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1.
Zhonghua Fu Chan Ke Za Zhi ; 54(12): 848-853, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874475

RESUMO

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women's Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions: The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Moduladores de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Hemorragia Uterina/etiologia , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Terapia Combinada , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Estudos Retrospectivos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Índice de Gravidade de Doença , Ultrassonografia
2.
JAMA ; 322(9): 868-886, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479143

RESUMO

Importance: Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects. Objective: To update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women. Data Sources: Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists. Study Selection: Discriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects. Data Extraction and Synthesis: Investigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model. Main Outcomes and Measures: Probability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality. Results: A total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication. Conclusions and Relevance: Tamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Área Sob a Curva , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Mutação , Guias de Prática Clínica como Assunto , Cloridrato de Raloxifeno/efeitos adversos , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco/métodos , Fatores de Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos
3.
Expert Opin Drug Saf ; 18(10): 1001-1008, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394044

RESUMO

Objectives: Bazedoxifene was found to be effective and well tolerated for the treatment and prevention of osteoporosis in postmenopausal women. This post-marketing surveillance study (PMSS) examined the safety of bazedoxifene in postmenopausal Korean women with osteoporosis, in a real-world setting. Methods: This PMSS was conducted from 2013 to 2017. A total of 3,423 subjects from 68 centers were enrolled and monitored for about 3 months (± 2 weeks). Bazedoxifene was prescribed at a dose of 20 mg/day. The safety of bazedoxifene was evaluated based on the number and nature of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and serious ADRs (SADRs) in routine medical practice. Results: The mean age of study subjects was 69.51 years. The incidence of AEs and ADRs was 6.11% and 3.86%, respectively, and significantly decreased with increasing age (p= 0.0007). AE and ADR rates with bazedoxifene treatment of 3 months or more were significantly lower than those of less than 3 months (AE, 3.64% vs 30.00%, p < 0.0001; ADR, 1.74% vs 24.38%, p < 0.0001). Conclusion: In this study, bazedoxifene was well tolerated in the management of postmenopausal osteoporosis in Korean women, including those aged 70 years or more.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Indóis/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/efeitos adversos , Feminino , Humanos , Incidência , Indóis/efeitos adversos , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , República da Coreia , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Fatores de Tempo
4.
Breast Cancer ; 26(6): 766-775, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31172425

RESUMO

BACKGROUND: Icariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting. RESULTS: Here, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis. CONCLUSION: These results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Tamoxifeno/efeitos adversos , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Neoplasias da Mama/tratamento farmacológico , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Epimedium/química , Feminino , Humanos , Células MCF-7 , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/uso terapêutico , Transfecção
5.
J Endocrinol ; 241(3): R111-R124, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30991355

RESUMO

In women with oestrogen receptor (ER)-positive early breast cancer, oestradiol is important for breast cancer development and progression. Endocrine therapy prevents the deleterious effects of oestradiol in breast tissue by systemically depleting oestradiol concentration (aromatase inhibitors) or preventing its local action in breast tissue (selective oestrogen receptor modulators i.e. tamoxifen), thereby improving oncological outcomes. Use of aromatase inhibitors in postmenopausal women and ovarian function suppression with either tamoxifen or aromatase inhibition in premenopausal women, consequent to systemic oestradiol depletion, exerts detrimental effects on skeletal health. The oestradiol-deficient state causes increased bone remodelling and a negative bone balance. This results in bone loss, microstructural deterioration and bone fragility predisposing to fractures. Similar effects are also seen with tamoxifen in premenopausal women. In contrast, use of tamoxifen in postmenopausal women appears to exert protective effects on bone but studies on fracture risk are inconclusive. The longevity of women with ER-positive breast cancer treated with adjuvant endocrine therapy emphasises the need to mitigate the adverse skeletal effects of these therapies in order to maximise benefit. In general, fractures are associated with increased morbidity, mortality and are a high socioeconomic burden. Whilst the efficacy of antiresorptive therapy in preventing bone mineral density loss in postmenopausal women has been established, further clinical trial evidence is required to provide guidance regarding fracture risk reduction, when to initiate and stop treatment, choice of agent and optimal management of bone health in premenopausal women receiving endocrine therapy. In addition, potential oncological benefits of antiresorptive therapies will also need to be considered.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/complicações , Quimioterapia Adjuvante , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/fisiologia , Estradiol , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Guias de Prática Clínica como Assunto , Pré-Menopausa , Receptores Estrogênicos/metabolismo , Medição de Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/uso terapêutico
6.
Support Care Cancer ; 27(10): 3813-3822, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30729298

RESUMO

PURPOSE: To clarify the profile of adverse events from endocrine therapies in older patients. METHODS: We surveyed 15 subjective symptoms including hot flashes, sweating, knuckle stiffness, knee/shoulder joint pain, limb numbness, lethargy, forgetfulness, depressive state, irritated state, genital bleeding, leukorrhea increase, vaginal dryness, bone fracture, and weight gain by a questionnaire among 2044 patients over 55 years old (total number of answered sheets, 8875) and compared the results according to age (56-69 years old vs. ≥ 70 years old) and type of therapy (aromatase inhibitors (AIs) vs. selective estrogen receptor modulators (SERMs)). Among patients 56-69 years old, 6093 and 314 responses were from patients treated with AIs (1477 patients) and SERMs (123 patients), respectively, and 2292 and 176 responses were from those ≥ 70 years old treated with AIs (581 patients) and SERMs (51 patients), respectively. RESULTS: In patients ≥ 70 years old, sweating, knuckle stiffness, knee/shoulder joint pain, limb numbness, and lethargy were significantly more frequent/severe with AIs than with SERMs. In those aged 56-69, knuckle stiffness and vaginal dryness were significantly more frequent with AIs than with SERMs, but the opposite occurred for hot flashes, leukorrhea increase, genital bleeding, and weight gain. CONCLUSIONS: Among patients ≥ 70 years old, many symptoms were significantly more frequent/severe with AIs than with SERMs, compared with those aged 56-69, which suggests a difference in the profile of adverse events according to the type of endocrine therapy and the patient's age. It is important to consider the benefits and risks of each treatment to optimize endocrine therapy for older patients.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos , Fatores Etários , Idoso , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Artralgia/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Feminino , Fraturas Ósseas/prevenção & controle , Fogachos/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Inquéritos e Questionários , Sudorese/efeitos dos fármacos , Tamoxifeno/uso terapêutico
7.
Breast Cancer ; 26(5): 535-543, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30734152

RESUMO

BACKGROUND: An association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. The efficacy of TAM dose escalation appears limited in poor TAM metabolizers. Since the chlorine atom on the side chain of toremifene (TOR) prevents 4-hydroxylation by CYP2D6, its contribution to active conversion of TOR is minor. We examined the role of TOR and its dose escalation among poor TAM metabolizers. METHODS: The pharmacokinetics (PK) and pharmacogenomics (PGx) of TAM and TOR were studied. Correlation between PK and CYP2D6 inhibitor use, smoking status, and PGx were examined by regression analysis. For patients showing low endoxifen levels, an intra-patient dose escalation of TOR was conducted, and TOR was increased from 40 to 120 mg for ≥ 24 weeks with PK sampling. Total activity was calculated as the sum of the concentration of each active metabolite adjusted by their respective in vitro activities. RESULTS: Fifty and 11 of the 273 participating patients had endoxifen levels < 15 and < 7.5 ng/mL, respectively. The CYP2D6 genotype was the major determinant for TAM activity (p < 0.01). Smoking status (p = 0.07) and the CYP2C19 phenotype (p = 0.07), but not the CYP2D6 genotype (p = 0.61), showed marginally significant effects on TOR activity. TOR activity increased significantly with dose escalation, even among poor TAM metabolizers, and was maintained for ≥ 24 weeks. CONCLUSION: TOR might be a valid alternative to TAM in patients predicted to be poor TAM metabolizers.


Assuntos
Neoplasias da Mama/metabolismo , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Genótipo , Moduladores Seletivos de Receptor Estrogênico/farmacocinética , Tamoxifeno/análogos & derivados , Toremifeno/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Inibidores do Citocromo P-450 CYP2D6/uso terapêutico , Feminino , Fogachos/etiologia , Humanos , Hidroxilação , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Fumar , Tamoxifeno/análise , Toremifeno/administração & dosagem , Toremifeno/efeitos adversos , Toremifeno/uso terapêutico
8.
Pathol Res Pract ; 215(5): 1089-1092, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30799070

RESUMO

It is well known that a large number of patients treated with Tamoxifen develops endometrial pathologies ranging from benign endometrial polyps and hyperplasia to adenocarcinomas, carcinosarcomas and adenosarcomas. UTROSCT (Uterine Tumor Resembling Ovarian Sex Cord Tumor) is defined as a mesenchymal tumors of the uterine corpus that morphologically resembles ovarian sex cord tumors, without recognizable endometrial stroma. To date only 4 cases have been reported in patients treated with tamoxifen. In this article, we describe an additional case occurring in a 62-years-old patient undergoing 3 years of Tamoxifen therapy for bilateral breast carcinoma. The present work represents a further evidence of the possible association between Tamoxifen therapy and UTROSCT. A comprehensive literature review on this topic is also provided.


Assuntos
Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tumores do Estroma Gonadal e dos Cordões Sexuais/induzido quimicamente , Tamoxifeno/efeitos adversos , Neoplasias Uterinas/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Comorbidade , Feminino , Humanos , Leiomioma/epidemiologia , Leiomioma/cirurgia , Pessoa de Meia-Idade
9.
Menopause ; 26(6): 611-621, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30694917

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of ospemifene for the treatment of moderate to severe vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA). METHODS: This 12-week, multicenter, double-blind phase 3 study randomized postmenopausal women (aged 40-80 years) with VVA and moderate to severe vaginal dryness as their most bothersome symptom to daily oral ospemifene 60 mg or placebo. Coprimary efficacy endpoints included changes from baseline to week 12 in percentages of vaginal parabasal and superficial cells, vaginal pH, and vaginal dryness severity with ospemifene versus placebo; other secondary endpoints were evaluated (weeks 4, 8, and 12). Safety was assessed by treatment-emergent adverse events (TEAEs) and endometrial biopsies. RESULTS: Women (n = 631; ospemifene [n = 316], placebo [n = 315]) had a mean age of 59.8 years, a mean body mass index of 27.2 kg/m, and most were white. Ospemifene significantly improved (P < 0.0001) the percentages of parabasal and superficial cells, vaginal pH, and severity of vaginal dryness severity compared with placebo at week 12; significant between-group differences were noted by week 4. Secondary endpoints of dyspareunia (P < 0.001), maturation value (P < 0.0001), and the Female Sexual Function Index (P < 0.05) also significantly improved with ospemifene versus placebo at week 12. Significantly more women responded (31.5% vs 6.0%; P < 0.0001) or were satisfied (49.2% vs 33.8%; P = 0.0007) with ospemifene versus placebo at week 12. No unexpected TEAEs, treatment-related serious TEAEs, thrombotic events, or endometrial hyperplasia or carcinoma were observed. CONCLUSIONS: Ospemifene was effective and well tolerated for the treatment of moderate-to-severe vaginal dryness in postmenopausal women with VVA.


Assuntos
Pós-Menopausa/fisiologia , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Índice de Gravidade de Doença , Tamoxifeno/análogos & derivados , Vagina/patologia , Doenças Vaginais/tratamento farmacológico , Vulva/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/tratamento farmacológico , Método Duplo-Cego , Dispareunia/tratamento farmacológico , Feminino , Fogachos/etiologia , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Resultado do Tratamento
10.
Aging Male ; 22(2): 89-101, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29508640

RESUMO

Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osteoporose/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Animais , Osso e Ossos/patologia , Modelos Animais de Doenças , Humanos , Masculino , Osteoporose/etiologia , Osteoporose/fisiopatologia , Neoplasias da Próstata/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos
11.
Bull Cancer ; 106(12S1): S75-S100, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-32008741

RESUMO

INTRODUCTION: Objectives: the purpose of this study is to assess TAM safety in terms of side effects and hormonal status, the persistence of the treatment over a five years time-frame and to report the remote follow-up data. METHODS: Fifty five patients were included patients between January 2001 and November 2002 at the Institut de cancérologie de Lorraine. The subjects were aged 50 years or less, premenopausal at diagnosis and treated with adjuvant TAM therapy at a daily dose of 20 mg, for an expected duration of 5 years, at a daily. After 2 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in the institution (1x/year). All data were retrospectively evaluated in 2019. RESULTS: In these 55 patients, the cumulative incidences of cysts and hot flushes 5 years after treatment were 68.5 % and 77.6 %, respectively. Of the 33 patients with chemoreactive amenorrhea, half had cycles which resumed within a median of 9 months. In the 10 patients without chemotherapy-induced amenorrhea, 4 had a cycle stop. Of these, 3 patients had cycles that, resumed within 1, 4 and 8 months. 34 patients (61.3 %) had taken Tamoxifen for at least 5 years. After 15 years of treatment, overall and progression-free survival was 90.7 % and 67.4 %, respectively. CONCLUSION: The observation of the tolerance to the treatment for 5 years and beyond, contributes to the quality of information delivered to future patients starting the treatment, allowing a better understanding and in the long term a better observance.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Pré-Menopausa , Tamoxifeno/efeitos adversos , Adulto , Amenorreia/induzido quimicamente , Antineoplásicos Hormonais/administração & dosagem , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/mortalidade , Institutos de Câncer , Quimioterapia Adjuvante , Feminino , Seguimentos , França , Fogachos/induzido quimicamente , Fogachos/epidemiologia , Humanos , Incidência , Cistos Ovarianos/induzido quimicamente , Cistos Ovarianos/epidemiologia , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/administração & dosagem , Fatores de Tempo
12.
Postgrad Med ; 130(8): 687-693, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30280946

RESUMO

OBJECTIVE: In the 1-year phase 3 Selective estrogens, Menopause, And Response to Therapy-5 trial, cumulative amenorrhea rates with conjugated estrogens/bazedoxifene (CE/BZA) were similar to placebo and higher than with conjugated estrogens/medroxyprogesterone acetate (CE/MPA). This post hoc analysis reports bleeding/spotting rates in 4-week intervals (cycles) and 3-month intervals (quarters) with these therapies and the percentage of cases attributable to spotting only. METHODS: Generally healthy postmenopausal women with menopausal symptoms recorded vaginal bleeding/spotting in daily diaries while receiving CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, CE 0.45 mg/MPA 1.5 mg, or placebo. RESULTS: A total of 1596 women in the modified intent-to-treat population contributed data. Incidence of bleeding/spotting was significantly (p < 0.001) lower with CE 0.45 mg/BZA 20 mg (0.54‒4.44%), CE 0.625 mg/BZA 20 mg (1.26‒5.02%), and placebo (1.55‒4.82%) compared with CE 0.45 mg/MPA 1.5 mg (8.81‒25.63%) in all 4-week cycles. Each quarter, <10% of women taking CE/BZA doses or placebo had bleeding/spotting, significantly (p < 0.001) less than the 21-36% with CE 0.45 mg/MPA 1.5 mg. Odds ratio for bleeding/spotting with CE 0.45 mg/BZA 20 mg vs CE 0.45 mg/MPA 1.5 mg was 0.1 in each quarter (95% CI, Q1-Q3: 0.1-0.2; Q4: 0.1-0.3). Across all treatments, most (88-100%) bleeding/spotting cases were spotting only. Mean days of bleeding/spotting were <1 per quarter with CE/BZA doses and placebo, which was significantly (p < 0.01) less than the 3-5 days per quarter with CE/MPA. CONCLUSIONS: Bleeding/spotting with CE/BZA treatment was similar to placebo and significantly less frequent than with CE/MPA treatment. Most cases were spotting only across all treatments.


Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/efeitos adversos , Indóis/efeitos adversos , Acetato de Medroxiprogesterona/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Terapia de Reposição de Estrogênios/métodos , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Indóis/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem
13.
Drug Dev Res ; 79(6): 275-286, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30284735

RESUMO

Breast cancer is the most common type of diagnosed cancers in women, difficult to treat, and has received international attention because of its aggressive nature and inherent drug resistance mechanisms. Development of a better selective estrogen receptor modulator with good therapeutic profile and less toxicity is very crucial in this scenario. This study was undertaken to evaluate and compare the in vitro and in vivo antitumor activities of ormeloxifene with other clinically used breast cancer drugs. Cytotoxic activity of ormeloxifene was compared with standard drugs, 4-hydroxytamoxifene and Adriamycin. Ormeloxifene (50 µM) concentration showed cytotoxicity of 75% and 82% in MDAMB-231 and 24% and 80% in MCF-7 cells, respectively, after 72 and 144 hr of incubation as displayed by cell viability assay. The same concentration of ormeloxifene was shown to exert 74% caspase-7 activation in MCF-7 cells after 24 hr of incubation by fluorescence resonance energy transfer assay. Cell cycle analysis proved that there was an increase in sub-G1 peak to 64.4% and 33.9% in MDAMB-231 and MCF-7 cells, respectively, after treatment using ormeloxifene (50 µM) for 48 hr. The nonobese diabetic-severe combined immunodeficiency mice bearing tumor xenografts of triple negative MDAMB-231 cells treated with ormeloxifene (3 mg/kg bw) showed significant regression in relative tumor volume compared to control. From the results obtained and as evidenced from prior literature, ormeloxifene in addition to contraceptive use, can be repositioned for the development of an efficacious anticancer drug. These data present the preclinical part of a well concerted effort to place ormeloxifene into further clinical trials.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/química , Benzopiranos/administração & dosagem , Benzopiranos/química , Neoplasias da Mama/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Animais , Antineoplásicos/efeitos adversos , Benzopiranos/efeitos adversos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos
14.
Heart ; 104(22): 1859-1863, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29720397

RESUMO

OBJECTIVE: A prolonged QTc (LQT) is a surrogate for the risk of torsade de pointes (TdP). QTc interval duration is influenced by sex hormones: oestradiol prolongs and testosterone shortens QTc. Drugs used in the treatment of breast cancer have divergent effects on hormonal status. METHODS: We performed a disproportionality analysis using the European database of suspected adverse drug reaction (ADR) reports to evaluate the reporting OR (ROR χ2) of LQT, TdP and ventricular arrhythmias associated with selective oestrogen receptor modulators (SERMs: tamoxifen and toremifene) as opposed to aromatase inhibitors (AIs: anastrozole, exemestane and letrozole). When the proportion of an ADR is greater in patients exposed to a drug (SERMs) compared with patients exposed to control drug (AIs), this suggests an association between the specific drug and the reaction and is a potential signal for safety. Clinical and demographic characterisation of patients with SERMs-induced LQT and ventricular arrhythmias was performed. RESULTS: SERMs were associated with higher proportion of LQT reports versus AIs (26/8318 vs 11/14851, ROR: 4.2 (2.11-8.55), p<0.001). SERMs were also associated with higher proportion of TdP and ventricular arrhythmia reports versus AIs (6/8318 vs 2/14851, ROR: 5.4 (1.29-26.15), p:0.02; 16/8318 vs 12/14851, ROR: 2.38 (1.15-4.94), p:0.02, respectively). Mortality was 38% in patients presenting ventricular arrhythmias associated with SERMs. CONCLUSIONS: SERMs are associated with more reports of drug-induced LQT, TdP and ventricular arrhythmias compared with AIs. This finding is consistent with oestradiol-like properties of SERMs on the heart as opposed to effects of oestrogen deprivation and testosterone increase induced by AIs. TRIAL REGISTRATION NUMBER: NCT03259711.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Inibidores da Aromatase/efeitos adversos , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos , Torsades de Pointes/induzido quimicamente , Potenciais de Ação/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiotoxicidade , Bases de Dados Factuais , Europa (Continente)/epidemiologia , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/mortalidade , Síndrome do QT Longo/fisiopatologia , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Torsades de Pointes/diagnóstico , Torsades de Pointes/mortalidade , Torsades de Pointes/fisiopatologia , Adulto Jovem
15.
Clin Cancer Res ; 24(15): 3510-3518, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29440181

RESUMO

Purpose: AZD9496 is an oral nonsteroidal, small-molecule inhibitor of estrogen receptor alpha (ERα) and a potent and selective antagonist and degrader of ERα. This first-in-human phase I study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity.Patients and Methods: Forty-five patients received AZD9496 [20 mg once daily (QD) to 600 mg twice daily (BID)] in a dose-escalation, dose-expansion "rolling 6" design. Safety, tolerability, and PK activity in each cohort were reviewed before escalating to the next dose. PK was determined by mass spectrometry. Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Objective tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.Results: Most common causally related AEs were diarrhea (35.6%), fatigue (31.1%), and nausea (22.2%), and seven patients had grade ≥3 AEs. Three patients experienced a dose-limiting toxicity: one each at 150 mg BID (abnormal hepatic function), 400 mg BID (diarrhea and elevated liver function tests), and 600 mg BID (diarrhea), and all were reversible. The maximum tolerated dose was not reached. Partial response was confirmed in one patient, who also had decreased tumor marker Ca15.3. Four patients had stable disease at 12 months' follow-up.Conclusions: AZD9496 is well tolerated with an acceptable safety profile, showing evidence of prolonged disease stabilization in heavily pretreated patients with ER+/HER2- advanced breast cancer. Clin Cancer Res; 24(15); 3510-8. ©2018 AACRSee related commentary by Jordan, p. 3480.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cinamatos/administração & dosagem , Indóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Cinamatos/efeitos adversos , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Indóis/efeitos adversos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2/genética , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos
16.
Cell Res ; 28(3): 336-358, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29393296

RESUMO

The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer.


Assuntos
Aldeído Desidrogenase/metabolismo , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/agonistas , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos , Transcrição Genética/efeitos dos fármacos , Aldeído Desidrogenase/antagonistas & inibidores , Inibidores da Aromatase/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Estudos de Coortes , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Metástase Neoplásica , Retinal Desidrogenase , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico
17.
Clin Cancer Res ; 24(10): 2312-2318, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29459457

RESUMO

Purpose: Levels of endoxifen, the most active metabolite of tamoxifen, vary by the highly polymorphic cytochrome P450 (CYP) 2D6 enzyme. We prospectively investigated tamoxifen efficacy by serum endoxifen levels and the tamoxifen activity score (TAS).Experimental Design: A prospective observational multicenter study included postmenopausal women with an estrogen receptor-positive breast cancer receiving first-line tamoxifen, 20 mg daily in the neoadjuvant or metastatic setting, recruited between February 2009 and May 2014. The primary endpoint was the objective response rate (ORR) using RECIST criteria 1.0. Secondary endpoints were clinical benefit (CB), progression-free survival (PFS), and tolerability of tamoxifen. The main analysis used logistic regression to relate ORR to serum endoxifen levels after 3 months. Endpoints were also related to other tamoxifen metabolites and to TAS.Results: Endoxifen levels were available for 247 of all 297 patients (83%), of which 209 with target lesions (85%). Median follow-up time for PFS was 32.5 months, and 62% progressed. ORR and CB were 45% and 84%, respectively. ORR was not related to endoxifen, and the OR of ORR was 1.008 per µg/L increase in endoxifen (95% confidence interval, 0.971-1.046; P = 0.56). In general, none of the endpoints was associated with endoxifen levels, tamoxifen metabolites, or TAS.Conclusions: Under the prespecified assumptions, the results from this prospective clinical trial do not suggest therapeutic drug monitoring of endoxifen to be of clinical value in postmenopausal women treated with tamoxifen for breast cancer in the neoadjuvant or metastatic setting. Clin Cancer Res; 24(10); 2312-8. ©2018 AACR.


Assuntos
Antineoplásicos Hormonais/farmacocinética , Neoplasias da Mama/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/farmacocinética , Tamoxifeno/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Monitoramento de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Receptores Estrogênicos/metabolismo , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos , Resultado do Tratamento
18.
Gynecol Endocrinol ; 34(2): 140-143, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28853624

RESUMO

Aim of this study was to evaluate the efficacy of ospemifene in the prevention of recurrent lower urinary tract infections in postmenopausal women with vulvovaginal atrophy. The study have a retrospective design. Thirty-nine patients were enrolled. Patients underwent clinical examination and urine culture. The urinary symptoms and the quality of life were evaluated with UTISA score, PUF and SF-36 questionnaires before and after treatment. All 39 patients received ospemifene 60 mg one tablet/daily for 6 months. Adverse effects and complications were assessed. Thirty-nine patients were enrolled in the study. Two patients experienced one new UTI episode and the mean number of positive urine culture decreased significantly after 6 months (3.65 ± 2.12 vs 0.25 ± 0.17, p < .0001). The mean number of urinary infection symptoms decreased significantly after treatment; dysuria reduced (4.76 ± 2.45 vs 0.89 ± 1.12). PUF score and SF-36 showed a statistically significant change (22.43 ± 5.89 vs 12.14 ± 3.21) and (52.86 ± 9.21 vs 83.43 ± 10.76). No adverse effects were reported and the total success rate was the 92.3% after 6 months at PGI-I. Ospemifene is a valid alternative with excellent tolerability for the UTIS prevention in postmenopausal patients.


Assuntos
Vaginite Atrófica/tratamento farmacológico , Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/análogos & derivados , Infecções Urinárias/prevenção & controle , Vulvovaginite/tratamento farmacológico , Idoso , Vaginite Atrófica/complicações , Vaginite Atrófica/fisiopatologia , Vaginite Atrófica/urina , Disuria/etiologia , Disuria/prevenção & controle , Feminino , Seguimentos , Hospitais Universitários , Humanos , Itália/epidemiologia , Perda de Seguimento , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Autorrelato , Índice de Gravidade de Doença , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Urina/microbiologia , Vulvovaginite/complicações , Vulvovaginite/fisiopatologia , Vulvovaginite/urina
19.
Menopause ; 25(3): 273-285, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29088019

RESUMO

OBJECTIVE: The aim of the study was to explore dose-related endometrial effects of conjugated estrogens/bazedoxifene (CE/BZA). METHODS: In this randomized, double-blind, phase 2 study, 408 nonhysterectomized, symptomatic (with hot flushes [HFs]) postmenopausal women received ≥1 dose of CE 0.3 or 0.625 mg alone or with BZA 5, 10, or 20 mg/d; placebo; BZA 5 mg/d alone; or CE 0.625 mg with medroxyprogesterone acetate 2.5 mg/d for 84 days. The primary outcome was endometrial thickness on transvaginal ultrasound. HF frequency and severity based on diaries were key secondary outcomes. RESULTS: CE 0.625 mg alone increased endometrial thickness compared with placebo (mean 5.5 vs 2.95 mm, P < 0.001); BZA countered this in a dose-related manner such that average thickness with the addition of BZA 5, 10, and 20 mg was 5.99, 4.33, and 3.54 mm, respectively. On average, endometrium was significantly less thick with CE 0.625 mg/BZA 20 mg than CE 0.625 mg (P < 0.001) and CE 0.3 mg/BZA 20 mg versus CE 0.3 mg (2.94 vs 3.92 mm, P < 0.05); endometrial thickness was similar to placebo with CE 0.625 mg/BZA 20 mg. Lower BZA doses failed to reduce endometrial thickness relative to the same dose of CE alone. Regimens containing CE 0.625 mg reduced HF frequency and severity versus placebo; CE 0.3 mg with BZA 10 or 20 mg was ineffective. CONCLUSIONS: BZA ≥20 mg is needed to counter endometrial growth resulting from treatment with CE 0.3 or 0.625 mg. CE 0.3 mg inadequately controls HFs if given with BZA 20 mg.


Assuntos
Endométrio/efeitos dos fármacos , Estrogênios Conjugados (USP)/administração & dosagem , Indóis/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Endométrio/diagnóstico por imagem , Estrogênios Conjugados (USP)/efeitos adversos , Estrogênios Conjugados (USP)/farmacologia , Feminino , Fogachos/tratamento farmacológico , Humanos , Indóis/efeitos adversos , Indóis/farmacologia , Pessoa de Meia-Idade , Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Ultrassonografia
20.
Anticancer Res ; 37(10): 5329-5341, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28982841

RESUMO

The benefits of five years of adjuvant endocrine therapy for oestrogen receptor (ER)-positive early breast cancer are well established. However, recent evidence suggests that extended endocrine treatment and ovarian suppression in selected groups of patients have significant advantages. In this article, we review the current evidence for adjuvant endocrine therapy in breast cancer with focus on extended adjuvant endocrine therapy and ovarian suppression, and also highlight the advantages and disadvantages of these therapeutic strategies. A literature search was performed through PubMed, Medline, and Cochrane using the following search terms: Endocrine therapy, Tamoxifen, Anastrazole, Ovarian Suppression, Exemestane, Letrozole and STS Inhibitors. All available evidence for adjuvant endocrine therapy was reviewed and summarised to assess the current guidance and the progress of the management of patients with ER-positive breast cancer. Extended endocrine therapy should be tailored according to patient needs dictated by their individual risk factors, molecular type of breast cancer, menopausal status, comorbidities, life style and risk of recurrence. Clinicians ought to discuss with patients the pros and cons of different adjuvant endocrine therapy approaches and highlight the potential side effects and toxicity.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Ovário/efeitos dos fármacos , Receptores Estrogênicos/antagonistas & inibidores , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Humanos , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Ovário/metabolismo , Ovário/fisiopatologia , Seleção de Pacientes , Receptores Estrogênicos/metabolismo , Fatores de Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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