Breast Cancer

Breast cancer is the second most common cancer among women after skin cancer. Most breast cancers occur in women over 60. Although rare, men can develop breast cancer, and their risk also increases with age.

Women who have had breast cancer are at high risk of developing cancer in the other breast. Having a close relative with breast cancer increases a woman's risk by 2 to 3 times. Women who had their first menstrual period at a young age, those in whom menopause occurred at a later age, and those who have never had children or who had their first child after 40 have an increased risk of developing breast cancer. Taking estrogen after menopause slightly increases the risk of breast cancer. The risk of breast cancer is also somewhat higher in women who are obese or who drink more than moderate amounts of alcohol.

Symptoms

The earliest symptom of breast cancer is often a lump or thickening in the breast or under the arm. In the early stages, the lump may move freely beneath the skin when it is pushed with the fingers. In more advanced stages, the lump may adhere to the chest wall or to the skin over it and cannot be moved. A change in the size, shape, or contour of the breast or in the appearance of the skin of the breast or nipple can be a symptom of breast cancer. Sometimes the skin may appear puckered or dimpled. The lump may be painful, but pain is an uncommon and unreliable sign. A discharge from the nipple may occur. Sometimes the breast becomes red and swollen.

Sometimes the breast feels normal, but the lymph nodes in the underarm feel like hard small lumps and may be slightly tender.

Screening

Because breast cancer has few symptoms in its early stages and because breast cancer is more easily cured if it is detected early, experts recommend that all older women be screened regularly for breast cancer. Women are encouraged to examine their breasts each month. They should examine their breasts on the same day each month, picking a date that is easy to remember.

A breast examination is a routine part of a physical examination. Experts recommend that women over 40 have an annual breast examination. A health care practitioner observes each breast for irregularities in the contour and the skin of the breast or nipple, feels (palpates) each breast to check for lumps or thickening of breast tissue, and checks the underarms for enlarged lymph nodes.

A mammogram is an x-ray of the breast. It detects many cancers that are too small to feel. However, because mammography is designed to be sensitive enough to detect the possibility of breast cancer at an early stage, it may identify a "suspected" cancer when none is present (a false-positive result). If the mammogram is not completely normal, magnetic resonance imaging (MRI) may be done. MRI is sometimes more sensitive for identifying small cancers. However, MRI is even more likely to produce false-positive results.

Having a mammogram can reduce the rate of death due to breast cancer in women over 50. Most experts agree that women aged 50 or older should have a mammogram every year or every other year. There is no upper age limit after which women can safely stop having mammograms. Women who are expected to live for at least 3 to 5 more years should continue to receive annual mammograms.

Diagnosis

When a lump or some other suggestive change is noted during breast self-examination or an examination by a health care practitioner, additional tests are needed to diagnose breast cancer.

Mammography is done to pinpoint the location of a lump found during an examination and to determine if there are other abnormalities in the same breast or the other breast. Ultrasonography may be used to determine if the lump is fluid-filled (cyst) or solid. Cysts are usually not cancerous. If the lump is solid, a biopsy is performed. In aspiration biopsy, a needle is used to remove some cells from the lump. A piece of tissue from the lump (incisional biopsy) or the entire lump (excisional biopsy) can be examined instead.

The tissue sample is examined under a microscope to determine whether cancer is present. Since a needle biopsy can miss some tumors, a negative result requires further testing. If cancer is detected, the sample is analyzed to determine the characteristics of the cancer cells and whether the cancer has spread. Understanding the characteristics allows the doctor to develop a profile of the cancer that guides the selection of treatment approaches.

Types and Staging

Breast cancer is described as in situ (not invasive), locally invasive, regionally invasive, or metastatic (distant). Cancers may also be described as glandular or ductal. A glandular cancer begins in the tissue that produces milk. A ductal cancer begins in the milk ducts, the tiny tube-like structures that channel milk to the nipple. Paget's disease of the breast is a type of ductal cancer. It often appears first as a crusty or scaly nipple sore or a discharge from the nipple. Another type is inflammatory breast cancer. Cancer cells in the skin block the lymphatic vessels in the breast, causing the breast to appear red, warm, and swollen. Inflammatory breast cancer often grows rapidly and has a poor outcome.

The stage of breast cancer is determined according to how much it has spread and is designated by a number (0 through IV) or described with a specific term. For example, carcinoma in situ is the earliest stage of breast cancer. In this stage, the cancer has not spread at all. Locally invasive cancer has spread into adjacent breast tissue. It may or may not extend into nearby lymph nodes or the chest wall. Metastatic cancer is cancer that has spread from the breast to other parts of the body. Breast cancer can spread to any area of the body, but it most often spreads to bones, liver, or the lungs, and sometimes even to the brain.

Breast cancer cells may or may not have receptors for the hormone estrogen, which stimulates the cancer to grow. Cancers that have receptors are called estrogen receptor-positive cancers. Estrogen receptor-positive breast cancers are most common among postmenopausal women, and outlook for cancer control is usually good. Similarly, some breast cancer cells have receptors for progesterone. The outlook is even better for breast cancers that are both estrogen receptor- and progesterone receptor-positive.

Another characteristic of breast cancer is the status of HER-2/neu receptors, which are found on all breast cancer cells. In about one third of breast cancers, the number of HER-2/neu receptors is increased (amplified or over-expressed). These cancers are faster growing and therefore more malignant than those with a normal level of HER-2/neu receptors. When doctors determine the profile of a breast cancer, they also include the cancer's proliferative index, which helps determine how rapidly the cancer cells are growing. A measure of the p53 gene or its product helps doctors determine how poorly the growth of the cancer is regulated. New tests for interpreting altered genes are improving the ability to determine who is at higher risk of recurrence and the likelihood of responding to treatments.

Treatment

A woman's preferences play an important role in determining treatment options. However, treatment options also depend on the type and stage of breast cancer and the woman's overall health.

Treatment almost always involves surgery. Depending on the size of the tumor and how many lymph nodes contain cancer cells, radiation therapy, chemotherapy, or both may be used after surgery. Sometimes, if a tumor is large, chemotherapy is given before surgery to reduce the size of the tumor. Treatment may include the use of hormone-blocking drugs or biologic preparations, such as antibodies, which help the body fight cancer. Often, a combination of therapies is used.

Surgery: There are two approaches used for surgery: breast-conserving surgery and mastectomy. In breast-conserving surgery, the surgeon removes the cancerous tumor and some surrounding tissue but leaves as much of the breast intact as possible. Surrounding tissue is removed to help improve the likelihood that the cancer will be cured. However, removing less tissue preserves more of the breast, allowing the woman to heal faster and keep more of the natural appearance of her breasts.

There are three types of breast-conserving surgery. A lumpectomy removes the least amount of surrounding tissue. A partial mastectomy (also called wide excision surgery) and a quadrantectomy remove the tumor and some additional surrounding tissue. Lymph nodes may be removed as well. Breast-conserving surgery is usually followed by radiation therapy to reduce the likelihood of recurrence in the remaining breast tissue. In early-stage breast cancer, results of breast-conserving surgery plus radiation therapy are equivalent to the results of mastectomy. However, mastectomy is usually done when the cancer is so widespread that all of the cancer cannot be removed unless the whole breast is removed.

A simple mastectomy involves removing the breast. In a modified radical mastectomy, the surgeon also removes the lymph nodes in the underarm area. In a radical mastectomy, the surgeon removes not only the lymph nodes in the underarm area but also the muscle under the breast.

Surgery to reconstruct the breast can be done at the time of the initial surgery or several months later. The decision depends on the nature and site of the cancer. Decisions regarding reconstructive surgery are very personal, and a woman should discuss the possibilities with her doctor. Since immediate reconstruction prolongs the length of the initial operation, an important factor in the decision is the woman's general health.

See the figure Surgery for Breast Cancer.

To determine whether the cancer has spread, doctors examine lymph nodes under the arm (sentinal lymph nodes). Contrast dye or a radioactive marker is injected into the breast at or near the cancer. The doctor identifies the lymph node (or nodes) where the dye or marker accumulates, so that they can be examined for evidence of cancer. This procedure has reduced the need for extensive surgery of the underarm area and the subsequent risk of long-term arm swelling (lymphedema). Knowing whether the cancer has spread is critical in determining what additional therapy is needed.

When a woman with breast cancer has one or more other life-threatening diseases that shorten her life expectancy, doctors may not recommend treatment to cure the cancer. However, they usually recommend a lumpectomy to prevent the cancer from causing sores or ulcers in the remaining breast tissue, which would be painful and reduce the woman's quality of life.

Radiation therapy: Radiation therapy is usually used after a woman undergoes surgery to remove the cancer. The goal is to kill cancer cells remaining at the site from which the tumor was removed and from surrounding areas. Radiation therapy is usually given over a period of several weeks. Swelling in the breast, reddening and blistering of the skin, and fatigue are common after radiation therapy, but these effects usually disappear after several months. The rate of breast cancer recurrence in the area where surgery was performed seems to decrease with age, so some experts do not recommend radiation therapy in all older women.

Chemotherapy: Chemotherapy is used to kill cancer cells that were not removed during surgery or killed by radiation therapy. Chemotherapy is generally recommended when staging tests suggest that the cancer has spread beyond the area of the breast.

The choice of chemotherapy drugs depends on several factors, including the type and stage of cancer. Chemotherapy drugs are usually given intravenously, but some can be taken by mouth. Commonly used drugs include cyclophosphamide, doxorubicin, epirubicin, fluorouracil, methotrexate, docetaxel, paclitaxel, and vinorelbine. Most women experience side effects, such as nausea and vomiting, fatigue, and hair loss, regardless of the drugs used, but the severity of the side effects depends on which drugs are used.

Trastuzumab, which is an antibody, is used primarily for treatment of more advanced breast cancers. However, increasingly, it is being used earlier in the treatment of cancers with increased HER-2/neu receptors.

Drugs that block the actions of estrogen and progesterone may be used when cancer cells have receptors for these hormones. Hormone-blocking drugs work better to control cancers that are positive for both estrogen and progesterone receptors than they do for breast cancers that are positive for only one or the other. Tamoxifen is the most commonly used estrogen-blocking drug. This drug increases the likelihood of survival in women whose cancers are estrogen receptor-positive. There are other newer drugs that block the effects of hormones. These so-called aromatase inhibitors have proven effectiveness and are now frequently being used before tamoxifen. Anastrozole, one such aromatase inhibitor, may improve survival and result in fewer side effects than tamoxifen does.

Outlook

Doctors regularly monitor women who have been treated for breast cancer to ensure that the cancer has not returned. Breast cancer that has spread beyond the lymph nodes is rarely cured. However, treatment may relieve symptoms, improve survival, and afford a good quality of life.

See the table How Lymph Node Status Influences Survival.