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MacCallum, J.; Cummings, Jeffrey L.; Dixon, J. Michael; Miller, W. R.

doi:10.1054/bjoc.2000.1120

Cited by 40 publications

(7 citation statements)

References 25 publications

(40 reference statements)

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“…This is consistent with previous findings that antiestrogen-resistant clones are rare and require remarkably prolonged selective pressure in vitro to isolate [29]. It should be pointed out that the concentrations of Tamoxifen in breast tumors from patients under endocrine therapy are mostly at 300–400 ng/g [30], or approximately 1 µM, which is slightly lower than that was used in this study. The requirement of higher levels of Tamoxifen could be attributed to the source of cells.…”

Section: Discussionsupporting

confidence: 93%

Response of Estrogen Receptor-Positive Breast Cancer Tumorspheres to Antiestrogen Treatments

Morrison

Wang

et al. 2011

PLoS ONE

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Estrogen signaling plays a critical role in the pathogenesis of breast cancer. Because the majority of breast carcinomas express the estrogen receptor ERα, endocrine therapy that impedes estrogen-ER signaling reduces breast cancer mortality and has become a mainstay of breast cancer treatment. However, patients remain at continued risk of relapse for many years after endocrine treatment. It has been proposed that cancer recurrence may be attributed to cancer stem cells (CSCs)/tumor-initiating cells (TICs). Previous studies in breast cancer have shown that such cells can be enriched and propagated in vitro by culturing the cells in suspension as mammospheres/tumorspheres. Here we established tumorspheres from ERα-positive human breast cancer cell line MCF7 and investigated their response to antiestrogens Tamoxifen and Fulvestrant. The tumorsphere cells express lower levels of ERα and are more tumorigenic in xenograft assays than the parental cells. Both 4-hydroxytamoxifen (4-OHT) and Fulvestrant attenuate tumorsphere cell proliferation, but only 4-OHT at high concentrations interferes with sphere formation. However, treated tumorsphere cells retain the self-renewal capacity. Upon withdrawal of antiestrogens, the treated cells resume tumorsphere formation and their tumorigenic potential remains undamaged. Depletion of ERα shows that ERα is dispensable for tumorsphere formation and xenograft tumor growth in mice. Surprisingly, ERα-depleted tumorspheres display heightened sensitivity to 4-OHT and their sphere-forming capacity is diminished after the drug is removed. These results imply that 4-OHT may inhibit cellular targets besides ERα that are essential for tumorsphere growth, and provide a potential strategy to sensitize tumorspheres to endocrine treatment.

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Section: Discussionsupporting

confidence: 93%

Response of Estrogen Receptor-Positive Breast Cancer Tumorspheres to Antiestrogen Treatments

Morrison

Wang

et al. 2011

PLoS ONE

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“…Previous observations about the relationship between body weight and TAM metabolism are controversial [45]. Regarding the relationship between BMI and plasma exposure of TAM and its metabolites, only the NDTAM Css showed a significant correlation (Fig.…”

Section: Discussionmentioning

confidence: 82%

Hormonal status affects plasma exposure of tamoxifen and its main metabolites in tamoxifen-treated breast cancer patients

Ximenez

Andrade

Marques

et al. 2019

BMC Pharmacol Toxicol

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BackgroundTamoxifen is considered a prodrug of its active metabolite endoxifen, which is dependent on the CYP2D6 and CYP3A enzymes. Tamoxifen pharmacokinetic variability influences endoxifen exposure and, consequently, its clinical outcome. This study investigated the impact of hormonal status on the pharmacokinetics of tamoxifen and its metabolites in TAM-treated breast cancer patients.MethodsTAM-treated breast cancer patients (n = 40) previously believed to have CYP3A activity within the normal range based on oral midazolam and phenotyped as CYP2D6 normal metabolizers using oral metoprolol were divided into two groups according to premenopausal (n = 20; aged 35–50 years) or postmenopausal (n = 20; aged 60–79 years) status. All patients were treated with 20 mg/day tamoxifen for at least three months. Serial plasma samples were collected within the 24 h dose interval for analysis of unchanged tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen quantified by LC-MS/MS. CYP activities were assessed using midazolam apparent clearance (CYP3A) and the metoprolol/alfa-hydroxymetoprolol plasma metabolic ratio (CYP2D6). CYP3A4, CYP3A5 and CYP2D6 SNPs and copy number variation were investigated using TaqMan assays.ResultsPostmenopausal status increased steady-state plasma concentrations (Css) of tamoxifen (116.95 vs 201.23 ng/mL), endoxifen (8.01 vs 18.87 ng/mL), N-desmethyltamoxifen (485.16 vs 843.88 ng/mL) and 4-hydroxytamoxifen (2.67 vs 4.11 ng/mL). The final regression models included hormonal status as the only predictor for Css of tamoxifen [β-coef ± SE, p-value (75.03 ± 17.71, p = 0.0001)] and 4-hydroxytamoxifen (1.7822 ± 0.4385, p = 0.0002), while endoxifen Css included hormonal status (8.578 ± 3.402, p = 0.02) and race (11.945 ± 2.836, p = 0.007). For N-desmethyltamoxifen Css, the final model was correlated with hormonal status (286.259 ± 76.766, p = 0.0007) and weight (− 8.585 ± 3.060, p = 0.008).ConclusionThe premenopausal status was associated with decreased endoxifen plasma concentrations by 135% compared to postmenopausal status. Thus, the endoxifen plasma concentrations should be monitored mainly in the premenopausal period to maintain plasma levels above the efficacy threshold value.Trial registrationRBR-7tqc7k.

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“…If inadvertent pregnancy occurs while on tamoxifen, it should be stopped immediately and the risks should be discussed. In case a patient wishes to become pregnant, at least a three-month tamoxifen wash-out period is required before one can safely become pregnant [ 32 , 33 ]. To the best of authors’ knowledge, this is the first case report of a synchronous BC–TC survivor becoming pregnant, although unplanned.…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen exposure in pregnancy after synchronous breast and thyroid cancer

Omar¹,

Abdel-Bary²,

Elsaka³

2020

ecancer

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Thyroid and breast cancer are the most common cancers among young women, which are either synchronous or metachronous, but the association is yet to be elucidated. With the improvement of diagnosis and treatment, there is an increase in breast and thyroid cancer survivors. Hence, attention is shifting towards survivorship. Here, we report the case of a young lady diagnosed with synchronous thyroid and breast cancer who unexpectedly became pregnant during tamoxifen treatment. After a multidisciplinary discussion, endocrine therapy was interrupted and she delivered a healthy baby at term. In conclusion, oncologists should be aware of breast and thyroid cancer co-occurrence and examinations should be conducted together in diagnosis and follow-up. Also, pregnancy is feasible and can be considered after synchronous breast and thyroid cancer diagnosis. Physicians need to emphasise the use of barrier contraceptives to patients undergoing endocrine therapy. However, the optimum timing for pregnancy after breast cancer and the safety of endocrine therapy interruption in hormonal-positive patients should be discussed and managed by a multidisciplinary team.

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Cited by 40 publications

References 25 publications

Response of Estrogen Receptor-Positive Breast Cancer Tumorspheres to Antiestrogen Treatments

Response of Estrogen Receptor-Positive Breast Cancer Tumorspheres to Antiestrogen Treatments

Hormonal status affects plasma exposure of tamoxifen and its main metabolites in tamoxifen-treated breast cancer patients

Tamoxifen exposure in pregnancy after synchronous breast and thyroid cancer

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