breast cancer, diseasecharacterized by the growth of malignant cells in themammary glands. Breast cancer affectsmales andfemales, although women are about 100 times more likely to develop the disease than men. Mostcancers in female breasts form shortly before, during, or aftermenopause; indeed, three-quarters of all cases are diagnosed after age 50. Generally, the older a woman is, the greater is her likelihood of developing breast cancer.

In the 20th and early 21st centuries, breast cancer was the leading cause of cancer death among women worldwide. By 2012, however, that remained true only in less-developed countries and among certain ethnic and racial groups, including Black and Hispanic women in theUnited States. In high-income countries,lung cancer had overtaken breast cancer as the leading cause of death from cancer in women.

Causes and symptoms

The exact causes of breast cancer are largely unknown, but both environmental and genetic factors are involved. Specificmutations in genes calledHER2,BRCA1,BRCA2,CHEK2, andp53 have been linked to breast cancer. These mutations may beinherited or acquired. Mutations that are inherited often substantially increase a person’s risk for developing breast cancer. For example, whereas some 12 percent of women in the general population develop breast cancer, roughly 45 to 65 percent of women who inheritBRCA mutations eventually develop the disease. Women who carry these mutations also have an increased risk ofovarian cancer. For men who carry mutations in BRCA1 or BRCA2, risk increases by 1.2 or 7.1 percent, respectively, by age 70. Research further suggests that older biological age, determined by measures ofmethylation at certain locations inDNA (seeepigenetics), is associated with increased breast cancer risk.

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In addition to genetic mutations, other factors, including prolonged exposure to the hormoneestrogen, as whenmenstruation starts before age 12 and continues beyond age 50, favor the development ofcancer. In postmenopausal women, breast cancer risk is increased markedly by elevated circulating concentrations ofsex hormones (estrogens andandrogens). Concentrations of these hormones have been found to be abnormally high in postmenopausal women who are obese, who drink alcohol, or who smoke. In addition, for all women, lack of exercise,obesity, use oforal contraceptives,alcohol consumption,smoking, and previous medical treatments involving chestirradiation are considered risk factors for breast cancer. Women who have had certain kinds ofbenigntumors are also more prone to developing breast cancer.

The most common symptom of breast cancer is an abnormal lump or swelling in the breast, but lumps may also appear beside the breast or under the arm. Other symptoms may include unexplained breast pain, abnormal nipple discharge, changes in breast texture, or changes in the skin on or around the breast.

Diagnosis

Earlydiagnosis greatly improves the odds of survival. When detected early, breast cancer has a very high five-year survival rate, and patients who reach this stage often go on to live long, healthy lives. Survival rates are lower for cancers that have spread locally, and they are very low for cancers that have metastasized, or spread, to distant parts of the body.

Breast cancer may be discovered by the patient during a regularbreast self-examination. When a self-exam is performed on a monthly basis, a woman becomes familiar with her breasts and can readily detect an abnormal change, such as a lump, a swelling, dimpling, or a change incontour, warranting immediate clinical examination. However, a change that is noticed through self-examination may not always be indicative of cancer. Alternatively, if the change found is cancer, the growth may already be fairly advanced.

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Before they arepalpable, growths in the breast may be detected through a procedure known asmammography, which entails the use ofX-rays to detect lesions in breasttissue. Mammography is often used for initialdiagnosis, but, in order to confirm the presence of cancer, a tissue sample (biopsy) usually must be taken. If cancer is suspected to have spread (metastasized) to nearbylymph nodes, they must also be sampled.Metastasis generally begins in a so-calledsentinel lymph node (the first lymph node invaded by cancer cells) and, in the case of breast cancer, spreads to axillary lymph nodes, which are located in and around the armpits.

Once cancer has been diagnosed, thetumor type and degree of invasiveness is assessed. Several imaging methods may be used to determine the degree of metastasis, including X-rays,computerized axial tomography (CAT) scans, ormagnetic resonance imaging (MRI). The presence ofreceptors for the hormones estrogen andprogesterone is also determined, because these receptors play an important role in the cancer’s development and in decisions regarding the appropriate treatment.

Types of breast cancer

Almost all cases of breast cancer begin in the glandular tissues that either producemilk (lobular tissue) or provide a passage for milk (ductal tissue) to the nipple. Cancers of these tissues are known aslobular carcinomas andductal carcinomas. Because these tissues are glandular, both cancers are referred to asadenocarcinomas. The most common type of tumor,infiltrating ductal carcinoma, is a single hard barely movable lump. This type of tumor accounts for about 70 percent of all cases. Fewer than 15 percent of all cases are lobularcarcinomas.

There are other types and subtypes of tumors, classified and named according to severalcriteria, including their outward appearance, cellularcomposition, cellular origin, and activity. At the cellular level, breast cancers can be distinguished on the basis ofreceptor status—that is, being either hormone-receptor positive or hormone-receptor negative. The former includes estrogen-receptor (ER) positive and progesterone-receptor (PR) positive breast cancers, so called because the tumorcells require estrogen or progesterone for growth. In some cases, tumors express both ER and PR proteins.ER-positive cancers are responsible for roughly 60 to 70 percent of breast cancer cases in women.

Breast tumors sometimes express a differentprotein, human epidermalgrowth factor receptor 2 (HER2).HER2 breast cancers tend to be aggressive, growing and spreading more quickly than hormone-receptor positive cancers, but they also are highly responsive totreatment. About one-quarter of breast cancers areHER2 positive.

Rare forms of breast cancer includePaget disease and inflammatorycarcinoma. Paget disease begins at the nipple and initially causes a burning, itching, or tender sensation. Eventually, the lesion becomes enlarged, cracks, oozes, and forms crusts.Inflammatory carcinoma is a rare type of breast cancer that results in swelling and reddening of the affected area. The area then becomes purplish, the skin is hot, and the nipple usually becomes crusted and retracted.

Inflammatory breast carcinoma is among the most aggressive types of breast cancer, spreading quickly to surrounding tissues. In addition, because adiscrete lump in the breast generally is not present, inflammatory carcinoma can be difficult to diagnose. Another highly aggressive form of the disease is triple negative breast cancer, in which tumor cells lack expression of ER, PR, andHER2 proteins. This makes treatment more difficult, since many agents for breast cancer specifically target one or more of these receptors.

Treatment

Any lump found in the breast should be examined by a physician for the possibility of cancer. If it is found to be malignant, treatment may entail surgery, radiation, or chemotherapy. Biological treatment is also an option.

Surgery is often the first method of treatment, and a range of procedures are used, depending on the type and progression of the cancer. Alumpectomy removes only the cancerous mass and a small amount of surrounding tissue; a simplemastectomy removes the entire breast; and amodified radical mastectomy removes the breast along withadjacent lymph nodes.Radical mastectomies involving removal of the breast, underlying muscle, and other tissue are rarely performed. Surgery is associated with a wide range of side effects, including changes in arm or shoulder mobility, swelling, infection, numbness, and, when lymph nodes are removed, fluid buildup in the region they were taken from. Partial or complete breast removal is often followed by cosmetic or reconstructive surgery.

Over the course of the late 20th and early 21st centuries, the treatment of breast cancer progressed steadily toward less-invasive approaches, primarily in order to prevent women from undergoing unnecessary operations and particular procedures such as radical mastectomy. Therationale for moving away from aggressive surgery was reinforced by a study of women with early-stage breast cancer whose tumors were relatively small and had not metastasized. Researchers determined that the removal of axillary lymph nodes (axillary lymph node dissection), which was once standard procedure and believed to prevent recurrence of disease, had no impact on five-year survival rates and in fact had left some patients susceptible to a host of complications, including infection.

Less-invasive treatments for breast cancer include radiation therapy, chemotherapy, and biological therapy.Radiation is usually employed—either to shrink tumors before surgery or to destroy small amounts of cancerous tissue remaining after surgery.Side effects of radiation include swelling or thickening of the breast, vomiting, fatigue,diarrhea, and skin irritations resembling sunburn.Chemotherapy, the use of chemicals to destroy cancerous cells, is commonly employed. Chemotherapeutic agents also attack normal cells to some degree, causing side effects that include hair loss, immune suppression, mouth sores, fatigue, and nausea.

Breast cancer can also be treated through biological therapy, in which chemical inhibitors are used to block the hormones that stimulate growth of cancer cells.Tamoxifen, for instance, is a common drug that blocks the ability of estrogen to stimulate tumor growth, andMegace (megestrol) blocks the action of progesterone by partially mimicking thehormone.Herceptin is a manufactured antibody that binds to growth factor receptors on the surface of cancer cells and thereby blocks cell proliferation.Letrozole is used toinhibit the synthesis of estrogen in postmenopausal women who have hormone-dependent breast cancers.

Prevention

Breast cancer cannot be completely prevented, but the risk of developing advanced disease can be greatly reduced by several means. For example, maintaining a healthy body weight, decreasingalcoholconsumption, and ceasing to smoke can each contribute to a reduction in breast cancer risk.

Research also suggests that dietary factors can influence breast cancer survival. For example, some women who have consumed adiet low in fat and high in vegetables, fruits, and grains over the course of years and are diagnosed with breast cancer have a reduced risk of dying from the disease. Long-term dietary changes can significantly benefit survival among women with breast cancer who exhibit characteristics ofmetabolic syndrome.

Early detection of subtle breast abnormalities is also important. Medical societies recommend a monthly breast self-examination for all women over the age of 20, a breast exam by ahealth care professional every three years for women 20–39 years old, and a yearly mammogram for all women 40 and older. Women at high risk of developing breast cancer may benefit from taking certain medications—namely aromatase inhibitors,raloxifene, or tamoxifen—to reduce their risk. Women who are at extreme risk, as determined by a very strong family history or the presence of mutatedBRCA genes, may opt forpreventive mastectomy.