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Biomedical subjects

N F Fritz

Publications and source records attributed to N F Fritz.

7 recordsLinked to original sources
PubMed1991

Alteration of endocrine parameters in premenopausal women with breast cancer during long-term adjuvant therapy with tamoxifen as the single agent.

Tamoxifen is used to treat selected patients at each stage of breast cancer. Although most clinical experience has been obtained with postmenopausal women, increasing numbers of premenopausal women will be treated with 5 or more years of adjuvant tamoxifen therapy following surgery. Indeed, the proposed use of tamoxifen to prevent breast cancer in high-risk women could result in its extended use during the childbearing years. We have monitored the changes in circulating hormone levels from the ovary and pituitary gland in premenopausal (41-47 years old) women with stage I or II breast cancer during adjuvant therapy with tamoxifen as the single agent for 4-72 months following a mastectomy. Each patient (total eight) continued to menstruate, and ovulation occurred. Circulating levels of luteinizing hormone and follicle-stimulating hormone (except in one woman) remained in the normal range (determined in 12 regularly menstruating women in a control group). The levels of estradiol, estrone, and progesterone were elevated onefold to threefold. Prolactin levels decreased by 30%-40%, but the levels of sex hormone binding-globulin were unaffected. These data demonstrate that premenopausal women taking tamoxifen are potentially at risk for pregnancy and must be counseled about barrier contraception. Furthermore, the impact of many years of ovarian stimulation by tamoxifen must be evaluated, especially in women with node-negative disease or in healthy women in whom tamoxifen is used to prevent breast cancer.

Adult↗
PubMed1988

Endocrine status of premenopausal node-positive breast cancer patients following adjuvant chemotherapy and long-term tamoxifen.

The endocrine status of 49 premenopausal women taking tamoxifen after completion of adjuvant chemotherapy for breast cancer was determined by radioimmunoassay from serial blood samples. Of these 49 women, 7 had regular menses, 14 had irregular menses, 23 were amenorrheic, and 5 had undergone hysterectomies. A group of 12 premenopausal women who had no history of breast cancer and were not taking tamoxifen served as a control group. Evidence of ovarian function (estradiol levels of greater than 100 pg/ml) was seen in 7 of 7, 9 of 14, 2 of 23, and 1 of 5 women with a clinical history of regular menses, irregular menses, amenorrhea, and hysterectomy, respectively. Supraphysiological levels of estradiol (greater than 350 pg/ml) were noted in 13 of 19 women with endocrine evidence of ovarian function. Supraphysiological progesterone levels (greater than 20 ng/ml) were also seen in 5 of 7 of the regularly menstruating women taking tamoxifen. Supraphysiological levels of estradiol were associated with elevated follicle-stimulating hormone levels, but there was no mean change in the luteinizing hormone levels. Minimum and maximum serum follicle-stimulating hormone levels were 1.9 and 9.0 mIU/ml in the 12 normal women and 5.2 and 24.3 mIU in the 13 women with supraphysiological estradiol levels. Our findings demonstrate that the majority of women who continue to menstruate while taking continuous tamoxifen following cytotoxic chemotherapy have supraphysiologic estradiol levels. This is a potential mechanism for failure of tamoxifen therapy in these premenopausal women.

Adenocarcinoma↗
PubMed1987

Long-term adjuvant therapy with tamoxifen: effects on sex hormone binding globulin and antithrombin III.

Plasma levels of luteinizing hormone, sex hormone binding globulin, and antithrombin III were measured in pre- and postmenopausal breast cancer patients receiving adjuvant combination chemotherapy or combination chemotherapy and long-term tamoxifen therapy. The aim was to determine the estrogen-like effects of tamoxifen. The premenopausal patients had received tamoxifen for between 434 and 2592 days and postmenopausal patients between 91 and 1560 days. Tamoxifen caused a consistent rise in sex hormone binding globulin in premenopausal (P less than 0.03) and postmenopausal (P less than 0.01) patients compared to chemotherapy controls. Luteinizing hormone levels were only significantly lowered (P less than 0.008) in premenopausal patients compared to chemotherapy controls. Antithrombin III levels were significantly depressed (P less than 0.001) in postmenopausal patients compared with chemotherapy controls. However, none of the patients had a value that was depressed by more than 30% of the laboratory control (the level of clinical significance). The mean for the group was 90% +/- 4 (mean +/- SD, N = 11). The estrogen-like rise in sex hormone binding globulin produced by adjuvant tamoxifen therapy could be advantageous for maintaining the antiestrogenic action of the drug. A decrease in antithrombin III occurred but was not within a range of clinical concern. We recommend, however, that patients with a history of thromboembolic disorders should be monitored carefully if placed on tamoxifen therapy.

Adult↗
PubMed1987

Endocrine effects of adjuvant chemotherapy and long-term tamoxifen administration on node-positive patients with breast cancer.

Ovarian and pituitary hormones were determined in pre- and postmenopausal breast cancer patients before and at intervals during adjuvant chemotherapy or chemotherapy plus tamoxifen (TAM). Chemotherapy did not affect gonadotrophin levels in postmenopausal patients; however, inclusion of TAM in the regimen produced a partial (approximately 50%) reduction in circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone. Gonadotrophin levels remained reduced as long as TAM therapy continued, at which time they rose to postmenopausal values. Chemotherapy (6-12 months) caused ovarian failure in premenopausal patients with decreases in estrogen (estrone plus estradiol) and rises in gonadotrophin levels to postmenopausal levels. Inclusion of TAM in the regimen caused an initial 3-fold rise in peak circulating estrogen levels before ovarian failure (6-9 months of therapy). Some younger patients (approximately 40 years of age) who had a short course (4 months) of chemotherapy plus TAM followed by continuous TAM therapy alone resumed ovulatory menstrual cycles. Estrogen, progesterone, and follicle-stimulating hormone levels were increased compared with control subjects. Those patients who experienced ovarian failure with adjuvant chemotherapy plus TAM only had a partial rise in gonadotrophins compared with patients receiving chemotherapy alone. TAM maintained the levels of gonadotrophins for as long as therapy was administered, at which time they rose to postmenopausal levels. Although TAM exhibited estrogen-like effects on gonadotrophins there was no estrogen-like increase in circulating prolactin levels in either pre- or postmenopausal patients. One patient experienced an estrogen receptor-positive recurrence during long-term tamoxifen therapy. Serum levels of tamoxifen and metabolites declined in the year prior to the recurrence and this was associated with a rise in gonadotrophins. This indicated noncompliance by the patient. Compliance can be monitored either directly with serum levels of TAM or by serial gonadotrophin determinations. We suggest that the optimal antitumor activity of TAM will be achieved in a low estrogen environment with continuous high levels of the drug in the serum. We recommend that patients undergoing long-term TAM therapy be monitored for complete ovarian failure and drug compliance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Strategies for breast cancer therapy with antiestrogens.

Current clinical research is focused upon the application of adjuvant therapy for the treatment of breast cancer. Combination chemotherapy is the most successful adjuvant therapy for premenopausal patients whereas the antiestrogen tamoxifen (1 or 2 yr) is successful in postmenopausal disease. We have developed a unifying strategy for the treatment of breast cancer. The thesis is based upon the application of continuous adjuvant therapy with tamoxifen in a low estrogen environment. Chemotherapy causes a chemical castration in premenopausal patients. In contrast, tamoxifen causes an increase in steroidogenesis. A combination of both approaches will work against each other until ovarian failure occurs. Patients should be checked for castration to provide a low estrogen environment in which tamoxifen, a competitive antagonist of estrogen action, can effectively work. Laboratory evidence using carcinogen-induced rat mammary tumor models demonstrates the efficacy of long-term therapy. Studies with the human breast cell line MCF-7 grown in athymic mice show that tamoxifen is a tumoristatic agent so that once the therapy is stopped, tumors can be regrown by estrogen administration. Patients should receive continuous tamoxifen therapy to prevent the growth-stimulating effects of adrenal steroids, environmental and phyto-estrogens.

Animals↗