to mastectomy was 1.1 % (95 % CI, 0.3 to 3.6) and from WLE to more extensive surgery was 5.5 % (95 % CI, 3.1 to 9.5). The authors concluded that MRI staging causes more extensive breast surgery in an important proportion of women by identifying additional cancer, however there is a need to reduce FP MRI detection. They stated that randomized trials are needed to determine the clinical value of detecting additional disease which changes surgical treatment in women with apparently localized breast cancer.

In a review on the utility of MRI for the screening and staging of breast cancer, Patani and Mokbel (2008) stated that while MRI can facilitate local staging, especially the evaluation of ipsilateral multi-centric or multi-focal lesions as well as synchronous contralateral disease that may be missed by conventional imaging; however, efficacy with respect to clinically relevant and patient oriented end-points has yet to be addressed in the context of clinical trials.

Computer-aided detection has been used to aid radiologists’ interpretation of contrast-enhanced MRI of the breast, which is sometimes used as an alternative to mammography or other screening and diagnostic tests because of its high sensitivity in detecting breast lesions, even among those in whom mammography is less accurate (e.g., younger women and those with denser breasts).  However, MRI has a high false-positive rate because of the difficulty in differentiating between benign and malignant lesions.  The use of CAD may also reduce the time needed to interpret breast MRI images, which currently takes much longer than reading mammograms. 

The BlueCross and BlueShield Association’s Technology Evaluation Center (TEC) Medical Advisory Panel (2006) assessed the evidence on the use of CAD with MRI of the breast by comparing the sensitivity, specificity, and recall rate (percentage of patients asked to come back for further evaluation) of MRI with and without the use of commercially available CAD systems in detecting malignant lesions, evaluating the extent of disease in women with cancer, or gauging the impact of treatment.  According to this assessment, many of the studies on the use of CAD with MRI of the breast mainly reported on the development of CAD systems, or testing new CAD approaches.  The assessment noted that few of them evaluated commercially available CAD systems.  Several of those that did, reported on the development and testing of approaches that underlie one of the commercially available systems (3TP); the assessment stated that it is not clear to what degree the current 3TP system has or has not been modified compared to these earlier approaches.  Although the studies had to have separate testing data sets to be included in the TEC assessment, these data sets often were enriched with more cancer cases or consisted exclusively of cases in which lesions had been found.  The TEC assessment found, as a result, the range of sensitivities and specificities cannot be applied to the populations usually found in a clinical setting.  The TEC assessment also found that many of the studies of CAD systems were retrospective, and reported primarily on their development and testing; thus, these studies lacked the rigor and generalizability of a large, prospective, well-designed study.

The TEC assessment stated that the literature is unclear on how CAD systems are to be used.  In the case of CAD with mammography, the radiologist reads the original films first, makes a diagnosis, and then reviews the CAD results.  The TEC assessment explained that, because CAD is not 100 % sensitive, lesions detected by mammography both before the use of CAD and after viewing the CAD results may be worked up.  Thus, CAD can add to the sensitivity of mammography, but not its specificity.  The TEC assessment noted, however, with MRI of the breast, the sensitivity is already high, and the focus is mainly on enhancing the specificity.  In some studies, it appears that CAD was intended as an adjunct to the initial MRI reading, just as with CAD and mammography.  In other studies, it was proposed as a way of speeding up the MRI reading process, and the precise protocol to be followed in reading the MRI images is unclear.  In addition, unlike in the case of CAD with mammography, in the documents regarding the FDA clearance it did not specify that CAD must be added only after an initial reading of the images alone, although it did say for one system that “patient management decisions should not be made based solely on the results of the CADstream analysis”.  The TEC assessment observed that the impact of CAD on the accuracy of MRI of the breast may depend partly on how the CAD results are incorporated into the reading and diagnostic process.

Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel concluded that there is insufficient evidence to evaluate if the use of CAD systems would maintain or increase the sensitivity, specificity, and recall rates of MRI of the breast.  The TEC assessment concluded that, given the inability to evaluate these intermediate outcomes, it is impossible to evaluate the impact of CAD on health outcomes such as treatment success and survival of patients with breast cancer.

Appendix

Breast Cancer Staging:

Information about breast cancer staging is available from the National Cancer Institute at the following website: http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page3.

Breast Cancer Risk Assessment Models:

Software for each of the breast cancer models referenced the American Cancer Society guidelines (Saslow, et al., 2007) is available via the internet:

• BRCAPRO Version 4.3, http://www4.utsouthwestern.edu/breasthealth/cagene/default.asp
• Claus model (BreastCa for Palm, version 1.0, copyright 2001) http://www.palmgear.com/index.cfm?fuseaction=software.showsoftware&prodID=29820
• Tyrer-Cuzick (IBIS Breast Cancer Risk Evaluation Tool, RiskFileCalc version 1.0, copyright 2004).  Available by contacting IBIS: ibis@cancer.org.uk.

Breast cancer risk can also be estimated online using the Gail Model Breast Cancer Risk Assessment Tool available from the National Cancer Institute's website: http://www.cancer.gov/bcrisktool/.