E.U.

Mammography is the only imaging screening modality that has been studied by multiple randomized controlled trials. Across those trials, mammography has been shown to reduce deaths due to breast cancer. The randomized trials that show a benefit from mammography are those in which mammography increased detection of invasive breast cancers before they spread to lymph nodes [1]. No randomized controlled trial has ever been performed on any other imaging screening modality and therefore there are no data showing that supplemental screening will or will not decrease mortality, though it is expected that other screening tests which increase detection of node-negative invasive breast cancers beyond mammography should further reduce breast cancer mortality.

Proving the mortality benefit of any supplemental screening modality would require a very large, very expensive randomized control trial with 15-20 years of follow-up. Given the speed of technological developments, any results would likely be obsolete by the trial’s conclusion. We do know that high-risk women having annual MRI screening are less likely to have advanced breast cancer than their counterparts who were not screened with MRI [2]. We also know that average-risk women who are screened with ultrasound in addition to mammography are unlikely to have palpable cancer in the interval between screens [3, 4] with the rates of such “interval cancers” similar to women with fatty breasts screened only with mammography. The cancers found only on MRI or ultrasound are mostly small invasive cancers (average size of about 1 cm), and the vast majority are node negative [5, 6]; MRI also finds some DCIS. These results suggest there is a benefit to finding additional cancers with supplemental screening, though it is certainly possible that, like mammography, some of the cancers found with supplemental screening are slow growing and may never cause a woman harm, even if left untreated.

Screening. “Diagnostic” mammography is monitored by the radiologist during the appointment and “screening” mammography is not. Indications for diagnostic mammography, rather than screening, include, but are not limited to, signs and symptoms of breast cancer such as a lump, bloody or spontaneous clear nipple discharge, skin or nipple retraction. If additional targeted imaging or follow-up is needed for an abnormality seen on the most recent prior breast imaging, a “diagnostic” appointment is also appropriate. In diagnostic breast imaging, additional views or ultrasound may be performed at the same visit if they are needed. The radiologist will interpret the breast imaging during the examination and the woman will leave with her results after a diagnostic mammogram. Women with a personal history of breast cancer can have their routine annual mammograms performed as diagnostic or screening examinations at many facilities. Diagnostic mammography is typically covered by insurance but subject to deductible and copay.

“Screening” mammography is fully covered by insurance under the Affordable Care Act for women over the age of 40 in the United States and may be covered for younger women, if recommended by her physician, depending on the insurance policy. Typically, screening mammograms are interpreted in a quiet, uninterrupted environment with the full benefit of prior examinations. Cancers are better detected and fewer unnecessary additional views (with associated radiation exposure) are recommended in the screening setting. Results are usually sent by mail to the patient within a few days to a week (by law not later than 30 days) after the appointment.

Depending on the patient’s age, risk level (for further explanation see section on Risk Assessment Tools) and breast density, additional screening tools, such as ultrasound or MRI, may be recommended in addition to mammography. The addition of another imaging tool after a mammogram will find more cancers than mammography/tomosynthesis alone (see Table: Summary of Cancer Detection Rates by Screening Method).

It is important to reassure the patient that it is normal for any screening test to find things that may need to be looked at more closely by use of additional testing. While some of these additional findings may be cancerous, the vast majority will not (this is known as a “false positive”); the only way to determine the importance of such findings is through additional imaging and sometimes biopsy.

Both 2D and 3D mammograms are x-ray technologies. X-rays have difficulty penetrating dense tissue and, as such, are more effective in fatty breasts than in extremely dense breasts. Early results suggest that ultrasound finds additional cancers hidden by dense tissue even after 3D mammography, though further study is warranted.

Ultrasound: Ultrasound is the only screening test suggested specifically for women with dense breasts as a supplement to mammography. In dense tissue, physician-performed or technologist-performed ultrasound has been shown to find an additional 2-4 cancers per 1000 women already screened by 2D or 3D/tomosynthesis mammography. Automated whole breast ultrasound, using special equipment, results in detection of another 2-3 cancers per 1000 women screened. Like all screening tools, ultrasound also detects many findings that are not cancer, but that may require follow-up imaging and/or biopsy. There is no x-ray radiation from ultrasound.

MRI: Contrast-Enhanced Magnetic Resonance Imaging (MRI) can find the most breast cancers of any imaging test currently in widespread use. Breast MRI reveals an average of 10 additional cancers per 1000 women screened after mammography, even when both mammography and ultrasound have been performed. The cancer-detection benefit is seen across all breast density categories.

A woman at very high risk for breast cancer (due to a known or suspected mutation in a breast cancer causing gene, or due to a greater than 20% lifetime risk for breast cancer according to the Claus, Tyrer-Cuzick, or other model that predicts risk for pathogenic BRCA mutation [1]) may be eligible to begin screening at age 25, or at least by age 30. In high-risk women, MRI is recommended annually, in addition to mammography, regardless of breast density, though before age 30 sometimes only MRI is performed due to the radiation sensitivity of younger breast tissue. Annual screening MRI is also recommended in women who have had prior radiation therapy to the chest at least 8 years earlier and before age 30, such as for Hodgkin’s lymphoma. Recently, the American College of Radiology recommended annual screening MRI also in women with a personal history of breast cancer diagnosed by age 50, and in women diagnosed later who have dense breasts [2]. Annual supplemental screening MRI can also be considered in women who have a personal history of atypical or risk lesions, such as lobular carcinoma in situ.

MRI of the breasts requires intravenous injection of gadolinium-based contrast and lying in a tunnel-like space that may be difficult for women with claustrophobia. There is no x-ray radiation from MRI. Gadolinium has been shown to accumulate in parts of the brain, but no adverse effects have been shown from this.

MRIs have many false positives (when additional testing or biopsy is recommended for a finding which is not cancer). The benefits and risks of MRI in women who are not at high risk are being studied. In most centers, MRI is a very expensive imaging test that is not covered by insurance unless a woman meets high-risk definitions, and a copay and/or deductible may be incurred. MRI cannot be performed in women with poor kidney function, pacemakers, or certain other metal implants.

The addition of screening ultrasound is usually only recommended in women with dense breasts. Screening MRI is used in high-risk women of all breast densities. If screening MRI is performed, there is no need for screening ultrasound.

Screening MBI, BSGI and Contrast-Enhanced Mammography may be offered to women with dense breasts or as an alternative to MRI at some centers. Further validation of such approaches is in progress.

In the U.S., the answer depends on the type of screening, patient’s insurance, risk factors, the state you practice in, and whether or not a law is in effect requiring insurance coverage for additional screening. In Illinois, for example, if ordered by a physician, a woman with dense breasts can receive an ultrasound without a copay or deductible. In New York as of January 1, 2017 all supplemental screening and diagnostic breast imaging are required to be fully covered (no copay/no deductible), though exceptions do exist. Generally, in other states, an ultrasound will be covered if ordered by a physician – but is subject to the copay and deductible of an individual health plan. In New Jersey, insurance coverage is provided for additional testing if a woman has extremely dense breasts. An MRI will generally be covered if the patient meets “high-risk” criteria*. In Michigan, at least one insurance company will cover a screening MRI for normal-risk women with dense breasts at a cost which matches the copay and deductible of a screening mammogram (which in most cases is zero). It is important for the patient to check with her insurance carrier prior to having an MRI. For insurance billing codes for additional breast screening, click here.

In Europe, national breast screening programs for women of average risk are offered free in nearly all European countries adhering to standards laid out in the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis. Variations do exist on the ages and risk factors of women invited to participate in routine screening, screening intervals, coverage and supplemental screening modalities utilized. Opportunistic mammography exists in some countries either as the sole screening system or in addition to the national breast screening program. Part of the cost is out of pocket payment or reimbursed by private insurance.

*For more information on high-risk criteria, see American Cancer Society guidelines: http://www.cancer.org/cancer/breastcancer/moreinformation/breastcancerearlydetection/breast-cancer-early-detection-acs-recs

Compared to standard digital mammography, 3D mammography (tomosynthesis) does improve the chance of finding cancer in most breasts. However, in women with extremely dense breasts, studies have shown mixed results as to whether 3D mammograms find more cancers than 2D mammograms. 3D does reduce the chance of having to return for additional diagnostic imaging for a false positive finding (false alarm).

Studies indicate there is benefit from screening ultrasound even after 3D mammography. Four large-scale studies [1-4] showed that ultrasound significantly improved detection of cancer even after the combination of 2D and 3D mammography in dense breasts. However, on average, ultrasound will also show more areas which need follow-up than does mammography. Some of those “finds” will be cancer, but the vast majority of these additional findings, determined after further imaging or biopsy, will be false positives.

If a patient has dense breasts, the answer is yes. In several large studies [1-4], including the ASTOUND [1] prospective multicenter trial in Italy, ultrasound significantly improved detection of cancer even after tomosynthesis (3D mammography) or the combination of 2D and 3D mammography in women with dense breasts. A 2020 prospective multicenter study [5] of abbreviated (“fast” or “mini”) MRI in 1444 women with dense breasts found an overall 3D mammography cancer detection rate of 6.2/1000 women screened vs. an overall abbreviated MRI cancer detection rate of 15.2/1000, a difference of 9/1000. If a patient has been recommended to have MRI screening because of her risk factors, she would still have MRI even if tomosynthesis is performed, regardless of her breast density. If screening MRI is performed, then screening ultrasound is not needed.

The American College of Radiology (ACR [1]) recommends all women, but especially Black women and women of Ashkenazi Jewish descent, undergo risk assessment and possible genetic testing by age 30 to identify those at higher risk who can then be counseled to begin earlier and more aggressive screening for breast cancer. All women benefit most from starting screening at least by age 40. In a recent analysis [2] from Harvard, Black, Hispanic, and Asian women have peak incidence of breast cancer in their 40s: it is especially important to start screening at least by age 40 in these groups.

The ACR, National Comprehensive Cancer Network (NCCN) [3], and American Society of Breast Surgeons, recommend annual MRI in the following subgroups of women:

• Women with known disease-causing BRCA1/2 mutation(s), other disease-causing mutation(s), or their untested first-degree relatives, should begin annual screening MRI only between age 25-29, adding annual digital mammography/tomosynthesis at age 30 and beyond.
  Note: There is emerging evidence that the benefit of mammography is relatively small in BRCA1 carriers prior to the age of 40; therefore, the ACR suggests BRCA1 mutation carriers may consider delaying mammography until age 40 only if they receive contrast-enhanced MRI annually starting at age 25. Annual mammography is of benefit in those with BRCA2 or other disease-causing mutations.
• Women with prior chest/mantle radiation therapy (cumulative dose of ≥ 10 Gy) before age 30 should begin MRI and annual mammography at age 25 or at least 8 years after completion of radiation, whichever is latest.
• Women with a calculated lifetime risk of breast cancer of ≥ 20%. Only models that include detailed family history such as Tyrer-Cuzick (which now includes breast density as a risk factor), BRCAPRO, BOADICEA, Claus, or Penn II, but not the Gail model, should be used to calculate risk for the purposes of MRI screening.
• Women with a personal history of breast cancer and dense breasts or diagnosis by age 50 regardless of breast density. A personal history of breast cancer is not included in risk models, but all women diagnosed with breast cancer at or before age 50 and treated with breast-conserving therapy have a ≥ 20% lifetime risk for a new breast cancer.
• Annual MRI may be considered in addition to annual mammography (with or without tomosynthesis) in women with a personal history of breast cancer diagnosed after age 50 and without dense breasts, and/or a history of lobular carcinoma in situ (LCIS) or prior atypia [e.g. atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH), or atypical papilloma].

In women who meet guidelines for MRI screening but are unable to tolerate it and who have dense breasts, the ACR suggests ultrasound be considered in addition to annual mammography. If MRI is performed, there is no benefit to screening ultrasound.

Where available, contrast-enhanced mammography may be a reasonable alternative to MRI for high-risk women, though further validation is warranted [4-6].

Gadolinium, a heavy metal, is injected intravenously as a contrast agent to help see breast cancer on MRI examinations. Most of the gadolinium is cleared by the kidneys. There are data showing that small amounts of gadolinium can accumulate in parts of the brain, especially after multiple MRI examinations. The importance of this finding is unknown and has not been linked to any known negative health effects in patients with normal kidney function. There appears to be more gadolinium retained by the body with certain types of contrast agents (so-called “linear” compounds) than with those that are more like a cage around the gadolinium (so-called “macrocyclic” compounds). When kidney function is less than normal, the dose of contrast used may be reduced. Gadolinium contrast should not be used in a patient who is pregnant or who may be pregnant. The Food and Drug Administration has concluded that the benefit of all approved gadolinium-based contrast agents far outweighs any hypothetical risks. Experts on our Medical Advisory Board agree, and we continue to recommend annual contrast-enhanced MRI for women at high risk. For further information, please see: https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm.