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1.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542023

RESUMO

We report a case of ischaemic stroke in a 34-year-old male recreational bodybuilder following a 3-month period of anabolic androgenic steroid (AAS) use and 1-month period of 'post-cycle therapy' (tamoxifen and clomiphene citrate), the latter treatments aimed at restoring normal endogenous testosterone production after initial AAS use. We hypothesise a transient drug-related prothrombotic state with paradoxical embolisation via an atrial septal defect which was later found on bubble echocardiogram. We highlight a rare but important cause of stroke in younger patients which is relevant given the increasing use of AAS misuse among casual fitness enthusiasts. We explore the various possible mechanisms by which AAS use can increase ischaemic stroke risk in such patients.


Assuntos
Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/diagnóstico por imagem , Doping nos Esportes , Exercício Físico/fisiologia , /diagnóstico por imagem , Congêneres da Testosterona/efeitos adversos , Administração Intravenosa , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aspirina/uso terapêutico , Atorvastatina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Clomifeno/administração & dosagem , Clomifeno/efeitos adversos , Ecocardiografia , Antagonistas de Estrogênios/administração & dosagem , Antagonistas de Estrogênios/efeitos adversos , Comunicação Interatrial/cirurgia , Humanos , Masculino , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos
2.
Lancet Oncol ; 22(2): 212-222, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33460574

RESUMO

BACKGROUND: Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer. METHODS: PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II-III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1-21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30). FINDINGS: Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9-29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2-90·6) for palbociclib plus endocrine therapy and 88·5% (85·8-90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76-1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3-4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths. INTERPRETATION: At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing. FUNDING: Pfizer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Piperazinas/administração & dosagem , Piridinas/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Modelos de Riscos Proporcionais , Piridinas/efeitos adversos , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Tamoxifeno/administração & dosagem
3.
Bull Cancer ; 107(11): 1171-1185, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-32988609

RESUMO

Breast cancer is the most frequently diagnosed cancer in women and the first cause of cancer death in France. Among the different subtypes of breast cancer, the predominant form is characterized by positive hormone receptors (more than 70% of breast cancers). Hormone therapy thus plays a key role in the strategy of management of these cancers both in adjuvant and metastatic situations. The two types of adjuvant hormone therapy used are selective estrogen receptor modulators and aromatase inhibitors. Fulvestrant, an anti-estrogen, is used alone or in combination with other molecules in metastatic situations. Hot flashes are one of the symptoms most frequently reported by patients under hormone therapy. Hormone replacement therapy, which is currently the most effective treatment for hot flashes, is contraindicated in patients with a personal history of breast cancer. Various therapeutic classes of drugs have been tested in this indication but without real efficacy in the various studies carried out to date, and moreover associated with non-negligible side effects. The recent discovery of the implication of the kisspeptin system located at the hypothalamic level in the mechanism of genesis of hot flashes opens the way to possible new symptomatic treatments for hot flashes. Neurokinin 3 receptor antagonists have shown encouraging preliminary results in postmenopausal cancer-free patients and could be considered in patients in hormonal therapy for breast cancer. Broader additional studies are needed to confirm these initial results.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/tratamento farmacológico , Fogachos/etiologia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Contraindicações de Medicamentos , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Fulvestranto/uso terapêutico , Humanos , Kisspeptinas/fisiologia , Ovário/efeitos dos fármacos , Ovário/cirurgia , Receptores da Neurocinina-3/antagonistas & inibidores , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Tamoxifeno/administração & dosagem , Tamoxifeno/uso terapêutico
4.
PLoS One ; 15(7): e0235232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735618

RESUMO

The tamoxifen-dependent Cre/lox system in transgenic mice has become an important research tool across all scientific disciplines for manipulating gene expression in specific cell types. In these mouse models, Cre-recombination is not induced until tamoxifen is administered, which allows researchers to have temporal control of genetic modifications. Interestingly, tamoxifen has been identified as a potential therapy for spinal cord injury (SCI) and traumatic brain injury patients due to its neuroprotective properties. It is also reparative in that it stimulates oligodendrocyte differentiation and remyelination after toxin-induced demyelination. However, it is unknown whether tamoxifen is neuroprotective and neuroreparative when administration is delayed after SCI. To properly interpret data from transgenic mice in which tamoxifen treatment is delayed after SCI, it is necessary to identify the effects of tamoxifen alone on anatomical and functional recovery. In this study, female and male mice received a moderate mid-thoracic spinal cord contusion. Mice were then gavaged with corn oil or a high dose of tamoxifen from 19-22 days post-injury, and sacrificed 42 days post-injury. All mice underwent behavioral testing for the duration of the study, which revealed that tamoxifen treatment did not impact hindlimb motor recovery. Similarly, histological analyses revealed that tamoxifen had no effect on white matter sparing, total axon number, axon sprouting, glial reactivity, cell proliferation, oligodendrocyte number, or myelination, but tamoxifen did decrease the number of neurons in the dorsal and ventral horn. Semi-thin sections confirmed that axon demyelination and remyelination were unaffected by tamoxifen. Sex-specific responses to tamoxifen were also assessed, and there were no significant differences between female and male mice. These data suggest that delayed tamoxifen administration after SCI does not change functional recovery or improve tissue sparing in female or male mice.


Assuntos
Neurônios/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Tamoxifeno/administração & dosagem , Tempo para o Tratamento , Administração Oral , Animais , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Membro Posterior/inervação , Membro Posterior/fisiologia , Humanos , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Fatores Sexuais , Corno Dorsal da Medula Espinal/citologia , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Corno Ventral da Medula Espinal/citologia , Corno Ventral da Medula Espinal/efeitos dos fármacos
6.
J Fr Ophtalmol ; 43(8): 727-730, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32620415

RESUMO

We report a case of a patient treated with tamoxifen 20mg daily as hormone therapy for breast cancer. On regular ophthalmological follow-up, tamoxifen maculopathy was detected on SD-OCT (Spectral Domain Optic Coherence Tomography, Carl Zeiss Meditec®), so the medication was discontinued. Despite discontinuation of the medication, the maculopathy progressed over time. We have been following our patient for seven years. Tamoxifen may produce a toxic maculopathy which may progress despite discontinuation of the medication. We consider our case interesting, given the lengthy follow-up of the patient with sequential SD-OCT images. To the best of our knowledge, our case represents the longest follow-up period for a patient with tamoxifen maculopathy. Moreover, we would like to stress the importance of screening in asymptomatic patients on this medication, in order to detect early pathological signs.


Assuntos
Monitorização Fisiológica , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/diagnóstico , Tamoxifeno/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Macula Lutea/efeitos dos fármacos , Macula Lutea/patologia , Degeneração Macular/induzido quimicamente , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Monitorização Fisiológica/métodos , Doenças Retinianas/patologia , Tamoxifeno/administração & dosagem , Tomografia de Coerência Óptica
7.
Med Hypotheses ; 143: 110091, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32663742

RESUMO

Breast cancer is the most common cancer in women and is the second most common cause of death in women. Estrogen plays an important role in breast tumor etiopathogenesis. Tamoxifen and other anti-estrogen drugs are used in breast cancer patients who have a positive estrogen receptor (ER). While angiotensin II plays a key role in breast cancer etiology and causes tamoxifen resistance, angiotensin 1-7 has been reported to may reduce the spread and invasion of breast cancer. During the COVID-19 infection, the virus blocks ACE2, and angiotensin 1-7 production discontinued. Angiotensin III production may increase as angiotensin II destruction is reduced. Thus, aminopeptidase upregulation may occur. Increased aminopeptidase may develop resistance to chemotherapy in breast cancer patients receiving chemotherapy. Estrogen can have a protective effect against COVID-19. Estrogen increase causes ER-α upregulation in T lymphocytes. Thus, estrogen increases the release of interferon I and III from T lymphocytes. Increasing interferon I and III alleviates COVID-19 infection. Tamoxifen treatment causes down-regulation, mutation, or loss in estrogen receptors. In the long-term use of tamoxifen, its effects on estrogen receptors can be permanent. Thus, since estrogen receptors are damaged or downregulated, estrogen may not act by binding to these receptors. Tamoxifen is a P-glycoprotein inhibitor, independent of its effect on estrogen receptors. It suppresses T cell functions and interferon release. We think tamoxifen may increase the COVID-19 risk due to its antiestrogen and P-glycoprotein inhibitory effects.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Infecções por Coronavirus/complicações , Resistencia a Medicamentos Antineoplásicos , Pneumonia Viral/complicações , Tamoxifeno/administração & dosagem , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Betacoronavirus , Neoplasias da Mama/complicações , Suscetibilidade a Doenças , Antagonistas de Estrogênios/administração & dosagem , Feminino , Humanos , Interferons , Pandemias , Receptor Tipo 2 de Angiotensina/metabolismo , Receptores Estrogênicos/metabolismo , Risco
8.
Obstet Gynecol ; 136(2): 323-332, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32649493

RESUMO

OBJECTIVE: To evaluate whether a short course of tamoxifen decreases bothersome bleeding in etonogestrel contraceptive implant users. METHODS: In a 90-day, double-blind randomized control trial, we enrolled etonogestrel implant users with frequent or prolonged bleeding or spotting. A sample size of 40 per group (N=80) was planned to compare 10 mg tamoxifen or placebo twice daily for 7 days after 3 consecutive days of bleeding or spotting no more than once per 30 days (maximum three treatments). Participants then entered a 90-day open-label study where all received tamoxifen if needed every 30 days (maximum three treatments). Participants used text messages to record daily bleeding patterns. Our primary outcome was the total number of consecutive amenorrhea days after the first treatment. Secondary outcomes included time to bleeding or spotting cessation and restart after first treatment, overall bleeding patterns, and satisfaction. RESULTS: From January 2017 to November 2018, 112 women enrolled in the study; 88 (79%) completed 90 days, and 79 (71%) completed 180 days. Participant characteristics did not differ between groups; mean age 24, majority identified as white not Hispanic with at least some college education. After the first treatment, the tamoxifen group reported an average of 9.8 (95% CI 4.6-15.0) more consecutive days of amenorrhea and more total days of no bleeding (amenorrhea or spotting) in the first 90 days (median 73.5 [range 24-89] vs 68 [range 11-81], P=.001). The placebo group showed a similar treatment benefit after first active use of tamoxifen in the open-label phase. At the end of the randomized study (first 90 days), women who received tamoxifen reported higher satisfaction (median 62 mm [range 16-100]) than those treated with placebo (46 mm [range 0-100]; P=.023). CONCLUSION: A short course of tamoxifen reduces problematic bleeding and improves satisfaction in users of etonogestrel implants. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02903121.


Assuntos
Anticoncepcionais Femininos/efeitos adversos , Desogestrel/efeitos adversos , Tamoxifeno/administração & dosagem , Hemorragia Uterina/tratamento farmacológico , Adolescente , Adulto , Amenorreia/tratamento farmacológico , Anticoncepcionais Femininos/administração & dosagem , Desogestrel/administração & dosagem , Método Duplo-Cego , Implantes de Medicamento/administração & dosagem , Implantes de Medicamento/efeitos adversos , Feminino , Humanos , Metrorragia/induzido quimicamente , Metrorragia/tratamento farmacológico , Resultado do Tratamento , Hemorragia Uterina/induzido quimicamente , Adulto Jovem
9.
Nat Commun ; 11(1): 3584, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681091

RESUMO

Responses to immunotherapy are uncommon in estrogen receptor (ER)-positive breast cancer and to date, lack predictive markers. This randomized phase II study defines safety and response rate of epigenetic priming in ER-positive breast cancer patients treated with checkpoint inhibitors as primary endpoints. Secondary and exploratory endpoints included PD-L1 modulation and T-cell immune-signatures. 34 patients received vorinostat, tamoxifen and pembrolizumab with no excessive toxicity after progression on a median of five prior metastatic regimens. Objective response was 4% and clinical benefit rate (CR + PR + SD > 6 m) was 19%. T-cell exhaustion (CD8+ PD-1+/CTLA-4+) and treatment-induced depletion of regulatory T-cells (CD4+ Foxp3+/CTLA-4+) was seen in tumor or blood in 5/5 patients with clinical benefit, but only in one non-responder. Tumor lymphocyte infiltration was 0.17%. Only two non-responders had PD-L1 expression >1%. This data defines a novel immune signature in PD-L1-negative ER-positive breast cancer patients who are more likely to benefit from immune-checkpoint and histone deacetylase inhibition (NCT02395627).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Imunoterapia , Linfócitos T/imunologia , Tamoxifeno/administração & dosagem , Vorinostat/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Receptores Estrogênicos/genética , Receptores Estrogênicos/imunologia , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento
10.
Expert Opin Pharmacother ; 21(12): 1493-1504, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32496137

RESUMO

INTRODUCTION: Despite its rarity, male breast cancer shows a steadily rising incidence. Given the absence of ad hoc prospective randomized clinical trials, treatment strategies are based on extrapolation from female breast cancer recommendations or solely on population-based data. AREAS COVERED: This review discusses the current treatment landscape for male breast cancer in the adjuvant and in the metastatic setting. The authors also discuss the biology and genomic landscape of male breast cancer. Original research and review articles, relative to the period 2010-2019, were included in the review of the literature. EXPERT OPINION: There is a major medical need to include male patients with breast cancer in prospective clinical trials. The call to equality in breast cancer care can be pursued via two divergent paths: (i) a gender-neutral delivery of breast cancer information and (ii) the creation of separate sections, for the more common female breast cancer and for the rare male ones. We propose to differentiate male breast cancer care, acknowledging unique onco-sexual and social needs that can be only partially shared.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama Masculina/tratamento farmacológico , Tamoxifeno/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama Masculina/patologia , Ensaios Clínicos como Assunto , Dano ao DNA , Reparo do DNA , Humanos , Masculino , Receptor ErbB-2/antagonistas & inibidores , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Resultado do Tratamento
11.
Am J Epidemiol ; 189(10): 1086-1095, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32338279

RESUMO

The association between use of aromatase inhibitors (AIs) and cardiovascular outcomes is controversial. While some observational studies have assessed the cardiovascular safety of AIs as upfront treatments, their cardiotoxicity as sequential treatments with tamoxifen remains unknown. Thus, we conducted a population-based cohort study using data from the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. We employed a prevalent new-user design to propensity-score match, in a 1:2 ratio, patients switching from tamoxifen to AIs with patients continuing tamoxifen between 1998 and 2016. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality). Overall, 1,962 patients switching to AIs were matched to 3,874 patients continuing tamoxifen. Compared with tamoxifen, AIs were associated with an increased risk of myocardial infarction (hazard ratio (HR) = 2.08, 95% confidence interval (CI): 1.02, 4.27). The hazard ratios were elevated for ischemic stroke (HR = 1.58, 95% CI: 0.85, 2.93) and heart failure (HR = 1.69, 95% CI: 0.79, 3.62) but not cardiovascular mortality (HR = 0.87, 95% CI: 0.49, 1.54), with confidence intervals including the null value. The elevated hazard ratios observed for the cardiovascular outcomes should be corroborated in future large observational studies.


Assuntos
Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/induzido quimicamente , Idoso , Antineoplásicos Hormonais/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Estudos de Coortes , Feminino , Cardiopatias/mortalidade , Humanos , Pessoa de Meia-Idade , Tamoxifeno/administração & dosagem , Reino Unido/epidemiologia
12.
Drugs Aging ; 37(5): 349-358, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32227289

RESUMO

Breast cancer is a disease of aging, and the incidence of breast cancer is projected to increase dramatically as the global population ages. The majority of breast cancers that occur in older adults are hormone-receptor positive, human epidermal growth factor receptor-2 (HER2)-negative phenotypes, with favorable tumor biology; yet, because of underrepresentation in clinical trials, less evidence is available to guide the complex care for this population. Providing care for older patients with metastatic breast cancer, with coexisting medical conditions, increased risk of treatment toxicity, and frailty, remains a clinical challenge in oncology. In this review, we provide an overview of the current evidence from clinical trials and subanalyses of older adults with hormone receptor-positive, HER2-negative metastatic breast cancer, highlighting data on the safety and efficacy of oral therapies, including endocrine therapy alone or in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and mammalian target of rapamycin (mTOR) inhibitors. In addition, we note the significant underrepresentation of older and frail adults in these studies. Current and future directions in research for this special population, in order to address significant knowledge gaps, include the need to improve long-term adherence to hormonal and targeted therapy, prospective clinical trials that capture clinical and biological aging endpoints, and the need for a multidisciplinary approach with integration of geriatric and oncology principles.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Superfície Celular/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Avaliação Geriátrica , Humanos , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico
13.
Ann Rheum Dis ; 79(5): 581-586, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32161056

RESUMO

OBJECTIVES: To examine the risk of incident breast cancer in women with rheumatoid arthritis (RA), and the risk of RA in women with a history of breast cancer, taking antihormonal treatment for breast cancer into account. METHODS: Using nationwide Swedish registers, women with new-onset RA diagnosed in 2006-2016 were identified and analysed using a cohort and a case-control design. Each patient with RA was matched on age, sex and place of residence to five randomly selected subjects from the general population. Through register linkages, we collected information on breast cancer, breast cancer risk factors (reproductive history and hormone replacement therapy) and socio-economy. The relative risk of breast cancer after RA was assessed using Cox regression, and the relative risk of RA in women with a history of breast cancer was assessed using conditional logistic regression. RESULTS: The risk of incident breast cancer in women with RA was reduced and the association was not attenuated by adjustment for breast cancer risk factors (HR=0.80, 95% CI 0.68 to 0.93). The risk of RA in women with a history of breast cancer was similarly reduced (OR=0.87, 95% CI 0.79 to 0.95). Women with breast cancer treated with tamoxifen (OR=0.86, 95% CI 0.62 to 1.20) or aromatase inhibitors (OR=0.97, 95% CI 0.69 to 1.37) did not have an increased risk of RA compared with women with breast cancer treated differently. CONCLUSIONS: The decreased occurrence of breast cancer in patients with RA is present already before RA diagnosis; these reduced risks are not readily explained by hormonal risk factors. Adjuvant antihormonal therapy for breast cancer does not seem to increase RA risk.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Artrite Reumatoide/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Sistema de Registros , Tamoxifeno/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Antineoplásicos Hormonais/administração & dosagem , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Suécia , Tamoxifeno/administração & dosagem
14.
Acta Oncol ; 59(6): 723-725, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32167397
16.
JAMA Netw Open ; 3(3): e201541, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32207833

RESUMO

Importance: The association between exposure to hormone-modulating therapy (HMT) as breast cancer treatment and neurodegenerative disease (NDD) is unclear. Objective: To determine whether HMT exposure is associated with the risk of NDD in women with breast cancer. Design, Setting, and Participants: This retrospective cohort study used the Humana claims data set from January 1, 2007, to March 31, 2017. The Humana data set contains claims from private-payer and Medicare insurance data sets from across the United States with a population primarily residing in the Southeast. Patient claims records were surveyed for a diagnosis of NDD starting 1 year after breast cancer diagnosis for the duration of enrollment in the claims database. Participants were 57 843 women aged 45 years or older with a diagnosis of breast cancer. Patients were required to be actively enrolled in Humana claims records for 6 months prior to and at least 3 years after the diagnosis of breast cancer. The analyses were conducted between January 1 and 15, 2020. Exposure: Hormone-modulating therapy (selective estrogen receptor modulators, estrogen receptor antagonists, and aromatase inhibitors). Main Outcomes and Measures: Patients receiving HMT for breast cancer treatment were identified. Survival analysis was used to determine the association between HMT exposure and diagnosis of NDD. A propensity score approach was used to minimize measured and unmeasured selection bias. Results: Of the 326 485 women with breast cancer in the Humana data set between 2007 and 2017, 57 843 met the study criteria. Of these, 18 126 (31.3%; mean [SD] age, 76.2 [7.0] years) received HMT, whereas 39 717 (68.7%; mean [SD] age, 76.8 [7.0] years) did not receive HMT. Mean (SD) follow-up was 5.5 (1.8) years. In the propensity score-matched population, exposure to HMT was associated with a decrease in the number of women who received a diagnosis of NDD (2229 of 17 878 [12.5%] vs 2559 of 17 878 [14.3%]; relative risk, 0.89; 95% CI, 0.84-0.93; P < .001), Alzheimer disease (877 of 17 878 [4.9%] vs 1068 of 17 878 [6.0%]; relative risk, 0.82; 95% CI, 0.75-0.90; P < .001), and dementia (1862 of 17 878 [10.4%] vs 2116 of 17 878 [11.8%]; relative risk, 0.88; 95% CI, 0.83-0.93; P < .001). The number needed to treat was 62.51 for all NDDs, 93.61 for Alzheimer disease, and 69.56 for dementia. Conclusions and Relevance: Among patients with breast cancer, tamoxifen and steroidal aromatase inhibitors were associated with a decrease in the number who received a diagnosis of NDD, specifically Alzheimer disease and dementia.


Assuntos
Antineoplásicos Hormonais , Inibidores da Aromatase , Neoplasias da Mama , Moduladores de Receptor Estrogênico , Doenças Neurodegenerativas , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Comorbidade , Moduladores de Receptor Estrogênico/administração & dosagem , Moduladores de Receptor Estrogênico/efeitos adversos , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/mortalidade , Estudos Retrospectivos , Fatores de Risco , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico
17.
Drugs Aging ; 37(5): 331-348, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32100240

RESUMO

The median age for breast cancer diagnosis is 62 years, but a disproportionate number of patients are over the age of 75 years and the majority of those have hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative cancers. This review provides a logical algorithm to guide providers through the many complicated issues involved in adjuvant systemic therapy decisions in older patients with hormone receptor-positive, HER2-negative breast cancer. For this subtype of breast cancer, the mainstay of treatment is surgery and adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor (AI). Adjuvant chemotherapy is added to the treatment regimen when the benefits of treatment are deemed to outweigh the risks, making the risk-benefit discussion particularly important in older women. Traditional tools for cancer risk assessment and genomic expression profiles (GEPs) are under-utilized in older patients, but yield equally useful information about cancer prognosis as they do in younger patients. Additionally, there are tools that estimate life-limiting toxicity risk from chemotherapy and life expectancy, which are both important issues in the risk-benefit discussion. For very low-risk cancers, such as non-invasive and small lymph node (LN)-negative cancers, the benefits of any adjuvant therapy is likely outweighed by the risks, but endocrine therapy might be considered to prevent future new breast cancers. For invasive tumors that are > 5 mm (T1b or larger) or involve LNs, adjuvant endocrine therapy is recommended. Generally, AIs should be included, though tamoxifen is effective and should be offered when AIs are not tolerated. Bone-preserving agents and high-dose vitamin D are options to preserve bone density or treat osteoporosis, especially in older women who are taking AIs. Where the risk-reducing benefit from adjuvant chemotherapy outweighs the toxicity risk, adjuvant chemotherapy should be considered. Adjuvant chemotherapy has similar benefits in older and younger patients and standard regimens are preferred. Several exciting clinic trials are underway and have included older patients, including those adding molecularly targeted agents, cyclin-dependent kinase (CDK) 4/6 inhibitors and everolimus, to endocrine therapy in the adjuvant setting. The high incidence of breast cancer in older women should drive us to design clinical trials for this population and emphasize their inclusion in ongoing trials as much as possible.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptores de Superfície Celular/metabolismo , Tamoxifeno/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Detecção Precoce de Câncer , Feminino , Avaliação Geriátrica , Humanos , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Receptor ErbB-2/metabolismo , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos
18.
Circulation ; 141(7): 549-559, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32065766

RESUMO

BACKGROUND: The association between aromatase inhibitors and cardiovascular outcomes among women with breast cancer is controversial. Given the discrepant findings from randomized controlled trials and observational studies, additional studies are needed to address this safety concern. METHODS: We conducted a population-based cohort study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study population consisted of women newly diagnosed with breast cancer initiating hormonal therapy with aromatase inhibitors or tamoxifen between April 1, 1998, and February 29, 2016. We usedCox proportional hazards models with inverse probability of treatment and censoring weighting to estimate hazard ratios (HRs) with 95% CIs comparing new users of aromatase inhibitors with new users of tamoxifen for each of the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality). RESULTS: The study population consisted of 23 525 patients newly diagnosed with breast cancer, of whom 17 922 initiated treatment with either an aromatase inhibitor or tamoxifen (8139 and 9783, respectively). The use of aromatase inhibitors was associated with a significantly increased risk of heart failure (incidence rate, 5.4 versus 1.8 per 1000 person-years; HR, 1.86 [95% CI, 1.14-3.03]) and cardiovascular mortality (incidence rate, 9.5 versus 4.7 per 1000 person-years; HR, 1.50 [95% CI, 1.11-2.04]) compared with the use of tamoxifen. Aromatase inhibitors were associated with elevated HRs, but with CIs including the null value, for myocardial infarction (incidence rate, 3.9 versus 1.8 per 1000 person-years; HR, 1.37 [95% CI, 0.88-2.13]) and ischemic stroke (incidence rate, 5.6 versus 3.2 per 1000 person-years; HR, 1.19 [95% CI, 0.82-1.72]). CONCLUSIONS: In this population-based study, aromatase inhibitors were associated with increased risks of heart failure and cardiovascular mortality compared with tamoxifen. There were also trends toward increased risks, although nonsignificant, of myocardial infarction and ischemic stroke. The increased risk of cardiovascular events associated with aromatase inhibitors should be balanced with their favorable clinical benefits compared with tamoxifen.


Assuntos
Inibidores da Aromatase , Isquemia Encefálica , Neoplasias da Mama , Bases de Dados Factuais , Insuficiência Cardíaca , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/mortalidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/mortalidade , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/mortalidade , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Reino Unido/epidemiologia
19.
Breast Cancer Res Treat ; 180(1): 157-165, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31975316

RESUMO

PURPOSE: To determine whether a red clover preparation plus dietary intervention administered to premenopausal women with breast cancer (BC), improves menopausal symptoms due to anti-oestrogen treatment, and hence promotes compliance with tamoxifen, prevents weight gain and is safe. METHODS: Surgically-treated premenopausal women with oestrogen receptor (ER) positive disease taking tamoxifen were recruited to a prospective double-blind randomized trial (NCT03844685). The red clover group (N = 42) received one oral tablet/day (Promensil® Forte) containing 80 mg red clover extract for 24 months. The placebo group (N = 39) received one oral tablet/day without active ingredient. All women were encouraged to follow a Mediterranean-type diet and keep active. Outcomes were Menopausal Rating Score (MRS), body mass index (BMI), waist and hip girth, insulin resistance, and levels of cholesterol, triglycerides, and sex hormones. As safety indicators, endometrial thickness, breast density, and effects of patient serum on ER-positive BC cell lines were investigated. RESULTS: MRS reduced significantly (p < 0.0001) with no between-group difference (p = 0.69). The red clover group had significantly greater reductions in BMI and waist circumference (p < 0.0001 both cases). HDL cholesterol increased significantly in both groups (p = 0.01). Hormone levels and insulin resistance changed little. Endometrial thickness remained constant (p = 0.93). Breast density decreased significantly in both groups (p < 0.0001). Proliferation and oestrogen-regulated gene expression didn't differ in cell lines treated with serum from each group. CONCLUSIONS: This is the first trial to assess red clover in BC patients on tamoxifen. The preparation proved safe clinically and in vitro, and was associated with reduced BMI and waist circumference, but the diet-lifestyle intervention probably improved the menopausal symptoms.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Suplementos Nutricionais , Estilo de Vida , Menopausa , Tamoxifeno/uso terapêutico , Trifolium , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etiologia , Terapia Combinada , Feminino , Fogachos/tratamento farmacológico , Fogachos/epidemiologia , Humanos , Pré-Menopausa , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Terapêutica , Trifolium/química
20.
BMC Cancer ; 20(1): 67, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996163

RESUMO

BACKGROUND: We previously reported that tamoxifen (TAM)-induced ovarian hyperstimulation (OHS) is associated with high serum concentrations of estradiol in premenopausal women with breast cancer. To investigate risk factors for TAM-induced OHS, we performed a retrospective multicenter study. METHODS: Premenopausal patients who received surgical therapy for endocrine-dependent breast cancer (n = 235) were recruited in this study and classified into 4 groups: group A, treated with TAM alone; group B, TAM treatment after 2-year-combined therapy with a gonadotropin-releasing hormone (Gn-RH) agonist; group C, TAM treatment after chemotherapy; group D, 5-year-combined therapy with TAM and a Gn-RH agonist. A serum estradiol value of more than 300 pg/mL or mean follicular diameter of more than 30 mm was defined as OHS. RESULTS: The incidence of OHS in group A (n = 13/26, 50.0%) was significantly higher than those in group B (n = 17/63, 27.0%), group C (n = 20/110, 18.2%), and group D (n = 0/36, 0%). The incidence of OHS was significantly correlated with aging, and the median serum concentration of estradiol in the presence of OHS was 823.0 pg/mL. The incidence of OHS (less than 47 years old) was 62.5% in group A, 48.6% in group B, and 28.2% in group C, respectively. Notably, the incidence rate of OHS following amenorrhea in group C (n = 13/20, 65.0%) was significantly higher than that in group B (n = 1/17, 5.9%). CONCLUSIONS: These findings indicate that the onset of OHS following amenorrhea was common in the post-chemotherapeutic group, while its ratio was low in the group after Gn-RH analog treatment, suggesting that combined treatment-based management involving TAM therapy is necessary for premenopausal patients with breast cancer.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Pré-Menopausa , Tamoxifeno/efeitos adversos , Adulto , Fatores Etários , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Esquema de Medicação , Estradiol/sangue , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Estadiamento de Neoplasias , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Estudos Retrospectivos , Tamoxifeno/administração & dosagem , Tamoxifeno/uso terapêutico
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