Breast

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Chapter 18 Breast

COMMON CLINICAL PROBLEMS FROM BREAST DISEASE

Pathological basis of breast signs and symptoms

Sign or symptom Pathological basis
Lump  

Fibrosis, epithelial hyperplasia and cysts in fibrocystic change Neoplasm or solitary cyst Benign neoplasm (usually fibroadenoma) Invasive neoplasm (carcinoma) Skin features   Impaired lymphatic drainage due to carcinoma Invasion of skin by carcinoma Increased blood flow due to inflammation or tumour Nipple   Tethering by invasive carcinoma Paget’s disease of nipple or eczema Breast pain   Benign breast changes Inflammatory lesion (e.g. mastitis) Microcalcification (on mammography) Dystrophic calcification associated with benign changes, e.g. cysts, sclerosing adenosis, or in situ or invasive carcinoma Axillary node enlargement Often due to metastatic breast carcinoma Bone pain or fracture Possibly due to metastatic breast carcinoma or associated with hypercalcaemia

NORMAL STRUCTURE AND FUNCTION

The physiological and pathological changes in a woman’s breasts vary during different phases of her life. This is due to the variations in hormone levels that occur before, during and after the period of reproductive life; hormones are important in the regulation of growth, development and function of the breast.

Structure

The main function of the breast is the production and expression of milk (Fig. 18.2).

Lobules

The lobules are the secretory units of the breast. Each lobule consists of a variable number of acini, or glands, embedded within loose connective tissue and connecting to the intralobular duct (Fig. 18.3). Each acinus is composed of two types of cell, epithelial and myoepithelial. The epithelial cells are secretory. Although synthesising milk only during the later stages of pregnancy and post-partum, they continuously secrete a variety of glycoproteins into the glandular lumens. They are surrounded by myoepithelial cells which contact with the basement membrane and may directly or indirectly control luminal cell function. The intralobular duct connects with the extralobular duct and this, together with the lobule, is called the terminal ductal lobular unit.

Ducts

The extralobular ducts within the same area link together to form subsegmental ducts, which link in turn to form segmental ducts. These drain into the lactiferous ducts and sinuses (Fig. 18.2) which empty on to the surface of the nipple through separate orifices. There are 15 to 20 lactiferous ducts, each draining a segment of breast. The ducts are lined by epithelial cells surrounded by myoepithelial cells. The connective tissue in which they lie is denser than that of the lobules, and they are surrounded by elastic tissue which helps in the drainage function of the ducts.

Cyclical variations

The breast undergoes minor changes during each menstrual cycle but these will vary if there is a failure of ovulation or if pregnancy intervenes. The breast is sensitive to changes in the levels of sex steroids during the different phases (Fig. 18.4). The lobular stroma becomes oedematous during the secretory phase, due to the effects of oestrogens, and this accounts for the breast fullness often felt in the premenstrual phase. An increase in the number of cells in mitosis occurs at days 22–24 of the cycle, coincident with the high peaks of oestrogen and progesterone; however, the numbers are never very high. A loss of cells occurs by apoptosis (Ch. 5) at the end of the cycle, due to a fall in hormone levels, so that an overall balance is maintained. In view of the changes that can occur in the breast in the second half of the menstrual cycle, it is better to examine clinically the breasts of a pre-menopausal woman in the first half of the cycle.

Pregnancy and lactation

During pregnancy, the lobules undergo controlled proliferation and enlargement in preparation for the synthetic and secretory activity of lactation. By the third trimester the number of acini in each lobule and the overall size of the lobules have markedly increased. The epithelial cells have become differentiated and they synthesise and secrete milk (Fig. 18.5). The various components of milk (casein, alpha-lactalbumin and milk fat globule membranes derived from the luminal surface of breast cells) are useful markers of the state of differentiation of breast cells, and because of this they have been extensively studied in breast disease.

Oestrogens, progesterone and prolactin, together with other hormones shown in Figure 18.1, are important in the development of the breast during pregnancy; however, once delivery occurs, the levels of sex steroids fall and it is prolactin that is necessary for the initiation of lactation. When breast feeding ceases there is a rapid involution of the differentiated lobular structure, and the breast returns to the pre-pregnancy structure.

CLINICAL FEATURES OF BREAST LESIONS

Most pathological lesions of the breast present as a lump or lumps. These can vary in their nature depending on their cause: well-circumscribed or ill-defined; single or multiple small nodules; soft or firm; mobile or attached to skin or underlying muscle. These features assist in the clinical distinction between benign breast lesions and breast carcinomas, but they are relatively weak discriminators on their own. Below the age of about 35, benign breast lumps are much more common than carcinomas. Most women with breast cancer are peri- or post-menopausal. The most likely type of lesion will vary with the age of the patient, although overlaps occur (Table 18.1). However, there can be exceptions and histological examination is mandatory for a definite diagnosis.

Physiological conditions can be confused with, or mimic, pathological conditions. A degree of tenderness and swelling of the breast in the premenstrual phase is common. Some women have naturally ‘lumpy’ breasts and this may become exaggerated in this phase of the menstrual cycle. Uneven proliferation of the glandular substance during pregnancy, and irregular involution after pregnancy and during and after the menopause, can result in lumps that are the outcome of physiological and not pathological events. Other manifestations of a pathological lesion within the breast are discharge from the nipple, eczema and ulceration of the skin of the nipple.

DIAGNOSTIC METHODS

Several methods are used to investigate breast lesions. The aim is to get a diagnosis and either negate surgery or be able to discuss management with the patient (i.e. pre-operative diagnosis). They include:

Screening for breast cancer

In several developed countries with a high incidence of breast cancer, such as the UK, screening programmes for the detection of early breast cancer have been introduced. Trials in Sweden and the USA strongly suggest that women whose cancers have been detected by regular mammographic screening have an increased survival rate. This is because the tumours are detected when they are either pre-invasive (in situ carcinoma) or invasive but small, with less risk of metastasis. Unscreened women present when the tumour has grown to a size sufficient to be felt, at which stage there is a higher probability of metastases.

In the UK, women between the ages of 50 and 69 are invited to attend for breast screening by mammography every 3 years. Suspicious features on the mammographic image, such as microcalcification and localised densities, are further investigated by ultrasonography and clinical examination, with histology of biopsy samples, and very occasionally cytology, providing the definitive diagnosis. Impalpable lesions detected in this way require an X-ray-directed guidewire to be inserted into them before surgery to help the surgeon find the right area.

Besides being smaller, the invasive tumours have a higher frequency of being of a more favourable histological type and lower grade. This, along with the lower incidence of lymph node metastasis, will contribute to the improved prognosis. The surgery for these early lesions is more likely to be conservative.

The greater density of the pre-menopausal breast means that mammography may be less reliable for screening women under 50 years.

INFLAMMATORY CONDITIONS

PROLIFERATIVE CONDITIONS OF THE BREAST

Proliferative conditions of the breast include a wide variety of morphological changes with consequently varied clinical features; because of this there has been much confusion about the terminology and significance of these conditions.

Fibrocystic change

The commonest proliferative condition of the breast is fibrocystic change. Although benign and non-neoplastic, it is important because:

Clinical and gross features

Proliferative lesions and their associated tissue responses generally occur between the ages of 30 and 55, with a marked decrease in incidence after the menopause. The incidence reaches a maximum in the years just before the menopause (Fig. 18.6).

The clinical features tend to vary with the age of the patient and the underlying pathological changes. In younger women, there is usually a diffuse granularity in one or more segments of the breast, with nodules up to 5 mm in diameter. The area may be tender, particularly in the premenstrual period. In women nearer the menopause, there is usually an ill-defined rubbery mass. The finding of discrete swelling indicates the presence of cysts. If fibrosis is a component of the proliferative lesion, the lump will be firm and therefore more difficult to differentiate clinically from carcinoma.

Surgery for benign conditions is now uncommon. If undertaken it is more common to find nodules of soft pink or grey tissue, up to 3 mm in diameter in younger women, whereas in women nearer the menopause cysts are frequently seen. These cysts can vary in size from 2 to 20 mm (Fig. 18.7) and, rarely, a solitary large cyst can be seen. The small cysts are often multiple. They frequently have a dark blue surface and, on opening, contain clear, yellowish or blood-stained fluid. The intervening tissue is usually firm due to the increase in fibrous tissue but the softer foci of epithelial proliferation can be seen and felt.