Breast cancer

Definition

Breast cancer is the formation of malignant cancer cells in milk glands (lobules) or ducts of the breast. These cells may form lumps or tumors and have the potential to become invasive, spreading to the lymph nodes and other parts of the body.

Description

Breast cancer is the second most common cancer in women, after skin cancer , and the second leading cause of cancer death in women after lung cancer . In 2007 an estimated 240,510 new breast cancer cases were diagnosed in the United States, of which more than 178,000 were invasive. An estimated 40,460 women died of the disease. One woman in eight was anticipated to develop breast cancer at some point in her life, up from one in 91 in 1908. Much of this increase is due to longer lifespan. However, lifestyle and environmental factors may also play a role.

About 70 to 80% of breast cancers are ductal carcinomas that originate in the milk ducts, the thin tubes that carry milk to the nipples. Lobular or glandular carcinoma begins in the lobes or lobules that produce milk. Lobular carcinoma is more likely than other breast cancers to occur in both breasts. Inflammatory breast cancer (IBC) is a rare form in which cancer cells block the lymph vessels in the breast skin.

Since early-stage breast cancer has few symptoms it is recommended that all older women be screened regularly to detect the disease when it is most easily cured, before the cancer has metastasized (spread) to the lymph nodes under the arm.

Demographics

Age is the most important risk factor for breast cancer. A woman's risk of developing breast cancer is one in

• 257 at ages 30–40
• 67 at 40–50
• 36 at 50–60
• 28 at 60–70
• 24 between 70 and 80.

Approximate 75% of breast cancers are diagnosed in women age 50 or older and 25% in women over 75.

Men account for less than 1% of breast-cancer patients. Their risk also increases with age and most male breast cancers are diagnosed between the ages of 60 and 70. African American men are three times more likely to die of breast cancer than white men.

Likewise although white women are more likely to develop breast cancer than black women, black women are more likely to die of the disease.

About 5 to 10% of breast cancers result from inherited mutations or changes in the breast-cancer susceptibility genes BRCA1 and BRCA2. Women with specific mutations in BRCA1 have a 65% risk of developing breast cancer by the age of 70. For mutations in BRCA2 the risk is 45%. However, even without BRCA mutations breast cancer appears to have a genetic component. Indications of a hereditary predisposition for breast cancer include:

• breast cancer in other family members, especially a mother, aunt, sister, or daughter
• male breast cancer in the family
• other multiple cancers in the family, especially prostate cancer
• breast cancer occurring 5 to 15 years earlier than expected by age alone
• two or more primary cancers in a single individual, such as breast and ovarian cancers or separate cancers in each breast
• an Ashkenazi (Eastern and Central European) Jewish background.

Other factors that increase a woman's risk of breast cancer include:

• having a first menstrual period before the age of 12
• never having children or having a first child after one's early 30s
• undergoing menopause after age 55
• dense breast tissue
• previous breast cancer or benign (noncancerous) breast disease
• treatment with radiation therapy to the breast or chest.

Nevertheless, most women who develop breast cancer have no known risk factors or family history.

Causes and symptoms

Most breast cancers in older women appear to be related to long-term exposure of cells to the female hormone estrogen. Genetic and environmental factors influence how much estrogen a woman produces, how the estrogen is metabolized, and how many years the breast tissue is exposed to high levels of estrogen. Early-onset menstruation and late-onset menopause increase lifetime exposure and pregnancy and breastfeeding decrease exposure. In addition there are two major pathways for the metabolism of estrogen: One leads to a metabolite that increases the risk of breast cancer and the other leads to a metabolite that may actually reduce the risk. Heredity and diet may influence the pathway that is utilized.

Early-stage breast cancer has few symptoms. The earliest symptom may be a thickening or lump in the breast or under arm. Other symptoms include:

• a change in the size, shape, contour, or feel of the breast, nipple, or areola (the dark area surrounding the nipple)
• a change in the appearance of the breast skin or nipple, such as a puckering or dimpling, ridges or pitting, crustiness or scaliness
• a breast that is red, swollen, and warm
• nipple tenderness or discharge
• a nipple that is pulled back or inverted.

Most breast cancers are first detected by screening during

• a self-examination
• an annual clinical breast exam by a healthcare professional
• an annual or biennial screening mammogram or x rays of the breasts, which can detect cancers that are too small to feel.

However, a 2006 study found that breast cancer diagnosis is often delayed in women aged 70 and older, in large part due to the underutilization of mammography in older women.

Diagnosis

Initial diagnosis

Detection of a lump or a suspicious area on a mammogram is followed by one or more of the following:

• mammography to determine the exact location of the lump and look for other abnormalities in either breast
• diagnostic mammography to obtain magnified views
• ultrasound, in which high-energy sound waves are bounced off internal tissue to produce a picture called a sonogram; often used to distinguish between a solid lump and a fluid-filled benign cyst
• magnetic resonance imaging (MRI) to obtain pictures that may be more detailed than a mammogram
• biopsy (the removal of cells or tissue) to be examined by a pathologist.

Four types of biopsies are used:

• fine-needle aspiration (FNA) biopsy, in which fluid or cells are withdrawn using a thin needle
• needle or core biopsy, in which a wide needle is used to remove tissue from a suspicious area that cannot be felt
• incisional biopsy, in which a piece of tissue is removed through an incision in the skin
• excisional or surgical biopsy, in which the entire lump or suspicious area and surrounding tissue are removed.

Since a needle biopsy can miss cancerous cells, a negative result usually requires a second biopsy. However, about 80% of surgical biopsies are negative for cancer.

In addition to an FNA biopsy, two other breastfluid sampling methods are sometimes used: nipple aspiration , in which gentle suction is used to withdraw fluid through the nipple, and ductal lavage, in which a hair-sized catheter or tube discharges a small amount of salt water through the nipple into the duct and sucks it back up along with cells. Another technology inserts a miniature camera through the nipple into a milk duct to look for cancerous cells.

Cell markers

Tumor-cell samples are tested for the presence of receptors for the female hormones estrogen and progesterone. About 70% of breast cancers are estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive. ER-positive cancer that grows in re-sponse to estrogen is the most common cancer in postmenopausal women. Receptor-positive cancers have a better prognosis than receptor-negative cancers and are more likely to respond to hormone therapies.

All breast-cancer cells have human epidermal-growth-factor receptor-2 (HER2), which causes the cells to grow and multiply. About 20 to 30% of breast cancers have increased amounts of HER2 and are considered HER2-positive. These cancers grow faster, are more likely to recur after treatment, and do not respond well to conventional chemotherapy .

Staging

Staging determines how far the cancer has progressed and whether it has metastasized. It may involve additional tests to determine the following:

• the size and exact location of the tumor
• whether the cancer has spread within the breast
• whether the cancer has spread to the underarm lymph nodes
• whether the cancer has spread to other parts of the body.

A sentinel lymph node (SNL) biopsy may be performed to help stage the cancer. The SNL is the node(s) to which an invasive cancer is most likely to spread first. A blue dye and/or radioactive marker is injected into the breast at or near the site of the cancer. It accumulates in and identifies the SNL, which is then biopsied and examined for the presence of cancer. This procedure has reduced the need for extensive removal of underarm nodes to determine the spread of the cancer.

Breast cancer is staged as follows:

• Stage O (in situ or noninvasive) is the earliest stage, in which the cancer has not spread beyond its site of origin in the breast. In ductal carcinoma-in-situ (DCIS) abnormal cells have not spread beyond the lining of the duct but have the potential to become invasive. In lobular carcinoma-in-situ (LCIS) abnormal cells are found in the lobules. LCIS rarely becomes invasive but increases the risk of cancer in either breast.
• Stage I is an early stage in which the cancer has not spread beyond the breast and the tumor is 2 centimeters (cm) or less in size.
• Stage II is an early stage in which the tumor is larger or the cancer has spread to the lymph nodes.
• Stage III is locally advanced with the cancer having spread to the lymph nodes and other nearby tissues.
• Stage IV is metastasized cancer that has spread beyond the breast and underarm lymph nodes to other parts of the body, usually the lungs, bones, liver, or sometimes the brain.
• IBC is stage III or IV cancer that has spread to the skin.
• Recurrent is cancer that has returned to the breast, chest wall, or other parts of the body after treatment.

Treatment

Breast cancer treatment and prognosis depend on the following:

• the type and stage of the cancer
• ER and PR levels in the tumor
• HER2 levels
• how fast the tumor is growing
• the woman's preferences
• the woman's age, menopausal status, and overall health.

For stages I through III the goals of treatment are to remove the cancer and reduce the risk of recurrence. For stage IV the goal is to treat the symptoms and prolong survival. If a woman has one or more life-threatening diseases in addition to breast cancer and a reduced life expectancy, the breast cancer is sometimes left untreated.

Treatment usually begins as soon as breast cancer is diagnosed, and treatment options are similar for younger and older women. Although breast cancer is often treated less aggressively in elderly women, prompt surgery followed by adjuvant treatment has been shown to decrease recurrence and increase survival. Adjuvant treatment may include:

• radiation therapy
• chemotherapy
• hormonal therapy
• biological therapy

Surgery and radiation are local therapies that destroy cancer cells in the breast, whereas the others are whole-body or systemic therapies that destroy cancer cells throughout the body. Many breast cancer patients receive a combination of local and systemic treatments.

Surgery

Treatment for breast cancer almost always involves surgery. However, surgery is rarely offered to women over 70 even though studies have shown that surgery controls breast cancer in older women better than hormone therapy alone.

Depending on the size of the tumor and how far the cancer has spread, surgery may be either breast-conserving or a mastectomy . Breast-conserving surgery removes the tumor and surrounding normal tissue, leaving as much of the breast as possible intact for faster healing and a more normal appearance. If the cancer has spread only within one breast, chemotherapy may be used to shrink the tumor before breast-conserving surgery. There are three types of breast-conserving surgery:

• A lumpectomy removes the tumor, a small amount of surrounding normal tissue, and usually some of the underarm lymph nodes. Elderly women with untreated breast cancer often have a lumpectomy to prevent painful sores and ulcers.
• A wide excision, segmental, or partial mastectomy removes a larger area of tissue surrounding the tumor, the lining over the chest muscles below the tumor, and often some of the underarm lymph nodes.
• A quadrantectomy removes one fourth of the breast and possibly lymph nodes.

There are three types of mastectomies:

• A simple or total mastectomy removes the breast and possibly some lymph nodes.
• A modified radical mastectomy removes the breast and underarm lymph nodes.
• A radical mastectomy removes the breast, underarm lymph nodes, and muscle under the breast.

Adjuvant therapies

Radiation therapy usually follows breast-conserving surgery and sometimes mastectomies. High-energy x rays or other forms of external radiation are used to kill any remaining cancer cells and prevent recurrence. Since the risk of breast-cancer recurrence in the same area following surgery appears to decrease with age, radiation therapy is not necessarily recommended for older women.

Chemotherapy is most often used after surgery and radiation therapy to destroy cancer that has spread beyond the breast. Although studies have shown that women aged 70 and older benefit as much as younger women from chemotherapy, adjuvant chemotherapy for breast cancer is controversial, tends to be used less frequently in elderly women, and must be individualized for them based on risk-benefit analysis. Sequential single-agent chemotherapy is preferable for elderly women with metastasized breast cancer.

Since most breast cancers in older women are hormone-receptor positive and grow and spread in response to estrogen and/or progesterone, hormone therapy is the most common adjuvant treatment for early breast cancer. It is also used to treat metastatic breast cancer in older women. Tamoxifen (a selective estrogen-receptor modulator (SERM), or antiestrogen is the most common hormonal therapy. It blocks the action of estrogen on ERs in the breast. Treatment with tamoxifen is often continued for five years. Older women may tolerate tamoxifen better than younger women and the longer they have been menopausal, the better the drug may be tolerated. However, the risks of side effects and complications from tamoxifen increase with age and include:

QUESTIONS TO ASK YOUR DOCTOR

• What stage is my breast cancer?
• Is my breast cancer ER- or PR-positive?
• Is it HER2-positive?
• What other tests might I need?
• What are my treatment options?
• Should I get a second opinion on my diagnosis and treatment options?
• Are there clinical trials that may be appropriate for me?
• What is my prognosis?

• weight gain
• depression
• increased risk for endometrial cancer, uterine sarcoma, and blood clots
• a 40% increased risk of heart attack, stroke, or pulmonary embolism.

Aromatase inhibitors such as letrozole may be used before or after treatment with tamoxifen. They inhibit the enzyme aromatase that is responsible for producing estrogen after menopause when it is no longer made in the ovaries. Postmenopausal women with hormone-dependent breast cancer are most likely to respond to treatment with aromatase inhibitors. However, they may increase the risk of osteoporosis or affect brain function.

Trastuzumab (Herceptin) is an antibody or biological therapy. It binds to HER2 on cancer cells, causing the body's immune system to destroy the cells.

Nutrition/Dietetic concerns

Although women in populations with low-fat diets are less likely to die of breast cancer, it is not known whether a low-fat diet or any other nutritional factors reduce breast-cancer risk. However, cruciferous vegetables of the cabbage family contain a compound that is broken down in the body to indole-3-carbinol (I3C). I3C may help shift estrogen metabolism toward the pathway of reduced breast-cancer risk.

Prognosis

Death rates from breast cancer have been declining since 1990, due, at least in part, to earlier detection and better treatment, and the breast cancer prognosis in older women is generally good. Almost 97% of women whose breast cancer is discovered early when it is still small and near the site of origin are alive five years later. However, the five-year-survival rate for women with metastasized breast cancer is only 23%. Although breast cancer that has spread beyond the lymph nodes is rarely cured, treatment can relieve symptoms, improve survival, and allow for good quality of life. IBC often grows very rapidly and has a poor prognosis.

KEY TERMS

Aromatase inhibitor —Letrozole, a medication for preventing or treating breast cancer in postmenopausal women by inhibiting the body's production of estrogen.

Biopsy —The removal of cells or tissue for examination by a pathologist.

BRCA1, BRCA2 —Breast-cancer susceptibility genes; specific mutations in these genes greatly increase the risk of breast and ovarian cancers.

Ductal carcinoma-in-situ (DCIS) —Breast cancer that has not spread beyond the lining of the milk duct.

Estrogen receptor (ER) —A protein on the surface of cells that binds the female hormone estrogen, initiating estrogenic effects.

HER2 —Human epidermal-growth-factor receptor-2, which is overproduced in HER2-positive breast cancers.

Inflammatory breast cancer (IBC) —A rare, very aggressive type of cancer that blocks the lymph vessels in the skin causing redness, warmth, and swelling of the breast.

Lobular carcinoma-in-situ (LCIS) —Breast cancer that is confined to the lobules or milk-producing glands.

Lumpectomy —Excision of a breast tumor and a limited amount of surrounding tissue.

Lymph node —Glands throughout the body that filter the lymphatic fluid.

Mammogram —A breast x ray used to detect cancer.

Mastectomy —Surgical removal of part or all of the breast and possibly associated lymph nodes and muscle.

Progesterone receptor (PR) —A cell-surface protein that binds the female hormone progesterone.

Raloxifene —A drug for treating osteoporosis that blocks the effects of estrogen.

Sentinel lymph node (SLN) —The node that breast cancer is most likely to invade first.

Tamoxifen —A drug that blocks the activity of estrogen and is used to prevent or treat breast cancer.

Trastuzumab —Herceptin, a monoclonal antibody that binds to HER2 causing the immune system to destroy the cell; used to treat HER2-positive breast cancer.

The long-term prognosis for ER-positive cancer is better than for ER-negative cancer, especially if the cells are also PR-positive. Aromatase inhibitors have improved survival among elderly women with breast cancer, and tamoxifen and trastuzumab have reduced the rate of recurrence. However, women who have had cancer in one breast remain at high risk for developing cancer in the other breast.

The outcome of breast-conserving surgery with radiation therapy for early-stage breast cancer is usually equivalent to the outcome of a mastectomy.

However, there is a 9% chance that a tumor will reappear on the chest wall following a mastectomy and about a 10% chance of recurrence following a lumpectomy and radiation therapy. There is a one in three chance of recurrence on the chest or skin following a lumpectomy without radiation therapy.

Prevention

Lifestyle factors that may increase the risk of breast cancer include:

• birth control pills
• obesity
• gaining weight after menopause, especially after natural menopause or age 60
• alcohol consumption, which can shift estrogen metabolism toward the higher-risk pathway with the effect increasing with the amount of alcohol consumed
• synthetic hormone-replacement therapy after menopause.

Factors that can reduce exposure to estrogen thereby reducing the risk of breast cancer include:

• exercising four or more hours per week, particularly by premenopausal women of low or normal weight
• breastfeeding
• drugs that lower estrogen production by the ovaries
• removal of one or both ovaries
• prophylactic or preventative mastectomy.

In 1998 the U.S. Food and Drug Administration approved the use of tamoxifen to help lower the risk of breast cancer in healthy high-risk women. A study of 13,000 pre- and post-menopausal high-risk women found a 40% reduction in breast cancers among those who took tamoxifen. A subsequent study found that either tamoxifen or raloxifene reduced the risk of breast cancer in high-risk post-menopausal women by about 50%. Although women taking raloxifene had fewer uterine cancers, blood clots , and cataracts than those taking tamoxifen, raloxifene increased the risk of blood clots and fatal strokes in women who were already at risk. Aromatase inhibitorslower the risk of second breast cancers in postmenopausal women.

Caregiver concerns

Caregivers should be aware of any visible changes in a woman's breasts, since older people sometimes ignore symptoms, believing that they are just part of old age. Caregivers should also assure that the proper medications are taken at the prescribed times.

Resources

BOOKS

Dixon, J. M., ed. ABC of Breast Diseases, 3rd ed. Malden, MA: BMJ Books/Blackwell, 2006.

Love, Susan M., and Karen Lindsey. Dr. Susan Love's Breast Book, 4th ed. Cambridge, MA: Da Capo Press, 2005.

PERIODICALS

Ferraro, Susan. “Self-Exams Are Passe? Believers Beg to Differ.” New York Times (December 26, 2006): F5.

Rao, Vittal S. R., et al. “Management of Early Breast Cancer in the Elderly.” International Journal of Cancer 120, no. 6 (March 15, 2007): 1155–1160.

“Surgery Best for Controlling Breast Cancer in Older Women.” Women's Health Weekly (March 2, 2006): 72.

Whitworth, Ariel. “Radiation Therapy Is Associated with Lower Risk of Breast Cancer Recurrence in Elderly Women.” Journal of the National Cancer Institute 98, no. 10 (May 17, 2006): 655.

OTHER

“Breast Cancer.” NIH Senior Health. October 26, 2006. http://nihseniorhealth.gov/breastcancer/toc.html (accessed February 28, 2008).

“Breast Cancer Facts & Figures 2007–2008.” American Cancer Society [cited March 9, 2008]. http://www.cancer.org/downloads/STT/BCFF-Final.pdf.

“Breast Cancer Issues for Elderly Women.” Y-Me National Breast Cancer Organization [cited March 9, 2008]. http://www.y-me.org/coping/survivorship/survivor-ship_for_elderly.php

“Breast Cancer Prevention.” National Cancer Institute February 22, 2008 [cited March 9, 2008]. http://www.cancer.gov/cancertopics/pdq/prevention/breast/Patient/page1.

“Breast Cancer Screening.” National Cancer Institute June 14, 2007 [cited March 9, 2008]. http://www.cancer.gov/cancertopics/pdq/screening/breast/Patient/page1.

“Breast Cancer Treatment.” National Cancer Institute February 7, 2008 [cited February 28, 2008]. http://www.cancer.gov/cancertopics/pdq/treatment/breast/patient/.

“Treatment of Breast Cancer in Men by Stage.” Cancer Reference Information. September 27, 2007 [cited February 28, 2008]. http://www.cancer.org/docroot/cri/content/cri_2_4_4x_treatment_of_male_breast_cancer_by_stage_28.asp

ORGANIZATIONS

American Cancer Society, 1599 Clifton Rd., NE, Atlanta, GA, 30329, (404) 320-3333, (800) ACS-2345, http://www.cancer.org.

National Alliance of Breast Cancer Organizations, 9 East Thirty-seventh Street, 10th Floor, New York, NY, 10016, (212) 889-0606, (888) 806-2226, [email protected], http://www.nabco.org.

Susan G. Komen Breast Cancer Foundation, 5005 LBJ Freeway, Suite 250, Dallas, TX, 75244, (972) 855-1600, (877) GO-KOMEN, http://www.komen.org.

Y-ME: National Breast Cancer Organization, 12 W. Van Buren, Suite 1000, Chicago, IL, 60607-3903, (312) 986-8338, (800) 221-2141, (312) 294-8597, http://www.y-me.org.

Margaret Alic Ph.D.