The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen Therapy

Pommier, Rodney F.; Woltering, Eugene A.; Keenan, Edward J.; Fletcher, William S.

doi:10.1001/archsurg.1987.01400230097017

Cited by 14 publications

(3 citation statements)

References 17 publications

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“…Clinically, tamoxifen has both antiestrogenic and estrogenic effects [9]. It has been previously reported that tamoxifen stimulates the adrenal gland to produce dehydroepiandrosterone, which in turn is aromatized to estrone and estradiol in peripheral tissues, thereby attenuating tamoxifen's antiestrogenic effects [13]. The estrogenic effects of tamoxifen have been hypothesized as decreasing serum cholesterol levels and diminishing the risk of coronary artery disease [14], increasing the risk of endometrial cancer [6,15], maintaining bone density [5], causing liver tumors [16], and increasing the risk of thromboembolic events [17].…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen and Gallstone Formation in Postmenopausal Breast Cancer Patients: Retrospective Cohort Study

et al. 2003

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Tamoxifen is being used successfully in breast cancer patients as adjuvant hormonal therapy. The aim of this retrospective cohort study is to evaluate the impact of tamoxifen on gallstone formation in postmenopausal breast cancer patients. A total of 3165 patients who were treated for invasive breast cancer between 1990 and 1997 were reviewed. The data were collected from four university hospitals in a population-based registry. Among these patients, 2462 were excluded from the study owing to improper follow-up and other reasons. Premenopausal patients were also excluded. Of the 703 patients included in the study, 457 had received adjuvant therapy including tamoxifen, and the other 246 had not. Gallstone formation was assessed by annual abdominal ultrasonography. The mean follow-up period was 4.6 years (range 1-7 years). There were no significant differences between the groups of breast cancer patients treated with or without tamoxifen regarding the age of the patients at the time of breast cancer diagnosis, the age at menopause, the duration between the onset of menopause and the time the breast cancer was diagnosed, the presence of diabetes, and the body mass index. At the end of 5 years the incidence of gallstone formation in tamoxifen-treated patients was 37.4%, whereas it was 2.0% in patients who did not receive tamoxifen ( p < 0.0001). The incidences of gallstones being detected in 171 tamoxifen-treated patients were 0.4%, 3.7%, 24.4%, 33.1%, and 37.4% cumulatively during the first, second, third, fourth, and fifth years, respectively. Hence adjuvant tamoxifen therapy leads to gallstone formation in postmenopausal breast cancer patients and is most apparent after 3 years of treatment.

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Section: Discussionmentioning

confidence: 99%

Tamoxifen and Gallstone Formation in Postmenopausal Breast Cancer Patients: Retrospective Cohort Study

et al. 2003

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“…This might impair the efficacy of tamoxifen therapy by competing out tamoxifen from ER in the tumor. A similar phenomenon has been implicated in the failure of tamoxifen therapy in postmenopausal women (205).…”

Section: B Indirect Actions Of Antiestrogensmentioning

confidence: 55%

Endocrine Pharmacology of Antiestrogens as Antitumor Agents*

Jordan¹,

Murphy²

1990

Endocrine Reviews

374

135

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“…Data from Swain and Lippman [11], Dorr and Fritz [84], Henderson [5], and Physicians Desk Reference (Medical Economics Co, Oradell NJ, 1991) progress have been described in as many as 20% of patients [37]. The mechanism of the withdrawal response is unclear, but in one trial patients with tumor progression had subsequent decreases in dehydroepiandrosterone (DHEA), estrone, and estradiol after tamoxifen was discontinued; when tamoxifen was reinstituted in patients who had hypophysectomy or oophorectomy, levels of all three steroids dramatically increased [38]. The authors suggested that in some patients tamoxifen was able to stimulate adrenal production of DHEA which was subsequently aromatized to estrogen resulting in tumor stimulation.…”

Section: Antiestrogensmentioning

confidence: 99%

Endocrine therapy for advanced breast cancer: A review

Muss

1992

Breast Cancer Res Tr

125

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More than 45,000 women will die of metastatic breast cancer in the United States in 1991. Endocrine therapy remains a major option for treatment of such patients, and results in complete plus partial response rates of 30% with a median duration of approximately one year. Postmenopausal status, increased age, a prolonged disease-free interval, bone and soft tissue metastases, and positive estrogen and progesterone receptors are all associated with an increased response to endocrine therapy. The use of additive hormonal therapy, specifically antiestrogens, progestins, and aromatase inhibitors, have replaced surgical ablative procedures in the majority of patients; response rates to antiestrogen therapy, progestin therapy, and aromatase inhibitors are similar, but antiestrogens have generally been associated with the most favorable therapeutic index. At present, there is no convincing evidence that either combinations of endocrine therapies or endocrine therapy combined with chemotherapy are associated with an improvement in survival for patients with metastatic disease. Future research efforts directed at defining the molecular mechanisms of endocrine activity should facilitate clinical trials of newer and potentially more effective agents. All patients with metastatic breast cancer should be considered for at least one trial of endocrine therapy provided their metastatic disease is not rapidly progressive or life-threatening.

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The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen Therapy

Cited by 14 publications

References 17 publications

Tamoxifen and Gallstone Formation in Postmenopausal Breast Cancer Patients: Retrospective Cohort Study

Tamoxifen and Gallstone Formation in Postmenopausal Breast Cancer Patients: Retrospective Cohort Study

Endocrine Pharmacology of Antiestrogens as Antitumor Agents*

Endocrine therapy for advanced breast cancer: A review

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