Breast Cancer in Brief

Incidence of Breast Cancer: ASR (World) (All ages) GLOBOCAN 2000

Breast cancer is the most common cancer in women in the world. According to the GLOBOCAN database of the International Agency for Research on Cancer (IARC), there were over a million new cases in the world in the year 2000, 579,285 occurring in more developed countries and 471,063 in the less developed countries. The highest rates in the world (>90 per 100,000) are in the USA and the Netherlands; the lowest (<6 per 100,000) are in Haiti and the Gambia. Since many more women live in less developed countries, however, the annual incidence rate of breast cancer is almost three times as high in the more developed countries (63 per 100,000 females, age standardized rate (world), versus 23 per 100,0000 in the less developed countries). Within developing countries, breast cancer has a higher incidence in upper social classes than in lower, in which cancer of the uterine cervix is more common. Breast cancer affects approximately 1 in 8 to 10 women in western nations.

Breast cancer is predominantly a hormone-dependent cancer, the risk of development being in part related to the duration of estrogen exposure during a woman's lifetime (and, in fact, to higher blood estrogen levels). Early menarche (younger than 12 years in western countries) and late menopause (over 55 years) increase the risk, as does a late (over 30 years of age) first pregnancy, while more pregnancies, and possibly the total duration of lactation, are associated with a lower risk. Increasing age, a family history in an immediate relative (particularly if young), previous history of breast cancer (or premalignant breast disease) or of certain other cancers, especially other conditions in which radiation has been given to the chest, such as Hodgkin's lymphoma or thyroid cancer, greatly increase the risk of developing breast cancer. Other potential risk factors such as smoking, alcohol and fat consumption may be relevant, but remain controversial. Although there is a close correlation between national per capita dietary fat intake and the incidence rate of breast cancer, fat consumption could be a surrogate marker for other aspects of a more affluent lifestyles. Of interest in this regard, however, are the low rates in wealthy South Korea (12.5 per 100,000) and Japan (31.3 per 100,000). Mutations in certain genes, particularly p53, BRCA1 and BRCA2, are associated with a markedly increased risk of developing the disease (which tends to occur at a much younger age), but mutations in these genes do not account for all familial cases, suggesting that other predisposing genes remain to be discovered. The relative importance of these various risk factors has not been well studied in developing countries, but higher pregnancy rates and dietary differences could well be relevant to the lower incidence. It should also be stated that in most women with breast cancer, a specific risk factor cannot be identified.

There are a number of subtypes of breast cancer. Most arise from ductal epithelium (i.e., the lining of the duct carrying milk from the cells which produce it). Intraductal lesions, including papillary carcinomas, arise from large ducts and in some cases do not penetrate the ductal basement membrane which lies beneath the lining cells of the ducts. Such cancers are not, then, invasive, and can be considered premalignant lesions (ductal carcinoma in situ, or DCIS). They are readily cured by surgical excision. Lobular carcinoma arises from the small end-ducts of the breast tissue and, like DCIS, may not penetrate the basement membrane of the lobules— so-called lobular carcinoma in situ. The most common invasive breast cancers in western countries, accounting for approximately 70% of breast cancers, are ductal carcinomas. The majority have no additional characteristic features, but subtypes, e.g., medullary, tubular and mucinous varieties, are occasionally observed. Lobular carcinomas account for some 10% of breast cancers. Paget's disease of the breast, which presents with eczematoid changes in the nipple with an underlying carcinoma (either intraductal or invasive), occurs in less than 5% of cases. Inflammatory breast cancer is characterized by dermal lymphatic invasion by cancer cells and redness and warmth of the skin. This may occur either at initial diagnosis or at the time of recurrence. Inflammatory breast cancer appears to be more common in North Africa (see next article), and may or may not represent a separate pathological entity. Rare breast cancers include adenocystic carcinoma, carcinosarcoma, squamous cell carcinoma or metaplastic carcinomas (with bony or cartilaginous elements). The advent of mammography in more affluent countries has revealed a broad range of premalignant lesions and breast hyperplasias (benign growths) that require considerable pathological expertise for their diagnosis. Many of these lesions may not become malignant in the lifetime of the woman, such that clinical decisions regarding treatment are not always easy.

Breast cancer is highly curable if detected early, and since the majority of breast cancers are first noticed by the patient (as a lump in the breast), public and professional education may be the single most important factors in increasing the rate of early detection. Unfortunately, in developing countries, the majority of patients—often as many as 80%, which is the inverse of the fraction in affluent nations—have advanced disease. Simply reducing the size of this problem would improve survival rates. Mammography has been widely accepted as being valuable in reducing mortality from breast cancer in women aged 50-69, but recent results from some countries have created some controversy in this regard.

Treatment may involve any of the primary cancer treatment modalities, including surgery, radiotherapy, chemotherapy and hormonal therapy, or a combination of these, depending upon the size of the lesion, the presence of lymphatic or distant spread, the estrogen (and progestogen) receptor status of the tumor, as well as the patient's menopausal status. Lumpectomy (removal of the tumor with preservation of the remainder of the breast) and radiation have been shown to be as effective as removal of the entire breast (mastectomy) in women with operable disease. Both chemotherapy and hormonal therapy (tamoxifen) have been shown to decrease the likelihood of recurrence after local therapy, tamoxifen, which blocks the binding of estrogen, being used in estrogen receptor positive cancers (sometimes in addition to chemotherapy). The role of antibodies directed against tumor cells, although active in patients with metastatic disease, is still under study in patients with less advanced disease. Results depend upon the extent of the disease as well, of course, as the therapy given. Recurrence or spread can occur many years after primary treatment. In more developed countries, mortality rates are about a third of incidence rates, but a much higher—although not precisely known—proportion of women with breast cancer die from their disease in less developed countries.

—Ian Magrath, INCTR