Montana
06-23-2006, 05:39 PM
Did your doctor ever discussed KI-67 with you? Has anyone ever had their KI-67 tested 2 weeks after starting Arimidex? Sue
http://www.medpagetoday.com/2005MeetingCoverage/2005SABCSMeeting/tb/2306
"An increase in Ki67 of 2.7-fold -- analyzed at the two-week mark -- results in a doubling of the risk of relapse, Mitchell Dowsett, Ph.D., of London's Royal Marsden Hospital reported at the San Antonio Breast Cancer Symposium. Differences in levels of the molecule measured before the start of treatment were not predictive, he said.
The magnitude of the hazard ratio was greater than that for tumor size in a multivariate analysis of 56 patients enrolled in the IMPACT study, Dr. Dowsett said:
For Ki67, the hazard ratio for relapse was 2.01 (with a 95% confidence interval of 1.28 to 3.15) for every 2.7-fold increase in the level two weeks after starting Arimidex treatment.
For tumor size, the hazard ratio for relapse was 1.67 (with a 95% confidence interval of 1.35 to 2.6) for every centimeter increase in diameter.
Ki67 is an indicator of cell proliferation rate and is already used to define the aggressiveness of late-stage breast cancer."
COX 2 Ki76 p53 linked.
Reduction in omega six intake plus incresed omega three increased apoptosis related to Cox2 Ki76 and P53
Chemo reduced but interestingly is trial saying level of reduction is independent of type or severity of tumour grade or nodal status.
One for your oncs to answer I think.
RB
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16507397&dopt=Abstract
1: Cancer Lett. 2003 Apr 10;193(1):17-24. Related Articles, Links
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Erratum in:
* Cancer Lett. 2004 Mar 18;205(2):227.
Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors.
Cheng J, Ogawa K, Kuriki K, Yokoyama Y, Kamiya T, Seno K, Okuyama H, Wang J, Luo C, Fujii T, Ichikawa H, Shirai T, Tokudome S.
Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
To clarify preventive effects of n-3 polyunsaturated fatty acids (PUFAs) against colorectal carcinogenesis, we performed a dietary intervention in patients polypectomized for colorectal adenomas/tumors. For the former the following dietary advice was given: (1) decrease intake of fat from 30 to 20% of the total; (2) decrease consumption of n-6PUFAs containing foods, and increase intake of n-3 PUFAs for 2 years. For the comparison group only decreased intake of fat (30-20%) was recommended. Samples of normal sigmoid colon mucosa, obtained by colonoscopic check once a year during the intervention period, were used to investigate COX-2, cell proliferation (Ki67 expression), p53, Bcl-2 and Bax by immunostaining and determine the apoptosis index (AI) by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) in 21 and 20 patients in experimental and comparison groups, respectively, who completed the 2 years of the intervention. After 24 months, the AI and positive cells of Bax and the ratio of Bax/Bcl-2 in normal sigmoid colon mucosa for the experimental group was significantly increased, whereas this change was not found in comparison group. These observations demonstrated for the first time that increased intake of n-3 PUFAs promotes apoptosis of normal colon mucosa in human which is related to effect on Bax or the balance of Bax and Bcl-2.
PMID: 12691819 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16507397&dopt=Abstract
1: Biomed Pharmacother. 2005 Oct;59 Suppl 2:S298-301. Related Articles, Links
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Study of COX-2, Ki67, and p53 expression to predict effectiveness of 5-flurouracil, epirubicin and cyclophosphamide with celecoxib treatment in breast cancer patients.
Chow LW, Loo WT, Wai CC, Lui EL, Zhu L, Toi M.
Hung Chao Hong Integrated Center for Breast Diseases, Department of Surgery, The University of Hong Kong Medical Center, Queen Mary Hospital, Pokfulam, China. lwcchow@hkucc.hku.hk
BACKGROUND: Cyclooxygenase-2 (COX-2) affects cell proliferation, apoptosis, and metastasis of breast cancer, and may also be involved in tumor angiogenesis through vascular endothelial growth factor. Ki67 and p53 are common markers of proliferation and apoptosis in tumor cells. This study investigated the change in expression of COX-2, Ki67, and p53 in solid tumors after the administration of chemotherapeutic drugs. MATERIALS AND METHODS: Fifty patients were eligible to be treated with preoperative 5-fluorouracil, epirubicin, and cyclophosphamide, with celecoxib (FECC). Tumor tissue samples from 10 patients who, diagnosed with invasive ductal carcinoma, completed chemotherapy were examined immunohistochemically for COX-2, Ki67, and p53. RESULTS: From the 60% of patients who expressed COX-2 and 90% who expressed Ki67 and p53 before treatment, 90% of patients revealed a lower intensity staining for each marker after FECC treatment. However, changes in expression of the three markers did not significantly correlate with tumor size, grade, axillary lymph node status. Immunostained slides clearly showed that the diaminobenzidine intensity was markedly reduced after the three-cycle FECC treatment, which implied the combined regimens be effective to the cancer patients. CONCLUSIONS: This study demonstrates a novel relationship between COX-2, Ki67, and p53 expression of human breast invasive ductal carcinomas. This functional relationship provides support for a potential therapeutic role of COX-2 inhibitors in human breast cancer.
PMID: 16507397 [PubMed - indexed for MEDLINE]
Ki67 is a measurement of the proliferative rate of a tumor which is determined utilizing a sample of the tumor. It is not a blood test. This study involved neoadjuvant therapy, wherein they gave the treatment (arimidex in this case) BEFORE they did the definitive surgery. The Ki67 was determined on interval fine-needle biopsies DURING THE COURSE OF the treatment.
Neoadjuvant therapy has the advantage of giving information right away on whether the treatment is working or not. Adjuvant therapy given after definitive surgery and/or radiation leaves one guessing. Keep reading on---they are working on different tumor markers, different agents to use with PET and MRI to detect microscopic and small amounts of residual or recurrent disease.
Hope this helped!
Not BC but interesting re potential communality of mechanism.
And links to FAS.
HER2 links to FAS.
Herceptin blocks FAS as one of its mechanisms per reports.
RB
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15172638&query_hl=24&itool=pubmed_DocSum
1: Oral Oncol. 2004 Aug;40(7):688-96. Related Articles, Links
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Expression of fatty acid synthase, ErbB2 and Ki-67 in head and neck squamous cell carcinoma. A clinicopathological study.
Silva SD, Agostini M, Nishimoto IN, Coletta RD, Alves FA, Lopes MA, Kowalski LP, Graner E.
Department of Oral Diagnosis, School of Dentistry of Piracicaba, UNICAMP, Av. Limeira 901, CP52, Areao, 13414-018, Brazil.
Fatty acid synthase (FAS) is a multifunctional enzyme responsible for the synthesis of saturated fatty acids using acetyl-CoA and malonyl-CoA as substrates. Overexpression of FAS has been reported in several human malignancies and suggested as a potential prognostic factor. ErbB2 (Her-2/neu), a transmembrane tyrosine kinase member of the ErbB receptor family, is known to be overexpressed in a variety of tumors and was recently shown to regulate FAS production in breast epithelial cell lines. Herein we analyzed by immunohistochemistry the expression of FAS, ErbB2, and the proliferation marker Ki-67 in 62 head and neck squamous cell carcinoma (HNSCC) samples. Approximately 78% of the cases were positive for FAS or ErbB2 at the cell membrane and 70% of the tumors that showed a high expression of FAS were also strongly positive for ErbB2 (Fisher's exact test, p = 0.01). The immunolabeling for both FAS and ErbB2 was stronger in histologically well-differentiated lesions. Additionally, Ki-67 expression was significantly associated with a poor prognosis (log-rank test, p = 0.03). Taken together, the results presented here suggest that ErbB2 regulates FAS expression in HNSCC and point out Ki-67 as a useful prognostic marker for these tumors.
PMID: 15172638 [PubMed - indexed for MEDLINE]
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