Effects of aromatase inhibitors on the ocular surface microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the effects of aromatase inhibitors(AIs)on the ocular surface microenvironment of the users.METHODS: A cross-sectional observational study was conducted. The study included postmenopausal women who received AIs treatment at galactophore department of our hospital from November 2022 to May 2023. Participants were divided into two groups based on the mechanism of AIs: the steroidal group and the non-steroidal group. The control group consisted of age-matched women who underwent occupational health examinations. All participants completed the ocular surface disease index(OSDI)questionnaire and underwent detailed ophthalmic examinations, including best-corrected visual acuity, intraocular pressure, axial length, corneal curvature, radius of curvature of curved lacrimal river surface, tear osmolarity, tear film break-up time, corneal fluorescein staining score, Schirmer Ⅰ test, and meibomian gland infrared score.RESULTS: There were no statistically significant differences in age, best-corrected visual acuity, intraocular pressure, axial length, and corneal curvature between control group and steroidal and non-steroidal group(P>0.05). The duration of drug treatment between the steroidal group and the non-steroidal group also showed no statistically significant difference(P>0.05). However, statistically significant differences were observed between the control group and the steroidal and non-steroidal group in OSDI scores, radius of curvature of curved lacrimal river surface, tear osmolarity, tear film break-up time, corneal fluorescein staining score, Schirmer Ⅰ test, and meibomian gland infrared score(P<0.05). The Schirmer Ⅰ test also showed statistically significant differences between the steroidal group and the non-steroidal group(P<0.05), while other data showed no statistically significant differences(P>0.05).CONCLUSION: Postmenopausal patients receiving AIs treatment experienced significant changes in the ocular microenvironment, with both decreased tear secretion and excessive tear evaporation contributing to the occurrence of dry eye. Notably, patients receiving non-steroidal AIs treatment showed a more significant reduction in main lacrimal gland secretion.

Perinatal exposure to an aromatase inhibitor glyphosate-base herbicide reduced male and female social behavior in juvenile age and the sexual behavior at adult female rats / Exposição perinatal ao inibidor da aromatase a base de glifosato reduz o comportamento social de machos e fêmeas e o comportamento sexual de ratas

Objectives: The herbicide glyphosate, a pesticide used in agriculture to control weeds, both in food crops and in other agricultural areas, has been identified as an endocrine modulator through the inhibition of aromatase activity and the activation of estrogen receptors. The present study examined the effects of a glyphosate-based herbicide (Roundup® (GLY-BH) on sexual dimorphism of rats after perinatal exposure to low and high GLY-BH in males and females offspring. Methods: Two groups of pregnant rats were treated with two doses of GLY-BH (50 or 150 mg/kg) from day 15 of gestation (GD15) to postnatal day 7 (PND7). Play fighting behavior was observed at the juvenile stage and during social and sexual behaviors in adulthood. Results: Perinatal GLY-BH exposure reduced male and female body weight at 28, 75, and 90 days of age. The play fighting behavior was decreased in both sexes, but female rats were more affected. The sexual behaviors were reduced only in females. Conclusions: Perinatal exposure to both doses of GLY-BH promoted sexually dimorphic effects in both juvenile and adulthood stages. These effects were attributed to the inhibition of aromatase activity induced by exposure to GLY-BH in the perinatal period.(AU)

Objetivos: O glifosato é um herbicida não seletivo, usado em muitas culturas alimentares e não alimentares e em áreas não agrícolas, sendo que os produtos a base de glifosato atuam como moduladores das funções endócrinas por meio da inibição da atividade da aromatase e da ativação de receptores de estrógeno. O presente estudo avaliou os efeitos do herbicida Roundup® (GLY-BH) à base de glifosato, em comportamentos sexualmente dimórficos de ratos após exposição perinatal a doses baixas e altas de GLY-BH no período perinatal. Métodos: Ratas prenhas foram tratadas com 50 ou 150 mg/kg de GLY-BH do 15º dia de gestação (GD15) ao 7º dia de lactação (LD7). O comportamento de luta/brincar foi observado na fase juvenil e os comportamentos social e sexual na idade adulta. Resultados: a exposição perinatal a GLY-BH reduziu o peso corporal de machos e fêmeas aos 28, 75 e 90 dias de idade. O comportamento de luta/brincar diminuiu em ambos os sexos, sendo as ratas foram as mais afetadas. O comportamento sexual foi reduzido apenas nas fêmeas. Conclusões: A exposição perinatal a ambas as doses do GLY- BH promoveu tanto na idade juvenil como na idade adulta, efeitos sexualmente dimórficos. Esses efeitos foram atribuídos à inibição da atividade da aromatase induzida exposição perinatal ao GLY-BH.(AU)

Analysis on the symptom clusters and influencing factors among breast cancer patients during aromatase inhibitors treatment / 中国实用护理杂志

Objective:To investigate the symptom clusters and influencing factors among breast cancer patients receiving aromatase inhibitor treatment and to provide a theoretical basis for the symptom clusters management.Methods:From April 2020 to January 2021, 253 breast cancer patients were recruited in Peking University Cancer Hospital by convenient sampling method. All the patients were cross-sectional investigated by the demographic and clinical characteristics questionnaire, the M.D. Anderson Symptom Inventory, the Hospital Anxiety and Depression Scale. The principal component analysis was used to extract the symptom clusters and the multiple linear regression was used to analyze the risk factors.Results:During the period of breast cancer patients receiving aromatase inhibitor treatment, three symptom clusters were identified: sick symptom cluster, treatment related-psychological symptom cluster, digestive symptoms cluster. The prevalence of the three symptom clusters was 49.4%(125/253), 45.1%(114/253), 22.5%(57/253), respectively. The median severity of the three symptom clusters was 2.80, 2.00, 0.67, respectively. Multiple linear regression analysis showed that anxiety and education level were the influencing factors of sick symptom cluster ( β=0.25, -0.25, all P<0.05), anxiety, depression and educational level were the influencing factors of treatment related-psychological symptom cluster ( β = 0.34, 0.20, -0.16, all P<0.05), anxiety, depression and chemotherapy history were the influencing factors of digestive symptom cluster ( β= 0.17, 0.18, -0.13, all P<0.05). Conclusions:Breast cancer patients with aromatase inhibitor treatment are affected by symptom clusters. In order to relieve the symptom clusters, we need pay attention to the mentation, the education level and prerious treatment of the patients.

Switching of hormone therapies in breast cancer women / Avaliação da mudança do esquema hormonioterápico em mulheres com câncer de mama

Abstract Objective The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer. Methods This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017. Results From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, 'disease progression' was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, 'presence of side effects' was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities. Conclusion The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.

Resumo Objetivo O objetivo do presente estudo foi analisar os motivos que levaram às mudanças no esquema hormonioterápico (HT) em mulheres com câncer de mama. Métodos Estudo transversal retrospectivo realizado no Hospital da Mulher de Campinas e consequente pesquisa de prontuários de mulheres diagnosticados com câncer de mama entre janeiro de 2012 e janeiro de 2017. Resultados De 1.555 mulheres em tratamento com HT, 213 (13,7%) mulheres tiveram HT alterado, tamoxifeno para anastrozol ou vice-versa. A maioria das mulheres incluídas no presente estudo que tiveram mudança de HT tinha > 50 anos, estava na pós-menopausa, era caucasiana e tinha pelo menos uma comorbidade. Os principais motivos de troca de HT foram devido a 'progressão da doença', ocorrendo em 124 (58,2%) casos e a 'presença de efeitos colaterais' (n = 65; 30,5%). Das mulheres que sofreram efeitos colaterais, 24 (36,9%) apresentaram comorbidades. Conclusão O presente estudo demonstrou uma baixa taxa na alteração de tamoxifeno para anastrozol. Entre as razõesmais comuns para alterar a HT estava a progressão da doença, que inclui recorrência do câncer, metástase ou aumento do tumor. Os efeitos colaterais foram a segunda causa e, além disso, a idade e as comorbidades foram fatores de risco para efeitos colaterais.

A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility / 亚洲男科学杂志(英文版)

Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio. In this subset of patients, and particularly in those with hypogonadism, elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic-pituitary-testicular axis by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production and impaired spermatogenesis. Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment. We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males. Overall, eight original articles were included and critically evaluated. Either steroidal (Testolactone) or nonsteroidal (Anastrozole and Letrozole) aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile. While the evidence is promising, future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.

Investigation of the occurrence of arthralgia and the quality of life of patients with breast cancer treated with aromatase inhibitors / 国际肿瘤学杂志

Objective To analyze the occurrence of arthralgia in patients with breast cancer treated with aromatase inhibitors,and to evaluate the impact of arthralgia on patients' quality of life.Methods One hundred and eighty seven patients with breast cancer treated with aromatase inhibitors in our hospital from December 2013 to December 2015 were selected.The occurrence and severity of arthralgia in patients were evaluated by using visual analogue scale method.The 36-item short-form health survey (SF-36) was used to evaluate patients' quality of life.The occurrence of arthralgia in patients was analyzed.In addition,the quality of life of breast cancer patients with and without arthralgia and those with different degree of arthralgia was compared.Results The incidence of arthralgia was 77.5％ (145/187) among 187 patients,of which 30.3％ was mild (44/145),40.0％ was moderate (58/145) and 29.7％ was severe (43/145).The scores of the rolephysical (16.73 ±7.34 vs.39.73 ± 12.54;t =9.18,P =0.02),physiological function (53.63 ± 12.91 vs.77.18 ± 9.82;t =7.49,P =0.04),mental health (53.18 ± 14.76 vs.75.14 ± 17.21;t =14.96,P =0.01),role-emotional (46.23 ± 14.30 vs.68.75 ± 15.93;t =12.17,P =0.02),bodily pain (40.35 ± 18.49 vs.91.48 ± 19.67;t =16.28,P =0.01),social function (60.14 ± 12.57 vs.89.22 ± 10.16;t =13.07,P =0.02),general health (45.52 ± 14.61 vs.60.78 ± 18.45;t =15.77,P =0.01) and vitality (55.31 ± 13.69 vs.68.22 ± 18.43;t =15.84,P =0.01) of patients with arthralgia were all lower than those of patients without arthralgia,with statistically significant differences.The scores of the role-physical (F =6.67,P =0.03),physiological function (F =10.94,P =0.02),mental health (F =11.32,P =0.02),role-emotional (F =11.49,P =0.02),bodily pain (F =15.71,P =0.01),social function (F =14.92,P =0.01),general health (F =9.98,P =0.02) and vitality (F =7.36,P =0.03) of different degree of arthralgia in patients with breast cancer had also statistical significance differences.Conclusion Arthralgia is more likely to occur in the treatment of breat cancer with aromatase inhibitors.Arthralgia and its severity can affect the patients' quality of life.

Effectiveness of bisphosphonate combined with activated vitamin D in patients with aromatase inhibitor-induced osteoporosis after breast cancer operation

OBJECTIVES: We compared the effectiveness of bisphosphonates combined with activated vitamin D administered for therapy of aromatase inhibitor-induced osteoporosis after a breast cancer operation and primary postmenopausal osteoporosis through propensity score matching. METHODS: Forty-eight postmenopausal patients with estrogen receptor-positive early breast cancer, who had postoperative adjuvant treatment with aromatase inhibitors and whose T-score of bone mineral density (BMD) decreased below −2.5 (AI group), and 48 patients of primary postmenopausal osteoporosis (PO group) enrolled in this retrospective observational study. They were administered monthly risedronate or minodronate, and daily alfacalcitol or eldecalcitol were combined. Their BMD (L2–4, L-BMD), serum-corrected calcium, serum phosphate, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), estimated glomerular filtration rate, urine calcium/creatinine ratio, intact-parathyroid hormone, and 25-hydroxy vitamin D were measured before treatment and until 24 months. RESULTS: L-BMD values increased with time compared with the baseline values in each group, and there was no significant difference in the groups. Percentage value of TRACP-5b decreased rapidly after 6 months and maintained low level until 24 months in both groups. Percentage value of BAP in the AI group decreased continuously until 24 months. In contrast, the percentage change in the PO group plateaued after 6 months. CONCLUSIONS: It is suggested that monthly oral bisphosphonate combined with activated Vitamin D is an effective therapy to increase BMD in the aromatase inhibitor-induced osteoporosis after breast cancer operation. Monitoring of kidney function and concentration of Ca in blood and urine may be necessary.

Advances in medical prevention of breast cancer / 中国肿瘤临床

The development of optimal strategies for breast cancer prevention is necessary given the high incidence in China. Several prospective randomized clinical trials have investigated the effects of various pharmacologic agents on the incidence of invasive and noninvasive breast cancer. This review aimed to summarize the different approaches to reduce the incidence of breast cancer.

Effect of the kidney-nourishing therapy on aromatase inhibitor-associated bone loss：a meta-analysis / 国际中医中药杂志

Objective The study systematically reviewed the therapeutic effect of the Kidney-Nourishing therapy on aromatase inhibitor-associated bone loss (AIBL).Methods The databases CNKI, CBM, VIP, Medline and the Cochrane Library were searched. Cochrane collaboration's tool for assessing risk of bias was adopted to assess the quality of trials. The Revman 5.3 software was used for the analysis on the outcome index such as bone minernal density and the level of serum estradiol.Results Meta-analysis was conducted on 11 randomly controlled clinical trials. All 11 studies were concducted in China, and the quality of researches was low. Meta-analysis revealed that the decrement of bone mineral density in the group receiving kidney-nourishing herbs was significantly smaller than that in the control group(P<0.001), theMD was -0.070, 95%CI was (-0.087, -0.053), but there was no significant difference between two groups in the outcome of the serum estradiol level (P=0.159), theMD was -2.622, 95%CIwas(-6.273, 1.030).Conclusion Kidney- Nourishing herbs can delay the process of aromatase inhibitor-associated bone loss, but may not influence the serum estrogen level.

Aromatase inhibitor(letrozole) is effective in activating the function of hypothalamus-pituitary-gonad axis in male patients with partial idiopathic hypogonadotropic hypogonadism / 中华内分泌代谢杂志

[Summary] Eighteen patients with idiopathic hypogonadotropic hypogonadism( IHH) receiving aromatase-inhibitor( AI) letrozole for at least 3 months were recruited.After 3 months′treatment, LH levels were increased from (2.1 ±1.5) IU/L to (3.6 ±3.7) IU/L(P=0.029), and FSH levels from (2.6 ±1.8) IU/L to (4.3 ±3.4) IU/L (P=0.003).Total testosterol was increased from (87 ±42) ng/dl to (166 ±200) ng/dl(P=0.082), and estradiol wasdecreasedfrom(22.7±18.7) pg/ml to (13.4±10.6) pg/ml(P=0.020).The average testis volume was increased[(14.3 ±3.9 vs 11.2 ±4.9) ml, P<0.01].Sperms were detected in 8 out of 9 patients who did seminal fluid test.The result of general linear model showed that LH(60 min) was significantly related with total testosterol increment( P=0.045) .

A retrospective study of 500 mg fulvestrant in recurrent or metastatic breast cancer patients pretreat-ed with the third generation of aromatase inhibitors / 中国癌症杂志

Background and purpose:The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clini-cal beneifts in patients with previous AI treatment. This study aimed to access the effcacy and safety of 500 mg fulves-trant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer.Methods:This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical beneift rate (CBR) and safety proifle.Results:After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9,P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1,P=0.022). Six patients stopped the treatment for intolerable adverse events.Conclusion:The treatment of 500 mg fulvestrant has a favorable effcacy and safety in treatment of post-AI ER positive postmenopausal patientswith metastatic breast cancer.

The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells

OBJECTIVES: Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. METHODS: Cortisol, aldosterone, testosterone, and 17β-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/17/19/21) and the hydroxysteroid dehydrogenases (3β-HSD2 and 17β-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. RESULTS: H295R cells exposed to EGb761 (10 and 100 μg/mL) showed a significant decrease in 17β-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17β-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/ Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. CONCLUSIONS: These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17β-HSD1, and lead to a decrease in 17β-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

Targets in anticancer research—A review.

Cancer is a complex disease characterized by a loss in the normal cell regulatory mechanisms that govern cell survival, proliferation, and differentiation. Current chemotherapeutics, as anticancer agents, are developing resistance to single drug and also to treatment therapies involving multiple drugs. Cross resistance associated with the specificity and selectivity of existing drugs has restricted the application of chemotherapy. Alternatively, these limitations have given better insight in understanding the underlying molecular mechanisms responsible for the development of various stages in cancer. In the light of this, continuous efforts are being made in order to identify and validate newer anticancer targets. This review presents some of the important targets that have been already reported, such as aromatase, farnesyl transferase, histone deacetylase, tyrosine kinase and cyclin-dependent kinase. A few molecules designed against these targets have successfully reached clinical trials. However, only limited marketed drugs are available from these classes. Besides, the review also highlights some of the other important targets and strategies that have also drawn considerable attention in the area of anticancer drug development such as, cancer stem cells and monoclonal antibodies. Further, the integration of the tools in molecular biology with the results from preclinical and clinical trials would strengthen the effectiveness of treatment regimens in cancer patients. There lies a much scope for designing promising lead compounds and treatment therapies against these established targets.

Advances in inhibitors of PI3K/Akt/mTOR pathway in treatment of advanced breast cancer / 肿瘤

The activation of phosphatidylinositol 3-kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway plays an important role in cell proliferation, metastasis and apoptosis, and it has been proved to be associated with resistance to aromatase inhibitors (AIs) and trastuzumab in patients with breast cancer. The clinical trial of estrogen receptor-positive advanced breast cancer has revealed that the targted therapy of inhibitors of PI3K/Akt signaling pathway in combination with AIs/human epidermal growth factor receptor-2 (HER2) could achieve a good response and improve the progression-free survival. The study and clinical application of everolimus, an inhibitor of PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway, are most ripe. This review focuses on the advances in the role of everolimus in the treatment of recurrent, metastatic and resistant breast cancer.

Clinical Study of Acupuncture Intervention in Muscle, Bone and Joint Pain Caused by Aromatase Inhibitors in the Treatment of Breast Cancer / 上海针灸杂志

Objective To investigate the clinical efficacy of acupuncture intervention in muscle, bone and joint pain caused by aromatase inhibitors in the treatment of breast cancer. Method One hundred and forty breast cancer patients with aromatase inhibitors-caused muscle, bone and joint pain were randomly allocated to groups A, B, C and D, 35 cases each. group A received ear acupuncture plus the intravenous drip of zoledronic acid;group B, ear acupuncture alone;group C, the intravenous drip of zoledronic acid alone;group D, oral administration of calcium carbonate and vitamin D3 chewable tablets and alfacalcidol soft capsules. The Brief Pain Inventory score was observed in every group before and after treatment. Bone mineral densities of the lumbar vertebrae were compared between the groups before and after treatment. Result In groups a and B, there was a statistically significant difference in the pain interference score at three, six and twelve weeks of treatment and at six weeks after the end of treatment compared with before treatment (P0.05). Conclusion Ear acupuncture can significantly relieve muscle, bone and joint pain caused by aromatase inhibitors and the pain relief is not related to bone mineral density, but muscle, bone and joint pain recurs in the patients after the treatment is discontinued. Zoledronic acid can not relieve the pain. Ear acupuncture plus zoledronic acid is not more effective than ear acupunctura alone in relieving the pain.

Aromatase inhibitor-associated musculoskeletal symptoms: incidence and associated factors / 대한외과학회지

PURPOSE: Arthralgia is the most common side effect in breast cancer patients receiving aromatase inhibitor (AI) therapy. Few studies have evaluated the risk factors, onset, and incidence of musculoskeletal pain in these patients. This study identifies the risk factors of AI-related severe arthralgia and their prevalence. METHODS: All the clinical and pathological records of postmenopausal patients diagnosed with invasive breast cancer using AI at Samsung Medical Center from January 2005 to November 2007 were reviewed. Multivariate logistic regression analyses were performed to evaluate the risk factors of AI-associated musculoskeletal symptoms (AIMSS) and factors associated with AI discontinuance. RESULTS: Among 299 patients, 69 patients (23%) experienced musculoskeletal symptoms attributed to AI use. In multivariate logistic regression analysis, no statistically significant outcome was found to confirm the risk factors for the development of AIMSS. Among the 69 patients who experienced AI-associated musculoskeletal symptoms, 29 (39.7%) discontinued AI use. Multivariate logistic regression analyses revealed an association of prior tamoxifen use with discontinuance of AI (P < 0.01; odds ratio, 4.27; 95% confidence interval, 1.74 to 10.50). CONCLUSION: Prior use of tamoxifen is related to discontinuation of AI due to AI-associated severe arthralgia. Special monitoring and proper pain control for these patients should be considered during the treatment period.

Neo-adjuvant endocrine therapy in breast cancer / 肿瘤研究与临床

Nco-adjuvant endocrine therapy has provided opened new alternatives for locally advanced breast cancer, especially for patient groups such as the elderly, those who are not suited for chemotherapy, and those whose response may not be optimal. The latest generation of endocrine therapy for breast cancer,aromatase inhibitors, has proved superior to tamoxifen in terms of toxicity and efficacy in the adjuvant setting.Compared with neo-adjuvant chemotherapy, the appropriate patients to receive nco-adjuvant endocrine therapy can achieve similar short-term benefit. However, because of fewer long-term follow up results, the overall prognosis is not clear.

Recovery of Ovarian Function with Aromatase Inhibitors: In Young Breast Cancer Patients (<45) with Chemotherapy-induced Amenorrhea / 한국유방암학회지

PURPOSE: The role and safety of aromatase inhibitors (AIs) in young breast cancer patients with chemotherapy-induced amenorrhea (CIA) has not been established. The goal of this study was to investigate the safety and efficacy of AIs in young breast cancer patients with CIA. METHODS: From December 2000 to December 2006, 58 patients with hormone receptor positive breast cancer under the age of 45 were treated with AIs as adjuvant therapy. All patients had amenorrhea for more than three consecutive months at the time of treatment. We evaluated the rates of recovery of ovarian function during the treatment, and analyzed the association of the recovery of ovarian function with age, body mass index (BMI), chemotherapy regimen, radiation therapy, and the use of tamoxifen. RESULTS: Recovery of ovarian function was observed in 16 patients (27.6%). The univariate analysis showed that ovarian function was more frequently recovered in patients younger than 40 yr of age, treated with chemotherapy regimens other than Cyclophosphamide, Methotrexate, 5-Flurouracil (CMF), without a history of tamoxifen therapy, and with a higher BMI. The multivariate analysis confirmed that the type of chemotherapy (p=0.034) and the history of tamoxifen therapy (p=0.043) were independent factors significantly associated with the restoration of ovarian function. CONCLUSION: The results of this study suggest that AIs should be considered, with caution in young women with CIA; these agents may promote the unwanted recovery of ovarian function. Especially, in those patients who were not treated with CMF chemotherapy or tamoxifen, where the rates of recovery of ovarian function were higher.

Role of Zoledronic Acid on Bone Loss by Letrozole / 한국유방암학회지

PURPOSE: The aromatase inhibitors cause bone loss by estrogen depletion. Zoledronic acid (ZA) can prevent bone mineral density (BMD) loss associated with the use of aromatase inhibitors. Accordingly interest has arisen in measuring surrogate markers of bone resorption to monitor the response of treatment of BMD loss in place of a radiologic assessment. This study was designed to determine whether ZA would prevent bone loss that is known to occur with letrozole and identified surrogate markers of bone resorption in an animal model. METHODS: In ovariectomized or sham-operated rat, we administrated ZA and letrozole to 5 different groups including: a sham operation control group (OC), a group in which an ovariectomy was performed followed by saline administration (OS), an ovariectomy with ZA treatment group (OZ), an ovariectomy with letrozole treatment group (OL) and an ovariectomy with ZA and letrozole combined treatment group (OZL). The levels of serum osteocalcin, serum bone alkaline phosphatase (BALP), serum calcium and urine N-telopeptide (NTX) and BMD were estimated and compared at the same periods for each group. The distinct microscopic findings of proximal tibia at week sixteen were also compared. RESULTS: Significantly reduced levels of urine NTX and significantly increased BMD were measured in the OZ group. In the OL group no difference was seen in in BMD in comparison to the OS group. However, a significant increase in BMD was measured in the OZL group. Urine NTX levels were measured and found to be lower in the OL group and significantly lower in the OZL group. Serum osteocalcin levels were similar to each other for each group. Levels of serum calcium and BALP were significantly lower in the OZL group than in the OS group. CONCLUSION: The combination treatment with ZA and letrozole is effective in the inhibition of bone resorption and in the preservation of BMD. Measurement of serum osteocalcin, urine NTX, and BMD, levels are recommended as surrogate markers for determining the response for the treatment of bone loss.

Management of adenomyosis in infertile women: comparison between laparotomic resection and administration of aromatase inhibitor (Experience in 55 cases).

The objective of this study was to observe the results of adenomyosis mangement with resection and administration of aromatase inhibitor. Cases of ademyosis in infertile women were collected for three years (January 1999 to December 2001) and the diagnoses were confirmed using transvaginal USG. Cases were grouped into two groups, i.e. group 1 (undergoing laparotomic resection) and group 2 (receiving treatment with aromatase inhibitor of anastrozole). Both groups were evaluated for changes in clinical symptoms, rate of successful pregnancy, and postoperative recurrency rate. During three years as many as 1619 infertility cases were managed, and among which 66 (4.07%) cases of adenomyosis were diagnosed with transvaginal USG. As many as 55 cases were analyzed, i.e., 32 cases underwent resection and 23 cases received aromatase inhibitor. Of 32 cases of surgical resection, the histopathological results showed 30 (93.75%) cases of adenomyosis and 2 (6.25%) cases of uterus myoma. In the group undergoing resection three cases (9.4%) were successfully pregnant, i.e., two cases had live birth, one case ended up with 6-week abortion. Moreover, 25 (78.1%) cases were not pregnant and 4 (12.5%) cases had recurrency, while 24 (75.35%) cases experienced disappearance of symptoms yet not pregnant. On the other hand, of 23 cases in the group receiving aromatase inhibitor 2 (8.6%) cases were able to be pregnant, one case had live birth and another case ended up with abortion, while 14 (59.1%) cases had disappearance of symptoms yet not pregnant. During three months of treatment with aromatase inhibitor, a reduction in the lesion size between 7.31 mm3 and 25.90 mm3 were observed with CI 95% (p < 0.001). In conclusion, treatment with aromatase inihibitor did not heal lesions, but only reduced the size of adenomyosis lesions. On the other hand, resection could heal lesions, yet recurrency of disease may occur (12.5%) after one postoperative year.