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  • 1
    Electronic Resource
    Electronic Resource
    Changes in hormone receptors and proliferation markers in tamoxifen treated breast cancer patients and the relationship with response (1998)
    Springer
    Breast cancer research and treatment 48 (1998), S. 11-20 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; tamoxifen ; estrogen receptor ; progesterone receptor ; Ki67 ; S-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim: To determine the effects of tamoxifen on the levels of hormone receptors and proliferation markers in the early phase of treatment and the relationship of the changes with tumor response in patients with primary breast cancer. Methods: Twenty-one women with primary, operable breast carcinomas were treated with tamoxifen 20 mg daily. Fine needle aspiration (FNA) was used to obtain samples prior to the start and at 14 days and 8-weeks post-treatment. From these samples estrogen receptor (ER), progesterone receptor (PgR), and Ki67 levels were determined using immunocytochemistry and ploidy and S-phase fraction (SPF) using flow cytometry. Tumor response was measured clinically according to UICC criteria. Results: There were 12 responders (2 CR, 10 PR) and 9 non-responders (2 NC, 7 PD). Responders were more likely to be ER + (p=0.002), PgR + (p=0.006), and low SPF (p=0.06). At 14 days post-tamoxifen, the median decrease in Ki67 (% cells staining) for responders was − 4.8 and for non-responders − 0.15 (p=0.005). This decrease was seen predominantly in ER + tumours. The difference in SPF was not significant. A decrease in ER was seen in 3/15 patients all of whom were responders. A rise in PgR was seen in 7/17 patients and all but one were responders. Similar changes for ER and PgR were seen at 8-weeks post-tamoxifen, although the reductions in Ki67 and SPF at that time point were not related to response. Conclusion: We have observed a decrease in Ki67 and ER and a rise in PgR after 14 days of treatment with tamoxifen that was related to subsequent response. This is the first study in which an early decrease in a proliferation marker has been shown to relate to subsequent clinical response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005973529921
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  • 2
    Electronic Resource
    Electronic Resource
    Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: A pilot study (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 51-59 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; neoadjuvant therapy ; FNA ; estrogen receptor ; progesterone receptor ; p53 ; Bcl‐2 ; Ki67 ; SPF ; ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim: To quantify the changes in biological molecular markers during primary medical treatment in patients with operable breast cancer and to assess their possible relationship with response to treatment. Methods: The treatment group consisted of 31 patients with operable breast carcinomas, median age 57 years (range 41–67), treated with four 3‐weekly cycles of chemotherapy with Mitoxantrone, methotrexate (± mitomycin C), and tamoxifen before surgery. Fine needle aspiration (FNA) was used to obtain samples from patients prior to and at 10 or 21 days post‐treatment. The following molecular markers were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Bcl‐2, and Ki67 measured by immunocytochemistry, and ploidy and S‐phase fraction (SPF) by flow cytometry. To evaluate the reproducibility of the technique, repeat FNA was performed in a separate non‐treatment control group of 20 patients and the same molecular markers assessed, two weeks after the first sample with no intervening treatment. Results: The non‐treatment control group showed a high reproducibility for the measurement of molecular markers from repeat FNA. In the treatment group there was a non‐significant reduction in SPF and a significant reduction (p = 0.005) in Ki67. Patients who responded to neoadjuvant therapy were more likely to have a reduction in these two markers than those who failed to respond. Similarly, a reduction in ER scores was observed between the first and second samples (p = 0.04). For PgR, the change between the first and second samples was not significant although there was a significant difference between responders and non‐responders (p = 0.03). All nine patients with an increase in PgR were responders. No significant changes in p53 or Bcl‐2 were observed during treatment. Conclusion: Molecular markers can be adequately measured from FNA samples prior to and during neoadjuvant therapy. Changes in cellular proliferation and hormone receptors have been shown that may be related to tumour response. These relationships should be assessed in a larger cohort of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006179511178
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  • 3
    Electronic Resource
    Electronic Resource
    WAF1/CIP1 protein expression in human breast tumors (1997)
    Springer
    Breast cancer research and treatment 43 (1997), S. 99-103 
    Details
    ISSN: 1573-7217
    Keywords: WAF1/CIP1 protein ; p53 protein ; breast cancer ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract WAF1/CIP1 is a cyclin-dependent kinase inhibitor which isdirectly induced by p53 and negatively controls cellproliferation. To test the hypothesis that increased levelsof WAF1 would be associated with a lowerS-phase fraction and better prognosis, WAF1 protein wasassessed by immunohistochemistry (IHC) in 115 node-negative humanbreast tumors, and results were correlated with establishedprognostic factors and clinical outcome. Nuclear staining wasobserved in malignant cells in 43% of tumors.In most (90%) of the positive tumors, theproportion of cells staining for WAF1 was low(〈 10%). WAF1 was not detected in thecytoplasm, or in non-malignant epithelium. Contrary to expectations,the accumulation of p53 protein, a surrogate markerof p53 inactivation, was weakly but positively associatedwith WAF1 expression (p=0.05). Surprisingly, therewas no significant correlation with S-phase fraction, ERor PgR status, tumor size, age, ploidy, nucleargrade, or survival. Conclusion: WAF1 expression is found inthe nuclei of a small fraction of cellsin human breast tumors. WAF1 status is notsignificantly associated with cell proliferation, other established prognosticfactors, or clinical outcome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005752829260
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Cytological evaluation of biological prognostic markers from primary breast carcinomas (1997)
    Springer
    Breast cancer research and treatment 44 (1997), S. 65-74 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; fine needle aspiration ; immunocytochemistry ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was undertaken to evaluate our abilityto detect multiple molecular markers of prognosis andresponse to treatment in fine needle aspirates (FNA)from patients with primary breast carcinomas. 147 patientswith operable primary breast carcinomas who had beenrecruited to a randomized trial of primary medicaltherapy (PMT) versus adjuvant chemoendocrine therapy were analysed.FNAs were taken prior to therapy and fromthis multiple slides were produced using cytospin cytocentrifugationand stored at − 80 °C for subsequentimmunocytochemical analysis (ICA). ICA was performed for oestrogenreceptor (ER), progesterone receptor (PgR), p53, Ki67, andBcl-2. Part of the aspirate was snap frozenand used for flow cytometric analysis of ploidyand S-phase fraction (SPF). In a subgroup of50 patients who had surgery prior to systemictherapy, as well as FNAs, sections were alsotaken from paraffin-embedded blocks and stained by ICAfor ER, PgR and p53 for validation. Inthese patients ER was additionally measured by enzymeimmunoassay (EIA) from frozen tissue taken at surgery.ER, PgR, p53, Bcl-2, and Ki67 were successfullydetected by ICA while ploidy and SPF weresuccessfully measured by flow cytometry from FNA material.The percentage positive values obtained were reasonable andas follows: 74% for ER, 70% for PgR,36% for p53, 80% for Bcl-2. 68% oftumours were aneuploid and 32% diploid. Significant relationshipsbetween these measurements were observed in accordance withexpectations. The concordance for ER, PgR, and p53from FNA when compared to ICA of matchinghistological sections was 91.5%, 75.5%, and 75% respectively.For ER the concordance between measurement by ICAof cytological and histological samples and by EIAof frozen tissue was 82.5% and 84% respectively.These results indicate that multiple molecular markers canbe adequately tested on cytological preparations from primarybreast tumours. These markers can be used todetermine prognosis and predict response to PMT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005717924761
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    Paper (German National Licenses)
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