Breast Cancer (2)

Pathology

Most breast cancers are epithelial tumors that develop from cells lining ducts or lobules; less common are nonepithelial cancers of the supporting stroma (angiosarcoma, primary stromal sarcomas, phyllodes tumor). Cancers are divided into carcinoma in situ and invasive cancer.

Carcinoma in situ is proliferation of cancer cells within ducts or lobules and without invasion of stromal tissue. Usually, ductal carcinoma in situ (DCIS) is detected only by mammography and is localized to one area; it may become invasive. Lobular carcinoma in situ (LCIS) is a nonpalpable lesion usually discovered via biopsy; it is rarely visualized with mammography. LCIS is not malignant, but its presence indicates increased risk of subsequent invasive carcinoma in either breast; about 1 to 2% of patients with LCIS develop cancer annually.

Invasive carcinoma is primarily adenocarcinoma. About 80% is the infiltrating ductal type; most of the remainder is infiltrating lobular. Rare forms include medullary, mucinous, and tubular carcinomas.

Paget's disease of the nipple (not to be confused with the metabolic bone disease also called Paget's disease) is a form of ductal carcinoma in situ that extends into the overlying skin of the nipple and areola, manifesting with an inflammatory skin lesion. Characteristic malignant cells called Paget cells are present in the epidermis. The cancer may be in situ or invasive.

Breast cancer invades locally and spreads initially through the regional lymph nodes, bloodstream, or both. Metastatic breast cancer may affect almost any organ in the body—most commonly, lungs, liver, bone, brain, and skin. Most skin metastases occur in the region of the breast surgery; scalp metastases also are common. Metastatic breast cancer frequently appears years or decades after initial diagnosis and treatment.

Estrogen and progesterone receptors, present in some breast cancers, are nuclear hormone receptors that promote DNA replication and cell division when they are bound to the appropriate hormones. Thus, drugs that block these receptors may be useful in treating tumors with the receptors. About 2⁄3 of postmenopausal patients have an estrogen-receptor positive (ER+) tumor. Incidence of ER+ tumors is lower among premenopausal patients. Another cellular receptor is human epidermal growth factor receptor 2 (HER2) protein; its presence correlates with a poorer prognosis at any given stage of cancer.

Symptoms and Signs


Most breast cancers are discovered as a lump by the patient or during routine physical examination or mammography. Less commonly, the presenting symptom is breast pain or enlargement or a nondescript thickening in the breast. Paget's disease of the nipple presents with skin changes, including erythema, crusting, scaling, and discharge; these usually appear so benign that the patient ignores them, delaying diagnosis for a year or more. About 50% of patients with Paget's disease of the nipple have a palpable mass at presentation. A few patients with breast cancer present with signs of metastatic disease (eg, pathologic fracture, pulmonary dysfunction).

A common finding during physical examination is a dominant mass—a lump distinctly different from the surrounding breast tissue. Diffuse fibrotic changes in a quadrant of the breast, usually the upper outer quadrant, are more characteristic of benign disorders; a slightly firmer thickening in one breast but not the other may be a sign of cancer. More advanced breast cancers are characterized by fixation of the lump to the chest wall or to overlying skin, by satellite nodules or ulcers in the skin, or by exaggeration of the usual skin markings resulting from lymphedema (so-called peau d'orange). Matted or fixed axillary lymph nodes suggest tumor spread, as does supraclavicular or infraclavicular lymphadenopathy. Inflammatory breast cancer is characterized by diffuse inflammation and enlargement of the breast, often without a lump, and has a particularly aggressive course.