Treatment of advanced breast cancer with tamoxifen: Evaluation of the dose-response relationship at two dose levels

Rose, Carsten; Theilade, Karen; Boesen, Else; M, Salimtschik; Dombernowsky, P; Brünner, Niels; Kjær, Mogens; Mouridsen, Henning T.

doi:10.1007/bf01805882

Cited by 23 publications

(5 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The patients belonged to a selected subgroup, in as much as they were all conPlasma estrogens and DFI 337 sidered candidates for endocrine treatment based on estrogen receptor values, long disease-free interval or other clinical characteristics suggesting a hormone-sensitive tumor [9]. Out of these 102 patients, 94 had a disease-free time period between their initial treatment and the time they obtained a diagnosis of relapse (the other 8 patients suffered from advanced disease at time of diagnosis).…”

Section: Methodsmentioning

confidence: 99%

Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Lønning

Helle

Johannessen

et al. 1996

Breast Cancer Res Tr

View full text Add to dashboard Cite

The influence of plasma estrogen levels on disease-free interval (time from primary treatment to first relapse, DFI) in breast cancer patients is not known. Any relation between plasma estrogens and the outcome in breast cancer patients may have implications considering use of hormone replacement therapy (HRT) in patients treated for breast cancer. We measured plasma estradiol (E2), estrone (E1), and estrone sulfate (E1S) in 92 postmenopausal women with breast cancer relapse and correlated plasma estrogen levels to the length of their disease-free interval (DFI1) and the length of the DFI in the subgroup of patients in whom this extended a time period of more than 2 years (DFI2). The length of DFI2 correlated negatively to plasma level of E1S (p < 0.025) and E2 (p < 0.05) and to the E2/E1 and E1S/E1 ratios (p < 0.05), while the length of DFI1 correlated negatively to plasma level of E1S (p < 0.025) and the E1S/E1 ratio (p< 0.005). We also analyzed for possible correlations between DFIs and plasma estrogen levels in subgroups based on tumor stage at diagnosis and previous therapy. In general, these subgroup analyses revealed negative correlations of statistical significance or borderline significance between the DFI1 and DFI2 and E2 and the E2/E1 ratio and non-significant negative correlations between plasma levels of E1S and DFI1 and DFI2. In particular, strong negative correlations between plasma estrogen levels and the length of DFI1 and DFI2 were found among patients responding to first line endocrine treatment for relapse and among patients with primar stage III tumors. Our findings suggest plasma E2 and E1S to stimulate the growth of micrometastases in patients treated for breast cancer.

show abstract

Section: Methodsmentioning

confidence: 99%

Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Lønning

Helle

Johannessen

et al. 1996

Breast Cancer Res Tr

View full text Add to dashboard Cite

show abstract

“…A wide inter-individual variability in steady-state concentrations of tamoxifen and its metabolites has been long recognized (27), yet these variable concentrations have not been associated with clinical outcomes (28;29) and dose-setting studies have not suggested that higher doses of tamoxifen improve the average response (28;30). Tamoxifen doses as low as 1 mg/day affect the cancer proliferation antigen Ki-67 equivalently to the typical dose of 20 mg/day (31;32).…”

Section: The Pharmacologic Evidencementioning

confidence: 99%

Genotype-guided tamoxifen therapy: time to pause for reflection?

Lash

Lien

Sørensen

et al. 2009

The Lancet Oncology

107

110

View full text Add to dashboard Cite

Tamoxifen remains a cornerstone of adjuvant therapy for early stage breast cancer patients with estrogen receptor-positive tumors. Accurate markers of tamoxifen resistance would allow prediction of tamoxifen response and personalization of combined therapies. Recently, it has been suggested that patients with inherited nonfunctional alleles of the cytochrome P450 CYP2D6 may be poor candidates for adjuvant tamoxifen therapy because women with these variant alleles have reduced concentrations of the tamoxifen metabolites that most strongly bind the estrogen receptor. In some studies, women with these alleles have a higher risk of recurrence than women with two functional alleles. However, dose-setting studies with clinical and biomarker outcomes, studies associating clinical outcomes with serum concentrations of tamoxifen and its metabolites, and a simple model of receptor binding, all suggest that tamoxifen and its metabolites should reach concentrations sufficient to achieve the therapeutic effect regardless of CYP2D6 inhibition. The ten epidemiology studies of the association between CYP2D6 genotype and breast cancer recurrence report widely heterogeneous results with relative risk estimates outside the range of reasonable bounds. None of the explanations proposed for the heterogeneity of results account adequately for the observed variability and no design feature sets apart any study or subset of studies as most likely to be accurate. The studies reporting a positive association may receive the most attention because they reported a result consistent with the profile of metabolite concentrations; not because they are more reliable by design. We argue that a recommendation for CYP2D6 genotyping of candidates for tamoxifen therapy, and its implicit conclusion regarding the association between genotype and recurrence risk, is premature.

show abstract

“…From September 1976 until February 1983, postmenopausal patients with advanced breast cancer entered one of four consecutive randomized studies of ET at the Department of Oncology ONA at the Finsen Institute [19][20][21][22][23]. These patients received either tamoxifen alone (30 or 90 mg daily) [19] or tamoxifen (30 rag) in combination with either diethylstilbestrol [20], medroxyprogesterone acetate [21], aminoglutethimide plus hydrocortisone [22], or halotestin [23].…”

Section: Methodsmentioning

confidence: 99%

“…These patients received either tamoxifen alone (30 or 90 mg daily) [19] or tamoxifen (30 rag) in combination with either diethylstilbestrol [20], medroxyprogesterone acetate [21], aminoglutethimide plus hydrocortisone [22], or halotestin [23].…”

Section: Methodsmentioning

confidence: 99%

Metastatic pattern and response to endocrine therapy in human breast cancer

Kamby¹,

Rose²

1986

Breast Cancer Res Tr

Self Cite

View full text Add to dashboard Cite

The effect of endocrine therapy in 465 postmenopausal patients with advanced breast cancer who entered four consecutive, randomized trials has been related to the site of the metastases. Patients received either tamoxifen (T) alone or T in combination with medroxyprogesterone acetate, diethylstilbestrol, halotestin, or aminoglutethimide. The overall response rate was 40%. Responses were most frequently seen in patients with metastases in soft tissue, and the duration of response to endocrine therapy in these patients was longer than for those with metastases in bone or viscera (p less than 0.00001). In addition, the response rate was inversely correlated with the number of main metastatic sites in patients with soft tissue metastases, whereas the response rate was not associated with the number of metastatic sites in patients with metastases in bone and viscera. Survival after first recurrence was significantly longer in responding patients with soft tissue lesions compared to those with recurrence in bone or viscera. In contrast, survival after first recurrence was identical in patients with nonresponding disease, irrespective of dominant site of metastases. The outcome of endocrine therapy depends partially upon the dominant site of metastases. This may reflect a difference in biological characteristics of human breast cancer tumor cells that metastasize to different sites.

show abstract

Treatment of advanced breast cancer with tamoxifen: Evaluation of the dose-response relationship at two dose levels

Cited by 23 publications

References 13 publications

Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Genotype-guided tamoxifen therapy: time to pause for reflection?

Metastatic pattern and response to endocrine therapy in human breast cancer

Contact Info

Product

Resources

About