Prevention of Bone Loss After Withdrawal of Tamoxifen

Cohen, Adi; Fleischer, Jessica; Johnson, Mariko K.; Brown, Ijeoma; Joe, Andrew K.; Hershman, Dawn L.; McMahon, Donald J.; Silverberg, Shonni J.

doi:10.4158/ep.14.2.162

Cited by 17 publications

(15 citation statements)

References 21 publications

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“…() and Nayak et al . () seem to be contradictory; it is known that tamoxifen behaves as a mixed agonist/antagonist of oestrogen receptors depending on the sensitivity of the tissue to oestrogen (Powles et al ., ; Cohen et al ., ).…”

Section: Pharmacodynamics and Pharmacogenomicsmentioning

confidence: 97%

Pharmacogenomics, pharmacokinetics and pharmacodynamics: interaction with biological differences between men and women

Franconi

Campesi

2014

British J Pharmacology

211

143

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Pharmacological response depends on multiple factors and one of them is sex-gender. Data on the specific effects of sex-gender on pharmacokinetics, as well as the safety and efficacy of numerous medications, are beginning to emerge. Nevertheless, the recruitment of women for clinical research is inadequate, especially during the first phases. In general, pharmacokinetic differences between males and females are more numerous and consistent than disparities in pharmacodynamics. However, sex-gender pharmacodynamic differences are now increasingly being identified at the molecular level. It is now even becoming apparent that sex-gender influences pharmacogenomics and pharmacogenetics. Sex-related differences have been reported for several parameters, and it is consistently shown that women have a worse safety profile, with drug adverse reactions being more frequent and severe in women than in men. Overall, the pharmacological status of women is less well studied than that of men and deserves much more attention. The design of clinical and preclinical studies should have a sex-gender-based approach with the aim of tailoring therapies to an individual's needs and concerns. LINKED ARTICLESThis article is part of a themed section on Biological Sex and Cardiovascular Pharmacology. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2014.171.issue-3 Abbreviations ACEI, inhibitor of angiotensin converting enzyme; ADE, adverse drug effect; ARB, antagonist of angiotensin receptor 1; CV, cardiovascular; CYP, cytochrome P450 enzymes; ET-1, endothelin-1; HMG-CoA, hydroxymethylglutaryl coenzyme A; OC, oral contraceptives; RAS, renin angiotensin system; SGD, sex-gender difference IntroductionOptimal pharmacological therapy depends on many factors. Some of these factors are biological (metabolism, genetic and epigenetic backgrounds, age and sex) (Becquemont et al., 2006), while others depend on the environment such as care provider-patient relationship. In view of the numerous biological (sex) and psychosocial-cultural (gender) differences, women and men can be considered as two different categories (Legato, 2009). However, sex-gender difference (SGD) only started to acquire the right relevance in the latter part of the last century, although Hippocrates, describing the symptoms of gout, had written 'A woman does not take the gout unless her menses has stopped ' (Enomoto and Endou, 2005), indicating a SGD in susceptibility rather than the development of a disease. The first pharmacological SGD was described in 1932 (Nicholas and Barron, 1932), when it was demonstrated that the hypnotic effect of hexobarbital lasted longer in female than in male rats. Later, it was shown that this difference is dependent on the metabolic process (Quinn et al., 1958). Nowadays, SGDs in pharmacokinetic parameters are well known and have been recently and extensively (Gandhi et al., 2004;Anderson, 2005;Franconi et al., 2007; 2011a,b;Soldin and Mattison, 2009). The SGDs in pharmacodynamics are not so well-known, but the...

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Section: Pharmacodynamics and Pharmacogenomicsmentioning

confidence: 97%

Pharmacogenomics, pharmacokinetics and pharmacodynamics: interaction with biological differences between men and women

Franconi

Campesi

2014

British J Pharmacology

211

143

View full text Add to dashboard Cite

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“…However, a rebound phenomenon is suspected. The interruption of tamoxifen combined with the rapid fall in estrogen levels induced by the AI may promote an accelerated loss of BMD following the switch [7,23,24]. McCaig et al [25] reported that stopping tamoxifen and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naive patients.…”

Section: Annals Of Oncology Original Articlesmentioning

confidence: 99%

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

et al. 2012

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Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T].Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models.Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements.Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < 22.5 standard deviation).Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

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“…Whereas tamoxifen is known to counteract BMD loss and to decrease bone fracture rate in postmenopausal women [13], the sequence of T followed by L had the worse effect on BMD. Likely, the interruption of T combined with the rapid fall in estrogen levels induced by L may promote an accelerated bone turnover and loss of BMD following the TL switch [14–16]. Indeed, bone turnover biomarkers changes induced by aromatase inhibitors (AIs) occur rapidly after initiation of treatment [16–21].…”

Section: Discussionmentioning

confidence: 99%

Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences

DeCensi

Sun

Guerrieri-Gonzaga

et al. 2014

Breast Cancer Res Treat

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Purpose To determine the effects of the BIG 1-98 treatments on bone mineral density. BIG 1-98 compared 5-year adjuvant hormone therapy in postmenopausal women allocated to four groups: tamoxifen (T); letrozole (L); 2-years T, 3-years L (TL); 2-years L, 3-years T (LT). Methods Bone mineral density T-score was measured prospectively annually by dual energy X-ray absorption in 424 patients enrolled in a sub-study after three (n=150), four (n=200), and five years (n=74) from randomization, and one year after treatment cessation. Prevalence of osteoporosis and the association of C-telopeptide, osteocalcin and bone alkaline phosphatase with T-scores were assessed. Results At 3 years, T had the highest and TL the lowest T-score. All arms except for LT showed a decline up to 5 years, with TL exhibiting the greatest. At 5 years, there were significant differences on lumbar T-score only between T and TL, whereas for femur T-score differences were significant for T vs. L or TL, and L vs. LT. The 5-year prevalence of spine and femur osteoporosis was highest on TL (14.5%, 7.1%) then L (4.3%, 5.1%), LT (4.2%, 1.4%) and T (4%, 0). C-telopeptide and osteocalcin were significantly associated with T-scores. Conclusions While adjuvant L increases bone mineral density loss compared with T, the sequence LT has an acceptable bone safety profile. C-telopeptide and osteocalcin are useful markers of bone density that may be used to monitor bone health during treatment. The sequence LT may be a valid treatment option in patients with low and intermediate risk of recurrence. Trial registration clinicaltrials.gov NCT00369850

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Prevention of Bone Loss After Withdrawal of Tamoxifen

Cited by 17 publications

References 21 publications

Pharmacogenomics, pharmacokinetics and pharmacodynamics: interaction with biological differences between men and women

Pharmacogenomics, pharmacokinetics and pharmacodynamics: interaction with biological differences between men and women

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences

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