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1.
Support Care Cancer ; 29(1): 187-191, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32328775

RESUMO

BACKGROUND: Anti-estrogen therapy is an effective intervention for preventing reoccurrence of hormone receptor-positive breast cancer in women. However, the side effects of anti-estrogen therapy, including urogenital symptoms, have been reported to cause significant morbidity. There is controversial data, mainly due to small sample sizes, reporting on the safety and efficacy of using vaginal estrogen to treat urogenital symptoms in patients on aromatase inhibitor therapy. METHODS: We proposed a prospective trial to measure the change in blood estradiol levels in postmenopausal women with hormone receptor-positive breast cancer undergoing treatment with aromatase inhibitors when treated with vaginal estrogen preparation, Estring, for their urogenital symptoms. Only 8 prospective patients were enrolled, and the study was amended to include 6 retrospective patients who were treated similarly. Blood estradiol levels were measured at baseline and at week 16 for all patients. RESULTS: The median age for all patients was 55 years, and the majority of them were treated with anastrozole. There was no significant difference between baseline and week 16 estradiol levels (p = 0.81). In addition, patients in the prospective group reported subjective improvement in their vaginal dryness symptoms questionnaires. CONCLUSIONS: The vaginal estrogen preparation, Estring, did not cause persistent elevations in serum estradiol levels and might be a safer option for women with significant urogenital symptoms requiring estrogen therapy. IMPLICATIONS FOR CANCER SURVIVORS: Vaginal estrogen preparation, Estring, might be an option for women with hormone receptor positive breast cancer who have persistent urogenital symptoms.


Assuntos
Anastrozol/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/sangue , Moduladores de Receptor Estrogênico/uso terapêutico , Estrogênios/efeitos adversos , Administração Intravaginal , Anastrozol/efeitos adversos , Moduladores de Receptor Estrogênico/efeitos adversos , Estrogênios/administração & dosagem , Estrogênios/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Estudos Retrospectivos , Doenças Vaginais/induzido quimicamente , Doenças Vaginais/tratamento farmacológico
2.
Support Care Cancer ; 29(1): 311-322, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32358778

RESUMO

PURPOSE: To assess the feasibility and efficacy of a non-hormonal hyaluronic acid (HLA) vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in postmenopausal women with a history of hormone receptor-positive (HR+) cancer. METHODS: For this single-arm, prospective longitudinal trial, we identified disease-free patients with a history of HR+ breast cancer treated with aromatase inhibitors or HR+ endometrial cancer treated with surgery and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1], 4-6 weeks [T2], 12-14 weeks [T3], 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). RESULTS: Of 101 patients, mean age was 55 years (range, 31-78), 68% (n = 69) were partnered, and 60% (n = 61) were sexually active. In linear mixed models, VAS/VuAS scores significantly improved at all assessment points (all p < 0.001). MSCL scores similarly improved (all p < 0.001). FSFI scores significantly improved from T1 to T2 (p < 0.03), T3 (p < 0.001), and T4 (p < 0.001). Severe vaginal pH (> 6.5) decreased from 26% at T1 to 19% at T4 (p = 0.18). CONCLUSIONS: HLA moisturization improved vulvovaginal health/sexual function of cancer survivors. While HLA administration 1-2×/week is recommended for women in natural menopause, a 3-5×/week schedule appears to be more effective for symptom relief in cancer survivors.


Assuntos
Inibidores da Aromatase/uso terapêutico , Sobreviventes de Câncer , Ácido Hialurônico/uso terapêutico , Vagina/patologia , Doenças Vaginais/tratamento farmacológico , Vulva/patologia , Adulto , Idoso , Atrofia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Estudos Prospectivos , Cremes, Espumas e Géis Vaginais/uso terapêutico
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.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(3): 275-282, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32762160

RESUMO

Aromatase is the rate-limiting enzyme in estrogen biosynthesis. The third generation aromatase inhibitors (AIs), represented by letrozoleand and anastrozole, can combine with aromatase, effectively reducing the estrogen level in the body. Because of its high efficiency, selectivity and reversibility, it has been used in the treatment of McCune-Albright syndrome, familial male-limited precocious puberty, gynecomastia, and adolescent boy with short stature. The good efficacy and safety of AIs have been observed. However, so far the drug instructions of AIs usually do not show indications for children; there are risks of adverse reactions involving liver and kidney function, lipid metabolism, hyperandrogenemia and bone metabolism; especially the long-term effects on reproductive system and bone metabolism are still not clear. Therefore, it is necessary to prescribe it carefully and follow up closely. It was not recommended that AIs be routinely used to improve adult height of adolescent boy with short stature. And more clinical evidences are needed for the safety and effectiveness of AIs prescribed in pediatrics.


Assuntos
Inibidores da Aromatase/uso terapêutico , Puberdade Precoce , Adolescente , Criança , Estrogênios , Humanos , Masculino
5.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(3): 283-290, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32762170

RESUMO

OBJECTIVE: To assess the efficacy and safety of aromatase inhibitors (AIs) combined growth hormone in treatment of adolescent boys with short stature. METHODS: One hundred and fifty-one short stature pubertal boys with age of 10-14 years and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention, the children were divided into recombinant human growth hormone (rhGH)+AI group ( n=108) and rhGH group ( n=43). All children were injected subcutaneously with rhGH 0.15-0.2 IU·kg -1·d -1, and those in rhGH+AI group were additionally given 2.5 mg/d letrozole or 1 mg/d anastrozole, orally for 12 months or longer. The children were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism, and other indicators were measured, and adverse reactions were monitored. RESULTS: After intervention, there were significant differences in ΔBA(bone age)/ΔCA(chronological age), ΔHtSDS BA(height standard deviation score based on bone age)and ΔPAH between rhGH+AI group and the rhGH group( P < 0.05 or P < 0.01). During follow-up, 63.9%of the children in the rhGH+AI group had elevated uric acid and 51.9%had decreased high-density lipoprotein (HDL); 25.9%showed severe acne, excitement, hyperactivity and irritability, 11.1%had knee pain; 4.6%had fracture; 2.8%had mild renal dysfunction; 1.9%had inactivity, drowsiness, memory loss and performance decline; 1.9%showed mild abnormal liver function; 0.9%showed impaired fasting glucose; 0.9%showed granulocytopenia. In the rhGH group, 11.6%of the children presented with knee pain and 2.3%with impaired fasting glucose. CONCLUSIONS: AI combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AI should be closely monitored during treatment.


Assuntos
Inibidores da Aromatase/uso terapêutico , Adolescente , Estatura , Criança , Transtornos do Crescimento , Hormônio do Crescimento Humano , Humanos , Masculino , Proteínas Recombinantes
6.
Medicine (Baltimore) ; 99(30): e21344, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791733

RESUMO

RATIONALE: Locoregional recurrence of breast cancer is a challenging issue for clinicians. Treatment options for unresectable recurrent estrogen receptor positive (ER+) breast cancer in previously irradiated area are limited. Some studies showed concomitant fulvestrant with radiation therapy might increase radiosensitivity compared with radiation alone in vitro, no in vivo reports yet. PATIENT CONCERN: Here, we present a case report and make a narrative review of concomitant fulvestrant with radiation therapy for unresectable locoregional recurrent ER+ breast cancer. The patient was treated with modified radical mastectomy in 2015, adjuvant chemotherapy, radiotherapy, followed by exemestane until November 2018, relapsed in internal mammary lymph nodes with sternum involved. DIAGNOSIS: The final diagnosis was breast cancer internal mammary lymph nodes metastasis with sternum involved. INTERVENTIONS: After diagnosis was made, concurrent fulvestrant with reirradiation as a palliative treatment were proposed under multiple disciplinary team. OUTCOMES: There was a good clinical response, enabling curative chance with radiation therapy to a total dose of 60 Gy. Computed tomography scan revealed no evidence of residual tumor. LESSONS: As far as we know, this is the first report concerning concomitant fulvestrant with reirradiation for unresectable locoregional recurrent ER+ breast cancer. Since no severe adverse events were observed, this strategy could be a suitable "loco-regional rescue therapy" to further reduce tumor progression or even reach a curative effect. Studies of this treatment strategy in randomized clinical trials are warranted to further assess its safety and effectiveness.


Assuntos
Neoplasias da Mama/terapia , Antagonistas do Receptor de Estrogênio/uso terapêutico , Fulvestranto/uso terapêutico , Reirradiação/métodos , Androstadienos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Terapia Combinada , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Mastectomia Radical Modificada/métodos , Pessoa de Meia-Idade , Medicina Narrativa/métodos , Recidiva Local de Neoplasia/cirurgia , Receptores Estrogênicos/metabolismo
9.
PLoS One ; 15(7): e0236506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730287

RESUMO

BACKGROUND: Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer. METHODS: This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group. RESULTS: Median treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients. CONCLUSIONS: Tamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fígado Gorduroso/diagnóstico , Tamoxifeno/efeitos adversos , Adulto , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Duração da Terapia , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Tamoxifeno/uso terapêutico
10.
BMC Womens Health ; 20(1): 118, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503562

RESUMO

BACKGROUND: Less than 10% of newly diagnosed breast cancer cases in Jordan are diagnosed in women 70 years or older. Treatment plans of such patients is less clear and could result in poor outcomes. In this paper, we describe clinical presentation, tumor characteristics and treatment outcomes in this population of breast cancer patients. METHODS: Consecutive patients aged 65 years or older with pathologically-confirmed diagnosis of breast cancer were included. Medical records and hospital databases were searched for patients' characteristics and treatment outcomes. RESULTS: A total of 553 patients, mean age ± SD (71 ± 5.1) years, were included. On presentation, 114 (20.6%) patients had metastatic disease and was mostly visceral (81; 71.1%). Patients with non-metastatic disease had poor pathological features including node-positive in 244 (55.6%), high grade (grade III) in 170 (38.7%) and lymphovascular invasion in 173 (39.4%). Patients were treated less aggressively; 144 (32.8%) patients with early-stage disease and 98 (86.0%) with metastatic disease never had chemotherapy. After a median follow up of 45 months, 5-year overall survival for the whole group was 67.6%. Survival was better for patients with non-metastatic disease (78.8% vs. 25.4%, P < 0.001) and for those with node-negative compared to node-positive disease (85.4% vs. 74.1%, P = 0.002). On Cox regression, only positive lymph nodes were associated with poor outcome in patients with non-metastatic disease (Hazard Ratio [HR], 1.75; 95% CI: 1.006-3.034, P = 0.048). CONCLUSIONS: Older Jordanian patients with breast cancer present with more aggressive features and advanced-stage disease that reflect poorly on treatment outcomes. Older patients were treated less aggressively with less than a third received any chemotherapy.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/mortalidade , Diagnóstico Tardio , Feminino , Humanos , Jordânia/epidemiologia , Mastectomia , Metástase Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
11.
Zhonghua Zhong Liu Za Zhi ; 42(5): 403-407, 2020 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-32482030

RESUMO

Objective: To investigate the occurrence and development of aromatase inhibitors (AIs) related bone loss in Chinese patients with postmenopausal early-stage breast cancer. Methods: Patients with estrogen receptor (ER) and (or) progesterone receptor(PR) positive postmenopausal early-stage breast cancer who received Letrozole, Anastrozole, or Exemestane as adjuvant therapy were enrolled. Before treatment, baseline bone mineral density (BMD), bone metabolism markers were examined and a lifestyle questionnaire was completed; BMD was examined annually during the treatment; Outpatient visits were conducted to record recurrent and fatal events. Results: From November 2013 to August 2016, 131 patients with breast cancer eligible for enrollment were enrolled. A total of 65 patients had normal baseline bone mass, and 68 patients had reduced bone mass. Letrozole was taken in 69 patients, anastrozole in 52 patients, and exemestane in 10 patients. With a median follow-up of 43.7 months, 100 patients could be evaluated for changes in bone mineral density. Bone mineral density of femoral neck, total hip, and lumbar spine L1 to 4 decreased year by year, and the decrease was the most significant in the first year, which decreased by 2.3%, 2.4%, and 3.9% respectively. Ten new cases of osteoporosis occurred in two years, eight of them occurred in the lumbar spine, all of whom had reduced bone mass at baseline. Among the 131 patients who completed the lifestyle questionnaire, the proportions of daily calcium supplementation and vitamin D were 28.2% and 7.6%, respectively; more than half (52.7%) of them lacked regular exercise. Conclusion: BMD was declining steadily in patients treated with AIs, especially in the first year. Lumbar spine is the most common osteoporosis site, early prevention and health education should be strengthened.


Assuntos
Inibidores da Aromatase/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Pós-Menopausa , Anastrozol/uso terapêutico , Androstadienos/uso terapêutico , Humanos , Letrozol/uso terapêutico , Estudos Prospectivos
12.
J Bone Miner Metab ; 38(5): 730-736, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405760

RESUMO

INTRODUCTION: Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment. MATERIALS AND METHODS: In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months. RESULTS: The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar. CONCLUSION: The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.


Assuntos
Alendronato/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Alendronato/farmacologia , Inibidores da Aromatase/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama/fisiopatologia , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Breast Cancer Res ; 22(1): 56, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32466779

RESUMO

BACKGROUND: Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI). METHODS: Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC. RESULTS: Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p < 0.001). Among the ESR1-mutated patients, 18/22 had a detectable mutation prior to progression, with a median delay of 110 days from first detection to PD. The detection of circulating ESR1 mutations was associated with a 4.9-fold (95% CI 3.0-8.0) increase in the risk of PD at 3 months. Using a threshold value of 25% or 100%, a CA-15.3 increase was also correlated with progression (p < 0.001 and p = 0.003, respectively). In contrast to ESR1, the CA-15.3 increase occurred concomitantly with PD in most cases, in 27/47 (57%) with a 25% threshold and in 21/25 (84%) with a 100% threshold. Using a threshold value of either 25% or 100%, cfDNA increase was not correlated with progression. CONCLUSION: The emergence of circulating ESR1 mutations is associated with a 4.9-fold increase in the risk of early PD during AI treatment in HR+MBC. Our results also highlighted that tracking circulating ESR1 mutations is more relevant than tracking CA-15.3 or cfDNA increase to predict progression in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02473120. Registered 16 June 2015-retrospectively registered after one inclusion (first inclusion 1 June 2015).


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , DNA Tumoral Circulante/sangue , Receptor alfa de Estrogênio/genética , Mucina-1/sangue , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , DNA Tumoral Circulante/genética , Estudos de Coortes , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Receptor alfa de Estrogênio/sangue , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
14.
J Steroid Biochem Mol Biol ; 202: 105697, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461092

RESUMO

Treatment of hormone sensitive breast cancer tumors with endocrine therapy such as antiestrogens or aromatase inhibitors has improved the outcome significantly. Studies including our own have shown that downregulation of ERα with pure antiestrogen fulvestrant in combination with aromatase inhibitors may prolong responsiveness of the tumors to endocrine therapy. Fulvestrant has been studied as second line or first line treatment for post-menopausal hormone receptor positive breast cancers as a single agent or in combination with AIs. Studies have also suggested that further escalation of dose may improve benefit. However, dose escalation of fulvestrant, which is administered via intramuscular injection, is difficult due to its poor solubility. To overcome this shortcoming of an injectable drug, a novel orally active antiestrogen, AZD9496 was developed. In addition to being orally active, AZD9496 is designed as a selective ERα downregulator (SERD). In the current study, we compared the effect of AZD9496 and fulvestrant on the growth of MCF-7Ca (human estrogen receptor positive MCF-7 cells stably transfected with human placental aromatase gene) xenografts grown in ovariectomized athymic nude mice. AZD9496 was also compared to fulvestrant in vitro as a single agent or in combination with anastrozole. Our current study shows that AZD9496 is equally effective as fulvestrant at controlling the growth of hormone sensitive human breast cancer tumors. Similar to fulvestrant, AZD9496 inhibits cellular aromatase activity through ERα mediated signaling. However, unlike fulvestrant, combination of AZD9496 with anastrozole did not produce increased tumor inhibition. Our results show that AZD9496 was significantly better at inhibiting cellular aromatase which contributed to its anticancer activity. Next, we measured the effect of AZD9496 on the mouse uterus. Uterine weight of mice treated with AZD9496 was significantly lower than that for mice treated with androstenedione. This reduction in uterine weight was due to AZD9496 mediated inhibition of aromatase activity and not a direct effect on uterine ERα expression. We also observed that anti-cancer efficacy of AZD9496 depended on its ability to inhibit cellular aromatase. These results suggest that AZD9496 may be a better alternative to fulvestrant due to its selectivity for mammary ER and ability to inhibit aromatase in addition of downregulating ERα that can be obtained upon oral administration. As such, AZD9496 may prove to be a better option than fulvestrant for the treatment of hormone sensitive human breast cancer.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cinamatos/uso terapêutico , Indóis/uso terapêutico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Anastrozol/farmacologia , Anastrozol/uso terapêutico , Animais , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Aromatase/metabolismo , Inibidores da Aromatase/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Cinamatos/farmacologia , Antagonistas do Receptor de Estrogênio/farmacologia , Antagonistas do Receptor de Estrogênio/uso terapêutico , Receptor alfa de Estrogênio , Feminino , Fulvestranto/farmacologia , Fulvestranto/uso terapêutico , Humanos , Indóis/farmacologia , Neoplasias Mamárias Experimentais/metabolismo , Camundongos Nus , Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/farmacologia
15.
Medicine (Baltimore) ; 99(20): e20199, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443342

RESUMO

INTRODUCTION: Resistance ovary syndrome (ROS) is a disease characterized by hypergonadotropic amenorrhea but with normal ovarian reserve. Currently, its pathogenesis is still unclear and the treatment methods are complex. Nevertheless, there are evident negative effects of this disease on females' physical and mental health such as gonadal dysplasia, infertility, anxiety, and depression. This article reports a case of successful ovulation induction and pregnancy with letrozole combined with HMG. This can provide clinical treatment guidelines for the disease. PATIENT CONCERNS: The patient underwent several hormone replacement cycles and ovulation induction cycles. But the dominant follicles were not extracted even after using large doses of gonadotropin. DIAGNOSIS: Resistant ovary syndrome; Primary infertility INTERVENTIONS:: Larger doses of letrozole combined with HMG were injected to stimulate ovulation and sensitize the ovaries during menstruation. This helped to examine the peripheral effects of letrozole in relation to gonadotropin. OUTCOMES: The patient displayed a dominant follicular growth and notable ovulation which resulted in a full-term pregnancy and successful delivery. CONCLUSIONS: The resistance ovary syndrome (ROS) can be treated and the findings from this case provides a possible treatment for ROS patients with infertility.


Assuntos
Inibidores da Aromatase/uso terapêutico , Letrozol/uso terapêutico , Insuficiência Ovariana Primária/tratamento farmacológico , Adulto , Inibidores da Aromatase/administração & dosagem , Quimioterapia Combinada/métodos , Feminino , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/tratamento farmacológico , Injeções Intramusculares/métodos , Letrozol/administração & dosagem , Nascimento Vivo , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Indução da Ovulação/métodos , Gravidez , Resultado do Tratamento
16.
Biochem Pharmacol ; 177: 113989, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32330493

RESUMO

Endocrine therapy is currently the main therapeutic approach for estrogen receptor-positive (ER+) breast cancer, the most frequent subtype of breast cancer in women worldwide. For this subtype of tumors, the current clinical treatment includes aromatase inhibitors (AIs) and anti-estrogenic compounds, such as Tamoxifen and Fulvestrant, being AIs the first-line treatment option for post-menopausal women. Moreover, the recent guidelines also suggest the use of these compounds by pre-menopausal women after suppressing ovaries function. However, besides its therapeutic efficacy, the prolonged use of this type of therapies may lead to the development of several adverse effects, as well as, endocrine resistance, limiting the effectiveness of such treatments. In order to surpass this issues and clinical concerns, during the last years, several studies have been suggesting alternative therapeutic approaches, considering the function of aromatase, ERα and ERß. Here, we review the structural and functional features of these three targets and their importance in ER+ breast cancer treatment, as well as, the current treatment strategies used in clinic, emphasizing the importance of the development of multi-target compounds able to simultaneously modulate these key targets, as a novel and promising therapeutic strategy for this type of cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Aromatase/genética , Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/genética , Androstadienos/uso terapêutico , Aromatase/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/antagonistas & inibidores , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Fadrozol/uso terapêutico , Feminino , Fulvestranto/uso terapêutico , Expressão Gênica , Humanos , Terapia de Alvo Molecular , Tamoxifeno/uso terapêutico
17.
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
18.
PLoS One ; 15(4): e0227256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315295

RESUMO

There is growing interest in leveraging real-world data to complement knowledge gained from randomized clinical trials and inform the design of prospective randomized studies in oncology. The present study compared clinical outcomes in women with metastatic breast cancer who received letrozole as first-line monotherapy in oncology practices across the United States versus patients in the letrozole-alone cohort of the PALOMA-2 phase 3 trial. The real-world cohort (N = 107) was derived from de-identified patient data from the Flatiron Health electronic health record database. The clinical trial cohort (N = 222) comprised postmenopausal women in the letrozole-alone arm of PALOMA-2. Patients in the real-world cohort received letrozole monotherapy per labeling and clinical judgment; patients in PALOMA-2 received letrozole 2.5 mg/d, continuous. Real-world survival and response rates were based on evidence of disease burden curated from clinician notes, radiologic reports, and pathology reports available in the electronic health record. Progression-free survival and objective response rate in PALOMA-2 were based on Response Evaluation Criteria in Solid Tumors v1.1. Concordance of survival and response rates were retrospectively assessed using inverse probability of treatment weighting-adjusted Cox regression analysis. Inverse probability of treatment weighting-adjusted Cox regression results showed similar median progression-free survival in the real-world and PALOMA-2 cohorts (18.4 and 16.6 months, respectively): the hazard ratio using real-world data as reference was 1.04 (95% CI, 0.69-1.56). No significant difference was observed in response rates: 41.8% in the real-world cohort vs 39.4% in the PALOMA-2 cohort (odds ratio using real-world data as reference: 0.91 [95% CI, 0.57-1.44]). These findings indicate that data abstracted from electronic health records with proper quality controls can yield meaningful information on clinical outcomes. These data increase confidence in the use of real-world assessments of progression and response as efficacy endpoints. Trial registration NCT01740427; Funding: Pfizer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Letrozol/uso terapêutico , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Intervalo Livre de Progressão , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Critérios de Avaliação de Resposta em Tumores Sólidos , Estados Unidos/epidemiologia
19.
Zhonghua Zhong Liu Za Zhi ; 42(3): 192-196, 2020 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-32252196

RESUMO

Luminal breast cancer is the most common subtype of breast cancer, representing more than 60% of all breast cancers. Endocrine resistance and late recurrence are two challenges in the treatment of luminal breast cancer. To overcome endocrine resistance in multiple levels, high-dose-fulvestrant can inhibit estrogen-receptor (ER)-dependent pathways, while targeted drugs can block ER-independent pathways.To reduce the risk of late recurrence in luminal breast cancer, recurrence prediction model should be formed. For patients with high risk of late recurrence, extended endocrine therapy, combination of ovarian function suppression (OFS) or vascular endothelial growth factor (VEGF) inhibitor could be utilized. Based on the challenges of the treatment, scientific research achievements can be used in clinical practice, and finally optimize the clinical treatment strategy.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Moduladores de Receptor Estrogênico/uso terapêutico , Fulvestranto/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/imunologia , Humanos , Recidiva Local de Neoplasia , Receptores Estrogênicos/metabolismo , Fator A de Crescimento do Endotélio Vascular
20.
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
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