Long-term Hormone Therapy Research Articles

Особливості клінічного перебігу передраку і раку вульви у жінок репродуктивного віку

Continuing increase of precancer, epithelial and invasive vulvar cancer rate significantly enlarges the proportion of this group of patients. Meanwhile, all the grounds to improve the system of early diagnosis and treatment of this pathology are given nowadays. No other localization of gynecological cancer proves such a close association with postmenopause and involute atrophic processes of this period of a woman’s life. The objective: is to study the features of the clinical course of cancer and precancerous lesions of the vulva in women of reproductive age. Materials and methods. From 2017 to 2020, 150 patients with dystrophic diseases, precancerous lesions and vulvar cancer were examined in the outpatient department of the National Cancer Institute. The age of patients in the study ranged from 18 to 49 years old (32±3.5). Menstrual function was unchanged in 98 (65%) of 150 women. The age of menarche varied from 11 to 18 years old (mean age – 14.5±0.3 years). The average duration of the menstrual cycle was 28±0.4 days. The doctor performed conservative treatment of «leukoplakia and kraurosis» for many months, and sometimes years, without histological clarification of the diagnosis. More than half (n=106; 71%) of patients underwent long-term and unreasonable anti-inflammatory or hormonal therapy with unsatisfactory results without cytological and / or histological examinations. Results. In the study of vulvar biopsies, the VIN diagnosis (28%) prevailed in comparison with the invasive tumor process (12%) and was asymptomatic in more than 50% of cases. Thus, the peak level of HPV was observed in young women (80%). HPV was represented by types of high oncogenic risk (16, 18, 31, 33) in 90% of cases and it was associated with a malignant process in 100% of cases. At the same time, the background disease in young patients is squamous cell hyperplasia, where the sequence of tumor development (VIN I - VIN II – VIN III) is more clearly traced and largely resembles the development of cervical cancer. It has been noted that in young women PVI is usually temporary, there is a faster spontaneous elimination of the virus and regression of existing HPV-associated pathology compared with menopausal women. Conclusion. Vulvar neoplasia is more common in the VIN form in women of reproductive age and in all cases, it is associated with human papillomavirus (HPV) of high oncogenic risk. Multicentric lesions are more typical for young patients. Keywords: vulva, cancer, precancer, anamnesis, vulvoscopy, histological examination.

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer

AimsThe safety and efficacy of stereotactic body radiotherapy (SBRT) in localised prostate cancer are now established through phase III randomised trials. Its utility in node-positive prostate cancer is restricted due to a lack of controlled studies specifically addressing this subgroup. Herein we report the safety and efficacy of SBRT in this subgroup. Materials and methodsIn total, 60 patients treated with SBRT to prostate and pelvis were analysed. All patients received neoadjuvant androgen deprivation therapy for at least 6 months and long-term adjuvant hormonal therapy (70% medical and 30% surgical). All patients were treated with daily image-guided rotational intensity-modulated radiotherapy. The dose delivered to the prostate and gross node was 35–37.5 Gy and 25 Gy in five fractions to the elective pelvic nodal region on alternate days. Acute and late toxicities were graded as per Radiation Therapy Oncology Group common toxicity criteria. ResultsForty-one (68%) patients had a Gleason score ≥8. The median prostate-specific antigen level at diagnosis was 39 ng/ml. Twenty (33%) patients had common iliac nodal uptake on initial prostate-specific membrane antigen positron emission tomography-computed tomography. After the median follow-up of 30 months, no acute or late Radiation Therapy Oncology Group grade ≥3 gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicities were 8.3% and 11.7%, respectively. Late grade 2 genitourinary and gastrointestinal toxicities were 3.3% and 8.3%, respectively. Late grade 3 genitourinary toxicity was seen in two (3.3%) patients. Three-year overall survival and biochemical failure-free survival was 89% and 77%, respectively. ConclusionSBRT to the prostate and pelvis is safe and efficacious in node-positive prostate cancer even with common iliac nodal involvement (stage M1a).

Facilitating the adherence journey of children, adolescents, and adults on long-term growth hormone therapy.

Growth hormone deficiency in children and adolescents is treated with recombinant growth hormone injections, with the aim of helping patients reach a final height that falls within their genetically predicted adult height. While this treatment is very successful, overcoming issues of patient adherence is a challenge at each stage of the treatment journey, from early childhood to adulthood. An advisory board of senior endocrine nurses convened to discuss what strategies and tools work well in achieving adherence, and the best practices they identified-including the key strategies of choice, information, teamwork, and support-were presented at the 2016 meeting of The Endocrine Society. The advisers agreed that key steps to improve adherence include: patient/carer-centric endocrine nursing services, good-quality education and support, patient autonomy (where possible), broader treatment choice (in terms of device and self-injection), optimal follow-up from childhood to adulthood, and sharing of best practices.

Функциональное состояние сосудистой стенки и плазменного звена гемостаза у женщин раннего постменопаузального периода на фоне длительной менопаузальной гормональной терапии

Цель исследования: оценка изменений функциональной активности сосудистой стенки и плазменного звена гемостаза у женщин раннего постменопаузального периода на фоне длительной низкодозовой менопаузальной гормональной терапии (МГТ). Материалы и методы: Обследовано 162 женщины в ранней постменопаузе. В основную группу вошли 84 пациентки, которым была назначена низкодозовая МГТ: 1 мг 17β-эстрадиола (E2) и 2 мг дроспиренона (ДРСП) — препарат Анжелик® (Байер Фарма, Германия). Контрольную группу составили 78 женщин, не получавших МГТ. Длительность наблюдения составила 5,2 [4,8; 5,7] лет. Исследовали антитромбогенную активность сосудистой стенки, лабораторные маркеры эндотелиальной дисфункции. Результаты: Несмотря на увеличение агрегационной активности тромбоцитов и более низкие значения активности антитромбина III у женщин на фоне МГТ, не было отмечено увеличения риска развития венозного тромбоза и эмболий, ишемического инсульта и случаев острого коронарного синдрома. К окончанию наблюдения установлено снижение антиагрегационного потенциала сосудистой стенки, более выраженное у женщин группы кон-троля. У женщин, принимавших МГТ, выявлено снижение концентрации фибриногена крови к окончанию исследования. На фоне МГТ отмечено значимое возрастание уровня метаболитов оксида азота, снижение уровней эндотелина-1 и асимметричного диметиларгинина к 12 мес наблюдения, но в дальнейшем отмечено повышение их уровней, не достигшее исходных значений. Заключение: Изменения функциональной активности эндотелия свидетельствуют об отсутствии негативного влияния на эндотелий сосудов длительной низкодозовой МГТ (1 мг E2/2 мг ДРСП). Objectives: to assess changes in the functional activity of the vascular wall and plasma hemostasis in women of early postmenopausal period under long-term low-dose menopausal hormone therapy (MHT). Patients/Methods: We examined 162 women in early postmenopause. The main group included 84 patients; they were prescribed a low-dose MHT: 1 mg of 17β-estradiol (E2) and 2 mg of drospirenone (DRSP) — Angelique® (Bayer Pharma, Germany). The control group consisted of 78 women did not taking MHT. The duration of observation was 5.2 [4.8; 5.7] years. Antithrombogenic activity of the vascular wall and laboratory markers of endothelial dysfunction were examined. Results: In women taking MHT we found increasing of platelet aggregation activity and lower antithrombin III activity, but did not reveal increased risk of venous thrombosis and embolism, ischemic stroke, and cases of acute coronary syndrome. By the end of observation decreasing of antiplatelet potential of the vascular wall, more expressed in women of the control group, was noted. In women taking MHT, blood fi brinogen concentration decreased by the end of the study. After 12 months of observation in women taking MHT we revealed significant increasing of nitric oxide metabolites, decreasing of endothelin-1 and asymmetric dimethylarginine; later their levels increased but did not reach the initial values. Conclusions: Changes in endothelial functional activity showed no adverse effect of long-term low-dose MHT (1 mg E2/DRSP 2 mg) on the vascular endothelium.

Re: Radiation Dose Escalation or Longer Androgen Suppression to Prevent Distant Progression in Men with Locally Advanced Prostate Cancer: 10-Year Data from the TROG 03.04 RADAR Trial.

No AccessJournal of UrologyUrological Survey1 Oct 2020Re: Radiation Dose Escalation or Longer Androgen Suppression to Prevent Distant Progression in Men with Locally Advanced Prostate Cancer: 10-Year Data from the TROG 03.04 RADAR Trial Samir S. TanejaMD Samir S. TanejaSamir S. Taneja More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001220.02AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Radiation Dose Escalation or Longer Androgen Suppression to Prevent Distant Progression in Men with Locally Advanced Prostate Cancer: 10-Year Data from the TROG 03.04 RADAR Trial." The Journal of Urology, 204(4), pp. 879–880 Suggested Reading : Survival outcomes of dose-escalated external beam radiotherapy versus combined brachytherapy for intermediate and high risk prostate cancer using the National Cancer Data Base. J Urol 2016; 195: 1453. Link, Google Scholar : Impact of hormonal therapy on intermediate risk prostate cancer treated with combination brachytherapy and external beam irradiation. J Urol 2010; 183: 546. Link, Google Scholar : 15-Year cause specific and all-cause survival following brachytherapy for prostate cancer: negative impact of long-term hormonal therapy. J Urol 2014; 192: 754. Link, Google Scholar © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 204Issue 4October 2020Page: 879-880 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Samir S. Taneja More articles by this author Expand All Advertisement Loading ...

Pelvic floor muscles contraction and sexual function are associated with hormonal treatment in women after breast cancer?

Introduction: Breast cancer has a high prevalence among women. It is known that breast cancer survivors can undergo a several alterations due to the treatment, including sexual dysfunction. Objective: This study aimed to determine the incidence of sexual dysfunction in women after breast cancer surgery, and assess the relationship between sexual dysfunctions and pelvic floor muscles (PFM) contraction, as well to verify if hormone therapy caused long-term occurrence of PFM weakness or sexual dysfunction. Methods: The sample was composed by 26 women with 48.4 ± 6.8 years which using hormone therapy treatment at least six months. Data on sexual dysfunction were collected through the Female Sexual Function Index- FSFI questionnaire and a section composed by demographic information. Furthermore, the PFM contraction was assessed using the PERFECT scale. Results: The results demonstrated a high rate of sexual dysfunction (64.3%) and a weak PFM contraction (2.31±1.3) among the women. In addition, a long-term hormone therapy had a negative association with PFM endurance and with the orgasm and satisfaction domains of the FSFI questionnaire. Conclusion: women using hormone therapy after breast cancer surgery had a high rate of sexual dysfunction and the long-term treatment of hormone treatment can be associated with a worsening of orgasm and sexual satisfaction in these women. Also, the use at long-term of hormone therapy had a negative association with the PFM endurance.

Long-term clinical outcomes of salvage pelvic radiation therapy for oligo-recurrent pelvic lymph nodes after definitive external-beam radiation therapy for non-metastatic prostate cancer.

Although salvage external-beam radiation therapy (EBRT) is an attractive treatment option for pelvic lymph nodal recurrence (PeNR) in patients with prostate cancer (PCa), limited data are available regarding its long-term efficacy. This study examined the long-term clinical outcomes of patients who underwent salvage pelvic radiation therapy (sPRT) for oligo-recurrent pelvic lymph nodes after definitive EBRT for non-metastatic PCa. Patients who developed PeNR after definitive EBRT and were subsequently treated with sPRT at our institution between November 2007 and December 2015 were retrospectively analyzed. The prescribed dose was 45–50.4 Gy (1.8–2 Gy per fraction) to the upper pelvis, with up to 54–66 Gy (1.8–2 Gy per fraction) for recurrent nodes. Long-term hormonal therapy was used as neoadjuvant and/or adjuvant therapy. The study population consisted of 12 consecutive patients with PeNR after definitive EBRT (median age: 73 years). The median follow-up period was 58.9 months. The 5-year overall survival, PCa-specific survival, biochemical failure-free, clinical failure-free, and castration-resistant PCa-free rates were 82.5, 100.0, 62.3, 81.8, and 81.8%, respectively. No grade 2 or higher sPRT-related late toxicities occurred. In conclusion, more than half of the study patients treated with sPRT had a long-term disease-free status with acceptable morbidities. Moreover, most of the patients maintained hormonal sensitivity. Therefore, this approach may be a promising treatment method for oligo-recurrent pelvic lymph nodes.

Increased frequency of ESR1 mutation in metastatic breast cancer by dosing selective estrogen receptor modulator followed by aromatase inhibitor.

In several recent studies on metastatic breast cancer (MBC), ligand binding domain mutations of the estrogen receptor, which is coded by the ESR1 gene, were induced by long-term endocrine therapy and resulted in acquired endocrine therapy resistance and poor outcomes. Knowledge of the association between the development of ESR1 mutation and the clinicopathologic features may guide the decision-making process of metastatic breast cancer treatment, including endocrine therapy. The aim of the present study was to evaluate the association between the development of ESR1 mutation and the clinicopathologic characteristics of patients with MBC. To evaluate the association between the development of ESR1 mutation and clinicopathologic features, a cohort of 22 patients with MBC were retrospectively analyzed using next generation sequencing. In 14 of 22 patients, four mutations were detected on the metastatic site, including Tyr537Ser, Glu542Asp, Leu536Arg and Arg548Cys. Univariate analysis demonstrated that the duration of aromatase inhibitor and selective estrogen receptor modulator treatment, as well as the age of treatment initiation for early-stage breast cancer, were significantly associated with the development of ESR1 mutation. ESR1 mutation was identified in all five patients who received selective estrogen receptor modulators in the adjuvant setting followed by aromatase inhibitors in the metastatic setting, as well as in two of the three patients who received no selective estrogen receptor modulators in adjuvant setting followed by aromatase inhibitors in the metastatic setting. In conclusion, the results of the present study suggested that administrating adjuvant selective estrogen receptor modulator followed by aromatase inhibitor for metastasis may increase the frequency of ESR1 mutation.

A prospective observational study of combinatorial abiraterone (AA) and radical radiotherapy (RT) in node-positive (N+) prostate cancer (PCa).

e17555 Background: The conventional treatment backbone of N+ PCa has been hormonal therapy (HT) alone. Nonetheless, evidence from the STAMPEDE trial suggests that there could be survival benefit with the addition of local RT or AA, and there may be synergy between RT and AA in these advanced patients. We therefore conducted a prospective observational study to evaluate the efficacy of combination AA+HT+RT in patients with N+ PCa. Here, we report the preliminary biochemical response and toxicity data. Methods: Patients with N+M0/N+M1a, biopsy-proven adenocarcinoma of the prostate were enrolled. Patients were staged by 68Ga-PSMA-PET or whole body MRI. Exclusion criteria were i) ECOG ≥2; ii) cardiac event of < 6 mo interval; iii) bone and visceral metastasis. Treatment protocol entailed 18 mo of combination AA (1000 mg plus 5 mg prednisolone once daily) and HT (LHRH agonist/antagonist); RT was delivered to the prostate (78 Gy) +/- pelvis (54 Gy with simultaneous boost of 60-66 Gy to grossly involved lymph nodes in M0 patients). This was matched against a control group that received long-term HT +/- RT (N = 38). Primary endpoint of this analysis was PSA ≤0.1 ng/ml at 6 mo; secondary endpoints were PSA ≤0.1 ng/ml, testosterone ≤0.7 nmol/l at 12 mo, and toxicity outcomes. Germline genetic profiling was performed in all patients. Results: From Feb 2017 to Aug 2019, 18 men were recruited to this study, with a median fu of 15 mo (range 6.0-35.0 mo). Median age was 66.0 y (IQR 62.0-71.0y); median baseline PSA was 18.2 ng/ml (range 3.0-272); 66.7% had GS 8-10 disease; and 22.2% had M1a disease. Combination AA+HT+RT achieved PSA of ≤0.1 ng/ml in 80.0% (N = 12) and 93.3% (N = 14) of patients at 6 mo and 12 mo, respectively, in contrast to 29.4% and 25.0% of patients who were treated with HT+RT and HT alone, respectively. We observed profound castration of 87.5% (N = 14) at 6 mo, and 91.7% (N = 11) at 12 mo. Four and 6 patients experienced acute G2 genitourinary and gastrointestinal toxicities during RT, respectively; 2 patients reported late G2 GU. One patient experienced G2 fatigue and G1 liver enzyme dysfunction, resulting in dose reduction of AA. Genetic testing revealed a patient with BRCA2 frameshift mutation; interestingly, this patient failed to achieve a PSA of ≤0.1 ng/ml at 12 mo. Conclusions: We demonstrate that combinatorial AA+HT and definitive RT is well tolerated, and yield a pronounced early PSA response in N+ PCa. Long-term data will inform if this early efficacy signal leads to improved survival in these patients.

Hormone Therapy for Transgender Women

Many transgender women seek hormone therapy to produce the feminizing characteristics of their self-identified gender. Clinical practice guidelines exist to make sure transgender women are receiving evidence-based treatment regimens. Therefore, nurse practitioners are at the forefront of ensuring medication safety and helping transgender women reduce modifiable risks for complications from long-term hormone therapy.

Outcomes of combined radiotherapy in high-risk prostate cancer

Radiotherapy is one of the radical treatment options used in patients with prostate cancer (PC). Many studies of combined radiotherapy (CRT) for PC have demonstrated good results in respect of response to treatment; however, the sequence of CRT steps and optimal interval between them have not been determined so far. Few randomized studies have been conducted in order to confirm the advantages of brachytherapy at the first or second step or determine the most effective interval between the contact and external beam RT. Therefore, it appears reasonable to evaluate different CRT techniques.Purpose. The goal of the study was to evaluate the outcomes of PC treatment depending on the sequence of CRT steps and the interval between them.Materials and methods. 53 patients with PC received 125I radiation therapy in combination with long-term hormone therapy (HT). Median follow-up was 38 months. Patients’ age varied from 54 to 81 years. All patients were in a high-risk group according to the D’Amico Risk Classification System. The patients were allocated to two groups: in Group 1, brachytherapy was used as the first step (n=31); in Group 2, it was applied after external beam therapy (EBT). The interval between the CRT steps could be less than 4 weeks (n=6), 4 – 7 weeks (n=17) and more than 8 weeks (n=30). Standard fractionation EBT with a total dose of 46 Gy using the VMAT technique was conducted. 125I prostate implants were inserted to reach a total dose of 110 Gy. Neoadjuvant (2 – 4 months) and adjuvant (not less than 24 months) regimens of HT were applied.Results. Five (9.4 %) patients had disease progression; two of them experienced only biochemical recurrence; distant metastases were diagnosed in three patients. Median time to disease progression was 29.9 months. One patient with a biochemical relapse died of acute myocardial infarction (1.9 %). Median five-year disease-free survival was 84.5±11.7 % in Group 1 and 83.5±9.1 (p=0.73) in Group 2. There were no significant differences in the incidence of toxicity depending on the sequence of CRT steps.Conclusion. EBT using 125I radiation sources in combination with long-term hormone therapy is an effective and safe treatment option for high-risk PC patients. No significant increase in the incidence of disease progression was observed when the interval between the CRT steps was increased to more than 8 weeks. Changes in the sequence of CRT steps do not affect response to treatment or incidence of radiation-related complications.

Interaction between postmenopausal hormone therapy and diabetes on cataract.

We investigated whether postmenopausal hormone therapy (HT) use interacts with diabetes, a risk factor for several age-related eye diseases. A cross-sectional analysis of women involved in the Canadian Longitudinal Study on Aging was performed. The random sample comprised of 15,320 community-dwelling women between ages 45 and 85 years old sampled from areas adjacent to 11 data collection centers across Canada. Information on menopausal status and HT were collected by self-report. Data on diabetes and eye disease were obtained by self-report of a physician diagnosis. Multivariable logistic regression was used. After adjusting for demographic, lifestyle, and health variables, a multiplicative interaction was identified such that HT use for 10 years or more was associated with a much higher odds of a report of cataract in women with type 2 diabetes (odds ratio = 2.44, 95% confidence interval 1.49, 3.99) but not in long-term HT users with no diabetes (odds ratio = 1.03, 95% confidence interval 0.87, 1.21) (interaction term P value = 0.013). HT use was not associated with glaucoma or macular degeneration. Long-term HT use and type 2 diabetes interact in their relationship with cataract. This novel finding should be confirmed. If confirmed, women with type 2 diabetes should be informed that long-term HT use increases their risk of cataract. : Video Summary:http://links.lww.com/MENO/A519.

Addition of abiraterone to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Model to estimate long-term survival, quality-adjusted survival, and cost-effectiveness.

204 Background: Results from randomised trials show adding abiraterone acetate plus prednisolone (AAP) to standard of care (SOC) improves disease-free and overall survival in men with prostate cancer (PC) starting long-term hormone therapy for first time. Formal assessment is required of whether funding AAP here shows appropriate use of resources. This cost-effectiveness decision model tests if giving AAP to these patients is cost-effective using costs from English National Health Service, the largest nation where STAMPEDE recruited. Methods: Health outcomes and costs were modelled using patient data from AAP comparison of STAMPEDE (recruitment 2011-14). This included 1917 men with high-risk, locally advanced metastatic or recurrent PC starting 1st-line hormone therapy. SOC was hormone therapy for ≥2 years with radiotherapy in pre-selected patients. If allocated to research group, AAP (AA 1000mg/day, P 5mg/day) was added to SOC. The model makes lifetime predictions of survival, costs and quality-adjusted lifeyears (QALYs), with costs and QALYs discounted at 3.5% annually. Sensitivity analyses were performed. Results: The model predicted AAP would extend survival (discounted quality-adjusted survival) by 2.68y (1.46 QALYs) for metastatic patients and 0.30y (0.29 QALYs) for non-metastatic. The cost of AAP means it is not currently cost-effective in this setting, including with Patient Access Scheme costs for AAP and enzalutamide and similar reductions for cabazitaxel and Ra. If AAP’s price reduces after patent expiry as expected (90% reduction on BNF cost), it would be cost-effective in both patient groups, with incremental cost-effectiveness ratios below £10,000 (US$12,665) per QALY. AAP could also dominate in non-metastatic patients (i.e. lower costs and higher QALYs than SOC alone). Conclusions: AAP could be cost-effective for patients with non-metastatic and metastatic disease with expected future pricing and may be cost-saving in the former. Policymakers should encourage license submissions and generic price reductions to facilitate use of AAP given cost-saving potential in addition to improving survival. Clinical trial information: NCT00268476.

Abstract P2-11-17: Expression levels of some genes associated with tumor shrinkage by neoadjuvant endocrine therapy were paradoxically related with poor prognosis in patients with ER-positive/HER2-negative operable breast cancer

Abstract Purpose: We previously published that the expression levels of 5 genes (ADCK2, CUL2, FAM13A, KRAS, LILRA2) related to tumor shrinkage by neoadjuvant endocrine therapy (NAET) were identified though the gene expression profiles (Goto-Yamaguchi L et al, Breast Cancer Res Treat. 72:353-362,2018). In this study, we examined whether expression levels of these 5 genes were associated with prognosis in patients with ER-positive/HER2-negative operable breast cancer. Methods: Formalin-fixed paraffin embedded tumor tissues before systemic treatment were provided by 273 patients with ER-positive/HER2-negative operable breast cancer receiving standard of care at our institute from June 2000 to January 2011. We examined gene expression levels of these 5 genes determined by real time-quantitative PCR using RNA extracted from the tumor samples. We analyzed the prognostic impact of these 5 genes in terms of relapse-free survival (RFS) and breast cancer-specific survival (BCSS). We also study the relationship between 5 genes expression and clinic-pathological factors. Results: Median follow-up time was 106 months. Among 5 genes, high expression levels of ADCK2 and CUL2 were significantly related with poor PFS (log-rank test, ADCK2: p=0.022, CUL2: p0.045) but not BCSS. On the other hand, high levels of FAM13A expression were significantly poor BCSS (log-rank test, p=0.042) but not RFS. Expression of KRAS and LILRA2 were not any correlation with prognosis. Multivariate analysis in terms of RFS revealed that ADCK2 was an independent prognostic factor (HR 2.26, 95%CI 1.04 to 5.07, p = 0.038). In addition, multivariate analysis in terms of BCSS revealed that FAM13A (HR 15.6, 95%CI 2.36 to 316.0, p = 0.0029), nodal status (HR 8.22, 95%CI 1.57 to 62.9, p=0.012) and PgR (HR 0.14, 95%CI 0.0068 to 0.93, p=0.042) were independent prognostic factors. Expression of ADCK2 and CUL2 were not associated with any clinic-pathological factors such as menopausal status, tumor size, nodal status, expression levels of ER and PgR, nuclear grade and ki67 labeling index. FAM13A expression was positively correlated with ki67 labeling index (chi-square test, p=0.0007). Conclusion: Despite the genes associated with tumor shrinkage by NAET, ADCK2, CUL2 and FAM13A among the genes were positively correlated with poor prognosis. This paradoxical phenomenon showed that endpoint of short-term endocrine therapy such as tumor shrinkage may not be reflect that of long-term endocrine therapy such as PFS and BCSS. Citation Format: Lisa Goto-Yamaguchi, Mutsuko Ibusuki-Yamamoto, Masako Takeno, Yositaka Fujiki, Mai Tomiguchi, Aiko Sueta, Yutaka Yamamoto. Expression levels of some genes associated with tumor shrinkage by neoadjuvant endocrine therapy were paradoxically related with poor prognosis in patients with ER-positive/HER2-negative operable breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-17.

Factors Associated with Endocrine Therapy Non-Adherence in Breast Cancer Survivors.

For women with hormone receptor positive breast cancer, long-term endocrine therapy (ET) can greatly reduce the risk of recurrence, yet adherence is low- particularly among traditionally underserved populations. The Carolina Breast Cancer Study oversampled Black and young women (<50 years of age). Participants answered an ET-specific medication adherence questionnaire assessing reasons for non-adherence. We used principal factor analysis to identify latent factors describing ET non-adherence. We then performed multivariable regression to determine clinical and demographic characteristics associated with each ET non-adherence factor. 1,231 women were included in analysis, 59% reported at least one barrier to ET adherence. We identified three latent factors which we defined as: habit - challenges developing medication-taking behavior; tradeoffs - high perceived side effect burden and medication safety concerns; and resource barriers - challenges related to cost or accessibility. Older age (50+) was associated with less reporting of habit (Adjusted Risk Ratio (aRR) 0.54[95% CI: 0.43-0.69] and resource barriers (aRR 0.66[0.43-0.997]), but was not associated with tradeoff barriers. Medicaid-insured women were more likely than privately-insured to report tradeoff (aRR:1.53 [1.10-2.13]) or resource barriers (aRR:4.43[2.49-6.57]). Black race was associated with increased reporting of all factors (habit: aRR 1.29[1.09-1.53]; tradeoffs: 1.32[1.09-1.60], resources: 1.65[1.18-2.30]). Barriers to ET adherence were described by three distinct factors, and strongly associated with sociodemographic characteristics. Barriers to ET adherence appear inadequately addressed for younger, Black, and publicly-insured breast cancer survivors. These findings underscore the importance of developing multi-faceted, patient-centered interventions that address a diverse range of barriers to ET adherence.

Update on Diabetes Mellitus and Glucose Metabolism Alterations in Prader-Willi Syndrome.

This review summarizes our current knowledge on type 2 diabetes mellitus (T2DM) and glucose metabolism alterations in Prader-Willi syndrome (PWS), the most common syndromic cause of obesity, and serves as a guide for future research and current best practice. Diabetes occurs in 10-25% of PWS patients, usually in adulthood. Severe obesity is a significant risk factor for developing of T2DM in PWS. Paradoxically, despite severe obesity, a relative hypoinsulinemia, without the expected insulin resistance, is frequently observed in PWS. The majority of PWS subjects with T2DM are asymptomatic and diabetes-related complications are infrequent. Long-term growth hormone therapy does not adversely influence glucose homeostasis in all ages, if weight gain does not occur. Early intervention to prevent obesity and the regular monitoring of glucose levels are recommended in PWS subjects. However, further studies are required to better understand the physiopathological mechanisms of T2DM in these patients.

Clinical features of pulmonary thromboembolism of eight children

Objective: To improve the diagnosis and therapy of childhood pulmonary thromboembolism (PTE) by analyzing the clinical features of this rare condition. Methods: A total of 8 pediatric patients (4 males, 4 females) with PTE diagnosed in the Children's Hospital of Zhejiang University School of Medicine from March, 2014 to March, 2019 were enrolled. The clinical manifestation, laboratory results, imaging findings, diagnosis and treatment were summarized. Results: Among these 8 cases, aged from 9 hours to 14 years and 10 months. Fever was found in 4 cases, cough aggravation in 4, short of breath in 3, chest pain in 2, abdominal and back pain in one, hemoptysis in 2, cyanosis in 1, and edema of lower extremities in 2. Physical examination found decreased breath sound in 2 cases, phlegm rale in 3, and pleural friction rub in one. Pleural effusion was found in 5 cases by ultrasound. Plasma D-dimer increased in 6 cases (0.66-9.96 mg/L) and hypersensitive C-reactive protein elevated in 5 cases (10.78-78.00 mg/L). Chest enhanced CT showed pulmonary artery or venous filling defects, including pulmonary artery embolism in 7 cases and pulmonary vein embolism in one. The primary disease of these patients included Mycoplasma Pneumoniae pneumonia in 4 cases, nephritis in 2 and postoperative congenital heart disease in 2. Apart from one case who withdrew the treatment and was discharged, the other 7 patients received anticoagulant treatment had good outcome. Conclusions: For children with Mycoplasma pneumoniae pneumonia, immune disorders, long-term hormone therapy, cardiovascular invasive operation or other high-risk factors, PTE should be considered when fever, cough aggravation, short of breath, chest and back pain with pleural effusion are present. Chest enhanced CT scan should be performed as soon as possible, and anticoagulation should be started once the diagnosis is confirmed.

Benefits and challenges in conducting long-term growth hormone therapy in patients with Prader-Willi syndrome

The purpose of this report is to comment the results from long-term growth hormone (GH) treatment of Bulgarian patients suffering from rare genetic disease-Prader-Willi syndrome (PWS) with reference to the age, body composition, complications and genetic etiology. Statistical analysis was performed by ANOVA with post hoc Kruskal-Wallis test and Dunn's multiple comparison tests. In 90% of the patients maternal uniparental disomy (mUPD) was found to be the cause of the disease. No cases due to imprinting defects are found. The BMI data shows no statistically significant difference between BMI at diagnosis (21.850), at the beginning of the GH therapy (21.852) and current BMI (24.09) - measured under the GH background. Early GH treatment allows to overcome arising obstacles in time and to improve the quality of life for PWS children and their families. During the fourteen years study period only ten patients were diagnosed with the disease. Ninety percent (n=9) of the children were found to be with maternal UPD (mUPD) and only one case was due to deletion in 15q11-13. These results are in agreement with other studies in the field which shows the need for reassessment and new robust statistical analysis of the frequency of genetic mechanisms for PWS.

Analysis of clinical characteristics and risk factors for pulmonary infection in elderly patients with hip fracture

Objective To investigate the clinical characteristics and risk factors for pulmonary infection in elderly patients with hip fracture after the treatment through a model of orthopedic-geriatric co-care, in order to provide prevention and control strategies. Methods Clinical data and laboratory results of elderly patients with hip fractures admitted into our hospital from January 2016 to May 2016 were collected.The differences in treatment outcome and adverse reactions were retrospectively compared between the two groups of patients with versus without pulmonary infection, and univariate and multivariate analysis of lung infection were performed. Results Of 207 patients, 43 were infected with pneumonia and 164 were not.The proportion of patients with the time interval<48 h from admission to surgery was 48.6%(86/177), and the time interval<1 week from admission to surgery was 98.9%(175/177). The average length of hospital stay was(7.9±3.5)days.There was no significant difference in the time interval from admission to surgery, the time spent on surgery, length of hospital stay, surgical procedure and inflammatory indicators between the pneumonia and non-pneumonia groups.Univariate analysis showed that advanced age, multiple primary diseases, primary lung diseases, chronic respiratory failure, cerebrovascular disease, sequelae of cerebrovascular disease, immune system disease or long-term oral hormone therapy and preoperative anemia were risk factors for pulmonary infection in elderly patients with hip fracture(P<0.05 or<0.01). Multivariate regression analysis showed that advanced age(OR=1.239, 95%CI: 1.016~1.595, P=0.051), preoperative anemia(OR=2.491, 95%CI: 1.148~5.403, P=0.021), sequelae of cerebrovascular disease(OR=3.987, 95%CI: 1.354~11.741, P=0.012), primary lung diseases(OR=4.404, 95%CI: 1.800~11.078, P=0.001)and immune system diseases(OR=17.166, 95%CI: 1.750~168.409, P=0.015)were independent risk factors for pulmonary infection in elderly patients with hip fracture. Conclusions The orthopedic-geriatric co-care model seems to be in favour of controlling the progress of pulmonary infection in elderly patients with hip fracture, and to shorten waiting time before surgery and length of hospital stay.However, advanced age and chronic diseases are unpreventable risk factors for pulmonary infection in elderly patients with hip fractures.Clinicians should pay attention to the high-risk population and take prevention and control strategies to prevent the occurrence and development of lung infections. Key words: Hip fractures; Respiratory tract infections; Risk factors

Long-Term Hormone Therapy Increases Mortality in Some PSA Patients

Long-Term Hormone Therapy Increases Mortality in Some PSA Patients