Malignant Neoplasms

MALIGNANT NEOPLASMS

Carcinoma of the breast is the most common cancer in women and affects 1 in 9 women in the United States. It is also the second most common cause of cancer death. The incidence is increasing and is higher in the United States than in Japan. Many risk factors have been identified.

The incidence increases with the following factors:

•         Age

•         Unusually long/intense exposure to estrogens (long length of reproductive life, nulliparity, obesity, exogenous estrogens)

•         Presence of proliferative fibrocystic changes, especially atypical hyperplasia

•         First-degree relative with breast cancer

Hereditary influences are thought to be involved in 5–10% of  breast cancers, with important genes as follows:

•         BRCA1 (error-free repair of DNA double-strand breaks) chromosome 17q21

•         BRCA2 (error-free repair of DNA double-strand breaks) chromosome 13q12.3

•         TP53 germline mutation (Li-Fraumeni syndrome)

Carcinoma in situ and risk of invasive carcinoma. About 35% of women with untreated DCIS will develop invasive cancer, usually in the same quadrant of the breast. About 35% of women with LCIS will develop invasive lobular or ductal car-cinoma, in either breast.

Breast cancer is most common in the upper outer quadrant. Gross examination of a breast cancer typically shows a stellate, white-tan, gritty mass. Clinically, it can cause:

•         Mammographic calcifications or architectural distortion

•         Palpable solitary painless mass

•         Nipple retraction or skin dimpling

•         Fixation of breast tissue to the chest wall

Paget disease of the nipple is an intra-epidermal spread of tumor cells from an underlying ductal carcinoma in situ or invasive ductal carcinoma. The tumor cells often lie in lacunae, and there can be a dermal lymphocytic infiltrate.

Histologic variants of breast cancer are as follows:

•         Preinvasive lesions include ductal carcinoma in situ (DCIS) and lobular carci-noma in situ (LCIS). Preservation of the myoepithelial cell layer distinguishes them from their invasive counterparts.

•         Invasive (infiltrating) ductal carcinoma is the most common form (>80% of cases). Microscopically, it shows tumor cells forming ducts within a desmoplas-tic stroma. About 70% of cases are ER/PR positive and 30% overexpress HER2

•         Invasive (infiltrating) lobular carcinoma (5–10% of cases) is characterized by small, bland tumor cells forming a single-file pattern.

•         Multifocal and bilateral disease occurs commonly.

°°    About 50% are ER/PR-positive; these tumors do not overexpress HER2.

•         Mucinous (colloid) carcinoma is characterized microscopically by clusters of bland tumor cells floating within pools of mucin. It has a better prognosis.

°°    Hormone receptors are positive; these tumors do not overexpress HER2.

•         Tubular carcinoma rarely metastasizes and has an excellent prognosis.

°°    Hormone receptors are positive; these tumors do not overexpress HER2.

•         Medullary carcinoma is characterized microscopically by pleomorphic tumor cells forming syncytial groups surrounded by a dense lymphocytic host response. It has a better prognosis.

Hormone receptors are negative; the tumors do not overexpress HER2.

•         Inflammatory carcinoma is related to tumor invasion into the dermal lymphat-ics with resulting lymphatic edema; it presents with red, warm, edematous skin. The prognosis is poor.

The term peau d’orange is used when the thickened skin resembles an orange peel. This is caused by the accentuation of the attachments of the suspensory ligaments of Cooper to the dermis.

Mammary Paget disease (Paget disease of the nipple) is commonly associated with an underlying invasive or in situ ductal carcinoma. It may present with ulceration, ooz-ing, crusting, and fissuring of the nipple and areola. Microscopic examination shows intraepidermal spread of tumor cells (Paget cells), with the cells occurring singly or in groups within the epidermis; there is often a clear halo surrounding the nucleus.

The prognosis of breast cancer depends on the following:

•         Axillary lymph node status as determined by sentinel node biopsy (SNB) or axillary dissection. In most cases, SNB is recommended to evaluate clinically tumor-free regional nodes.

•         Size of tumor

•         Histological type and grade of tumor

•         ER/PR receptor status is used to select patients for endocrine forms of therapy.

•         Overexpression of HER2/neu is associated with more aggressive behavior than other types of breast cancer; patients may respond to therapy with trastu-zumab.

Treatment of breast cancer depends on the stage and other tests.

•         Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) as measured by ELISA are used to guide treatment decisions with node-negative breast cancer, along with multiparameter gene expression analysis.

•         Cancer antigen 15-3 (CA 15-3), cancer antigen 27.29 (CA 27.29), and carcino-embryonic antigen (CEA) are used to monitor patients with metastatic disease undergoing therapy.

Although the majority of cancers in the breast are primaries, cancer from other organs can spread to the breast. Lung cancer may spread by contiguity or via the lymphatics.