Effects Of Tamoxifen In Women Research Articles

Tamoxifen for relapse of ovarian cancer.

Tamoxifen is an important drug for treating breast cancer. Ovarian cancer cells are known to possess receptors for hormones and may thus also respond to tamoxifen. Tamoxifen is used to treat breast cancer in women whose tumours have oestrogen receptors. Since ovarian cancers also commonly have oestrogen receptors, it has been suggested that tamoxifen may be of some benefit. The objective of this review was to assess the effects of tamoxifen in women with relapsed ovarian cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2009. Cochrane Gynaecological Cancer Group Trials Register, MEDLINE from 2002 to April 2009, EMBASE from 2002 to April 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field, as well as drugs companies. Randomised and non-randomised studies of tamoxifen in women with ovarian cancer who have not responded to conventional chemotherapy. Only trials involving 10 or more patients were included. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. The search strategy identified 1392 unique references of which 1360 were excluded on the basis of title and abstract. The remaining 32 articles were retrieved in full, but none satisfied the inclusion criteria. Only observational data from single arm studies of women treated with tamoxifen were reported. We are unable to make any evidence-based recommendations as we found no comparative studies assessing the effectiveness of tamoxifen in women with recurrent ovarian cancer. There is limited evidence on anti-tumour activity from phase 2 studies, but these contain no data on the effect of tamoxifen on symptom control, QOL or the prolongation of life.

Association of tamoxifen (TAM) and TAM metabolite concentrations with self-reported side effects of TAM in women with breast cancer.

The positive effects of tamoxifen (TAM) on breast cancer recurrence and survival as well as on overall mortality have led to its use as the predominant adjuvant therapy among women with breast cancer. However, the association of TAM intake with undesirable side effects has been reported in numerous studies. This analysis was carried out to assess whether the concentrations of TAM or TAM metabolites, N -desmethyltamoxifen ( N -DMT) and 4-hydroxytamoxifen (4-OHT), were associated with self-reported side effects of TAM. Participants were 99 breast cancer patients who had been taking TAM for at least 30 days. Each participant completed a questionnaire that was used to ascertain whether she experienced certain specific symptoms while taking TAM. In addition, each woman provided a blood sample that was used to measure plasma concentrations of TAM, N -DMT, and 4-OHT by high performance liquid chromatography. Results of the analysis showed that women who experienced at least one TAM-related side effect had significantly higher levels of TAM than women not experiencing any TAM-related side effects. Furthermore, women who reported experiencing visual problems had significantly higher levels of both TAM and N -DMT compared to those women who reported experiencing no visual problems. The levels of 4-OHT were negatively associated with the occurrence of vaginal discharge. The results of this study suggest that the self-reported occurrence of certain symptoms during TAM treatment is related to TAM metabolism. Future studies should assess subgroups of women with specific TAM and TAM metabolite profiles to determine whether alternate, equally effective therapies would decrease their risk of experiencing certain undesirable side effects.

Estimates of the likely prophylactic effect of tamoxifen in women with high risk BRCA1 and BRCA2 mutations.

The development of breast cancer control strategies in women at high genetic risk of breast cancer is an important issue. The likely benefit of chemopreventive approaches is of particular interest. Tamoxifen tends to be more effective in both prevention and treatment of oestrogen receptor positive tumours than oestrogen receptor negative. In this study, we combine the oestrogen-receptor specific effects of tamoxifen from randomized preventive or therapeutic trials with the oestrogen receptor status of tumours in BRCA1 and BRCA2 mutation positive women from published tumour surveys to obtain estimates of the likely effect of tamoxifen administration in mutation carriers. We used a simple two-stage procedure to estimate the benefit as a weighted average of the effect on oestrogen receptor positive tumours and oestrogen receptor negative, and using a more complex hierarchical modelling approach. Using the simple procedure and deriving the estimates of benefit from both primary prevention and therapeutic trials, we obtain an estimated reduction in risk of breast cancer from administration of tamoxifen in BRCA1 mutation positive women of 13% (RR=0.87, 95% CI 0.68–1.11). The corresponding estimated reduction in BRCA2 mutation positive women was 27% (RR=0.73, 95% CI 0.59–0.90). Using the more complex models gave essentially the same results. Using only the primary prevention trials gave smaller estimates of benefit in BRCA1 carriers but larger estimates in BRCA2, in both cases with wider confidence intervals. The benefit of prophylactic use of tamoxifen in BRCA1 mutation carriers is likely to be modest, and the effect in BRCA2 mutation carriers somewhat greater.British Journal of Cancer (2002) 86, 218–221. DOI: 10.1038/sj/bjc/6600064 www.bjcancer.com© 2002 The Cancer Research Campaign

Tamoxifen for relapse of ovarian cancer.

Tamoxifen is an important drug for treating breast cancer. Ovarian cancer cells are known to possess receptors for hormones and may thus also respond to tamoxifen. Tamoxifen is used to treat breast cancer in women whose tumours have oestrogen receptors. Since ovarian cancers also commonly have oestrogen receptors, it has been suggested that tamoxifen may be of some benefit. The objective of this review was to assess the effects of tamoxifen in women with relapsed ovarian cancer. We searched the Cochrane Gynaecological Cancer Group trials register and references from relevant articles. We also contacted researchers and drug companies. Randomised and non-randomised studies of tamoxifen in women with ovarian cancer who have not responded to conventional chemotherapy. Only trials involving 10 or more patients were included. One reviewer assessed eligibility and extracted data from non-randomised studies. Two reviewers were to have independently assessed the quality and extracted data from any randomised trials found. Eleven non-randomised series, one non-randomised phase two study and two randomised trials were included. Only observational data from women treated with tamoxifen are reported. Sixty of 623 women (9.6%) treated with tamoxifen achieved an objective response to treatment. However this varied from 0% to 56% in different studies. Stable disease, for variable periods of four weeks or more, was observed in 131 of 411 (31.9%) women from eight studies. There were not enough data to assess duration of response, survival, or the palliative effect of tamoxifen on symptom control or quality of life. There is some evidence from observational studies that tamoxifen may produce a response in a modest proportion of women with relapsed ovarian cancer. However, there are no reliable data from randomised controlled trials.

Surveillance for endometrial cancer in women receiving tamoxifen.

Recent studies showing a protective effect of tamoxifen in women at high risk for breast cancer have expanded the indications of the drug. While acting as an estrogen antagonist in the breast, tamoxifen can have estrogenic effects on the endometrium; consensus opinion is that tamoxifen increases the risk for endometrial cancer. Because an increasing number of women are taking tamoxifen, a strategy for gynecologic surveillance is needed. Studies examining the relation between risk for endometrial cancer and tamoxifen use have conflicting results. However, because of an overall interpretation that tamoxifen use slightly increases risk for endometrial cancer, some researchers advocate routine ultrasonography and endometrial biopsy for screening asymptomatic women receiving tamoxifen. This paper reviews the literature on endometrial cancer in women taking tamoxifen and the usefulness of various screening methods in this setting. Risk factors and screening criteria for endometrial cancer in the general population are discussed, and a strategy for surveillance of women taking tamoxifen is proposed. Patients should be screened for signs or symptoms of endometrial abnormality before taking tamoxifen. This evaluation, which should include a careful history, pelvic examination, and Papanicolaou smear, should be repeated annually while the patient is receiving tamoxifen. Although transvaginal ultrasonography is not recommended for routine screening, it is indicated if an adequate pelvic examination cannot be performed or if additional risk factors are present. The likelihood of abnormality is greater for patients who have abnormal bleeding, discharge, abnormal glandular cells on Papanicolaou smear, or an endometrial measurement on ultrasonography of more than 8 mm; these findings should prompt an aggressive evaluation of the endometrium.

Tissue-selective actions of estrogen analogs.

The biological actions of estrogen analogs have frequently confounded prevailing views regarding the mechanism of estrogen action. Agents originally intended as antifertility drugs are now used clinically to promote ovulation. The early work with antiestrogens as antifertility agents lead to the realization that triphenylethylene antiestrogens suppressed the growth of breast tumors. The subsequent ubiquitous clinical use of tamoxifen for adjuvant breast cancer therapy is a direct result of this research. Basic studies using tamoxifen and related antiestrogens revealed the previously unsuspected tissue selective actions of these compounds. This peculiar property is being taken advantage of to gain new insight into the molecular mechanisms of estrogen action. This property also forms the basis for an exciting new approach to hormone replacement therapy to prevent postmenopausal osteoporosis and cardiovascular disease. The laboratory rat played an integral and essential part in each of these developments. The success of the ovariectomized rat model in predicting the tissue selective effects of tamoxifen in women greatly increases confidence that this animal model will be useful in development of a new generation of estrogen analogs designed specifically for postmenopausal hormone replacement.