Mammographic density, lobular involution, and risk of breast cancer

Abstract

In this review, we propose that age-related changes in mammographic density and breast tissue involution are closely related phenomena, and consider their potential relevance to the aetiology of breast cancer. We propose that the reduction in mammographic density that occurs with increasing age, parity and menopause reflects the involution of breast tissue. We further propose that age-related changes in both mammographic density and breast tissue composition are observable and measurable phenomena that resemble Pike's theoretical construct of 'breast tissue ageing'. Extensive mammographic density and delayed breast involution are both associated with an increased risk of breast cancer and are consistent with the hypothesis of the Pike model that cumulative exposure of breast tissue to hormones and growth factors that stimulate cell division, as well as the accumulation of genetic damage in breast cells, are major determinants of breast cancer incidence. (1994) proposed that variations in the rate or extent of the decrease in the number and size of breast lobules with increasing age, referred to as breast tissue involution, might be an important factor in the aetiology of breast cancer. They also drew attention to similarities between the histological changes of involution and changes in radiological features of the breast, which were then described in terms of Wolfe's patterns and are now usually referred to as 'mammographic density'.Since then, there have been advances in our understanding of the relationship between both breast histology and mammographic density to the risk of breast cancer, and of the factors that influence these features. Vachon et al (2007a) recently drew attention to similarities between age-related breast involution and mammographic density.In this review, we discuss some of the literature related to mammographic density, breast tissue involution, and breast cancer risk. We propose that age-related changes in mammographic density and breast involution are closely related phenomena, and consider their potential relevance to the aetiology of breast cancer in the light of the Pike model of mammary carcinogenesis. MAMMOGRAPHIC DENSITY AND BREAST CANCER RISKThe radiographic appearance of the breast varies among women of the same age because of variations in breast tissue composition (see further in 'Age and breast tissue composition' section below) and the X-ray attenuation properties of the different types of tissue (Johns and Yaffe, 1987). Fat attenuates X-rays least and appears dark on a mammogram, whereas stroma and epithelium attenuate X-rays more and appear white.Wolfe (1976a, b) related these variations in the appearance of the mammogram to the risk of breast cancer using a qualitative classification with four categories: N1 for breast tissue comprising mainly fat; P1 and P2 for the appearance of ductal prominence of less than 25% or greater than 25%, respectively, or more of the breast area; and DY extensive 'dysplasia'. Subsequently, the American College of Radiology introduced the ...

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