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PubMed2003

[Hormone therapy, chemotherapy and immunotherapy in breast carcinoma. The best strategy for your patient].

Modern treatment of cancer of the breast is based on established prognostic factors (patient age, receptor status, tumor size, lymph node involvement, tumor grading), and thus takes the patient's individual risk profile into account. In addition to the antiestrogen, tamoxifen, new hormonal preparations, such as the aromatase inhibitors, hold out promise of improved results from adjuvant treatment in elderly women. In premenopausal women, additional hormone blockade by means of GnRH analogs is of advantage. Neoadjuvant (preoperative) chemotherapy protocols will enable rapid evaluation of new therapeutic options. When metastases have developed, treatment with hormonal drugs is indicated in the case of slowly progressing disease (low risk), while clinically progressive metastasization (high risk) requires cytostatic chemotherapy. Here, studies involving more recent substances with improved tolerability, and tumor-specific antibodies, confirm an improvement in the prognosis. The concentration of drug treatment in interdisciplinary centers is a necessary element of quality assurance and therapeutic optimization.

Adult↗
PubMedDate not supplied

Matrix metalloproteinase-9 (MMP-9) immunoreactive protein has modest prognostic value in locally advanced breast carcinoma patients treated with an adjuvant antiestrogen therapy.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved with tumour invasion and metastasis. Controversial data exists concerning the prognostic value of MMP-9 in breast carcinoma. We examined, here, whether the MMP-9 immunoreactive protein would correlate with--the prognosis in breast carcinoma treated with hormonal adjuvant therapy. MATERIALS AND METHODS: The MMP-9 status was determined immunohistochemically from primary tumour specimens in 168 postmenopausal breast cancer patients with a locally advanced (N+) disease treated with antiestrogen for three years after the primary therapy. RESULTS: A positive immunostaining for MMP-9 was found in 61.3% of 168 primary tumours without any significant correlation to clinical stage, histology or hormone receptor status. MMP-9 immunoreactivity did not correlate with the survival when the entire study population was included in the analysis. There was, however, a compromised disease-free survival in a subgroup of patients presenting with an estrogen receptor-negative and MMP-9-positive tumour. The 5-year disease-free survival was only 37% in those patients, when it was 63% in the patients with a tumour negative for both estrogen receptor and MMP-9. CONCLUSION: We suggest that the prognostic value of MMP-9 immunoreactivity in the primary tumour is not generally strong in breast carcinoma, but it might correlate with the clinical benefit of an antiestrogen therapy, since MMP-9 positivity seemed to correlate with early recurrence in patients with an estrogen receptor-negative primary tumour.

Aged↗
PubMed1985

The oestrogen antagonists, tamoxifen and FC-1157a, display oestrogen like effects on human lymphocyte functions in vitro.

We studied the in vitro effects of two anti-oestrogens (tamoxifen and FC-1157a) on human lymphocyte functions in pokeweed mitogen (PWM) stimulated cultures. Addition of 1-100 nmol/l of tamoxifen or FC-1157a to PWM cultures significantly increased the number of immunoglobulin secreting cells. This concentration of tamoxifen did not affect the proliferative response. Further experiments with fractionated lymphocyte subpopulations showed that the anti-oestrogens displayed their enhancing effect by inhibiting the suppressive function of T8+ cells. The anti-oestrogens had no significant effect on the T-independent activation of B cells with Epstein-Barr virus. We conclude that the anti-oestrogens display an effect on the functions of human lymphocytes similar to that previously reported for oestradiol (Paavonen, Andersson & Adlercreutz, 1981).

Antibody-Producing Cells↗
PubMed1998

Antiestrogen therapy: uncertainties and risk assessment.

Tamoxifen is by far the most clinically tested antiestrogenic drug currently used as adjuvant therapy for breast cancer and it continues to provide considerable benefit in this setting. The balance from clinical trials indicates a strong association between the use of tamoxifen and an increase in uterine tumors (three to sixfold). In rats, tamoxifen is a mutagenic, genotoxic hepatocarcinogen. These actions are not related to its estrogen antagonist activity but have been shown to be as a result of metabolic activation of this drug by cytochrome P450 enzymes, resulting in irreversible binding to cellular DNA. The mechanism of endometrial cancer associated with tamoxifen treatment is unclear, although there are two plausible hypotheses: (1), tamoxifen causes damage and mutation to DNA in uterine cells or (2), it promotes the development of endometrial tumors through its estrogen agonist activity. The evidence for a genotoxic effect of tamoxifen in the uterus is highly contentious and, on balance, we have concluded that it is more likely that the estrogenic effects of tamoxifen promote tumor development.

Animals↗