Tamoxifen for the Prevention of Breast Cancer: Current Status of the National Surgical Adjuvant Breast and Bowel Project P-1 Study

Fisher, Bernard; Costantino, Joseph P.; Wickerham, D. Lawrence; Cecchini, Reena S.; Cronin, Walter M.; Robidoux, André; Bevers, Therese B.; Kavanah, Maureen; Atkins, James N.; Margolese, Richard G.; Runowicz, Carolyn D.; James, Joan; Ford, Leslie G.; Wolmark, Norman

doi:10.1093/jnci/dji372

Cited by 1,181 publications

(826 citation statements)

References 54 publications

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“…Since both drugs have similar effects on bone metabolism and turnover, there is a clear AI class effect on bone health in postmenopausal women with hormone-sensitive breast cancer. Tamoxifen has been reported to have some beneficial effects on bone turnover and fracture risk in AI aromatase inhibitor, CI confidence interval, PINP procollagen type I N terminal propeptide, sCTX serum C-terminal telopeptides, uNTX urinary N-terminal telopeptides, ALP alkaline phosphatase postmenopausal women [4,[20][21][22], but the results here show that these positive effects do not carry over once tamoxifen therapy is discontinued. Our study showed an increase in bone turnover that could eventually lead to bone loss.…”

Section: Discussionmentioning

confidence: 61%

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

McCaig

Renshaw

Williams

et al. 2009

Breast Cancer Res Treat

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International audienceALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen ( = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption

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Section: Discussionmentioning

confidence: 61%

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

McCaig

Renshaw

Williams

et al. 2009

Breast Cancer Res Treat

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show abstract

“…Tamoxifen is the most widely used drug for the prevention of hormone-receptorpositive breast cancer (BC), 1 the treatment of ductal carcinoma in situ, 2 the adjuvant treatment of premenopausal BC 3 and the therapy of male BC. 4 Nevertheless, its clinical effectiveness varies among individuals.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial

et al. 2010

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The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19*17 and two single-nucleotide polymorphisms for the gene SULT1A1 were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (P ¼ 0.035). In an exploratory analysis, among 58 women with a CYP2D6*2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (P ¼ 0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmacogenomics in tailoring tamoxifen treatment.

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“…These recommendations included annual magnetic resonance imaging in addition to mammography, given the up to 25% lifetime risk of breast cancer and the consideration of chemoprevention, because many CHEK2 breast cancers are estrogenreceptor positive. 18,19 As prostate cancer risks are elevated in individuals with the 1100delC mutation, CHEK2-positive men with a first-degree relative with prostate cancer are recommended to begin prostate cancer screening 5-10 years before the earliest diagnosis in a close relative. 20,21 Given that CHEK2 mutations have been seen to increase risks of thyroid, ovarian, kidney, and colon cancer, we advised screening for these cancers in the context of a positive family history of these cancers.…”

Section: Discussionmentioning

confidence: 99%

The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience

Mauer

Pirzadeh‐Miller

Robinson

et al. 2014

Genetics in Medicine

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Tamoxifen for the Prevention of Breast Cancer: Current Status of the National Surgical Adjuvant Breast and Bowel Project P-1 Study

Cited by 1,181 publications

References 54 publications

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial

The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience

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