This study, sponsored by the American College of Surgeons, is enrolling women with clinical T1 or T2 N0 M0 breast cancer who will be undergoing breast-conserving therapy (BCT), bilateral iliac bone marrow aspirations and sentinel lymph node dissection (SLND).

THE OBJECTIVES ARE:

1. To estimate the prevalence and to evaluate the prognostic significance of sentinel node micrometastases detected by immunohistochemistry (IHC).
2. To estimate the prevalence and to evaluate the prognostic significance of bone marrow micrometastases detected by immunocytochemistry (ICC).
3. To evaluate the hazard rate for regional recurrence in women whose sentinel nodes are negative by hematoxylin and eosin (H&E) staining.
4. To provide a mechanism for identifying women whose sentinel nodes contain metastases detected by H&E, so that these women can be considered as candidates for Study Z0011 (see below).
   

The purpose of this study is to evaluate the accuracy and long-term outcome of sentinel node biopsy in a large group of women across the United States. The sentinel lymph node(s) and bone marrow aspirate will be sent to an independent laboratory for immunohistochemistry studies. The results of these studies will not be released to physicians or patients since the importance of these results is uncertain. All participants will be monitored for cancer recurrence.

For further information please contact Simbi Acharya at 312.926.9930
or s-acharya@northwestern.edu

Women with clinical stage T1 or T2 N0 M0 breast cancer will undergo sentinel lymph node dissection with breast-conserving therapy. Women who are found to have a sentinel node containing metastatic breast cancer, as documented on frozen section, touch prep or permanent section evaluation by hematoxylin and eosin (H&E) staining, will be randomized to one of two arms:

• Arm 1: Completion axillary lymph node dissection (ALND).
• Arm 2: No immediate additional axillary surgery or axillary-specific radiation.

Women in both arms will have whole-breast radiation and systemic adjuvant therapy. Women who participate in this study may also be registered to study Z0010, but this is not required for participation in Z0011.

THE PRIMARY OBJECTIVES ARE:

Long-term: To assess whether overall survival for patients randomized to Arm 2 (no ALND) is essentially equivalent to (or better than) that for patients assigned to Arm 1 (completion ALND).
Short-term: To quantify and compare the surgical morbidities associated with SLND plus ALND versus SLND alone.

This study is trying to determine if axillary node removal contributes to the cure of breast cancer. Participants will be followed to determine the long-term effects of sentinel lymph node dissection alone, on patients with positive sentinel nodes, and whether patient outcomes differ with standard axillary dissection.

For further information please contact Simbi Acharya at 312.926.9930
or s-acharya@northwestern.edu

Funded by Avon, this one-year study uses the recently FDA-approved digital mammography to determine whether breast density changes with the menstual cycle.

PRIMARY OBJECTIVES:

1. To determine if breast density, as measured by digital mammography, fluctuates significantly during the menstrual cycle.
2. To determine if breast density, as determined by a trained mammographer, fluctuates significantly during the menstrual cycle.

SECONDARY OBJECTIVE:

1. To determine if fluctuations in breast density vary with patient characteristics such as body mass index or level of breast cancer risk.

THE BASIC ELIGIBILITY CRITERIA ARE:

• Women must be between ages 30-50 and be premenopausal
• Women must be undergoing annual mammography
• Women must have a clinical breast exam that is not suspicious for malignancy
• Women must not have been diagnosed with breast cancer
• Women cannot be taking hormones such as oral contraceptives and hormone replacement therapy or tamoxifen
• Women cannot be pregnant nor planning pregnancy during the study
  

This study will provide important information on the relationship of breast density to the menstrual cycle, which has clinical implications for the scheduling of mammography in the population of premenopausal women undergoing diagnostic or screening breast imaging.

For further information please contact Simbi Acharya at 312.926.9930
or s-acharya@northwestern.edu

This five-year study funded by Avon is evaluating the effects of tamoxifen on breast density using the recently FDA-approved digital mammography technique. Effects of tamoxifen will be closely monitored to see if they are related to hormone fluctuations.

PRIMARY OBJECTIVES:

1. To determine if breast density, as measured by digital mammography, decreases in premenopausal women taking tamoxifen for breast cancer treatment or risk reduction.
2. To determine if breast density, as determined by a trained mammographer, decreases in premenopausal women taking tamoxifen for breast cancer treatment or risk reduction.
3. To determine if tamoxifen-induced symptoms in estrogen target tissues correlate with change in salivary hormones.

SECONDARY OBJECTIVES:

1. To determine the effect of tamoxifen on salivary steroids in regularly cycling and amenorrheic women on tamoxifen.
2. To determine the relationship between changes in breast density and tamoxifen-induced alterations in sex steroid levels as measured in the saliva.

THE BASIC ELIGIBILITY CRITERIA ARE:

• Women must be between ages 20-45 and premenopausal
• Women must be initiating tamoxifen as the sole systemic treatment for carcinoma or breast cancer risk reduction
• Women cannot have bilateral breast cancer
• Women must be undergoing annual mammography
• Women cannot have taken tamoxifen in the past for more than one month
• Women cannot be pregnant or planning pregnancy during the study

This study will provide important information about the effect of tamoxifen therapy on breast density in premenopausal women and correlate changes in breast density with changes in sex steroid levels in the saliva.

For further information please contact Simbi Acharya at 312.926.9930
or s-acharya@northwestern.edu

Partially funded by ProDuct Health, Inc., the purpose of this study is to evaluate whether findings from ductal lavage are accurate compared to biopsy and to establish the best way to combine ductal lavage and biopsy techniques. Ductal lavage is a new technique to collect breast ductal cells. Prior to undergoing a recommended breast biopsy for microcalcifications, the participant will undergo ductal lavage and ductography.

THE BASIC ELIGIBILITY CRITERIA ARE:

• Women must be over the age of 18 years
• Recommendation to have a breast biopsy to evaluate mammographically detected microcalcifications
  

ADDITIONAL CRITERIA INCLUDE:

• Not currently pregnant or within the past 12 months
• Has not lactated within the prior 12 months
• No chemotherapy within the past six months
• Never taken tamoxifen or raloxifene
• No active infection in the breast to be studied
• No known allergy to lidocaine, prilocaine, bupivacaine or iodine
  

For further information please contact Carol Baird at 312.926.0890
or cbaird@nmff.org

The increased use of screening mammography has resulted in a dramatic increase in the detection rate of ductal carcinoma in situ (DCIS). Unlike the more common invasive carcinoma, which has the ability to spread to other parts of the body, DCIS is a problem that is localized to the breast and has a very small risk of cancer death. Little is known about the natural history of DCIS because it has traditionally been treated with mastectomy, but it is believed that if left untreated it will progress to invasive carcinoma. However, the time to progression may be extremely prolonged. This has led to a bewildering variety of treatments for DCIS including mastectomy, lumpectomy and radiation, or lumpectomy alone. Tamoxifen may be added to any of these treatments.

Since the survival differences among treatments are very small, other factors such as the importance to a woman of retaining her breast, her attitude toward further surgery and the importance to her of very small differences in outcome should be major factors in the decision-making process. However, these things are often difficult for a physician to assess or a patient to articulate in the emotionally charged atmosphere surrounding a new cancer diagnosis.

We have used the technique of decision analysis to develop a model that predicts which treatment a patient should prefer based on her answer to a series of questions. Some of these questions are directly related to DCIS treatment issues, while others address general attitudes toward risk. For the initial testing of this model, we propose to study 90 women who have already been treated for DCIS.

WE WILL DETERMINE:

1. If the model predicts the treatment they actually chose.
2. Their perception of and satisfaction with the involvement in the treatment decision-making process.
3. Whether the model would be useful to women making a decision about DCIS treatment.
   

Results obtained from this study will allow us to refine the model prior to testing its use in women with newly diagnosed DCIS and will provide important information about patient priorities in the treatment of this condition.

For further information please contact Simbi Acharya at 312.926.9930
or s-acharya@northwestern.edu

Chemotherapy results in premature menopause for the majority of young women who receive it. Estrogen replacement is not routinely given to women with breast cancer due to concerns that it will stimulate tumor growth. Women made prematurely menopausal are at increased risk for the development of cardiovascular disease and osteoporosis. Tamoxifen has been shown to protect menopausal women with breast cancer from these conditions, but its effects in premenopausal women are poorly studied. This study will compare blood cholesterol levels and bone density in premenopausal women receiving chemotherapy alone and those receiving chemotherapy plus tamoxifen over a period of two years.

PATIENTS ARE ELIGIBLE FOR THIS STUDY IF THEY ARE:

• Newly diagnosed breast cancer patients
• Premenopausal
• Never had chemotherapy before
• Have stage I or II breast cancer
  

For further information please contact Simbi Acharya at 312.926.9930
or s-acharya@northwestern.edu

The Study of Tamoxifen and Raloxifene, or STAR, the largest breast cancer prevention study in history, is recruiting volunteers at more than 400 centers across the United States, Canada and Puerto Rico. The trial will include 22,000 postmenopausal women at increased risk for breast cancer to determine whether the osteoporosis prevention drug raloxifene (Evista®) isas effective in reducing the incidence of breast cancer as tamoxifen (Nolvadex®) has proven to be. STAR is a study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) and is supported by the National Cancer Institute (NCI).

Tamoxifen was shown to reduce the chance of developing breast cancer by about 50% in the Breast Cancer Prevention Trial (BCPT), a study of over 13,000 pre- and postmenopausal women at high risk of breast cancer. Participants taking tamoxifen also had fewer fractures of the wrist, hip and spine. The FDA approved tamoxifen to reduce the incidence of breast cancer in women at increased risk of the disease in October 1998. Raloxifene was approved in December 1997 to prevent osteoporosis and has been in clinical trials for about seven years. Raloxifene has shown a breast cancer risk reduction similar to that of tamoxifen but has not yet been tested in high-risk women. Both drugs are known to increase the risk of blood clots in large veins and the lungs. Tamoxifen increases risk of endometrial cancer; to date, raloxifene has not demonstrated this effect. An important part of STAR will be to compare the long-term safety of both drugs.

Women who participate in STAR must be at least 35 years old, postmenopausal and have an increased risk of breast cancer as determined by their age, family history and other risk factors. Potential volunteers will receive a free breast cancer risk assessment. If they are determined to be at high risk and decide to participate in the study, patients will be randomly assigned to receive either 20 mg tamoxifen or 60 mg raloxifene daily for five years. All participants will have regular follow-up examinations, blood tests, mammograms and gynecologic examinations. The study drug is provided free of charge.

ADDITIONAL CRITERIA INCLUDE:

• Not currently pregnant or within the past 12 months
• Has not lactated within the prior 12 months
• No chemotherapy within the past six months
• Never taken tamoxifen or raloxifene
• No active infection in the breast to be studied
• No known allergy to lidocaine, prilocaine, bupivacaine or iodine
  

For further information please contact Jennifer Clauson at 312.926.3407
or j-clauson@northwestern.edu

Funded by the American Cancer Society, this six-month study will measure whether consuming a soy product that contains phytoestrogens will result in slower, more controlled growth of cells in breast tissue.

PATIENTS MUST MEET THE FOLLOWING CRITERIA TO BE ELIGIBLE:

• A woman with a personal history of breast cancer, a high-risk breast lump or a close relative (mother, sister or daughter) with breast cancer
• 30-60 years old
• Not pregnant
• Not taking oral contraceptives or hormone drugs
• Not allergic to soy

PARTICIPANTS WILL:

• Attend three clinical visits
• Report food intake
• Provide blood, breast fluid (via suction) and breast cells (obtained by nipple duct lavage)
• Consume a soy supplement or placebo
  

For further information, please contact Kim Thedford at 312.503.0026
or kjuhl@northwestern.edu.

Angiostatin and endostatin are two compounds which appear to act as potent antiangiogenic agents. Though these compounds appear to have antiangiogenic activity in a number of preclinical cell line and animal model systems, it has been difficult to manufacture them. Angiostatin is a multidomain protein containing up to five kringle domains linked by cystein bridges. Ongoing studies suggest that different kringle domains are important in mediating the antiangiogenic activity of angiostatin. Dr Gerald Soff has shown that angiostatin can be generated in vivo. Plasmin contains five kringle domains. Proteolysis cleaves off a small portion of kringle 5 thus generating the active antiangiogenic angiostatin. Autoproteolysis was shown to be enhanced when free sulfhydryl donors are present. Specifically in cell-free systems, angiostatin was produced from human plasma after treatment with tissue plasminogen activator (tPA) to degrade plasminogen to plasmin in the presence of captopril.

This Phase I/II trial is being funded by the National Cancer Institute and is for patients with metastatic breast cancer. This protocol will begin the scientific process of investigating the clinical efficacy of these agents in breast cancer. More specifically, it will be used to determine the toxicity of tPA plus the free sulfhydryl donor captopril in patients with advanced breast cancer.

PRIMARY OBJECTIVE:

Assess the toxicity of combining captopril with continuous infusion tPA in patients with progressive, metastatic breast cancer. Measure the in vivo generation of angiostatin by Western analysis.

SECONDARY OBJECTIVE:

Assess the antitumor effect of combining captopril with continuous infusion tPA in patients with progressive, metastatic breast cancer.

ELIGIBILITY REQUIREMENTS FOR THIS STUDY INCLUDE BUT ARE NOT LIMITED TO:

• Progressive, metastatic breast cancer. Measurable disease is not required
• Patients must have received at least one systemic treatment for metastatic disease
• ECOG performance status of 0, 1 or 2
• Pretreatment granulocyte count of >=1500/mm3 and platelet count of >=100,000/mm3
• Adequate renal function as documented by a serum creatinine <=1.8 mg/dL
• Normal PT, aPTT and fibrinogen levels
• Adequate hepatic function as documented by a serum bilirubin <=1.5 mg/dL, regardless of whether patients have liver involvement secondary to tumor. Aspartate transaminase (SGOT) must be <=3x institutional upper limit of normal. Serum albumin must be normal
• >=4 weeks elapsed since completion of radiotherapy, chemotherapy, biologic or endocrine therapy. Measurable disease must be outside of a previously irradiated field
• No prior history of stroke, TIA or symptoms of cerebral ischemia
• Cannot currently be receiving anticoagulation therapy
  

This will be conducted as a dose-escalating trial of three dose levels with at least three patients treated at each level. Study treatment will be administered for five consecutive days. Only one treatment cycle will be allowed in this pilot trial.

For more information please contact Maggie Patton at 312.908.4048
or m-patton@northwestern.edu

Tarceva™ (erlotinib) is an experimental selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. The EGFR is a protein found on the surface of many tumor cells that may control tumor growth.

THE STUDY WILL EVALUATE IF TARCEVA IS EFFECTIVE AND SAFE IN TWO DIFFERENT SETS OF PATIENTS:

• Patients with disease progression on or after treatment with an anthracycline, a taxane and capecitabine
• Patients with disease progression on or after therapy with at least one chemotherapy regimen for locally advanced or metastatic disease
  
  All eligible patients will receive this oral (taken by mouth) experimental study drug.
  

INCLUSION CRITERIA INCLUDE BUT ARE NOT LIMITED TO:

• Histologically documented, incurable, locally advanced or metastatic breast cancer
• Disease progression on or after therapy with an anthracycline, a taxane and capecitabine, or with disease progression on or after therapy with at least one chemotherapy regimen for locally advanced or metastatic disease
• Measurable disease of ³2 cm (³1 cm on spiral CT scan)
• ECOG performance status of 0 to 2
  

EXCLUSION CRITERIA INCLUDE BUT ARE NOT LIMITED TO:

• Other primary malignancies within five years except for adequately treate carcinoma in situ of the cervix or basal or squamous cell skin cancer
• INR > 4.0 for patients receiving warfarin
• Symptomatic or untreated brain metastases
• Radiotherapy, immunotherapy, hormonal therapy or chemotherapy within 21 days prior to Day 0 (six weeks for nitrosoureas or mitomycin); prior therapy with an agent designed to target either the EGFR or EGFR-specific tyrosine kinase activity
  

Approximately 200 women will participate in this study at approximately 40 centers in the United States. Patients will remain on study until disease progression. Patients will be followed for survival every two months thereafter.

For more information please contact Maggie Patton at (312) 908-4048
or m-patton@northwestern.edu

The ubiquitin-proteasome pathway plays an essential role in the degradation of most short- and long-lived intracellular proteins in eukaryotic cells. At the heart of this degradative pathway is the 26S proteasome, an ATP-dependent, multicatalytic protease. Proteolytic degradation of damaged, oxidized or misfolded proteins is part of the “housekeeping” role for the 26S proteasome. In addition, the 26S proteasome also plays a vital role in degrading regulatory proteins that govern the cell cycle, transcription factor activation, apoptosis and cell trafficking. The ubiquitin-proteasome pathway also plays an important role in regulating cell cycle, neoplastic growth and metastasis.PS-341 is a potent and reversible inhibitor of the ubiquitin-proteasome pathway. The antineoplastic effects of PS-341 appear to result from several distinct biological activities and have been observed in a number of cellular assays. The results indicate that PS-341 can inhibit cell growth, leading ultimately to cytotoxicity by a mechanism involving apoptosis. Of interest is the ability of PS-341 to induce apoptosis even in cells that overexpress bcl2 and are resistant to other chemotherapeutics. PS-341 also inhibits the degradation of p53, stabilizes the CDK inhibitor p21 and inhibits the activation of NF-kB by a mechanism involving the stabilization of the inhibitor protein IkBa.

This is a phase II clinical trial in patients with metastatic breast cancer being supported by the NCI. Eligible patients are required to have received one prior chemotherapy ( + Herceptin) treatment for metastatic disease. Normal organ function is required to participate.

PRIMARY OBJECTIVE:

To determine the objective tumor response in patients receiving PS-341.

SECONDARY OBJECTIVES:

Estimation of the progression-free survival of patients receiving PS-341, evaluation of toxicities related to PS-341 and correlative laboratory studies to assess the activity of PS-341 in individual patients.

ELIGIBILITY REQUIREMENTS FOR THIS STUDY INCLUDE BUT ARE NOT LIMITED TO:

• Patients must have histologically confirmed adenocarcinoma of the breast that is metastatic. Measurable disease is required
• May have received prior hormonal therapy for metastatic disease
• One chemotherapy regimen (Herceptin) for metastatic disease is required. Patients relapsing while receiving or within six months of completing adjuvant chemotherapy will be considered to have failed one regimen for metastatic disease.
• Patients must have normal organ and bone marrow function
• Patients with known brain metastases are excluded
  

PS-341 will be administered twice weekly, intravenously, for two weeks followed by a one-week break (three-week cycle)

For more information please contact Maggie Patton at (312) 908-4048
or m-patton@northwestern.edu