cancer

Chapter 27 Breast cancer




Questions


image Why does breast cancer occur?

image What are its clinical and pathological features?

image How can we treat breast cancer?

Breast cancer is the second most common cause of cancer deaths in industrialized societies. The disease most commonly affects women during the fifth to seventh decades but may affect young women and even adolescents.




Aetiological factors


Breast cancer is a common malignancy and, therefore, it is not uncommon to find more than one affected individual within families. However, predisposition to breast cancer is conferred by a specific inherited genetic defect in a small minority (less than 5%). Studies of large family trees led to the discovery of the BRCA-1 and BRCA-2 genes, mutations within which have been shown to be associated with a very high risk of breast cancer development. Mutations may occur at many different positions within these genes. Females from families possessing such inherited mutations require especially careful screening for breast cancer. Affected individuals may develop breast cancer at an early age (e.g. the third decade) and the cancers that develop often show characteristic (but not entirely specific) features.


Several other clinicopathological factors apart from an inherited predisposition are associated with an increased risk of breast cancer development. Many of these factors result in increased exposure of breast tissue to circulating oestrogens. Such factors include obesity, early menarche, late menopause and nulliparity. Cancer within one breast is associated with an increased risk of cancer within the contralateral breast, suggesting that a ‘field change’ has occurred within the patient’s breast tissue.



Clinical presentation


Breast cancer mostly presents clinically from the primary tumour, most commonly as a breast mass but sometimes with breast pain or a nipple discharge. The disease may, however, present at an advanced stage with symptoms of the metastases (e.g. epilepsy from a cerebral metastasis; Fig. 3.27.1).


image

Fig. 3.27.1 The progression of breast cancer from a primary tumour.



Pathological features


Breast cancer may exist as preinvasive in-situ disease, in which cancer cells are contained within the breast ducts and lobules, or as invasive disease in which the cancer cells have progressed beyond the confines of the ductal and lobular system into the surrounding connective tissue. Invasive breast cancer may grow directly into the overlying skin or the chest wall, metastasize via lymphatics to regional axillary or internal mammary artery lymph nodes or metastasize via the bloodstream to distant organs (Fig. 3.27.1).


The histological growth pattern of in-situ and invasive breast cancers is diverse but 75% of invasive breast cancers are classed as ductal in type. Accurate pathological assessment of tumour grade and stage is essential for correct patient management. The grade of a breast cancer is a histological assessment of the aggressiveness of the tumour. The stage of the tumour is an assessment of how advanced the disease process is and is dependent upon the characteristics of the primary tumour together with the presence of regional or distant metastases. Prognosis is linked to both the tumour grade and the stage, with high-grade and/or high-stage tumours behaving the most aggressively and associated with a worse clinical outcome. The detailed histological features affecting prognosis in invasive breast carcinoma have been particularly well characterized (Table 3.27.1).


Table 3.27.1 Major histological prognostic factors in invasive breast carcinoma



































Tumour characteristic Good prognosis Poor prognosis
Tumour typea Tubular carcinoma Metaplastic carcinoma
Tumour size Small; especially < 10 mm Large
Tumour grade 1 3
Vascular invasion by tumour Absent Present
Lymph node metastases No Yes
Hormone receptor status Oestrogen receptor positive Oestrogen receptor negative
Growth factor receptor (HER-2) status Negative Positive

a Histologically, 75% are classified as invasive ductal carcinoma; certain unusual histological subtypes possess a better or worse prognosis than invasive ductal carcinoma as illustrated here.


Pathologists can further help to determine prognosis for patients with breast cancer by determining the hormone receptor and growth factor receptor (HER-2) status of the tumour, using immunohistochemistry. Approximately 75% of invasive breast carcinomas express oestrogen receptors within the nucleus of the carcinoma cells and a similar proportion express progesterone receptors. The growth of tumours expressing these receptors is usually dependent on circulating oestrogens and progression of the tumours can often be slowed significantly using drugs that block the effect of oestrogens on the carcinoma cells (e.g. tamoxifen) or reduce the production of circulating oestrogens (e.g. anastrazole). HER-2 is a growth factor receptor expressed on the cytoplasmic membranes of the carcinoma cells in abnormally high quantities in approximately 30% of invasive breast cancers. Overexpression of this receptor is associated with poor prognosis but also predicts response to the specific growth factor receptor-blocking agent trastuzumab (Herceptin).

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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on cancer

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