Health-Related quality of life by 31-item Cervantes scale in breast cancer survivors undergoing adjuvant endocrine therapy

ABSTRACT Introduction Instruments to manage adverse effects of endocrine therapy with Aromatase inhibitors (AI) may improve adherence and persistence to treatment and Health-Related Quality of Life (HRQL). The 31-item Cervantes Scale (CS-31) is an HRQL questionnaire with particularities of the perimenopausal and postmenopausal period that could be an appropriate instrument to assess HRQL in Breast Cancer (BC) survivors. Objective This study aimed to perform additional validation of the CS-31 for BC survivors undergoing adjuvant endocrine therapy. Methods This prospective study was performed at three time points named T0, T1, and T2: initial, intermediate, and final follow-up period, respectively, totaling 24 months of follow-up. At each time point, the participants completed the CS-31, Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), and Hospital Anxiety and Depression Scale (HADS). The internal consistency, construct validity, responsiveness analyses, and known-group validity of CS-31 were evaluated. Results This study included 89 postmenopausal women diagnosed with hormone receptor-positive early BC in adjuvant endocrine therapy with AI. The internal consistency was good (Cronbach's alpha = 0.89). Construct validity received a positive rating, with 100% of results consistent with prior hypotheses. A prospective improvement in HRQL was identified for the CS-31 Global Score and FACIT-F Total Score and for most of their domains. Furthermore, women with anxiety and depression by HADS presented worse HRQL by CS-31. Conclusion The authors identified that the CS-31 seems to be appropriate for use in oncology medical routine and may help to monitor adverse effects and HRQL of BC survivors during adjuvant endocrine therapy.

Terapia endocrina para la prevención primaria del cáncer de seno: Revisión sistemática y metaanálisis actualizado / Endocrine therapy for primary prevention of breast cancer: Systematic review and updated meta-analysis

Introducción. Debido a que el cáncer de seno es una enfermedad asociada a una significativa tasa de morbilidad y mortalidad cuando se diagnostica en el período sintomático, se han hecho enormes esfuerzos orientados hacia la prevención primaria de esta enfermedad. Métodos. Se realizó una búsqueda de todos los experimentos clínicos aleatorizados que evaluaran la eficacia de la terapia endocrina para la reducción del riesgo de desarrollar cáncer de seno. La calidad metodológica de los estudios seleccionados fue valorada utilizando la herramienta de la Colaboración Cochrane para medir el riesgo de sesgo en ensayos aleatorizados. Se evaluó la heterogeneidad de los estudios primarios elegibles utilizando los estadísticos T², I², H². El sesgo de publicación fue evaluado mediante el test de Harbord y mediante la gráfica de funnel plot. La medida de efecto utilizada en este metaanálisis fue el riesgo relativo (RR) con el cálculo de los intervalos de confianza (IC) del 95%. Resultados. Encontramos doce experimentos clínicos aleatorizados que reclutaron a 68.180 mujeres, las cuales fueron asignadas al azar para recibir algún tipo terapia endocrina para reducir el riesgo de desarrollar cáncer de seno o placebo. La terapia endocrina en conjunto redujo el riesgo proporcional de cáncer de seno (invasivo más in situ) en un 42 %, resultado estadísticamente significativo RR 0,58 (IC95% 0,50 ­ 0,69). Conclusiones. La terapia endocrina es el manejo estándar de prevención en mujeres sanas con riesgo de desarrollar cáncer de seno no hereditario.

Introduction. Because breast cancer is a disease associated with a significant morbidity and mortality rate when diagnosed in the symptomatic period, enormous efforts have been made towards the primary prevention of this disease. Methods. A search was conducted for all randomized clinical trials evaluating the efficacy of endocrine therapy in reducing the risk of developing breast cancer. The methodological quality of the selected studies was assessed using the Cochrane Collaboration tool to assess risk of bias in randomized trials. Heterogeneity of eligible primary studies was assessed using the T², I², H² statistics. Publication bias was evaluated using the Harbord test and the funnel plot. The effect measure used in this meta-analysis was the relative risk (RR) with the calculation of the 95% confidence intervals (CI).Results. We found twelve randomized clinical trials that recruited 68,180 women who were randomly assigned to receive some type of endocrine therapy to reduce the risk of developing breast cancer or placebo. Endocrine therapy as a whole reduced the proportional risk of breast cancer (invasive plus in situ) by 42%, a statistically significant result RR 0.58 (95% CI 0.50 - 0.69). Conclusions. Endocrine therapy is the standard preventive management in healthy women at risk of developing non-hereditary breast cancer.

The VES?13 and G?8 tools as predictors of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients: A single?center study

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity. Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ?70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy?seven consecutive patients aged ?70 diagnosed with non?metastatic hormone?responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES?13 score ?3 or G?8 score ?14) and fit (VES?13 score <3 or G?8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients. Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value. Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ?70.

Effects of letrozole combined with human menopausal gonadotropin on pregnancy rate and prognosis in patients with refractory polycystic ovary syndrome / 中国基层医药

Objective:To investigate the effects of letrozole combined with human menopausal gonadotropin (HMG) on pregnancy rate and prognosis in patients with refractory polycystic ovary syndrome (PCOS).Methods:A total of 102 patients with refractory PCOS who received treatment in Jinhua Hongyue Women's and Children's Hospital between May 2019 and May 2020 were included in this study. They were randomly assigned to observation and control groups ( n = 51/group). All patients received the same treatment in the early period. During later ovulation induction period, patients in the control group were administered HMG and those in the observation group were given letrozole combined with HMG. Before treatment and 3 months after treatment, sex hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2), testosterone (T)], arterial hemodynamic indicators around the follicle [end diastolic velocity (EDV), peak systolic velocity (PSV), pulsation index (PI)], endometrial thickness and classification were compared between the two groups. The ovulation rate and pregnancy rate as well as pregnancy outcomes at 6 months of follow-up were recorded in each group. Results:After 3 months of treatment, FSH, LH, E 2 and T levels in each group were significantly decreased compared with those before treatment (all P < 0.05). FSH, LH, E 2 and T levels in the observation group were (1.85 ± 0.45) U/L, (9.86 ± 1.47) U/L, (81.25 ± 10.47) pmol/L, (1.75 ± 0.26) nmol/L, respectively, which were significantly lower than those in the control group [(3.12 ± 1.47) U/L, (12.58 ± 2.14) U/L, (109.25 ± 27.14) pmol/L, (3.58 ± 0.76) nmol/L, t = 5.90, 7.48, 6.87, 16.27, all P < 0.05). EDV in each group was significantly decreased after 3 months of treatment compared with that before treatment (both P < 0.05). After treatment, EDV in the observation group was significantly lower than that in the control group [(3.12 ± 1.42) cm/s vs. (5.14 ± 1.89) cm/s, t = 21.14, P < 0.001]. PSV in each group was significantly increased after treatment compared with that before treatment (both P < 0.05). After treatment, PSV in the observation group was significantly higher than that in the control group [(13.36 ± 2.01) cm/s vs. (10.24 ± 2.47) cm/s, t = 4.21, P < 0.001]. In each group, PI measured after treatment was not significantly different from that measured before treatment (both P > 0.05). After treatment, endometrial thickness in the observation group was significantly higher than that in the control group [(9.09 ± 1.58) mm vs. (8.41 ± 1.42) mm, t = 2.28, P < 0.05]. Ovulation rate in the observation group was significantly higher than that in the control group [88.24% (45/51) vs. 70.59% (36/51), χ2 = 4.85, P < 0.05]. There were no significant differences in endometrial type, biochemical pregnancy, clinical pregnancy rate, abortion rate, and premature delivery rate between the two groups (all P > 0.05). Conclusion:Letrozole combined with HMG has an ideal effect on refractory PCOS. It can improve the levels of sex hormones, restore the hemodynamic status in ovarian stroma and increase ovulation rate.

Indices in dental image exams for bone mineral density evaluation of aromatase inhibitor users

Abstract We evaluated the accuracy of radiomorphometric indices (RI) and fractal dimension (FD) for screening bone mineral density (BMD) in postmenopausal patients who had breast cancer and were using aromatase inhibitors (AI). The sample consisted of 40 participants. Digital panoramic radiography (DPR) and cone beam computed tomography (CBCT) were evaluated along with dual-energy X-ray absorptiometry (DXA), which is the gold standard for detecting low BMD. According to the T-scores of DXA, the subjects were assigned into two groups: with normal BMD and with low BMD (osteopenia and osteoporosis). The area under the curve (AUC), sensitivity, and specificity with their respective confidence intervals were determined for DPR and CBCT. For DPR indices, AUC ranged from 52.6 to 75.8%. The mandibular cortical width (MCW) had the highest AUC. For FD, the total trabecular index had the highest sensitivity, while the index anterior to the mental foramen (MF) had the highest specificity. In CBCT, the AUC ranged from 51.8 to 62.0%. The indices with the highest AUC were the molar (M) and anterior (A). The symphysis (S) index had the highest sensitivity and the posterior (P) index had the highest specificity. Sensitivity and specificity were adequate for the computed tomography index (Inferior; CTI [I]). Therefore, MCW, FD of the mandible angle, and total trabecular ROI in DPR and the CTI (I), M, P, and A indices in CBCT proved to be promising tools in distinguishing individuals with low BMD. Cutoff point for these indices could be a useful tool to investigate low BMD in postmenopausal women taking AI.

Leiomioma parasitario retroperitoneal: reporte de un caso / Retroperitoneal parasitic leiomioma: A case report

Resumen ANTECEDENTES: Los leiomiomas parasitarios son una variante poco común de la miomatosis uterina. Se han identificado en la pared abdominal, intestino delgado, muñón cervical o vaginal, vasos iliacos, ovarios, colon sigmoides y en el omento mayor. OBJETIVO: Reportar un caso clínico de leiomioma parasitario retroperitoneal y revisar la bibliografía al respecto. CASO CLÍNICO: Paciente de 57 años, con diagnóstico de NIC-III y hemorragia uterina anormal. Acudió a consulta debido a una sensación de masa y dolor abdominal, pérdida de peso subjetiva, hiporexia, disfagia y plenitud gástrica de cuatro meses de evolución. En los estudios de extensión se documentó una masa retroperitoneal grande y elevación de los marcadores tumorales Ca 125 y Ca 19-9. La resección de la masa se efectuó mediante laparotomía, con hallazgo histopatológico de mioma parasitario. CONCLUSIÓN: Los leiomiomas parasitarios deben considerarse en el diagnóstico diferencial de pacientes con antecedente de histerectomía o miomectomía, sobre todo en el contexto de la morcelación. El tratamiento consiste en cirugía o inhibidores de la aromatasa y análogos de la hormona liberadora de gonadotropina (leiomiomatosis peritoneal diseminada).

Abstract BACKGORUND: Parasitic leiomyomas are a rare entity, defined as an unusual variant of uterine myomatosis. Have been documented in the abdominal wall, small intestine, cervical or vaginal stump, iliac vessels, ovaries, sigmoid colon, and greater omentum. OBJECTIVE: To report a clinical case of retroperitoneal parasitic leiomyoma and review the literature. CLINICAL CASE: A 57-year-old patient with a diagnosis of CIN-III and secondary abnormal uterine bleeding, who consulted for a sensation of abdominal mass and pain, subjective weight loss, hyporexia, dysphagia and gastric fullness, of four months of evolution. Extension studies document a large retroperitoneal mass and elevation of tumor markers Ca 125 and Ca 19-9. We practice surgical management of her gynecological pathology and resection of the mass by laparotomy, with histopathological finding of myoma. CONCLUSION: Parasitic leiomyomas should be suspected in patients with a detected mass and a history of hysterectomy or myomectomy, especially in the context of morcellation. The treatment of this condition is surgical and, in cases of disseminated peritoneal leiomyomatosis, pharmacological treatments have been used with aromatase inhibitors and gonadotropin-release hormone analogues.

Parâmetros clínicos, periodontais, nutricionais e imaginológicos em pacientes em uso de inibidores de aromatase / Clinical, periodontal, nutritional and imaginological parameters in patients using aromatase inhibitors

A osteoporose é uma doença sistêmica multifatorial, caracterizada pela redução da massa óssea. A osteoporose pode ser primária ou secundária ao uso de medicamentos como os inibidores de aromatase. Estes medicamentos interferem com a conversão de andrógenos a estrogênios, reduzindo a produção destes e sendo indicados para tratamento do câncer de mama dependente de estrógeno. O diagnóstico da osteoporose é baseado em critérios densitométricos da Organização Mundial de Saúde com referência na classificação do T-score, realizada pela técnica de absorciometria de energia dupla de raios X (DXA). Por se tratar de uma doença sistêmica, a osteoporose também afeta os ossos maxilares. Entretanto, a ocorrência e extensão de perda de estrutura do osso alveolar na osteoporose, bem como o risco destes pacientes à doença periodontal e perdas dentárias não estão claramente definidos. Este estudo teve como objetivo identificar os parâmetros clínicos, periodontais, nutricionais e bioquímicos envolvidos na perda óssea em pacientes em uso de inibidores de aromatase. A perda óssea foi avaliada por absorciometria dupla de raios-X (DXA). Foram coletados dados sobre estado nutricional, antropométrico, bucal e periodontal e qualidade de vida relacionada à saúde bucal (OHRQoL). Citocinas e adipocinas foram quantificadas na saliva e soro. Foi realizado um estudo transversal do tipo caso-controle, com um grupo de comparação, no serviço de densitometria óssea do Hospital Mater Dei, no período de 2018 a 2021. A amostra foi constituída por 72 mulheres divididas em dois grupos: em uso de inibidores de aromatase (IAs) (n=40) e pacientes sem uso de inibidores de aromatase (controle) (n=32). Do total da amostra, 39 pacientes (57,4%) foram diagnosticados com perda de massa óssea. Os resultados mostraram que as mulheres idosas em uso de inibidores de aromatase (p=0,009) e fumantes (p=0,034) apresentaram maior perda óssea. Não houve diferença significativa entre os grupos considerando-se as comorbidades analisadas. A análise antropométrica demonstrou que os indivíduos em uso de inibidores de aromatase com perda óssea apresentaram menor peso (p=0,028). O modelo de regressão revelou que a única variável que explica a perda óssea é o uso de antirreabsortivos sendo a perda óssea significativamente reduzida nos indivíduos que usaram esse medicamento (p=0,022). Embora a frequência de periodontite tenha sido semelhante comparando todos os grupos, maiores valores de IL-6 (p=0,004); IL-1ß (p=0,002) e IL-33 (p=0,006) na saliva foram relacionados à pior condição periodontal. Indivíduos que usaram inibidores de aromatase foram 1,18 mais propensos a relatar uma melhor qualidade de vida relacionada à saúde bucal (OHRQoL) do que os controles. Conclusão: Enquanto idade avançada, tabagismo e menor peso são fatores associados à perda óssea, o uso de antirreabsortivos foi fator protetor em indivíduos em uso de inibidores de aromatase.

Osteoporosis is a multifactorial systemic disease characterized by reduced bone mass. Osteoporosis can be primary or secondary to the use of drugs such as aromatase inhibitors. These drugs interfere with the conversion of androgens to estrogens, reducing their production and are indicated for the treatment of estrogen-dependent breast cancer. The diagnosis of osteoporosis is based on densitometric criteria of the World Health Organization with reference to the T-score classification, performed by the technique of dual energy x-ray absorptiometry (DXA). Because it is a systemic disease, osteoporosis also affects the jaw bones. However, the occurrence and extent of loss of alveolar bone structure in osteoporosis, as well as the risk of these patients for periodontal disease and tooth loss, are not clearly defined. This study aimed to identify clinical, periodontal, nutritional and biochemical determinants involved with bone loss in patients using aromatase inhibitors. Bone loss was assessed by dual X- ray absorptiometry (DXA). Data on nutritional, anthropometric, oral and periodontal status and oral health-related quality of life (OHRQoL) were collected. Cytokines and adipokines were quantified in saliva and serum. A cross-sectional case-control type study, with a comparison group, was conducted at the bone densitometry service of Hospital Mater Dei from 2018 to 2021. The sample consisted of 72 women divided into two groups: using aromatase inhibitors (AIs) (n=40) and patients not using aromatase inhibitors (control) (n=32). Of the total sample, 39 patients (57.4%) were diagnosed with bone loss. The results showed that elderly women using aromatase inhibitors (p=0.009) and smokers (p=0.034) had greater bone loss. There was no significant difference between the groups considering the analyzed comorbidities. Anthropometric analysis showed that individuals using aromatase inhibitors with bone loss had lower weight (p=0.028). The regression model revealed that the only variable that explains bone loss is the use of antiresorptive drugs, with bone loss significantly reduced in individuals who used this medication (p=0.022). Although the frequency of periodontitis was similar comparing all groups, higher values of IL-6 (p=0.004); IL-1ß (p=0.002) and IL-33 (p=0.006) in saliva were related to worse periodontal status. Subjects who used aromatase inhibitors were 1.18 times more likely to report a better oral health-related quality of life (OHRQoL) than controls. Conclusion: While advanced age, smoking and lower weight are factors associated with bone loss, the use of antiresorptives was a protective factor in individuals using aromatase inhibitors.

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018-2021)

Cancer, which is the uncontrolled growth of cells, is the second leading cause of death after heart disease. Targeting drugs, especially to specific genes and proteins involved in growth and survival of cancer cells, is the prime need of research world-wide. Indole moiety, which is a combination of aromatic-heterocyclic compounds, is a constructive scaffold for the development of novel leads. Owing to its bioavailability, high unique chemical properties and significant pharmacological behaviours, indole is considered as the most inquisitive scaffold for anticancer drug research. This is illustrated by the fact that the U.S. Food and Drug Administration (FDA) has recently approved several indole-based anticancer agents such as panobinostat, alectinib, sunitinib, osimertinib, anlotinib and nintedanib for clinical use. Furthermore, hundreds of studies on the synthesis and activity of the indole ring have been published in the last three years. Taking into account the facts stated above, we have presented the most recent advances in medicinal chemistry of indole derivatives, encompassing hot articles published between 2018 and 2021 in anticancer drug research. The recent advances made towards the synthesis of promising indole-based anticancer compounds that may act via various targets such as topoisomerase, tubulin, apoptosis, aromatase, kinases, etc., have been discussed. This review also summarizes some of the recent efficient green chemical synthesis for indole rings using various catalysts for the period during 2018-2021. The review also covers the synthesis, structure‒activity relationship, and mechanism by which these leads have demonstrated improved and promising anticancer activity. Indole molecules under clinical and preclinical stages are classified into groups based on their cancer targets and presented in tabular form, along with their mechanism of action. The goal of this review article is to point the way for medicinal chemists to design and develop effective indole-based anticancer agents.

Inhibidores de la aromatasa para estatura baja en niños y adolescentes de sexo masculino / Aromatase inhibitors for short stature in male children and adolescents

Resumen Los inhibidores de la aromatasa son fármacos disponibles por vía oral que inhiben la conversión de la testosterona en estradiol. Los estrógenos desempeñan un papel esencial en la maduración del cartílago de crecimiento y del cierre epifisario, evento que marca el final del proceso de crecimiento esquelético. Por este motivo, los inhibidores de la aromatasa se han probado como una intervención para mejorar la talla en niños y adolescentes de sexo masculino mediante el retraso en la maduración esquelética al disminuir la concentración de estradiol en la placa de crecimiento. Se resumen los resultados de una revisión sistemática Cochrane en la cual se evaluaron la eficacia y la seguridad de los inhibidores de la aromatasa para el tratamiento de la estatura baja en niños.

Abstract Aromatase inhibitors are orally administered drugs that inhibit the conversion of testosterone to estradiol. Estrogens have an important role in growth plate maturation and epiphyseal closure. Thus, aromatase inhibitors have been used to improve final height in male children and adolescents by delaying skeletal maturation through a decrease in estradiol concentration. The results of a Cochrane systematic review evaluating the efficacy and safety of aromatase inhibitors for the treatment of short stature in children are summarized below.

Use of aromatase inhibitors in patients with breast cancer is associated with deterioration of bone microarchitecture and density

ABSTRACT Objective: To evaluate changes in bone density and architecture in postmenopausal women with breast cancer (BC) and use of aromatase inhibitor (AI). Subjects and methods: Thirty-four postmenopausal women with BC, without bone metastasis, renal function impairment and who were not receiving bone-active drugs were selected from a population of 523 outpatients treated for BC. According to the presence of hormonal receptors, HER2 and Ki67, seventeen had positive hormonal receptors and received anastrozole (AI group), and seventeen were triple-negative receptors (non-AI group), previously treated with chemotherapy. Areal bone mineral density (aBMD) and vertebral fracture assessment (VFA) analyses were performed by DXA; vBMD and bone microarchitecture were evaluated by HR-pQCT. Fracture risk was estimated using the FRAX tool. Results: No patient referred previous low-impact fracture, and VFA detected one moderate vertebral fracture in a non-AI patient. AI patients showed lower aBMD and BMD T-scores at the hip and 33% radius and a higher proportion of osteoporosis diagnosis on DXA (47%) vs non-AI (17.6%). AI group had significantly lower values for vBMD at the entire, cortical and trabecular bone compartments, cortical and trabecular thickness and BV/TV. They also had a higher risk for major fractures and for hip fractures estimated by FRAX. Several HR-pQCT parameters evaluated at distal radius and distal tibia were significantly associated with fracture risk. Conclusion: AI is associated with alterations in bone density and microarchitecture of both the cortical and trabecular compartments. These findings explain the overall increase in fracture risk in this specific population.

Letrozole: an emerging array of hope for infertile women

Ovulation induction has been a major breakthrough in the management of female infertility since many decades. Letrozole, an aromatase inhibitor has been used as a potential therapy for ovulation induction. A large number of clinical evidences have been emerging which cite the beneficial role of Letrozole in conditions like anovulatory infertility, polycystic ovary syndrome (PCOS), unexplained infertility and an incipient role in endometriosis- related infertility with regards to higher live-birth rates. Letrozole is a superior alternative to Clomiphene citrate (CC) which has been used conventionally as ovulation inducer. Clomiphene citrate has certain well-defined disadvantages, whereas Letrozole overcomes these limitations to a reasonable extent. The peripheral anti-estrogenic effect of CC leads to prolonged depletion of estrogens receptors, adversely affecting endometrial growth and development as well as quantity and quality of cervical mucus. Persistent blockade of estrogen receptor leads to CC resistance and is associated with reduced ovulation and pregnancy rates. Available evidences suggest Letrozole is superior to CC owing to the lack of persistent anti-estrogenic action due to its short half- life and lack of action on estrogen receptors. This typically leads to monofollicular growth and also higher live birth rates. The current evidences suggest that Letrozole can be placed as first line therapy for the management of infertility due to PCOS and unexplained infertility.

Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status / 한국유방암학회지

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer.METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis.RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188).CONCLUSION: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

Research on the intervention of Internet+ platform on the whole bone health management of aromatase inhibitors in breast cancer patients / 中国实用护理杂志

Objective@#To explore the influence of nursing intervention on bone health of breast cancer patients in aromatase inhibitors (AIs) treatment.@*Methods@#Totally 120 breast cancer patients receiving AIs treatment were randomly divided into the observation group (60 cases) and the control group (60 cases), and bone mineral density was measured. After that, the control group was routinely instructed to take calcium supplements, given health lectures, and real-time management. The observation group were given whole-process bone health management intervention based on "Internet+" on the basis of routine nursing. After 1 year, osteoporosis knowledge questionnaire and bone mineral density test were conducted in the two groups.@*Results@#Score of Osteoporosis Knowledge Test of observation group was 21.38±3.29, and 12.54±5.03 of control group, comparing the two groups was statistically significant (t=10.27, P < 0.05); before intervention bone mineral density of observation group was (1.042±0.138) g/cm2, and (1.058±0.127) g/cm2 of control group, comparing the two groups has no statistical significance, comparable (t=1.053, P > 0.05); after intervention the bone mineral density of observation group was (0.951±0.108) g/cm2, and (0.854±0.100) g/cm2 of control group, the comparison between the two groups was statistically significant (t=5.937, P<0.05). After intervention, the incidence of osteoporosis in the observation group was 21.67% (13/60), which was significantly higher than 35.00% (21/60) in the control group (χ2=4.279, P<0.05).@*Conclusion@#Whole-course nursing intervention can promote bone health of AIs patients with breast cancer.

Changes in Cardiac Autonomic Modulation in Women with Breast Cancer Using Aromatase Inhibitors and the Relation with Biochemical Variables / Alterações na Modulação Autonômica Cardíaca em Mulheres com Câncer de Mama em Uso de Inibidores de Aromatase e sua Relação com Variáveis Bioquímicas

Abstract Background: The use of autonomic modulation as a predictor of cardiovascular risk in women with breast cancer is important. Objective: To evaluate the cardiac autonomic modulation of postmenopausal women using aromatase inhibitors for breast cancer treatment, as well as its relation with the following biochemical variables. Methods: Postmenopausal women who did not have breast cancer (n = 33) and postmenopausal women with breast cancer (n = 15). For evaluation of the autonomic modulation the heart rate was recorded beat-to-beat for 30 minutes and the series of RR intervals obtained were used to calculate the following heart rate variability indices: Mean RR ms, SDNN (standard deviation of all normal RR intervals, expressed in milliseconds) ms, Mean HR, RMSSD (square root of the mean of the squared differences between adjacent normal RR interval) ms, NN50 (number of pairs of successive NNs that differ by more than 50 ms) count, pNN50% (proportion of NN50 divided by total number of NNs), RRtri (RR triangular), TINN (triangular interpolation of NN interval) ms, SD1 ms, SD2 ms, LF ms2, HF ms2, LH/HF ms2. The values of biochemical variables (fasting glycemia, triglycerides, HDL-cholesterol, and C-reactive protein) were analyzed by blood sample. Results: Lower values of heart rate variability indices were observed in postmenopausal women with breast cancer in relation to postmenopausal women who did not have breast cancer: Mean RR (p = 0.03); SDNN (p = 0.03); RMSSD (p = 0.03); NN50 count (p = 0.03); pNN50 % (p = 0.03); RRtri (p = 0.02); SD1 (p = 0.01); SD2 (p = 0.02); LF ms2 (p = 0.01); HF ms2 (p = 0.03).There was an inversely proportional correlation between the indices SDNN, SD2, and HFms2 with triglycerides (SDNN p = 0.04; SD2 p = 0.04; HF ms2 p = 0.04). No statistically significant correlations were found between heart rate variability indices and others variables. Statistical significance was set at 5% for all analyses. Conclusion: Women with breast cancer present reduced autonomic modulation and in these women of heart rate variability indices are inversely correlated with triglyceride values.

Resumo Fundamentos: A modulação autonômica como um preditor de risco cardiovascular em mulheres com câncer de mama é importante. Objetivos: Avaliar a modulação autonômica em mulheres pós-menopausa em uso de inibidores de aromatase como tratamento de câncer de mama, e sua relação com algumas variáveis bioquímicas. Métodos: Foram avaliadas mulheres pós-menopausa sem câncer de mama (n = 33) e mulheres pós-menopausa com câncer de mama (n = 15). Para avaliação da modulação autonômica, a frequência cardíaca (FC) foi registrada batimento a batimento por 30 minutos, e as séries de intervalos RR obtidas foram usadas para o cálculo dos seguintes índices de variabilidade da frequência cardíaca: média de RR ms, SDNN (desvio padrão de todos os intervalos RR normais) ms, FC, RMSSD (raiz quadrada da média das diferenças ao quadrado entre os intervalos RR normais adjacentes) ms, contagem NN50 (número de pares de NNs sucessivos que se diferem em mais de 50 ms), pNN50% (proporção de NN50 dividida pelo número total de NNs), RRtri (RR triangular), TINN (interpolação triangular do intervalo NN) ms, DP1 ms, DP2 ms, LF (baixa frequência) ms2, HF (alta frequência) ms2, LH/HF ms2. Os valores das variáveis bioquímicas (glicemia de jejum, triglicerídeos, HDL-colesterol, e proteína C reativa) foram analisadas das amostras de sangue. O nível de significância adotado nas análises estatísticas foi de 5%. Resultados: As mulheres pós-menopausa com câncer de mama apresentaram menores índices de variabilidade da frequência cardíaca em comparação àquelas sem câncer de mama: média de RR (p = 0,03); SDNN (p = 0,03); RMSSD (p = 0,03); contagem NN50 (p = 0,03); pNN50% (p = 0,03); RRtri (p = 0,02), DP1 (p = 0,01), DP2 (p = 0,02); LF ms2 (p = 0,01); HF ms2 (p = -0,03). Observou-se uma correlação inversamente proporcional dos índices SDNN, DP2 e HF ms2 com triglicerídeos (SDNN p = 0,04, DP2 p = 0,04; HF ms2 0,04). Não houve correlação significativa entre os índices de variabilidade da frequência cardíaca e as demais variáveis. Conclusão: Mulheres com câncer de mama apresentam modulação autonômica diminuída e índices de variabilidade da FC inversamente correlacionados com valores de triglicerídeos.

PARAGON (ANZGOG-0903): a phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression / 부인종양

OBJECTIVE: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER+). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER+ and/or progesterone receptor (PR)-positive (PR+) recurrent/metastatic gynecological cancers. METHODS: Postmenopausal women with ER+ and/or PR+ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%–48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1–3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8–11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS. CONCLUSION: A subset of asymptomatic patients with ER+ and/or PR+ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents.

A pilot study of gonadotropin-releasing hormone agonist combined with aromatase inhibitor as fertility-sparing treatment in obese patients with endometrial cancer / 부인종양

OBJECTIVE: This study aims to evaluate the effects and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH agonist) combined with aromatase inhibitor (AI) in preserving the fertility of obese women with grade 1 endometrial cancer (EC). METHODS: This study recruited obese EC patients who wished to preserve their fertility. The treatment regimen consisted of intramuscular GnRH agonist 3.75 mg every 4 weeks and oral AI 2.5 mg daily. The maintenance regimen was the same as the initial treatment regimen. Primary outcomes included response rate, time to complete response (CR), and time to recurrence; pregnancy outcomes included the time to pregnancy, pregnancy rate and live birth rate. RESULTS: Six obese patients with EC were included in this study, with the age (mean±standard deviation [SD]) of 30.5±3.3 years and body mass index (mean±SD) of 35.0±1.4 kg/m2. CR rate was 100%, and time to CR was 3–6 months. None of the patients had recurrence after a median follow-up of 4.0 years (range, 1.3–7.0 years). The most common side effects were menopause-like symptoms. Among these patients, no weight gain was observed during treatment. The pregnancy rate and live birth rate was 50.0% and 75.0%, respectively, with a median time to pregnancy of 2.4 years (range, 1.0–5.5 years). CONCLUSION: The combination of GnRH agonist and AI demonstrated promising long-term effect in young obese EC patients who wished to preserve their fertility. No weight gain side effects were observed. Further studies with a larger sample size are needed to fully evaluate this novel treatment regimen.

Advance in Aromatase Inhibitor Related Arthralgias (review) / 中国康复理论与实践

Estrogen deficiency, inflammatory reactions, metabolic disorders, etc., are considered to be possible mechanisms leading to arthralgias (or joint pain) associated with aromatase inhibitors (AIs) in breast cancer patients. The use of exercise and other non-pharmacological means (such as vitamin D, Omega-3 fatty acids, acupuncture, etc.) may relieve AIs-related arthralgia, and exercise may play a direct or indirect role to deal with the related pathogenesis. But the results of the studies are still controversial.

Evaluation of menopause and treatment choice of breast cancer patients before endocrine therapy / 中华肿瘤杂志

Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Endometriosis / Endometriosis

Resumen La endometriosis es una enfermedad inflamatoria benigna, dependiente de estrógeno, que se caracteriza por la presencia de glándulas y estroma endometrial en un sitio distinto a la cavidad uterina. Las principales teorías sobre su patogénesis involucran la menstruación retrograda, La metaplasia del epitelio germinal, y la diseminación metastásica. Las lesiones típicamente se localizan en la pelvis; en ovarios, ligamentos uterosacros y saco de Douglas, sin embargo también pueden encontrarse fuera de esta. La enfermedad ocasiona un cuadro clínico variado que involucra dismenorrea, dispareunia, dolor pélvico e infertilidad. Su diagnóstico definitivo ES quirúrgico. El tratamiento médico es solo sintomático y no curativo, mientras que el quirúrgico pese a ser curativo, presenta variables tasas de recurrencia. Las técnicas de reproducción asistida mejoran significativamente las tasas de nacimientos en caso de infertilidad asociada a la enfermedad.

Abstract Endometriosis is a benign, estrogen dependent, inflammatory disease, which is characterized by the presence of endometrial glands and stroma in a site different from the uterine cavity. The main theories about it's pathogenesis involve retrograde menstruation, metaplasia of the germinal epithelium, and metastatic spread. The lesions are typically located in the pelvis; in ovaries, utero sacral ligaments and Douglas pouch, but can also have an extra pelvic location. This disease has a variable clinical presentation that involves dysmenorrhea, dyspareunia, pelvic pain and infertility. It's definitive diagnosis is surgical. Medical treatment is only symptomatic and non-curative, while the surgical treatment despite being curative has important recurrence rates. Assisted reproduction techniques are very useful to improve birth rates in case of infertility associated with the disease.