Adjuvant Tamoxifen in Early Breast Cancer: Occurrence of New Primary Cancers

Fornander, Tommy; Cedermark, Björn; Mattsson, Anders; Skoog, Lambert; Theve, Tolle; Askergren, J; Rutqvist, Lars‐Erik; Glas, Ulla; Silfverswärd, Claes; Somell, Anders; Wilking, Nils; Hjalmar, Marie-Louise

doi:10.1016/s0140-6736(89)91141-0

Cited by 860 publications

(314 citation statements)

References 24 publications

Supporting

Mentioning

294

Contrasting

Unclassified

Order By: Relevance

“…All oesophageal and gastric cancer diagnoses occurring within 1 year of follow-up after the primary breast cancer diagnosis were excluded to minimise surveillance bias, that is, a patient with a newly diagnosed breast cancer would be more likely to have another cancer diagnosis detected because of the ongoing diagnostic investigations for the breast cancer. As widespread use of tamoxifen in Sweden only began in the late 1980s (Fornander et al, 1989), we considered the cohort of women diagnosed with breast cancer up to the end of December 1987 as being unexposed to tamoxifen, whereas the cohort diagnosed after that date was considered potentially exposed. Women younger than 50 years of age at the time of the breast cancer diagnosis were considered premenopausal and were excluded from the analysis.…”

Section: Discussionmentioning

confidence: 99%

“…It has been widely used in the treatment of oestrogen-dependent breast cancer since the drug was introduced about 30 years ago, and its use in Sweden has been widespread since the late 1980s (Fornander et al, 1989). To explore the potential role of sex hormonal influence in the aetiology of oesophageal and gastric adenocarcinoma, we investigated whether tamoxifen-treated postmenopausal women with breast cancer were at increased risk of developing oesophageal or gastric adenocarcinoma in a nationwide Swedish population-based cohort study.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden

et al. 2006

View full text Add to dashboard Cite

In a population-based cohort study of all women aged over 50 years with breast cancer in the Swedish Cancer Register in 1961 -2003, those diagnosed before 31 December 1987 were regarded as unexposed to tamoxifen, whereas those diagnosed after that date were considered potentially exposed. Crosslinkages within the Cancer Register and the Registers of Death and Emigration enabled follow-up. Standardised incidence ratios (SIRs) of oesophageal and gastric cancer represented relative risks. Among 138 885 cohort members contributing with 1 075 724 person-years of follow-up, we found a nonsignificantly increased risk of oesophageal adenocarcinoma during the potential tamoxifen exposure period (SIR 1.60, 95% confidence interval (CI) 0.83 -3.08), but the risk estimates decreased with increasing latency interval. No association was observed during the unexposed period. No increased risk of cardia adenocarcinoma was identified in either period. The risk of non-cardia gastric adenocarcinoma was increased in the potential tamoxifen period (SIR 1.27, 1.03 -1.57), and almost doubled (SIR 1.86, 95% CI 1.10 -3.14) in the period of longest latency (10 -14 years). The corresponding overall SIR was increased in the unexposed group also, but here SIR did not increase with longer latency intervals. An increased risk of tobacco-related tumours, that is, oesophageal squamous-cell carcinoma and lung cancer, was limited to the unexposed cohort, indicating that confounding by smoking might explain the increased SIR during the unexposed period. We concluded that there might be a link between tamoxifen and risk of non-cardia gastric adenocarcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Despite initial response all such tumours eventually become resistant to this anti-oestrogen after a median duration of remission of about 18 months (Cole et al, 1971;Patterson et al, 1981). Although it acts as an oestrogen antagonist with respect to the tumour, tamoxifen is oestrogenic with respect to bone (Turken et al, 1989), the liver (Bertelli et al, 1988) and the endometrium (Fornander et al, 1989). Potential causes of treatment failure may result from tamoxifen, or its metabolites (Osborne et al, 1991) becoming oestrogenic with respect to the tumour (Howell et al, 1990) or from tamoxifen becoming sequestered away from the oestrogen receptor (ER) and rendered inactive (Pavlick et al, 1992).…”

mentioning

confidence: 99%

Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer

Howell

Defriend²,

Robertson³

et al. 1996

Br J Cancer

183

View full text Add to dashboard Cite

Summary We have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-' and during the sixth month was 12.6 ng ml-l. The AUCs were 140.5 and 206.8 ng day ml-' on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Sideeffects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed 'no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer.

show abstract

“…These studies were either too small or data was just not collected. There was also a question of whether the high dose of tamoxifen (40 mg. daily) used by Fornander and coworkers [116] was responsible for their findings but the report by Fisher [119] neutralized the argument because NSABP studies all use 20mg. tamoxifen daily.…”

Section: Selective Estrogen Receptor Modulation and Chemopreventionmentioning

confidence: 99%

“…This again was selective ER modulation. Stimulate one target site to produce growth and block the growth of another target site.There was a very quick response from the clinical community to the warnings [113] that longterm tamoxifen treatment could be associated with an increase in the incidence of endometrial cancer [114][115][116] but not all reported studies [117,118] found increases in endometrial cancer associated with tamoxifen treatment. These studies were either too small or data was just not collected.…”

mentioning

confidence: 99%

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

Jordan¹,

Brodie²

2007

Steroids

259

183

View full text Add to dashboard Cite

The enthusiasm with which the clinical community has embraced the use of antiestrogenic therapy to treat breast cancer is based upon the proven record of success that first the nonsteroidal antiestrogen tamoxifen and then the aromatase inhibitor have demonstrated in clinical trial. The reasons for the enthusiasm are obvious. Antihormonal therapy, particularly aromatase inhibition to create a "no estrogen state" in the postmenopausal breast cancer patient is effective, saves women's lives, is contributing successfully to reducing the national mortality from breast cancer, is relatively cheap and has fewer side effects and easy administration (oral) than any other anticancer strategy. However, the successful application of a therapeutic strategy to block the known growth stimulation property of estrogen in breast cancer was not greeted with such enthusiasm 40 years ago.Estrogen is essential for life. Without the critical role of estrogenic steroids, reproduction would not be possible. Based on emerging knowledge from laboratory studies, the value of modulating the steroid environment during the menstrual cycle was advanced to clinical testing during the 1950's as a means of oral contraception. The results of these studies were to change society forever.The Worcester Foundation for Experimental Biology is the place where Gregory Pincus established the scientific principles necessary to propose clinical testing of the oral contraceptive and M.C. Chang subsequently established the first protocols to perform in vitro fertilization. Simply stated, the Worcester Foundation was, at that time, the world center for steroid endocrinology and reproductive biology. Over the years, hundreds of scientists have trained at the Foundation and subsequently spread their knowledge throughout the world [1]. However, fashions in research change and new opportunities emerge.In 1971, President Nixon made a national commitment to seek a cure for cancer by signing the National Cancer Act. Mahlon Hoagland, the President of the Worcester Foundation, responded to the initiative by appointing Professor Elwood V. Jensen, Director of the Ben May Cancer Research Laboratory at the University of Chicago, to be a member of the Foundation's Scientific Advisory Board. Jensen had discovered the estrogen receptor (ER) as the putative mechanism of estrogen action in its target tissues [2]. The known link between estrogen and breast cancer suggested that "antiestrogenic strategies" might have potential as therapeutic Correspondence to: V. Craig Jordan, v.craig.jordan@fccc.edu. Present Address: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be d...

show abstract

Adjuvant Tamoxifen in Early Breast Cancer: Occurrence of New Primary Cancers

Cited by 860 publications

References 24 publications

Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden

Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden

Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

Contact Info

Product

Resources

About