Mammographic density, breast cancer risk and risk prediction

Abstract

In this review, we examine the evidence for mammographic density as an independent risk factor for breast cancer, describe the risk prediction models that have incorporated density, and discuss the current and future implications of using mammographic density in clinical practice. Mammographic density is a consistent and strong risk factor for breast cancer in several populations and across age at mammogram. Recently, this risk factor has been added to existing breast cancer risk prediction models, increasing the discriminatory accuracy with its inclusion, albeit slightly. With validation, these models may replace the existing Gail model for clinical risk assessment. However, absolute risk estimates resulting from these improved models are still limited in their ability to characterize an individual's probability of developing cancer. Promising new measures of mammographic density, including volumetric density, which can be standardized using full-field digital mammography, will likely result in a stronger risk factor and improve accuracy of risk prediction models. IntroductionVariation in the radiographic appearance of the breast reflects differences in tissue composition [1]: darker regions indicate fat tissue and lighter regions represent dense tissue, primarily fibroglandular tissue consisting of the functional elements or parenchyma, and supporting elements or stroma [2]. The proportion of the lighter or dense regions on the mammogram, characterized as mammographic density (MD), has consistently been one of the strongest risk factors for breast cancer, with risk estimates that are three-to five-fold greater for women in the highest quartile of density than for women of similar age in the lowest quartile [3]. As increased MD is common in the population, with 26% to 32% of women in the general population having densities of 50% or greater (Table 1), 16% to 32% of breast cancers may be attributed to this trait [4,5], with an even larger estimated proportion among premenopausal women [6].The magnitude and consistency of the MD and breast cancer association place its importance as a breast cancer risk factor alongside age, the presence of atypia on a breast biopsy, or carrying a highly penetrant breast cancer susceptibility gene (for example, BRCA1 and BRCA2) [7], the latter two which are rare in the population and responsible for only a small proportion of breast cancer. However, until recently, MD has not been used in clinical risk prediction models or clinical decision making. The purpose of this review is to summarize the evidence and strength of MD as a risk factor, review the studies that have evaluated MD in risk prediction, and discuss the implications of incorporating this trait into clinical practice for improving breast cancer risk assessment. Part I. Mammographic density as a risk factor for breast cancerThe association between MD and breast cancer has been investigated in more than 50 studies over the last three decades. These studies have varied in their approaches to the measurement of MD ...

A case‐control study to assess the impact of mammographic density on breast cancer risk in women aged 40–49 at intermediate familial risk

“…Association of MD with breast cancer risk independently of other known risk factors has previously been shown in the average-risk population 11,13,17,47 and in another group of women at higher-than average risk. 39 Continuous-p 5 0.4 1 Tyrer-Cuzick 10-year relative estimate is adjusted for age at recruitment but not for BMI.…”

“…and M.K.). Both relative and absolute measures of dense areas were obtained using the semiautomatic computerised interactive thresholding programme Cumulus 11,27 that provides estimates of total breast area (cm 2 ) and absolute density (cm 2 ). Percent density and nondense breast area were computed from these.…”

“…Women with a moderate family history of breast cancer may be offered annual mammography from age 40 to 49. 6,7 Mammographic density (MD) is a strong risk factor for breast cancer, both in terms of relative and attributable risk, [10][11][12] in pre-and postmenopausal women. 13 MD reporting using the BI-RADS system is mandatory in many parts of the United States.…”

The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme – a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone

“…4,[94][95][96][97][98][99][100] Women with high breast density have been reported to have a four to six times increased risk of developing breast cancer compared with those with low breast density, 95,[101][102][103][104][105] and high breast density has also been linked to an increased risk of cancers not detected at screening, 4,8,96,106,107 larger tumour size [108][109][110] and positive lymph nodes. 109,[111][112][113] The underlying cause of these links are thought to be numerous, and early studies hypothesised that a significant reason for an increase in breast cancer incidence with higher density breasts was as a result of a 'masking bias' that made mammographic screening less sensitive to cancer detection.…”

Projecting Individualized Absolute Invasive Breast Cancer Risk in US Hispanic Women

“…First, the HRM had modest discriminatory accuracy, which highlights the need for considering additional risk factors, such as mammographic density (26)(27)(28)(29) or genetic variants (30,31). Nevertheless, an advantage of the HRM, like BCRAT, is that the information required is available from self-report.…”