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  • 1
    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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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Variation in endometrial thickening in women with amenorrhea on tamoxifen (1998)
    Springer
    Breast cancer research and treatment 48 (1998), S. 81-85 
    Details
    ISSN: 1573-7217
    Keywords: tamoxifen ; endometrial thickening ; plasma estradiol ; amenorrhea ; endometrial cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tamoxifen is reported to increase the risk of endometrial cancers mostly in postmenopausal women. In the Royal Marsden chemoprevention programme, we noted that premenopausal women at the start of tamoxifen/placebo who developed amenorrhea may be at special risk of endometrial cancer. The aim of this report was to investigate recently amenorrheic women by measuring plasma estradiol (E2), follicular stimulating hormone (FSH), and endometrial thickness (ET) by transvaginal ultrasound (TVUS). ET readings and E2 levels were available in the same proportion of women on tamoxifen or placebo. Women on placebo developed amenorrhea with upper limit of E2 readings of 450 pmol/L. In both postmenopausal women and recently amenorrheic women with low E2 (≤ 450 pmol/L), tamoxifen significantly increased endometrial thickening (p 〈 0.0001 and 〈 0.005 respectively). Conversely, tamoxifen did not result in endometrial thickening in women with high E2 (〉 450 pmol/L), with a trend to lower ET readings (p=0.07). Finally, all five women who developed endometrial cancer were premenopausal at the start of tamoxifen/placebo. Two of these five women were asymptomatic with increased ET readings (17 mm and 17 mm) and low E2 levels (32 and 51 pmol/L). These results indicate that women who develop amenorrhea on tamoxifen may be at special risk of endometrial cancer. Tamoxifen causes endometrial thickening in amenorrheic women with low E2 but has an opposite antiestrogenic effect in women with high E2. We recommend that women who develop amenorrhea on tamoxifen especially in the presence of endometrial thickening, low E2 levels, and/or gynaecological symptoms warrant further investigations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005999008736
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    Paper (German National Licenses)
    Fulltext
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