MY STORY: Prologue
My aunt received a breast cancer diagnosis at age 40, and she died at age 60, in 1970. Then, in 1975, my mother’s breast cancer was found at age 55, but only after she was examined for nipple retraction; on mammography, the cancer had been obscured by dense breast tissue. Mom had 2 metastatic nodes but participated in the earliest clinical trials of chemotherapy and lived free of breast cancer for another 41 years. Naturally I thought that, were I to develop this disease, I would want it found earlier. Ironically, it was, but only because I had spent my career trying to understand the optimal screening approaches for women with dense breasts—women like me.
Cancers are masked on mammography in dense breasts
For women, screening mammography is an important step in reducing the risk of dying from breast cancer. The greatest benefits are realized by those who start annual screening at age 40, or 45 at the latest.1 As it takes 9 to 10 years to see a benefit from breast cancer screening at the population level, it is not logical to continue this testing when life expectancy is less than 10 years, as is the case with women age 85 or older, even those in the healthiest quartile.2–4 However, despite recent advances, the development of 3D mammography (tomosynthesis) (FIGURE 1) in particular, cancers can still be masked by dense breast tissue. Both 2D and 3D mammograms are x-rays; both dense tissue and cancers absorb x-rays and appear white.
Breast density is determined on mammography and is categorized as fatty, scattered fibroglandular, heterogeneously dense, or extremely dense (FIGURE 2).5 Tissue in the heterogeneous and extreme categories is considered dense. More than half of women in their 40s have dense breasts; with some fatty involution occurring around menopause, the proportion drops to 25% for women in their 60s.6 About half of breast cancers have calcifications, which on mammography are usually easily visible even in dense breasts. The problem is with noncalcified invasive cancers that can be hidden by dense tissue (FIGURE 3).
3D mammography improves cancer detection but is of minimal benefit in extremely dense breasts
Although 3D mammography improves cancer detection in most women, any benefit is minimal in women with extremely dense breasts, as there is no inherent soft-tissue contrast.7 Masked cancers are often only discovered because of a lump after a normal screening mammogram, as so-called “interval cancers.” Compared with screen-detected cancers, interval cancers tend to be more biologically aggressive, to have spread to lymph nodes, and to have worse prognoses. However, even some small screen-detected cancers are biologically aggressive and can spread to lymph nodes quickly, and no screening test or combination of screening tests can prevent this occurrence completely, regardless of breast density.
Get smart about dense breasts
MRI provides early detection across all breast densities
In all tissue densities, contrast-enhanced magnetic resonance imaging (MRI) is far better than mammography in detecting breast cancer.8 Women at high risk for breast cancer caused by mutations in BRCA1, BRCA2, p53, and other genes have poor outcomes with screening mammography alone—up to 50% of cancers are interval cancers. Annual screening MRI reduces this percentage significantly, to 11% in women with pathogenic BRCA1 mutations and to 4% in women with BRCA2 mutations.9 Warner and colleagues found a decrease in late-stage cancers in high-risk women who underwent annual MRI screenings compared to high-risk women unable to have MRI.10
The use of MRI for screening is limited by availability, patient tolerance,11 and high cost. Research is being conducted to further validate approaches using shortened screening MRI times (so-called “abbreviated” or “fast” MRI) and, thereby, improve access, tolerance, and reduce associated costs; several investigators already have reported promising results, and a few centers offer this modality directly to patients willing to pay $300 to $350 out of pocket.12,13 Even in normal-risk women, MRI significantly increases detection of early breast cancer after a normal mammogram and ultrasound, and the cancer detection benefit of MRI is seen across all breast densities.14
Most health insurance plans cover screening MRI only for women who meet defined risk criteria, including women who have a known disease-causing mutation—or are suspected of having one, given a family history of breast cancer with higher than 20% to 25% lifetime risk by a model that predicts mutation carrier status—as well as women who had chest radiation therapy before age 30, typically for Hodgkin lymphoma, and at least 8 years earlier.15 In addition, MRI can be considered in women with atypical breast biopsy results or a personal history of lobular carcinoma in situ (LCIS).16
Screening MRI should start by age 25 in women with disease-causing mutations, or at the time of atypical or LCIS biopsy results, and should be performed annually unless the woman is pregnant or has a metallic implant, renal insufficiency, or another contraindication to MRI. MRI can be beneficial in women with a personal history of cancer, although annual mammography remains the standard of care.17–19
MRI and mammography can be performed at the same time or on an alternating 6-month basis, with mammography usually starting only after age 30 because of the small risk that radiation poses for younger women. There are a few other impediments to having breast MRI: The woman must lie on her stomach within a confined space (tunnel), the contrast that is injected may not be well tolerated, and insurance does not cover the test for women who do not meet the defined risk criteria.11