scholarly journals New opportunities of pharmacogenetics approach to personalized tamoxifen therapy (updated systematic review)

2020 ◽  
pp. 42-56
Author(s):  
M. I. Savelyeva ◽  
I. V. Poddubnaya
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Current Data ◽  
Tamoxifen Treatment ◽  
Individual Response ◽  
Active Metabolites ◽  
Tamoxifen Metabolites ◽  
High Interindividual Variability ◽  
Genes Encoding ◽  
Personalized Approach

Tamoxifen is the selective modulator of estrogen receptors. Nowadays, it is widely used in the treatment of ER(+) breast cancer and substantially decreases the risks of recurrence and disease progression. However, high interindividual variability in response is observed, calling for a personalized approach to tamoxifen treatment. Tamoxifen is metabolized by cytochrome P450, resulting in the formation of active metabolites, including 4-hydroxy-tamoxifen and endoxifen. The effectiveness and success of treatment depends largely on concentrations of the active tamoxifen metabolites in blood plasma. Polymorphisms in the genes encoding these enzymes are proposed to influence on pharmacokinetics and pharmacodynamics of tamoxifen. Therefore, pharmacogenetic approach may form the basis of personalized treatment of breast cancer. In the updated systematic review, we analyze all current data about the potential use of genotyping of CYP2D6, CYP2С19, CYP3A4/5, CYP2B6 to predict an individual response on tamoxifen treatment.

Perspectives of pharmacogenetics approach to personalized tamoxifen therapy

2017 ◽  
Vol 1 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Marina I. Savelyeva ◽  
Julia S. Panchenko ◽  
Irina A. Urvantseva ◽  
Anna K. Ignatova ◽  
Irina V. Poddubnaya
Keyword(s):  
Breast Cancer ◽  
Current Data ◽  
Tamoxifen Treatment ◽  
Individual Response ◽  
Active Metabolites ◽  
Tamoxifen Metabolites ◽  
High Interindividual Variability ◽  
Genes Encoding ◽  
Personalized Approach ◽  
Success Of Treatment

Tamoxifen is the selective modulator of estrogen receptors. Nowadays, it is widely used in the treatment of ER(+) breast cancer and substantially decreases the risks of recurrence and disease progression. However, high interindividual variability in response is observed, calling for a personalized approach to tamoxifen treatment. Tamoxifen is metabolized by cytochrome P450, resulting in the formation of active metabolites, including 4-hydroxy-tamoxifen and endoxifen. The effectiveness and success of treatment depends largely on concentrations of the active tamoxifen metabolites in blood plasma. Polymorphisms in the genes encoding these enzymes are proposed to influence on pharmacokinetics and pharmacodynamics of tamoxifen. Therefore, pharmacogenetic approach may form the basis of personalized treatment of breast cancer. In this systematic review, we analyze all current data about the potential use of genotyping of CYP2D6, CYP3A4/5, CYP2B6 to predict an individual response on tamoxifen treatment.

scholarly journals Does Exercise Have a Preventive Effect on Secondary Lymphedema in Breast Cancer Patients Following Local Treatment - A Systematic Review

Breast Care ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. 380-385 ◽  
Author(s):  
Freerk T. Baumann ◽  
Alexandra Reike ◽  
Michael Hallek ◽  
Joachim Wiskemann ◽  
Vanessa Reimer
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Strength Training ◽  
Local Treatment ◽  
Exercise Group ◽  
Current Data ◽  
Cochrane Library ◽  
Breast Cancer Patients ◽  
Preventive Effect ◽  
Secondary Lymphedema

Background: Secondary lymphedema (SL) is a possible side effect of breast cancer treatment. Current data describe a positive influence of exercise on upper lymphedema. This systematic review evaluates studies examining a potential preventive effect of exercise on SL incidence. Methods: A systematic literature search of PubMed, LIVIVO, and the Cochrane Library was performed. Results: 8 randomized controlled trials were included in the review. 3 studies investigated the effect of strength training, and 5 the effect of combined exercise therapy. 5 studies included participants without lymphedema at study entry, and 3 studies included both patients with and without lymphedema. The partly significant results showed that progressive strength training as well as combined dynamic exercise therapies consisting of physiotherapy, physical therapy, and/or kinesiotherapy are safe and can prevent SL. Onset as well as diagnosis of lymphedema were significantly decreased in 5 studies in the exercise group. Conclusion: All 8 studies included indicate a potential preventive effect of exercise on SL; however, further research is needed.

scholarly journals Opportunities of the pharmacogenetic approach to personalized tamoxifen breast cancer therapy: case reports

2019 ◽  
Vol 21 (1) ◽  
pp. 24-30
Author(s):  
Marina I Savelyeva ◽  
Irina A Dudina ◽  
Juliya S Zaharenkova ◽  
Anna K Ignatova ◽  
Kristina A Ryzhikova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Effects ◽  
Case Reports ◽  
Tamoxifen Resistance ◽  
Premenopausal Women ◽  
Individual Response ◽  
Clinical Effects ◽  
Active Metabolites ◽  
Clinical Value ◽  
Luminal A

Tamoxifen is the selective modulator of estrogen receptors. Nowadays, it is widely used for treatment of premenopausal women with ER(+) breast cancer likewise for postmenopausal women with treatment contraindications to aromatase inhibitors. Tamoxifen is a prodrug which is metabolized by cytochrome P450 (CYP): CYP2D6, CYP3A4, CYP3A5, CYP2C9, CYP2C19 to active metabolites. There is high variability in the CYP genes therefore differences in tamoxifen metabolism, tamoxifen individual response and efficacy are observed among patients. This article presents two clinical case reports. Both patients have breast cancer luminal A subtype, similar prognosis and are administered tamoxifen but they have diverse clinical effects. Patients responded to the survey questionnaire, then samples of buccal epithelium were taken for genetic analysis of CYP2D6*4, CYP3A5*3, CYP3A4*17, CYP2C9*2,3, CYP2C19*2,3, ABCB1 gene mutations by use of real time PCR. In patient A samples were detected significant mutations in CYP2D6 (*1/*4), CYP3A5 (*3/*3) и CYP2С9 (*2/*3), but there were no mutations detected in patient B. It is interesting that patient B has had prominent tamoxifen adverse effects, such as flushes, ostealgia, faintness, after 1 month of tamoxifen therapy. Patient A has taken tamoxifen for 19 months without any adverse effects. Also there is a review in this article about clinical value of different CYP2D6, CYP3A5, CYP2C9 polymorphisms. Additionally, we make a suggestion about the role of polymorphisms in tamoxifen adverse effects and the way of solution for problems of tamoxifen resistance. We suppose that routine genetic study before tamoxifen administration would help to predict individual intolerance and increase the efficacy of treatment.

scholarly journals Microsurgical techniques in the treatment of breast cancer-related lymphedema: a systematic review of efficacy and patient outcomes

Breast Cancer ◽  
2021 ◽  
Author(s):  
Konstantinos Gasteratos ◽  
Antonios Morsi-Yeroyannis ◽  
Nikolaos Ch. Vlachopoulos ◽  
Georgia-Alexandra Spyropoulou ◽  
Gabriel Del Corral ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Patient Outcomes ◽  
Systematic Reviews ◽  
Donor Site ◽  
Surgical Techniques ◽  
Current Data ◽  
Lymph Vessel ◽  
Compression Garments ◽  
Breast Cancer Related Lymphedema

Abstract Introduction Secondary lymphedema is the abnormal collection of lymphatic fluid within subcutaneous structures. Patients with lymphedema suffer a low quality of life. In our study, we aim to provide a systematic review of the current data on patient outcomes regarding breast cancer-related lymphedema (BCRL), and the most prevalent reconstructive techniques. Methods A PubMed (MEDLINE) and Scopus literature search was performed in September 2020. Studies were screened based on inclusion/exclusion criteria. The protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO), and it was reported in line with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results The search yielded 254 papers from 2010 to 2020. 67 were included in our study. Lymphaticovenous anastomosis (LVA)—a minimally invasive procedure diverting the lymph into the dermal venous drainage system—combined with postoperative bandaging and compression garments yields superior results with minimal donor site lymphedema morbidity. Vascularized lymph node transfer (VLNT)—another microsurgical technique, often combined with autologous free flap breast reconstruction—improves lymphedema and brachial plexus neuropathies, and reduces the risk of cellulitis. The combination of LVA and VLNT or with other methods maximizes their effectiveness. Vascularized lymph vessel transfer (VLVT) consists of harvesting certain lymph vessels, sparing the donor site’s lymph nodes. Conclusion Together with integrated lymphedema therapy, proper staging, and appropriate selection of procedure, safe and efficient surgical techniques can be beneficial to many patients with BCRL.

scholarly journals Tamoxifen Exposure during Pregnancy: A Systematic Review and Three More Cases

Breast Care ◽  
2019 ◽  
Vol 15 (2) ◽  
pp. 148-156 ◽  
Author(s):  
Barbara Buonomo ◽  
Antonella Brunello ◽  
Stefania Noli ◽  
Loredana Miglietta ◽  
Lucia Del Mastro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Young Women ◽  
Tamoxifen Treatment ◽  
Review Of The Literature ◽  
Hormone Receptor Positive ◽  
Premenopausal Patients ◽  
Exposure During Pregnancy ◽  
Challenging Situation ◽  
Barrier Contraception

Tamoxifen is frequently used as adjuvant treatment in premenopausal patients with hormone receptor-positive early breast cancer. According to guidelines, the use of nonhormonal barrier contraception is recommended during tamoxifen treatment and up to 3 months after its interruption prior to attempting conception. Nevertheless, when conception occurs inadvertently during tamoxifen treatment, the effects on the fetus and on the course of pregnancy are still not completely known. Here, we report 3 cases of young women who accidentally became pregnant while taking tamoxifen and perform a systematic review of the literature to provide more elements for better and clear multidisciplinary counselling of women facing this challenging situation.

scholarly journals Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer

2021 ◽  
Vol 11 (3) ◽  
pp. 201
Author(s):  
Thomas Helland ◽  
Sarah Alsomairy ◽  
Chenchia Lin ◽  
Håvard Søiland ◽  
Gunnar Mellgren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tamoxifen Treatment ◽  
Prediction Algorithm ◽  
Endocrine Treatment ◽  
Cyp2d6 Genotype ◽  
Active Metabolites ◽  
Metabolic Resistance ◽  
Metabolite Concentrations ◽  
Tamoxifen Efficacy ◽  
Endoxifen Concentration

Tamoxifen is an endocrine treatment for hormone receptor positive breast cancer. The effectiveness of tamoxifen may be compromised in patients with metabolic resistance, who have insufficient metabolic generation of the active metabolites endoxifen and 4-hydroxy-tamoxifen. This has been challenging to validate due to the lack of measured metabolite concentrations in tamoxifen clinical trials. CYP2D6 activity is the primary determinant of endoxifen concentration. Inconclusive results from studies investigating whether CYP2D6 genotype is associated with tamoxifen efficacy may be due to the imprecision in using CYP2D6 genotype as a surrogate of endoxifen concentration without incorporating the influence of other genetic and clinical variables. This review summarizes the evidence that active metabolite concentrations determine tamoxifen efficacy. We then introduce a novel approach to validate this relationship by generating a precision endoxifen prediction algorithm and comprehensively review the factors that must be incorporated into the algorithm, including genetics of CYP2D6 and other pharmacogenes. A precision endoxifen algorithm could be used to validate metabolic resistance in existing tamoxifen clinical trial cohorts and could then be used to select personalized tamoxifen doses to ensure all patients achieve adequate endoxifen concentrations and maximum benefit from tamoxifen treatment.

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