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  • Reviewed: 09/23/2010
CANCER ADVANCES IN FOCUS: Breast Cancer
Yesterday
  • In 1975, the incidence rate for female breast cancer in the United States was 105 new cases diagnosed for every 100,000 women in the population; the mortality rate was 31 deaths for every 100,000 women.

  • Among women diagnosed with breast cancer during the period from 1975 through 1977, about 75% survived their disease at least 5 years. Among white women, the 5-year relative survival rate was 76%; among African American women, it was 62%.

  • Mastectomy was the only accepted surgical option for breast cancer treatment.

  • Only one randomized trial of mammography for breast cancer screening had been completed. Several other trials and the joint National Institutes of Health (NIH) and American Cancer Society (ACS) Breast Cancer Detection Demonstration Projects were just beginning.

  • Clinical investigation of combination chemotherapy, using multiple drugs with different mechanisms of action, and of hormonal therapy as postsurgical (adjuvant) treatment for breast cancer was in its earliest stages.

  • In the mid-1970s, clinical evaluation of the drug tamoxifen, a selective estrogen receptor modulator (SERM), as a hormonal treatment for breast cancer was just beginning.

  • No gene associated with an increased risk of breast cancer had yet been identified.

Today

  • In 2007, the latest year for which we have updated statistics, the U.S. incidence rate for female breast cancer was approximately 125 new cases diagnosed for every 100,000 women in the population; the mortality rate was approximately 23 deaths for every 100,000 women. Although the incidence rate in 2007 was higher than that in 1975, this rate has been declining since 1998-1999, when it peaked at a rate of 141 new cases for every 100,000 women in the population. The breast cancer death rate in the United States has been declining steadily since 1989-1990, when it peaked at a rate of 33 deaths for every 100,000 women.

  • Among women diagnosed with breast cancer during the period from 1999 through 2006, 90% were expected to survive their disease at least 5 years. Among white women, the 5-year relative survival rate was 91%; among African American women, it was 78%. The increase in breast cancer survival seen since the mid-1970s has been attributed to both screening and improved treatment.

  • Breast-conserving surgery (lumpectomy) followed by local radiation therapy has replaced mastectomy as the preferred surgical approach for treating early-stage breast cancer.

  • Routine mammographic screening is an accepted standard for the early detection of breast cancer. The results of eight randomized trials, the NIH-ACS Breast Cancer Detection Demonstration Projects, and other research studies showed that mammographic screening can reduce the mortality from breast cancer.

  • Combination chemotherapy is a standard of care in the adjuvant treatment of operable breast cancer. The goal of this systemic therapy is to eradicate cancer cells that may have spread beyond the breast. Neoadjuvant chemotherapy, or chemotherapy given before surgery to reduce the size of the tumor and to increase the chance of breast-conserving surgery, is also an option.

  • Hormonal therapy with SERMs (such as tamoxifen) and aromatase inhibitors is now standard in the treatment of women with estrogen receptor-positive breast cancer, both as adjuvant therapy and in the treatment of advanced disease. Estrogen receptor-positive breast cancer cells can be stimulated to grow by the hormone estrogen. SERMs interfere with this growth stimulation by preventing estrogen from binding to the estrogen receptor. In contrast, aromatase inhibitors block estrogen production by the body. Food and Drug Administration (FDA)-approved aromatase inhibitors include anastrozole, exemestane, and letrozole.

  • Tamoxifen and another SERM, raloxifene, have been approved by the FDA as treatments to reduce the risk of breast cancer in women who have an increased risk of developing the disease.

  • The monoclonal antibody trastuzumab is an accepted treatment for breast cancers that overproduce a protein called human epidermal growth factor receptor 2, or HER2. This protein is produced in abnormally high amounts by about 20% of breast tumors. Breast cancers that overproduce HER2 tend to be more aggressive and are more likely to recur. Trastuzumab targets the HER2 protein specifically, and this antibody, in conjunction with adjuvant chemotherapy, can lower the risk of recurrence of HER2-overproducing breast cancers by about 50% in comparison with chemotherapy alone.

  • Several breast cancer susceptibility genes have now been identified, including BRCA1, BRCA2, TP53, and PTEN/MMAC1. Approximately 60% of women with an inherited mutation in BRCA1 or BRCA2 will develop breast cancer sometime during their lives, compared with about 12% of women in the general population. Women with inherited BRCA1 or BRCA2 gene mutations also have an increased risk of ovarian cancer.

Tomorrow

  • We will use our rapidly increasing knowledge in the fields of cancer genomics and cell biology to develop more effective and less toxic treatments for breast cancer and to improve our ability to identify cancers that are more likely to recur. Moreover, we will use this knowledge to tailor breast cancer therapy to the individual patient. For example, gene expression analysis has led to the identification of five subtypes of breast cancer that have distinct biological features, clinical outcomes, and responses to chemotherapy. This knowledge can be exploited in the development of treatment strategies based on the specific characteristics of a woman’s tumor. Furthermore, a patient’s response to chemotherapy is influenced not only by the genetic characteristics of their tumor but also by inherited variations in genes that affect the body’s ability to absorb, metabolize, and eliminate drugs. Our growing knowledge should enable prediction of tumor responses to individual chemotherapy drugs or classes of drugs, as well as the likelihood of severe adverse effects from them. This knowledge should also aid in the development of more individualized treatments and permit the design of more effective and less toxic chemotherapy agents.

  • We will use our increasing knowledge of the immune system to enhance the body’s ability to recognize and destroy cancer cells. The knowledge we have acquired thus far has facilitated the development of several promising breast cancer treatment vaccines that are currently under clinical evaluation.

  • We will use advanced technologies, including genomic technologies, to improve our ability to detect breast cancer at its earliest stages, when it is most treatable, and to better define individual risk for this disease.

  • We will strive to understand, address, and eliminate factors that contribute to the higher mortality from breast cancer experienced by African American women compared with women of other racial and ethnic groups.

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Glossary Terms

adjuvant therapy (A-joo-vunt THAYR-uh-pee)
Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.
anastrozole (an-AS-troh-zole)
An anticancer drug that is used to decrease estrogen production and suppress the growth of tumors that need estrogen to grow. It is a type of nonsteroidal aromatase inhibitor.
aromatase inhibitor (uh-ROH-muh-tays in-HIH-bih-ter)
A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone-dependent breast cancer.
BRCA1
A gene on chromosome 17 that normally helps to suppress cell growth. A person who inherits certain mutations (changes) in a BRCA1 gene has a higher risk of getting breast, ovarian, prostate, and other types of cancer.
BRCA2
A gene on chromosome 13 that normally helps to suppress cell growth. A person who inherits certain mutations (changes) in a BRCA2 gene has a higher risk of getting breast, ovarian, prostate, and other types of cancer.
breast cancer (brest KAN-ser)
Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.
combination chemotherapy (KOM-bih-NAY-shun KEE-moh-THAYR-uh-pee)
Treatment using more than one anticancer drug.
drug (drug)
Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.
estrogen receptor (ES-truh-jin reh-SEP-ter)
A protein found inside the cells of the female reproductive tissue, some other types of tissue, and some cancer cells. The hormone estrogen will bind to the receptors inside the cells and may cause the cells to grow. Also called ER.
exemestane (EK-seh-MEH-stayn)
A drug used to treat advanced breast cancer and to prevent recurrent breast cancer in postmenopausal women who have already been treated with tamoxifen. It is also being studied in the treatment of other types of cancer. Exemestane causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor. Also called Aromasin.
Food and Drug Administration (... ad-MIH-nih-STRAY-shun)
An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.
gene (jeen)
The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
gene expression (jeen ek-SPREH-shun)
The process by which a gene gets turned on in a cell to make RNA and proteins. Gene expression may be measured by looking at the RNA, or the protein made from the RNA, or what the protein does in a cell.
genomics (jeh-NOH-mix)
The study of the complete genetic material, including genes and their functions, of an organism.
hormonal therapy (hor-MOH-nul THAYR-uh-pee)
Treatment that adds, blocks, or removes hormones. For certain conditions (such as diabetes or menopause), hormones are given to adjust low hormone levels. To slow or stop the growth of certain cancers (such as prostate and breast cancer), synthetic hormones or other drugs may be given to block the body’s natural hormones. Sometimes surgery is needed to remove the gland that makes a certain hormone. Also called endocrine therapy, hormone therapy, and hormone treatment.
human epidermal growth factor receptor 2 (HYOO-mun eh-pih-DER-mul grothe FAK-ter reh-SEP-ter ...)
A protein involved in normal cell growth. It is found on some types of cancer cells, including breast and ovarian. Cancer cells removed from the body may be tested for the presence of human epidermal growth factor receptor 2 to help decide the best type of treatment. Human epidermal growth factor receptor 2 is a type of receptor tyrosine kinase. Also called c-erbB-2, HER2/neu, and human EGF receptor 2.
immune system (ih-MYOON SIS-tem)
The complex group of organs and cells that defends the body against infections and other diseases.
letrozole (LET-ruh-zole)
A drug used to treat advanced breast cancer in postmenopausal women. Letrozole causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor. Also called Femara.
lumpectomy (lum-PEK-toh-mee)
Surgery to remove abnormal tissue or cancer from the breast and a small amount of normal tissue around it. It is a type of breast-sparing surgery.
mammography (ma-MAH-gruh-fee)
The use of film or a computer to create a picture of the breast.
mastectomy (ma-STEK-toh-mee)
Surgery to remove the breast (or as much of the breast tissue as possible).
monoclonal antibody (MAH-noh-KLOH-nul AN-tee-BAH-dee)
A type of protein made in the laboratory that can bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.
neoadjuvant therapy (NEE-oh-A-joo-vant THAYR-uh-pee)
Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy.
ovarian cancer (oh-VAYR-ee-un KAN-ser)
Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).
p53 gene (… jeen)
A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer.
PTEN
A protein that helps control many cell functions, including cell division and cell death. Mutations (changes) in the gene that makes PTEN are found in many types of cancer and other diseases. It is a type of tumor suppressor protein. Also called PTEN tyrosine phosphatase.
radiation therapy (RAY-dee-AY-shun THAYR-uh-pee)
The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.
raloxifene (ral-OX-ih-feen)
The active ingredient in a drug used to reduce the risk of invasive breast cancer in postmenopausal women who are at high risk of the disease or who have osteoporosis. It is also used to prevent and treat osteoporosis in postmenopausal women. It is also being studied in the prevention of breast cancer in certain premenopausal women and in the prevention and treatment of other conditions. Raloxifene blocks the effects of the hormone estrogen in the breast and increases the amount of calcium in bone. It is a type of selective estrogen receptor modulator (SERM).
randomized clinical trial (RAN-duh-mized KLIH-nih-kul TRY-ul)
A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.
relative survival rate (REH-luh-tiv ser-VY-vul …)
A way of comparing survival of people who have a specific disease with those who don’t. The percentage of survivors is usually determined at specific times, such as 2 years and 5 years after diagnosis or treatment. The relative survival rate shows whether the disease shortens life.
selective estrogen receptor modulator (seh-LEK-tiv ES-truh-jin reh-SEP-ter MAH-juh-lay-ter)
A drug that acts like estrogen on some tissues but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are selective estrogen receptor modulators. Also called SERM.
tamoxifen (tuh-MOK-sih-FEN)
A drug used to treat certain types of breast cancer in women and men. It is also used to prevent breast cancer in women who have had ductal carcinoma in situ (abnormal cells in the ducts of the breast) and in women who are at a high risk of developing breast cancer. Tamoxifen is also being studied in the treatment of other types of cancer. It blocks the effects of the hormone estrogen in the breast. Tamoxifen is a type of antiestrogen. Also called tamoxifen citrate.
toxic (TOK-sik)
Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.
trastuzumab (tras-TOO-zoo-mab)
A drug used to treat breast cancer that is HER2-positive (expresses the human epidermal growth factor receptor 2). It is also used with other drugs to treat HER2-positive stomach cancer that has not already been treated and has spread to other parts of the body. It is being studied in the treatment of other types of cancer. Trastuzumab binds to HER2 on the surface of HER2-positive cancer cells, and may kill them. It is a type of monoclonal antibody. Also called Herceptin.
vaccine (vak-SEEN)
A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

Table of Links

1http://www.cancer.gov/cancertopics/factsheet/cancer-advances-in-focus