Version May 2024
INTRODUCTION — Increased breast density impairs the detection of abnormalities on mammography and increases the risk for a breast cancer diagnosis but has not been associated with increased risk of death due to breast cancer. Passage of legislation in multiple states in the United States regarding mammography reporting of breast density and follow-up for women with dense breasts has led to renewed discussion about the optimal screening protocol for early detection of breast cancer in women who have dense breast tissue on mammography [1,2].
This topic will discuss the classification of breast density and data regarding possible pros versus cons of obtaining supplemental testing beyond mammography. Screening for breast cancer and breast imaging are discussed elsewhere. (See "Screening for breast cancer: Strategies and recommendations" and "Screening for breast cancer: Evidence for effectiveness and harms" and "Breast imaging for cancer screening: Mammography and ultrasonography".)
In this topic, we will use the term “woman/en” to describe genetic females. However, we recognize that not all people with breasts identify as female, and we encourage the reader to consider transgender and gender nonbinary individuals as part of this larger group.
DEFINITION AND CLASSIFICATION — Breast tissue comprises skin, blood vessels, ductal and stromal elements of the glands (which appear radio-opaque or white on mammography), and fat (which appears radiolucent or black on mammography). Mammographic breast density is defined as the relative amount of radio-opaque (white) elements to radiolucent (black) fat on the image.
Breast density does not correlate with physical examination findings [3,4]. Breast density is a radiologic finding and cannot be predicted without obtaining a mammogram [5,6]. Increase in the proportion of radio-opaque elements leads to greater mammographic breast density. Having mammographically dense breasts is normal and common, occurring in 47 to 50 percent of the population [7,8].
Increased breast density may obscure the detection of a benign mass or, more importantly, a breast cancer. Reduced sensitivity of mammography in younger women in part is related to increased mammographic density due to a higher proportion of breast epithelial and stromal elements in younger breasts [9].
Classifying breast density — There are several ways to report mammographic breast density. The most commonly used method is the Breast Imaging Reporting and Data System (BI-RADS), fifth edition, 2012, in which the determination of breast density is made by the radiologist using visual assessment that is subject to inter-rater variability.
Computerized quantification programs are available, but are used largely as research tools. As these objective computer-based methods are not widely adopted, most state laws requiring breast density notification to patients are based on the less reproducible method of visual assessment.
BI-RADS classification — BI-RADS is based on a scale that identifies breast tissue density as being in one of four categories [10]:
●A – Almost entirely fatty
●B – Scattered areas of fibroglandular density
●C – Heterogeneously dense (may obscure small masses)
●D – Extremely dense (lowers the sensitivity of mammography)
For most purposes, the term "dense breasts" refers to either heterogeneously dense or extremely dense breasts (categories C or D), accounting for approximately 47 to 50 percent of women in the general United States screening population [7,8]. Mammographic examples of each of these categories of breast density are shown in the figure (image 1).
The 2012 fifth edition BI-RADS lexicon assigns breast density based on the presence of any patch of dense tissue [10]. Earlier editions of BI-RADS used percentages of dense tissue relative to fat to report a quartile (<25 percent, 25 to 50 percent, 50 to 75 percent, and >75 percent dense).
Moderate variability among readers in the assignment of dense breast tissue categories (BI-RADS C and D) has been reported at both the interobserver and intraobserver level (kappa values from 0.4 to 0.6) [11,12]. As an example, in one observational series of 83 radiologists interpreting 216,783 screening mammograms of 145,123 women aged 40 to 89 years, the percentage of mammograms categorized as dense breast tissue ranged from 6 to 85 percent [11,13-15]. Additionally, there is variability over time in the density of a patient’s breast density, especially with changes in weight or hormonal status (eg, phase of menstrual cycle, postmenopausal versus premenopausal status, or exogenous hormone use) [16-20].
Computer-based breast density assessment — With computer-based assessment of breast density, assignment of breast density categories is less variable than among human readers [21]. This computer-based technology performs an automated volumetric assessment using digital mammography data, although it can fluctuate based on patient positioning as the amount of retroglandular fat included in the measurement can vary [22,23]. Computer-based systems demonstrate moderate to substantial agreement (kappa values ranging from 0.6 to 0.7) with BI-RADS categorization by human readers [24-26]. However, there is up to 14 percent variability among vendor systems in assignment of a dense breast category [24].
Factors affecting breast density measurement — There is much variation in the physical composition of the breast. Differing proportions of fat, connective tissue, and ductal and lobular elements contribute to differences in mammographic breast density. Mammographic density is not related to the size or the firmness of the breast [3,4]. Breast density is greater in younger women and also varies with menopausal status, genetic factors, parity, use of estrogen, use of chemoprevention (tamoxifen), and body habitus [27,28]. There is also operator dependence in interpreting breast density on mammography [11].
Breast density can vary during different phases of the menstrual cycle, with slightly increased density in the luteal as compared with the follicular phase [16,29]. This suggests that mammographic sensitivity may be slightly improved in menstruating women by obtaining mammograms during the follicular phase (ie, first and second weeks after menses), particularly for women who have ever used oral contraceptives [29].
Use of menopausal hormone therapy slows the age-related change from dense to fatty breast tissue. In a longitudinal study, this was more pronounced for women taking combination estrogen and progestin than for those taking estrogen alone [30]. Short-term (one to two months) cessation of hormone therapy prior to mammography, although advised by some clinicians, had no effect on mammographic recall rates in a randomized trial [31].
Breast density is inversely related to patient age, and dense breasts are most commonly associated with women under age 50 years or in those who are premenopausal. An international cross-sectional study showed that breast density declines are greatest during transition to menopause [32]. However, many older women still have dense breasts (up to 44 percent of women in their 60s and 36 percent of women in their 70s) [33].
Finally, there is evidence that interpreting breast density may be somewhat subjective, with variability between radiologists. In a retrospective study of approximately 217,000 mammograms interpreted by 83 radiologists, 37 percent of mammograms overall were rated as showing dense breasts [11]. Across radiologists, this percentage ranged from 6 to 85 percent. Among patients with consecutive mammograms read by different radiologists, 17 percent had discordant results in regards to a dense versus a nondense assessment.
BREAST DENSITY AND BREAST CANCER RISK — The presence of dense breast tissue on mammography affects breast cancer risk in two ways: dense tissue can obscure an underlying cancer, decreasing the sensitivity of mammography to detect small lesions [34-37]; and increased density is an independent risk factor for breast cancer [38], as most cancers develop in the glandular parenchyma. However, increased breast density is not associated with increased mortality from breast cancer [39].
While increased breast density is an independent risk factor for breast cancer, the extent to which breast density affects risk for breast cancer is not absolutely established. The best estimates are that, compared with the general population, the relative risk of developing breast cancer is 1.2 for women with heterogeneously dense breasts and 2.1 for women with extremely dense breasts [40,41]. Reports indicating a relative risk of four- to sixfold are based on a comparison of women in the 90th percentile to women in the 10th percentile for breast density [35,42,43], which inflates the risk and does not represent the average population [44]. Absolute risk, rather than relative risk, is a more meaningful reflection of the impact of breast density. In terms of absolute risk, a 45-year-old woman with average breast density, no family history of breast cancer, and no prior breast biopsy has a 0.7 percent five-year breast cancer risk compared with a woman with similar characteristics, except for extremely dense breast tissue, whose five-year breast cancer risk is 1.3 percent [45].
Breast density alone does not determine breast cancer risk: the relative risk conferred by breast density in part depends on a woman's other risk factors for breast cancer (see "Factors that modify breast cancer risk in women", section on 'Dense breast tissue'):
●Breast density was not an independent risk factor for breast cancer in a cohort of women at very high risk for breast cancer who underwent magnetic resonance imaging (MRI) [46].
●Black women have a higher likelihood of having fatty breasts (and therefore less dense breasts) than White women, but they have a higher risk for developing aggressive breast cancers, suggesting differences in the biology of the tumors [5,6,47].
●Asian individuals have higher breast density but a lower than average incidence of breast cancer [5,48-50].
●Increasing age increases the risk for breast cancer, as does increasing body mass index (BMI), but age and obesity are associated with decreasing breast density [51,52].
●A large study using data from the Breast Cancer Surveillance Consortium (BCSC) noted that the interval cancer rate was highest in the subset of women with dense breasts who also had an elevated five-year risk for breast cancer, which was less than a quarter of all women with dense breasts (24 percent) [53].
A risk assessment calculator for persons with dense breast is available. (calculator 1)
BREAST DENSITY AND PRIMARY SCREENING FOR BREAST CANCER — Mammography is the primary screening tool for breast cancer and has been shown in multiple randomized controlled trials to reduce the death rate from breast cancer. (See "Screening for breast cancer: Strategies and recommendations" and "Screening for breast cancer: Evidence for effectiveness and harms".)
However, even in the best circumstances, mammography may miss up to 20 percent of underlying breast cancers [54]. The sensitivity of mammography is inversely correlated with breast density, especially with older film-screen analog techniques [55].
Digital mammography — Digital mammography is more sensitive than film mammography for dense breasts [56,57] and is preferred (when available) for women with increased breast density [58].
In the United States, digital mammography has largely replaced film mammography [59]. Data from the Breast Cancer Screening Consortium (BCSC), a database of multiple screening programs in the United States, showed that in women with fatty or scattered fibroglandular breasts, the sensitivity of film-screen mammography is 85 to 86 percent but decreases to 79 percent in women with heterogeneously dense breasts and further decreases to 68 percent in women with extremely dense breasts [60]. Using digital mammography, the sensitivity of mammography for women without dense breasts (fatty or scattered fibroglandular breasts, 78 to 87 percent) was similar to the sensitivity for women with heterogeneously dense breasts (82 percent) and women with extremely dense breasts (84 percent). (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Digital mammography'.)
Digital breast tomosynthesis — The technique of digital breast tomosynthesis (DBT) is increasingly available in the United States. The National Comprehensive Cancer Network (NCCN) has updated its guidelines for women with an average risk of breast cancer by adding "consider" annual tomosynthesis screening starting at age 40 years [61]. For average-risk women, there is no need for additional supplemental screening with other modalities when DBT is performed as the initial screening examination.
If women who have dense breasts have access to tomosynthesis screening, some experts suggest that tomosynthesis may be preferred over standard mammography, although this is not the standard of care [62]. DBT techniques, DBT among women with average breast density, and the potential for higher radiation exposure are described separately. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Digital breast tomosynthesis (DBT)' and "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Digital versus film screen mammogram'.)
Although no randomized controlled trials comparing DBT and digital mammography in women with dense breasts have been performed, clinical studies suggest that, compared with digital mammography, screening DBT has greater sensitivity for cancer detection while decreasing the recall rate from screening mammography [63-70]. In one prospective observational study including approximately 2600 women with dense breasts, three-dimensional (3D) mammography detected an additional 5.4 to 6.2 cases of cancer per 1000 screens performed in women with dense breasts [71].
Multiple studies have shown that DBT may have the greatest effect at reducing false-positives in women with dense breasts and may have the greatest impact on improving cancer detection in women with heterogeneously dense breasts [66,68,72,73]. In one study, among approximately 3200 self-referred asymptomatic women with dense breasts and negative digital mammograms, an additional four breast cancers per 1000 screens were detected by DBT (95% CI 1.8-6.2) [73]. While breast ultrasound detected even more occult cancers (7.1 per 1000 screens, 95% CI 4.2-10.0), more than half of additional breast cancers in women with dense breasts could be detected by DBT. The risk profile of this self-referred group is not known, which makes it difficult to generalize these results to any specific population.
DBT may have a particular value for breast cancer screening in women with dense breasts and who are at increased risk of breast cancer. In an observational study including over 500,000 participants, screening with DBT versus digital mammography was associated with a lower risk of advanced breast cancer among the 3.6 percent of participants who had extremely dense breasts and ≥1.67 percent five-year risk of breast cancer (absolute risk difference -0.53, 95% CI -0.97 to -0.1) [74]. However, no benefit for DBT was observed among those with extremely dense breasts but without an increased risk.
BREAST DENSITY AND SUPPLEMENTAL SCREENING FOR BREAST CANCER — Some cancers are mammographically occult and can be detected only by other breast imaging studies or physical examination. Whether performing supplemental screening to identify mammographically occult cancers provides more benefit than harm is not established.
Approximately one-half of women undergoing screening mammography have dense breasts, making dense breasts both normal and common [75]. Implementing supplemental screening after negative mammography in women with dense breasts (including heterogeneously dense and extremely dense breasts) could expose 48 to 50 percent of the screening population to potential false-positive screening results with associated anxiety and the need for breast biopsy, and there is no direct evidence that such supplemental screening affects mortality from breast cancer.
A smaller percentage of the population (about 10 percent) have BI-RADS (Breast Imaging Reporting and Data System) category D extremely dense breast tissue, and therefore focusing supplemental screening on this population separately has been evaluated in some studies. (See 'BI-RADS classification' above.)
Evidence and expert consensus remains unclear as to the risk-benefit balance of supplemental screening for the modalities discussed below.
Modalities under investigation for supplemental screening
Whole-breast ultrasound screening — Two types of ultrasound have been investigated for supplemental screening: handheld ultrasound and automated breast ultrasound. Automated breast ultrasound uses an automated transducer to standardize image acquisition; however, these automated systems are not widely available. In both approaches, the breast is systematically scanned in orthogonal planes, and selected images are recorded. Although the majority of studies assessing the use of ultrasound for supplemental screening in women with dense breasts have been performed with handheld ultrasound, limited initial data of automated ultrasound suggests that the two types of ultrasound are comparable for supplemental screening [76].
Whole-breast ultrasound screening can detect early-stage, mammographically occult breast cancers in women with dense breast tissue, but the additional screening test carries a substantial risk for false-positive results. When used as a supplement to mammography, ultrasound can improve the sensitivity of screening at the expense of decreased specificity, with increased need for follow-up imaging, an increased breast biopsy rate, and breast biopsies with benign results leading to patient anxiety.
The majority of cancers found by ultrasound (88 to 93 percent) are invasive [8,77,78], and most are node-negative [8,79]. The addition of ultrasound to mammographic screening has yet to be shown to reduce breast cancer mortality [80].
Findings from representative studies on the use of ultrasound for supplemental screening for women (the majority among patients with dense breasts) are described below:
●A secondary analysis of the Japan Strategic Anti-cancer Randomized Trial (J-START) evaluated 19,213 patients (40 to 49 years of age) who were assigned to either mammography with ultrasonography or mammography alone [81]. Among all patients, sensitivity for cancer detection was higher in the intervention group than the control group (93.2 percent [95% CI, 87.4-99.0 percent] versus 66.7 percent [95% CI, 54.4-78.9 percent]). Among those patients with dense breasts, sensitivity was also higher in the intervention group (93.2 percent [95% CI, 85.7-100.0 percent] versus 70.6 percent [95 percent CI, 55.3-85.9 percent]). However, in all patients, specificity was lower in the intervention group (86.8 percent [95% CI, 86.2-87.5 percent] versus 91.8 percent [95% CI, 91.2-92.3 percent]), and recall rates (13.8 percent [95% CI, 13.1-14.5] versus 8.6 percent [95% CI, 8.0-9.1 percent]), and biopsy rates were higher (5.5 percent [95% CI, 5.1-6.0 percent] versus 2.1 percent [95% CI, 1.8-2.4 percent]). Limitations also include the young age of the participants.
●The large prospective, multicenter study conducted through the American College of Radiology Imaging Network (ACRIN Protocol 6666) evaluated the diagnostic yield of screening handheld ultrasound in addition to mammography in high-risk asymptomatic women with at least heterogeneously dense breasts on mammography and one additional risk factor for breast cancer [82]. The study found that adding screening ultrasound to mammography identified an additional 4.3 cancers per 1000 women screened but increased the number of false-positive results (positive predictive value for mammography alone was 22.6 versus 11.2 percent for mammography plus ultrasound).
●In a 2023 meta-analysis of three cohort studies conducted among women with dense breasts, the combination of mammography and ultrasonography detected two more cancer cases (95% CI 1-5 more) per 1000 screened women than mammography alone (0.45 versus 0.30 percent, RR 1.78, 95% CI 1.23 to 2.56) [83].
●In a systematic review of 12 studies of screening ultrasound in populations with varying cancer risk factors, ultrasound was associated with an additional 11.9 to 106.6 biopsies per 1000 examinations (median, 52.2), with detection of an additional 0.3 to 7.7 cancers (median, 4.2) [8].
●The addition of ultrasound to mammography increases sensitivity for small cancers, but greatly decreases specificity. In a 2016 systematic review of studies of supplemental screening with ultrasound (either handheld or automated whole breast) in women with dense breasts and a negative mammogram, greater than 90 percent of positive test results were false-positive [12]. The sensitivity of ultrasonography was 80 to 83 percent, the specificity was 86 to 94 percent, and the positive predictive value was 3 to 8 percent. The recall rates were 14 percent. In a subsequent 2020 meta-analysis including 21 studies in women with dense breasts, the addition of supplemental ultrasound screening increased the sensitivity (96 versus 74 percent with mammography alone) and decreased the specificity of (87 versus 93 percent for mammography alone) for the detection of breast cancer [84].
●The use of supplemental ultrasound led to a fivefold increase in the number of unnecessary biopsies, compared with mammography alone [8]. The positive biopsy rate for biopsies generated by supplemental screening ranged between 6 to 8 percent, compared with 25 to 40 percent for biopsies generated by screening mammography alone [76,85].
●In multiple studies, the recall rate of supplemental screening ultrasound was approximately twice that of mammography and the biopsy rate was three times greater than that of mammography [77,82,86-91].
●In a cost-effectiveness study using three simulation models, supplemental ultrasound for women aged 50 to 74 years with heterogeneously or extremely dense breasts and a negative mammogram would cost more than USD $100,000 per quality-adjusted life-year (QALY) gained [92]. Biennial supplemental screening for women aged 50 to 74 years was more cost-effective than annual screening for women aged 40 to 74 years, but neither strategy met generally accepted thresholds for cost-effectiveness. Compared with mammography alone, supplemental ultrasound was predicted to prevent 0.36 additional cancer deaths and lead to an additional 354 biopsies per 1000 women screened biennially for 25 years.
Magnetic resonance imaging — Contrast-enhanced dynamic breast magnetic resonance imaging (MRI) has increased sensitivity for cancer detection in women who are at high risk for breast cancer (>20 to 25 percent lifetime risk), including women with known deleterious gene mutations (such as BRCA1 or BRCA2 mutations), women with sufficiently strong family histories of breast and/or ovarian cancer, and women who received mantle radiation for Hodgkin lymphoma [93]. However, the American Cancer Society finds data insufficient to recommend for or against MRI for supplemental screening solely for women with increased breast density [93], and there is concern that MRI in women with dense breasts may be associated with a high false-positive rate leading to unnecessary biopsies and possible overdiagnosis [94].
Data are limited on the use of supplemental screening MRI in women who are at low or average risk and have dense breasts.
●In a systematic review of three studies of MRI after a negative mammogram, the sensitivity of MRI ranged from 75 to 100 percent, the specificity from 78 to 94 percent, and the positive predictive value from 3 to 33 percent [12]. Recall rates were 23 to 24 percent, and 3.5 to 28.6 additional cancers were found per 1000 examinations, of which 34 to 86 percent were invasive. Most women in these studies were at increased risk for breast cancer, in addition to having increased breast density.
●In another ACRIN 6666 study in women without BRCA mutations or breast cancer who had three negative screening rounds with mammography and supplemental ultrasound over two years, breast MRI identified an additional six cases of invasive breast cancer among 334 women [77]. For women who had dense breasts and a negative mammogram, supplemental ultrasound yielded no additional malignancies that were not found on either mammography or MRI but did yield additional false-positives. This suggests that women who receive MRI for supplemental screening after a negative mammogram should not also receive screening ultrasound.
●A large Dutch trial (the DENSE trial) investigating the use of supplemental screening MRI in women with extremely dense breasts demonstrated a reduction in interval cancers; women with extremely dense breasts screened with mammography and supplemental MRI were diagnosed with fewer interval breast cancers over a two-year study period (2.5 versus 5 breast cancers per 1000 screenings) [95].
Widespread use of MRI for supplemental breast cancer screening is limited by the high cost, lack of wide availability, and potential adverse reactions to contrast medium. Use of gadolinium required for breast MRI is associated with nephrogenic systemic fibrosis in patients with renal disease, although this is now extremely rare given the use of newer gadolinium-based agents. Review of precautions regarding MRI and the use of gadolinium can be found elsewhere. (See "Principles of magnetic resonance imaging" and "Patient evaluation for metallic or electrical implants, devices, or foreign bodies before magnetic resonance imaging" and "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging".)
Emerging technologies — Multiple other supplemental screening methods are being investigated, including the use of abbreviated MRI, molecular breast imaging, and contrast-enhanced mammography. Although some centers are now routinely performing these examinations, they have yet to be broadly adopted into routine clinical practice as supplemental screening tools in women with dense breast tissue.
In order to implement more widespread supplemental MRI screening, an abbreviated protocol has been developed that is briefer in duration for the patient and requires fewer images for interpretation. This abbreviated technique is described in more detail below as it is considered an emerging technology, even though some practices are now routinely performing it.
Abbreviated first post-contrast acquisition subtracted (FAST) MRI — Routine screening dynamic contrast-enhanced breast MRI requires the patient to lay prone on the MRI table for approximately 20 to 50 minutes as images are obtained in a dynamic series both with and without the administration of intravenous gadolinium contrast agents. An abbreviated protocol with fewer sequences, taking only three to five minutes of acquisition time, appears to have equivalent diagnostic accuracy and is faster for the radiologist to interpret. Such abbreviated protocols may make screening MRI less costly and more accessible to women with dense breasts. Examples of studies using an abbreviated MRI protocol include:
●A small preliminary study of the use of an abbreviated MRI screening protocol in women with mild to moderate risk, including women with dense breasts and negative mammograms and ultrasounds, reported an incremental cancer detection rate of 18.2 per 1000, with a negative predictive value of 99.8 percent [96].
●In a multicenter study in the United States and Germany including over 1400 women with dense breasts, screening with both abbreviated MRI and digital breast tomosynthesis (DBT) demonstrated an increase in the invasive cancer detection rate with MRI compared with DBT (11.8 versus 4.8 cancers per 1000 women screened) [97]. In addition, the combined sensitivity for detection of invasive and in situ cancers was higher for abbreviated MRI compared with DBT (95.7 percent [95% CI, 79.0-99.2] versus 39.1 percent [95% CI, 22.2-59.2]). The specificity for detection of combined invasive and in situ cancers, however, was lower for abbreviated MRI compared with DBT (86.7 percent [95% CI, 84.8-88.4] versus 97.4 percent [95% CI, 96.5-98.1]).
There are no data demonstrating mortality outcomes using abbreviated MRI as a screening modality.
Molecular breast imaging — Molecular breast imaging (MBI) techniques for supplemental screening in women with dense breasts and negative mammography, using gamma cameras and, most commonly, intravenous Tc99m-Sestamibi, are approved in the United States by the US Food and Drug Administration (FDA), although they are not in widespread use. While initial studies used a higher radiation technique, a new technique uses a very low radiation dose, which alters the risk-benefit profile of this modality. Early clinical studies with a low-dose technique demonstrate that the addition of supplemental MBI detects an incremental 8.8 per 1000 cancers with only a small decrease in specificity [98].
Contrast-enhanced mammography — Contrast-enhanced mammography is a dual-energy technique that allows for acquisition of a low-energy image comparable to a mammogram and a subtracted image displaying contrast uptake following injection of an intravenous iodinated contrast agent. In the diagnostic setting, the sensitivity has been shown to be equivalent to MRI among women at increased risk of breast cancer [99], although it has not been compared with MRI in women with dense breasts. However, it may be superior to mammography alone. As an example, in a 2017 study from Japan, this imaging technique detected substantially more cancers in women with dense breasts than mammography alone [100]; this technique may have a role in supplemental screening.
Legislation in the United States — There are no large prospective studies to support supplemental whole-breast ultrasound or MRI screening of average-risk women with dense breast tissue on mammography. Nonetheless, many US states have adopted dense breast legislation, and additional states are considering such legislation. At a minimum, these laws require that patients be informed of their breast density, that dense breast tissue may be a risk factor for breast cancer, and that dense tissue may interfere with cancer detection. In 2023 the U.S. Food and Drug Administration (FDA) published updates to the Mammography Quality Standards Act (MQSA) of 1992, requiring mammography facilities to notify patients about the density of their breasts [101]. This update will go into effect in 2024. While this FDA-mandated notification does not recommend supplemental screening, it will encourage women with dense breasts to talk to their health care provider about their risk and if they may benefit from supplemental screening.
However, only some states have mandated insurance coverage for supplemental tests [92], and it is quite possible that the patient's insurance may not cover the supplemental test and the woman will incur significant out-of-pocket expenses should she choose to undergo supplemental screening.
Explaining breast density to patients — A study reports that the language used by breast density notifications in states, where mandated, generally exceeded recommended readability levels, scored poorly on understandability ratings, and generally did not correlate with state literacy levels [102]. When women are informed about mammographically identified increased breast density, it is thus important to discuss the fact that “dense breast tissue” is a normal mammographic finding noted in almost half of all women and to discuss the pros and cons of supplemental screening prior to initiating such screening [103]. The clinician and the patient should review the risks and the potential benefits, including the risk of a false-negative mammogram, the risk of a false-positive supplemental finding potentially leading to follow-up imaging or a benign breast biopsy, and the potential risk of overdiagnosis if an in situ breast cancer is detected. An informational tool to facilitate this discussion is included in a table (table 1).
There is no legislation related to breast density and supplemental screening outside of the United States.
Risk stratification for supplemental screening — Medical evidence and expert consensus guidelines support determining the patient’s risk of breast cancer and using this risk stratification information to help guide the discussion with the patient regarding screening strategies and whether supplemental breast cancer screening is indicated.
Breast density is not incorporated into the calculation of risk by most of the risk models developed to estimate the lifetime probability of developing breast cancer and/or the probability of carrying a known deleterious gene mutation that predisposes to breast cancer [104]. None of the major breast cancer screening guidelines advise that breast density be used as the sole factor in determining the need for additional screening beyond mammography. Different models have been validated in different populations and vary in taking into account a woman's family history of breast, ovarian, or other cancers, prior breast biopsies, current age, age of menarche/menopause, age of first pregnancy, and other factors. (See "Screening for breast cancer: Strategies and recommendations", section on 'Breast cancer risk determination'.)
High risk (>20 percent lifetime risk) — Routine supplemental screening breast MRI, as an adjunct to mammography, is recommended for women who have a lifetime risk >20 percent according to the risk models, regardless of breast density. (See "Cancer risks and management of BRCA1/2 carriers without cancer", section on 'Cancer surveillance'.)
Breast density for such women is not a relevant factor, and ultrasound is unnecessary for women who are undergoing MRI examination [77]. The cancer detection rate of supplemental MRI is greater than that of supplemental ultrasound. Supplemental ultrasound found no additional cancers beyond those seen on the combination of mammography and MRI in a large multi-institutional trial in high-risk women [77].
Women with dense breasts who also have other high-risk factors (such as known deleterious gene mutations, prior mantle radiation exposure, and sufficiently strong family history) should follow the supplemental screening guidelines for high-risk women that may include annual supplemental MRI in addition to annual mammography [93]. (See "Screening for breast cancer: Strategies and recommendations", section on 'Models predicting pathogenic BRCA1/2 mutations' and "Cancer risks and management of BRCA1/2 carriers without cancer", section on 'Cancer surveillance'.)
The American College of Radiology [105,106] and the Society of Breast Imaging [75] recommend screening ultrasound for women in this high-risk group who are unable to undergo MRI (for various reasons including claustrophobia not amenable to anxiolytic therapy, presence of a cardiac pacemaker or other MRI incompatible device, history of severe reaction including anaphylaxis to gadolinium). There is limited evidence that contrast-enhanced mammography may have a role in this setting as well, although further data are needed before this technique is routinely adopted into practice [105]. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging" and "Patient evaluation for metallic or electrical implants, devices, or foreign bodies before magnetic resonance imaging".)
Average or low risk (<15 percent lifetime risk) — There is a lack of medical evidence to routinely recommend supplemental screening with either MRI or ultrasound in average-risk women who have dense breasts [87]. Advice regarding supplemental screening varies among organizations:
●The United States Preventive Services Task Force (USPSTF) in 2016 found that evidence is insufficient to assess the balance of benefits and harms of adjunctive screening using breast ultrasound, MRI, DBT, or other methods in women with dense breasts and an otherwise negative mammogram [12,107].
●Supplemental screening MRI guidelines from the American Cancer Society state that screening MRI is not recommended for low-risk women [93].
●For women with dense breasts as their only risk factor for breast cancer, the American College of Radiology states that "the addition of ultrasound to screening mammography may be useful for incremental cancer detection" [75]. They also note that a decision not to offer ultrasound screening, due to issues of test reproducibility, high false-positive rates, operator dependency, and a low positive predictive value for biopsy recommendations, is acceptable within the standard of care. Some breast imaging centers may decide not to offer screening ultrasound examination.
●There are no recommendations regarding screening breast ultrasound from the American Cancer Society, the American College of Obstetrics and Gynecology, the American Academy of Family Physicians, or the American College of Physicians.
Intermediate risk (15 to 20 percent lifetime risk) — There are no consensus guidelines to recommend for or against supplemental screening ultrasound in women with intermediate risk and dense breasts. Recommendations for MRI in women at intermediate risk for breast cancer (not solely determined by breast density) are inconclusive.
●American Cancer Society screening MRI guidelines advise that supplemental screening MRI may or may not be recommended as an adjunct to mammography in women who have an intermediate-risk profile [93].
●For women with a 15 to 20 percent lifetime risk of breast cancer, appropriateness criteria from the American College of Radiology rate supplemental screening MRI as 7 and supplemental ultrasound as 5 on a scale of 1 (not recommended) to 9 (highly recommended) based on expert consensus and review of medical evidence [106].
Supplemental MRI screening in women of intermediate risk with BI-RADS class D extremely dense breast tissue is an option, recognizing that this will find some cancers but also likely result in increased false positives, with a resultant increase in biopsies, cost, possibly overdiagnosis, and patient anxiety, with no evidence of a reduction of breast cancer specific or overall mortality.
Supplemental screening ultrasound may be more widely accessible and may be less expensive than supplemental MRI in this intermediate-risk population; however, neither is routinely covered by insurance for this risk category in most states.
Many experts suggest that in women who are at intermediate risk for breast cancer, the decision to undergo supplemental screening with either ultrasound or MRI should be made after a discussion between the patient and her clinician to determine the patient's personal preferences. Components of the discussion that help with decision-making by patients who have dense breasts include information about the meaning of breast density, the patient’s level of risk for breast cancer, risk-reduction methods, potential benefits and harms of breast cancer screening, availability of screening methods, and insurance coverage. A resource for clinicians to use during the discussion is provided in a table (table 1) [103].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Screening for breast cancer".)
SUMMARY AND RECOMMENDATIONS
●Classification of breast density – For most purposes, the term "dense breasts" refers to either heterogeneously dense or extremely dense breasts (categories C or D of the Breast Imaging Reporting and Data System [BI-RADS], fifth edition). Considerable reader variability has been noted in assigning the dense breast tissue categories. (See 'BI-RADS classification' above.)
●Factors affecting breast density – Breast density is a normal mammographic finding. Multiple factors contribute to breast density in women, including age, genetics, body habitus, parity, use of estrogen, and phase of the menstrual cycle. Dense breasts are found in approximately 50 percent of women undergoing mammography, including up to 44 percent of women in their 60s. (See 'Factors affecting breast density measurement' above.)
●Dense breasts and breast cancer risk – The presence of dense breast tissue on mammography decreases the sensitivity of mammography and is an independent risk factor for breast cancer, as most cancers develop in the glandular parenchyma. However, the extent to which breast density affects the risk for breast cancer is not absolutely established, and increased breast density has not been associated with increased breast cancer mortality. (See 'Breast density and breast cancer risk' above.)
●Imaging for women with dense breasts
•Digital mammography – Digital mammography is more sensitive than film mammography for dense breasts and is preferred, when available, for women with increased breast density. Digital breast tomosynthesis (DBT) compared with digital mammography may decrease the recall rate for women with dense breasts but may somewhat increase the radiation exposure rate, depending on the type of DBT available. (See 'Digital mammography' above.)
•Digital breast tomosynthesis – For women who have dense breasts, there are limited data to suggest that DBT may be preferred over standard mammography, especially in women with heterogeneously dense breasts, although this is not the standard of care. DBT does have some benefit over digital mammography for those with extremely dense breasts who are also at an elevated risk of breast cancer. If a woman does not have access to DBT, screening mammography remains the standard of care. (see 'Digital breast tomosynthesis' above)
●Breast density alone should not determine the need for supplemental screening – None of the major breast cancer screening guidelines advise that breast density be used as the sole factor in determining the need for additional supplemental screening beyond mammography. Medical evidence and expert consensus guidelines support determining the patient’s risk of breast cancer and using this risk stratification information to help guide the discussion with the patient. (See 'Breast density and supplemental screening for breast cancer' above.)
•Role of supplemental screening whole breast ultrasound – There are no large prospective studies to support whole-breast ultrasound screening of average-risk women with dense breast tissue on mammography. Nonetheless, in the United States, many states have adopted dense breast legislation requiring that patients be informed of their breast density, that dense breast tissue may be a risk factor for breast cancer, and that dense tissue may interfere with cancer detection. Some laws specifically recommend supplemental screening with ultrasound, but only some of those states mandate insurance coverage for this additional screening. (See 'Breast density and supplemental screening for breast cancer' above and 'Legislation in the United States' above.)
•Role of supplemental screening magnetic resonance imaging – Supplemental screening with magnetic resonance imaging (MRI) is limited by high false-positives and additionally by higher cost, lack of wide availability, and potential adverse reactions to contrast medium. (See 'Magnetic resonance imaging' above.)
●Supplemental screening recommendations
•For those with dense breasts and low/average breast cancer risk – We suggest that most women with dense breasts and no additional risk factors for breast cancer (ie, average or low risk) not undergo supplemental screening (Grade 2C). After discussion of the potential risks and benefits associated with such screening (table 1), some women may reasonably opt to not undergo supplemental screening while others will opt to have supplemental screening. For average and low-risk women who choose to undergo supplemental screening, ultrasound or MRI are options. (See 'Risk stratification for supplemental screening' above.)
•For those with dense breasts and intermediate (15 to 20 percent lifetime) breast cancer risk – There are no consensus guidelines to recommend for or against supplemental screening in women with dense breasts and intermediate breast cancer risk. For women with dense breasts and an intermediate risk, supplemental screening with ultrasound or MRI are options. (See 'Intermediate risk (15 to 20 percent lifetime risk)' above.)
•For those with dense breasts and high (>20 percent lifetime) breast cancer risk – Routine supplemental screening breast MRI, as an adjunct to mammography, is recommended for all women who have a lifetime risk >20 percent, regardless of breast density. (See 'High risk (>20 percent lifetime risk)' above and "Cancer risks and management of BRCA1/2 carriers without cancer", section on 'Cancer surveillance'.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
