Related Pages Cancer Advances In Focus Index 1

Yesterday

• Approximately 75% of women diagnosed with breast cancer survived their disease at least 5 years.
• Mastectomy was the only accepted surgical option for breast cancer treatment.
• Only one randomized trial of mammography for breast cancer screening had been conducted.
• Clinical investigation of combination chemotherapy, using multiple drugs with different mechanisms of action, and of hormonal therapy as post-surgical (adjuvant) treatment for breast cancer was in its earliest stages.
• Hormonal treatment of inoperable or advanced breast cancer with tamoxifen, a selective estrogen receptor modulator (SERM), was being investigated but had not yet been approved by the U.S. Food and Drug Administration (FDA).
• Genes associated with an increased risk of breast cancer had not yet been identified.

Today

• Nearly 90% of women diagnosed with breast cancer will survive their disease at least 5 years.
• Breast-conserving surgery (lumpectomy) followed by local radiation therapy has replaced mastectomy as the preferred surgical approach for treating women with early-stage breast cancer.
• Routine mammographic screening is an accepted standard for the early detection of breast cancer. The results of eight randomized trials and of the National Cancer Institute-American Cancer Society Breast Cancer Detection Demonstration Projects established that mammographic screening can reduce mortality from breast cancer.
• Combination chemotherapy has become standard in the adjuvant treatment of women with early-stage 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 being studied in clinical trials.
• 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 its receptor. In contrast, aromatase inhibitors block estrogen production by the body. FDA-approved aromatase inhibitors include anastrozole, exemestane, and letrozole.
• Tamoxifen and another SERM, raloxifene, have been shown in clinical trials to prevent the development of invasive breast cancer in women at high risk of this disease. Tamoxifen has already been approved by the FDA as a breast cancer prevention drug.
• The monoclonal antibody trastuzumab is being used to treat breast cancers that overproduce a protein called human epidermal growth factor receptor 2, or HER2. This protein is overproduced in about 20% of breast cancers. These HER2-overproducing cancers tend to be more aggressive and are more likely to recur. Trastuzumab targets the HER2 protein, and this antibody, in conjunction with adjuvant chemotherapy, can lower the risk of HER2-overproducing breast cancer recurrence by 50% compared with chemotherapy alone.
• The study of large groups of related individuals (kindreds) has led to the identification of several breast cancer susceptibility genes, including BRCA1, BRCA2, TP53, and PTEN/MMAC1. Mutations in BRCA1 and BRCA2 account for approximately 80-90% of all hereditary breast cancers, and women who carry mutations in these genes have a lifetime risk of breast cancer that is roughly 10 times greater than that of the general population.

Tomorrow

We will exploit our rapidly increasing knowledge of genetics, molecular biology, and immunology to develop even more effective and less toxic treatments for breast cancer. We will expand our ability to target and disrupt the effects of molecular changes that cause breast cells to become cancerous. In addition, we will use this knowledge to personalize breast cancer therapy. 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 should allow the development of treatment strategies based on an individual's tumor characteristics.
• A patient's response to chemotherapy is influenced not only by the tumor's genetic characteristics but also by inherited variation in genes that affect a person's ability to absorb, metabolize, and eliminate drugs. This knowledge should allow prediction of tumor response to and the likelihood of severe adverse effects from individual chemotherapy drugs or classes of drugs. It should also aid in the design of more effective and less toxic chemotherapeutic agents.

Glossary Terms

An unexpected medical problem that happens during treatment with a drug or other therapy. Adverse effects do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. Also called adverse event.

A quickly growing cancer.

A process in which anything complex is separated into simple or less complex parts.

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.

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.

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.

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.

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.

An operation to remove the breast cancer but not the breast itself. Types of breast-conserving surgery include lumpectomy (removal of the lump), quadrantectomy (removal of one quarter, or quadrant, of the breast), and segmental mastectomy (removal of the cancer as well as some of the breast tissue around the tumor and the lining over the chest muscles below the tumor). Also called breast-sparing surgery.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

The process of identifying a disease, such as cancer, from its signs and symptoms.

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.

Breast cancer that has not spread beyond the breast or the axillary lymph nodes. This includes ductal carcinoma in situ and stage I, stage IIA, stage IIB, and stage IIIA breast cancers.

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.

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 FDA 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 Food and Drug Administration.

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.

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.

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.

The study of genes and heredity. Heredity is the passing of genetic information and traits (such as eye color and an increased chance of getting a certain disease) from parents to offspring.

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 HER2/neu to help decide the best type of treatment. HER2/neu is a type of receptor tyrosine kinase. Also called c-erbB-2, human EGF receptor 2, and human epidermal growth factor receptor 2.

Transmitted from parent to child by information contained in the genes.

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.

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.

The study of the body's immune system.

Transmitted through genes that have been passed from parents to their offspring (children).

Describes a condition that cannot be treated by surgery.

Cancer that has spread from where it started in the breast into surrounding, healthy tissue. Most invasive breast cancers start in the ducts (tubes that carry milk from the lobules to the nipple). Invasive breast cancer can spread to other parts of the body through the blood and lymph systems. Also called infiltrating breast cancer.

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.

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.

The use of film or a computer to create a picture of the breast.

Surgery to remove the breast (or as much of the breast tissue as possible).

A type of protein made in the laboratory that can locate and 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.

The state of being mortal (destined to die). Mortality also refers to the death rate, or the number of deaths in a certain group of people in a certain period of time. Mortality may be reported for people who have a certain disease, live in one area of the country, or who are of a certain gender, age, or ethnic group.

Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

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.

In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

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.

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).

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.

To come back or to return.

In medicine, an improvement related to treatment.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

A drug that acts like estrogen on some tissues but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. Also called selective estrogen receptor modulator.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

Treatment using substances that travel through the bloodstream, reaching and affecting cells all over the body.

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.

Treatment.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

A monoclonal antibody that binds to HER2 (human epidermal growth factor receptor 2), and can kill HER2-positive cancer cells. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Trastuzumab is used to treat breast cancer that is HER2-positive and has spread after treatment with other drugs. It is also used with other anticancer drugs to treat HER2-positive breast cancer after surgery. Trastuzumab is also being studied in the treatment of other types of cancer. Also called Herceptin.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.