A Study to Determine the Clinical Significance of Molecular Detection of Breast Cancer in the Blood of Stage IV Breast Cancer Patients

This study is designed to determine whether molecular detection of breast cancer cells in the peripheral blood of Stage IV breast cancer patients is a clinically relevant predictor of progression-free and overall survival. Stage IV breast cancer patients who have measurable breast cancer metastases and are initiating a regimen of systemic therapy are eligible for enrollment. Multi-marker real-time RT-PCR analysis will be performed on peripheral blood specimens from 92 breast cancer patients and 120 healthy volunteers. Peripheral blood specimens from breast cancer patients will be obtained at the time of study entry (prior to initiation of systemic therapy) and at serial time points during follow-up. Subjects will be followed longitudinally until death, although the study has been powered so that the primary objective can be addressed after 12 months of follow-up. Healthy volunteers will be asked to provide a blood sample at time of enrollment but will not be followed.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

Inclusion Criteria - Stage IV breast cancer patients

1. Patient age must be \> 21 years.
2. Patient must have a tissue diagnosis of invasive breast cancer.
3. Patient must have documented evidence of metastatic disease.
4. Patient must have measurable lesions.
5. Patients must be initiating systemic therapy. Patients receiving hormonal therapy, and/or chemotherapy alone or in combination with other therapies are eligible.
6. Patient must have an ECOG performance status of 0, 1, or 2.
7. Patient must be available for follow-up.
8. Patient or their authorized legally acceptable representative must consent to be in the study and must have signed and dated an approved consent form which conforms to federal and institutional guidelines.
9. The patient with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patients have been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).

Inclusion Criteria - Healthy volunteers

A volunteer will be eligible for inclusion in this study only if ALL of the following criteria apply:

1. Volunteer age must be \> 21 years.
2. Volunteer or their authorized legally acceptable representative must consent to be in the study and must have signed and dated an approved consent form which conforms to federal and institutional guidelines.
3. Patients with benign breast disease are eligible for enrollment.
4. The volunteer with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided both of the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patient has been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).

Exclusion Criteria:

Exclusion Criteria - Stage IV breast cancer patients

A patient will be ineligible for inclusion in this study if ANY of the following criteria apply:

1. No documented metastatic disease.
2. No measurable lesions.
3. Bone only and/or brain metastasis.
4. Patient is not initiating a new regimen of systemic therapy.

• BACKGROUNDValagussa P, Bonadonna G, Veronesi U. Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients. Cancer. 1978 Mar;41(3):1170-8. doi: 10.1002/1097-0142(197803)41:33.0.co;2-i. PMID 638961
• BACKGROUNDGhossein RA, Carusone L, Bhattacharya S. Review: polymerase chain reaction detection of micrometastases and circulating tumor cells: application to melanoma, prostate, and thyroid carcinomas. Diagn Mol Pathol. 1999 Dec;8(4):165-75. doi: 10.1097/00019606-199912000-00001. PMID 10617272
• BACKGROUNDDiel IJ, Kaufmann M, Goerner R, Costa SD, Kaul S, Bastert G. Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis. J Clin Oncol. 1992 Oct;10(10):1534-9. doi: 10.1200/JCO.1992.10.10.1534. PMID 1403032
• BACKGROUNDAllard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004 Oct 15;10(20):6897-904. doi: 10.1158/1078-0432.CCR-04-0378. PMID 15501967
• BACKGROUNDCristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004 Aug 19;351(8):781-91. doi: 10.1056/NEJMoa040766. PMID 15317891
• BACKGROUNDBaker MK, Mikhitarian K, Osta W, Callahan K, Hoda R, Brescia F, Kneuper-Hall R, Mitas M, Cole DJ, Gillanders WE. Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology. Clin Cancer Res. 2003 Oct 15;9(13):4865-71. PMID 14581359