1. What is the purpose of the trial?
   

   TAILORx—the Trial Assigning IndividuaLized Options for Treatment (Rx)—is designed to determine whether adjuvant hormonal therapy alone is as effective as adjuvant hormonal therapy in combination with chemotherapy for certain women with early-stage breast cancer. Trial results will help individualize treatment for each breast cancer patient in order to achieve improved clinical outcomes.

2. Who is eligible to enroll in TAILORx?

   Women with estrogen receptor and/or progesterone receptor positive, lymph node negative (cancer that has not spread to the lymph nodes), HER2/neu negative breast cancer are eligible to enroll in TAILORx. The tumor size must be 1.1 to 5.0 cm (or 0.5 mm to 1.0 cm, with unfavorable histologic features). Participants must meet standard clinical criteria and be medically suitable candidates for adjuvant chemotherapy.

3. What does the trial involve?

   All patients who agree to participate in the trial will have a molecular test performed on a sample of the tumor that has already been removed. This test does not require an additional biopsy or other procedures. The specimen will be sent to a laboratory for the test to be done. It takes about 7 to 10 days from the time a specimen is received at the laboratory for a doctor to get the results of the test. These results will be used to guide therapy.

4. What are the primary objectives of the trial?

   The primary objectives of TAILORx are twofold:

   • To determine whether adjuvant hormonal therapy with chemotherapy is better than adjuvant hormonal therapy alone in women whose tumors fall in a range where the benefit from chemotherapy is uncertain as indicated by a molecular test. The primary study endpoint is disease-free survival. Another primary endpoint is overall survival.
   • To create a tissue and specimen bank for patients enrolled in this trial, including formalin-fixed, paraffin-embedded tumor specimens, tissue microarrays, plasma, and DNA obtained from peripheral blood. This resource will be critical for evaluating emerging clinical cancer tests.

5. What is the molecular test used in this trial?

   The molecular test is called Oncotype DX^TM. It is a test that analyzes the expression pattern of certain genes in breast tumors. The test can more precisely estimate a woman's risk of cancer recurrence than standard characteristics that doctors normally use to assess recurrence risk (e.g., tumor size, tumor grade, and other characteristics of the tumor). The Oncotype DX test that is being used in this trial has been commercially available since 2004. Genomic Health, Inc. (Redwood City, Calif.), the company that developed the test, performs the assay in its own laboratory. It has been performed on tumor specimens from over 10,000 breast cancer patients thus far.

6. How will the Oncotype DX test be used to guide therapy?
   

   The test result is expressed as a "Recurrence Score." The higher the score, the greater the chance of having a recurrence of breast cancer if a woman is treated with hormonal therapy alone. The treatment that patients will receive in this trial will depend upon the results of the Recurrence Score.

   • If the Recurrence Score is 10 or less, it is estimated that approximately 95 percent of patients or more may live long term without a distant disease recurrence with hormonal therapy alone. These patients will only receive hormonal therapy. About 25 percent of patients are estimated to have a Recurrence Score in this range.
   • If the Recurrence Score is 26 or higher, the risk of recurrence is about 30 percent with hormonal therapy alone, and may be reduced to about 10 percent with the addition of chemotherapy. These patients will receive chemotherapy and hormonal therapy. About 30 percent of patients are estimated to have a Recurrence Score in this range.
   • If the Recurrence Score is 11 to 25, the risk of recurrence is about 7 percent to 16 percent with hormonal therapy alone. Patients who have a Recurrence Score in this range will be randomly assigned to receive chemotherapy plus hormonal therapy (the standard treatment arm) versus hormonal therapy alone (the experimental treatment arm). About 44 percent of patients are estimated to have a Recurrence Score in this range.

7. What is randomization and why is it necessary?

   Randomization is like flipping a coin. The treatment will be assigned by chance. This procedure is commonly used in clinical trials when new treatment approaches are being tested, and when there is uncertainty about the best treatment approach. Patients with a Recurrence Score of 11 to 25 will be randomly assigned to receive, or not to receive, chemotherapy because the benefit of chemotherapy is uncertain in this group, even though chemotherapy would normally be recommended for this group based upon standard characteristics, such as tumor pathology, traditionally used in clinical practice.

8. Why is randomization not being used for all patients participating in this study?

   Patients who have a low Recurrence Score (10 or lower) or high Recurrence Score (26 or higher) will not be randomized. Patients with a low Recurrence Score will be assigned to receive hormonal therapy alone, and patients with a high Recurrence Score will be assigned to receive chemotherapy plus hormonal therapy. Patients in these groups are being directly assigned, rather than randomized, to treatment because researchers already know that chemotherapy is not beneficial or is very unlikely to be beneficial for those who have a low Recurrence Score, and is very likely to be beneficial for those who have a high Recurrence Score.

9. What treatments will be used in the trial?

   All treatments used in this trial, including chemotherapy and hormonal therapy, are commercially available and are not considered experimental. The choice of exactly what type of chemotherapy and hormonal therapy will be used will be left to the discretion of the treating physician.

   Hormonal therapies in the trial are assigned based on menopausal status and include tamoxifen and the aromatase inhibitors anastrozole, letrozole and exemestane. Women on the chemotherapy arm of the trial will receive one of several standard combination chemotherapy regimens considered to be the best available standard care today.

10. What are some of the side effects caused by these medications?

    The most likely side effects of chemotherapy include nausea, vomiting, hair loss, fatigue, anemia, and infection. Some of these side effects can be relieved with medications. Side effects of hormonal therapy include hot flashes, osteoporosis, and vaginal discharge and/or dryness. If a woman has not entered menopause, some of the treatments may cause premature menopause or sterility.

11. Will insurance cover the cost of this trial?

    The Oncotype DX test that is being used in this trial is an established diagnostic test in the United States that was recently approved for coverage by Medicare. The test is commercially available, and the Genomic Health laboratory is certified by federal and state agencies in the United States to perform this test.

    The cost of the Oncotype DX test will be billed to the patient's insurance company. The treatments and other routine tests done as part of this trial are considered standard care, and also will be billed to the patient's insurance company. Medicare and commercial insurance companies usually cover the routine costs of care required in clinical trials. Coverage may not, however, be the same from plan to plan. Should participants be unsuccessful in receiving reimbursement for all or some of the cost of the Oncotype DX test after appealing to their insurance carrier, they will have no financial responsibility for the Oncotype DX test.

12. What treatment would normally be given to someone who did not participate in the trial?

    All patients with breast cancer require surgery, or surgery plus radiation therapy. Patients with estrogen receptor- and/or progesterone receptor-positive early-stage breast cancer receive hormonal therapy given for a period of at least five years. There are several types of hormonal therapy, but the treatment usually consists of pills taken once or twice daily. In addition, patients participating in this trial meet standard clinical criteria for administering chemotherapy, which would generally be considered part of standard treatment.

13. Who is conducting the trial?

    This trial is being conducted by the North American Breast Cancer Intergroup, which includes all of the major National Cancer Institute (NCI)-funded cooperative groups in the United States and Canada. The trial will be coordinated by the Eastern Cooperative Oncology Group (ECOG), which is one of the major groups that are participating in the trial. Other participating groups include the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Cancer and Acute Leukemia Group B (CALGB), the Southwest Oncology Group (SWOG), the North Central Cancer Treatment Group (NCCTG), the National Cancer Institute of Canada (NCIC), and the American College of Surgeons Oncology Group (ACOSOG). These groups include networks of researchers, physicians, and health care professionals at public and private institutions across the United States and Canada. They conduct clinical trials on all types of adult cancers. The groups receive funding from the NCI and other sources. The goal of these groups is to control, effectively treat, and ultimately cure cancer. These groups provide research results to individuals and the medical community through scientific publications and professional meetings.

To view Spanish versions of the TAILORx press release and Q&A, please go to http://www.cancer.gov/newscenter/pressreleases/TAILORxReleaseSpanish.

For a complete set of links and other information related to TAILORx, go to http://www.cancer.gov/clinicaltrials/digestpage/TAILORx.

To view a press release on TAILORx, go to http://www.cancer.gov/newscenter/pressreleases/TAILORxRelease.

For more information about the NCI-sponsored clinical trials groups, please visit:

http://www.ecog.org
http://ncctg.mayo.edu
http://www.swog.org
http://www.calgb.org
http://www.acosog.org
http://www.nsabp.pitt.edu

National Cancer Institute of Canada Clinical Trials Group: http://www.ctg.queensu.ca

# # #

• National Cancer Institute Fact Sheet 1.4, NCI's Clinical Trials Cooperative Group Program ¹
  (http://www.cancer.gov/cancertopics/factsheet/NCI/clinical-trials-cooperative-group)
• National Cancer Institute Fact Sheet 7.20, Adjuvant and Neoadjuvant Therapy for Breast Cancer ²
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/adjuvant-breast)
• Breast Cancer Home Page ³
  (http://www.cancer.gov/cancertopics/types/breast)
• Taking Part in Cancer Treatment Research Studies ⁴
  (http://www.cancer.gov/clinicaltrials/Taking-Part-in-Cancer-Treatment-Research-Studies)

How can we help?

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• Call NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237)
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Glossary Terms

A rapidly progressing cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of white blood cells to be produced and enter the blood stream.

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.

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 condition in which the number of red blood cells is below normal.

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 laboratory test to find and measure the amount of a specific substance.

The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Treatment with drugs that kill cancer cells.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Treatment using more than one anticancer drug.

To heal or restore health; a treatment to restore health.

In medicine, a fluid that comes out of the body. Discharge can be normal or a sign of disease. Discharge also means release of a patient from care.

The length of time after treatment for a specific disease during which a patient survives with no sign of the disease. Disease-free survival may be used in a clinical study or trial to help measure how well a new treatment works. Also called DFS and disease-free survival time.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

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.

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

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.

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.

A condition marked by extreme tiredness and inability to function due lack of energy. Fatigue may be acute or chronic.

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.

A description of a tumor based on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer.

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.

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.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

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.

A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.

A U.S. federal health insurance program for people aged 65 years or older and people with certain disabilities. Medicare pays for hospital stays, medical services, and some prescription drugs but people who receive Medicare must pay part of their healthcare costs.

The time of life when a woman’s ovaries stop producing hormones and menstrual periods stop. Natural menopause usually occurs around age 50. A woman is said to be in menopause when she hasn’t had a period for 12 months in a row. Symptoms of menopause include hot flashes, mood swings, night sweats, vaginal dryness, trouble concentrating, and infertility.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.

NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. It conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://www.cancer.gov. Also called National Cancer Institute.

The study of cancer.

A condition that is marked by a decrease in bone mass and density, causing bones to become fragile.

Blood circulating throughout the body.

Medical doctor.

The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma.

A condition in which the ovaries stop working and menstrual periods stop before age 40. Natural menopause usually occurs around age 50. A woman is said to be in menopause when she hasn’t had a period for 12 months in a row. Symptoms of menopause include hot flashes, mood swings, night sweats, vaginal dryness, trouble concentrating, and infertility. Premature menopause can be caused by some cancer treatments, surgery to remove the ovaries, and certain diseases or genetic conditions. Also called early menopause, premature ovarian failure, and primary ovarian insufficiency.

The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins.

Describes cells that have a protein to which the hormone progesterone will bind. Cancer cells that are progesterone receptor positive need progesterone to grow and will usually stop growing when treated with hormones that block progesterone from binding. Also called PR+.

Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).

When referring to an experiment or clinical trial, the process by which animal or human subjects are assigned by chance to separate groups that compare different treatments or other interventions. Randomization gives each participant an equal chance of being assigned to any of the groups.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

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

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.

A group or layer of cells that work together to perform a specific function.

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.

Having to do with the vagina (the birth canal).

To eject some or all of the contents of the stomach through the mouth.