Morphometric studies of age related changes in normal human breast and their significance for evolution of mammary cancer.

Abstract

SUMMARY Ageing changes in the normal human female breast were studied to determine their significance for the evolution of mammary cancer. Employing the morphometric techniques of point counting and planimetry, objective quantitative measurements were made of the structure of the normal female breast in 58 subjects from the prepubertal to late postreproductive period. The relative amounts of epithelial and connective tissue varied with age, and the epithelial elements (combined lobular and extralobular) were unevenly distributed within the gland, with lower containing more than upper quadrants. The upper outer quadrant, however, usually contained the largest proportion of lobular units, which may relate to the higher incidence of lobular carcinoma found in this quadrant. Involution was shown to be a premenopausal rather than postmenopausal phenomenon. Mammary dysplastic changes were uncommon in all age groups.Normal human breast morphology has been well documented at both light and electron microscopical levels.'-8 Similar studies have also been conducted in breasts containing clinical carcinomas in order to determine early malignant and premalignant changes.9-l" The extent to which normal ageing processes contribute to these changes is uncertain, however, since these are poorly documented. The present study was undertaken to establish on a quantitative basis the normal sequence of morphological changes that take place in the non-neoplastic female breast from the prereproductive to postreproductive periods. Particular attention was devoted to determining features that might have relevance for the subsequent evolution of breast cancer. Material and methods BREAST SAMPLESSubcutaneously removed mammary glands, excluding the nipple and axillary tail, were routinely collected from female subjects at necropsy. The breasts were fixed in buffered formalin for three to seven days depending on size and fat content. In all, 58 breasts were processed covering the seven decades from 10 to 80 years, and each group contained at Accepted for publication 8 November 1984 least eight samples. No bilateral specimens were taken. PREPARATION FOR SUBGROSS ANALYSISAfter fixation, breasts were sliced coronally (2 mm slices) on an Excel Boston slicing machine and labelled on their superior and lateral extremities to aid orientation. Where necessary, fixation was continued for a further 24 h. Whole slices were stained with Harris's haematoxylin, dehydrated in graded ethanol (70%, 95%, and 100%), and cleared and stored in methyl salicylate.'2 PREPARATION FOR LIGHT MICROSCOPY After qualitative and quantitative examination at the subgross level tissue blocks were removed for histology. Twenty blocks (five from each quadrant), each measuring 1-5 x 1-5 x 0-2 cm, were selected at random from five alternate slices. Before processing for light microscopy blocks were washed in several changes of absolute alcohol over a period of three days to remove all traces of methyl salicylate. After processing for routine histology 8 ,um sections were stai...

Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue

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Biomarkers of Dietary Energy Restriction in Women at Increased Risk of Breast Cancer

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