Hormone Therapy In Postmenopausal Women Research Articles

Safety and efficacy of low-dose esterified estrogens and methyltestosterone, alone or combined, for the treatment of hot flashes in menopausal women: a randomized, double-blind, placebo-controlled study

This study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in menopausal women. The 0.30-mg esterified estrogens and 0.30-mg methyltestosterone combination was the lowest effective dose, and our results are consistent with the known safety profile of estrogen and androgen combination products.

Optimal adjuvant hormonal therapy in postmenopausal women with hormone-receptor-positive early breast cancer: have we answered the question?

Adjuvant endocrine therapy is the most important systemic treatment for postmenopausal women with hormone-receptor-positive early breast cancer following surgery. Most trials have shown that the third-generation aromatase inhibitors, anastrozole, letrozole (LET), and exemestane, significantly prolong disease-free survival compared with tamoxifen. However, an overall survival benefit with aromatase inhibitors was observed in only three trials to date, in retrospective analyses from selected groups of patients: sequential analysis in the Austrian Breast & Colorectal Study Group 8, switch analysis in the Intergroup Exemestane Study, and analysis of initial letrozole in Breast International Group 1-98 study. Although the priming effect observed in preclinical models and breast cancer patients provides a rationale for sequencing adjuvant endocrine treatment with tamoxifen and aromatase inhibitors, the optimal strategy for adjuvant endocrine treatment has yet to be determined. This review discusses aromatase inhibitor monotherapy, sequential adjuvant treatment with tamoxifen followed by an aromatase inhibitor, and sequential adjuvant treatment with an aromatase inhibitor followed by tamoxifen. Available data in support of and against each strategy is evaluated. The safety profiles of tamoxifen and aromatase inhibitors is also examined.

Is the decrease in breast cancer incidence related to a decrease in postmenopausal hormone therapy?

Following the Women's Health Initiative (WHI) publication in mid 2002, a drastic decrease in hormone therapy for postmenopausal women has been observed worldwide. Since 2007, the reported incidence in breast cancer has declined. Most authors have linked this decline to the reduction in hormone treatment. In this paper we discuss why these ecological observations are not fully convincing and focus on the importance of screening and variations in other risk factors to interpret this decline in breast cancer.

Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD

Differential cerebral metabolic effects of various hormone therapy formulations, and their associations with cognitive status, remain to be established. The principal aim of the current study was to assess relationships between regional cerebral metabolism and estrogen-based hormone therapies. Postmenopausal women (n=53) at elevated risk for Alzheimer's disease (AD) were on estrogen-containing hormone therapy for at least one year prior to enrollment in a prospective, randomized clinical trial. Subjects underwent an FDG-PET scan, along with neuropsychological, medical, and demographic assessments at time of enrollment, to be repeated one year following randomization to hormone therapy continuation versus discontinuation, and results from analyses of the baseline assessments are reported here. Across all subjects, years of endogenous estrogen exposure correlated most closely with metabolism in right superior frontal gyrus (p<0.0005). Women taking 17β-estradiol (E) performed three standard deviations higher in verbal memory than women taking conjugated equine estrogen (CEE), and their verbal memory performance positively correlated with metabolism in Wernicke's (p=0.003) and auditory association (p=0.002) areas. Women taking progesterone-plus-estrogen had lower metabolism than women taking unopposed estrogen within the mesial and inferior lateral temporal regions (p<0.0005) and the inferior frontal cortex, contralateral to Broca's area (p<0.0005). In conclusion, particular areas of relatively preserved metabolism were seen in women with more years of endogenous estrogen exposure, as well as in women taking estradiol-based formulations or estrogen therapies unopposed by progesterone, together suggesting regionally specific neuroprotective estrogenic effects.

Tissue factor pathway inhibitor polymorphisms in women with and without a history of venous thrombosis and the effects of postmenopausal hormone therapy

Postmenopausal hormone therapy is associated with marked reduction in tissue factor pathway inhibitor (TFPI) levels, and low TFPI levels have been associated with increased risk of venous thrombosis. Polymorphisms in the TFPI gene may affect the expression of TFPI. We aimed to investigate the influences of such polymorphisms on plasma TFPI levels and to investigate the effect of hormone therapy. Four single nucleotide polymorphisms in the TFPI gene (the -287T/C and the -399C/T polymorphisms in the 5' upstream region, and the intron 7 -33T/C and the exon 9 874G/A polymorphisms) were studied with regard to frequency, phenotype, and their influence on hormone therapy in postmenopausal women with a history of venous thrombosis (n = 138), in healthy postmenopausal women (n = 202), and in normal controls (n = 212). The frequencies of the -287C and the -33C variants were nonsignificantly lower in cases than in controls, and the polymorphisms were associated with slightly higher levels of free TFPI antigen (-287C; P = 0.076) and higher TFPI activity (-33C; P < 0.001). The -399T variant showed equal distribution in cases and controls, but was associated with lower levels of TFPI activity (P = 0.036). Conventional-dose hormone therapy induced significant reductions in TFPI levels irrespective of genotypes. In healthy women treated with low-dose hormone therapy, the reduction in TFPI levels was less pronounced with the -287C variant (P = 0.054). Our study indicates that polymorphisms in the TFPI gene may be of importance for plasma TFPI levels and for the effects of hormone therapy.

American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer

To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer. A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. The Update Committee recommends that postmenopausal women with hormone receptor-positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy.

Hormone therapy in postmenopausal women affects hemispheric asymmetries in fine motor coordination

Evidence exists that the functional differences between the left and right cerebral hemispheres are affected by age. One prominent hypothesis proposes that frontal activity during cognitive task performance tends to be less lateralized in older than in younger adults, a pattern that has also been reported for motor functioning. Moreover, functional cerebral asymmetries (FCAs) have been shown to be affected by sex hormonal manipulations via hormone therapy (HT) in older women. Here, we investigate whether FCAs in fine motor coordination, as reflected by manual asymmetries (MAs), are susceptible to HT in older women. Therefore, sixty-two postmenopausal women who received hormone therapy either with estrogen (E) alone ( n = 15), an E-gestagen combination ( n = 21) or without HT (control group, n = 26) were tested. Saliva levels of free estradiol and progesterone (P) were analyzed using chemiluminescence assays. MAs were measured with a finger tapping paradigm consisting of two different tapping conditions. As expected, postmenopausal controls without HT showed reduced MAs in simple (repetitive) finger tapping. In a more demanding sequential condition involving four fingers, however, they revealed enhanced MAs in favour of the dominant hand. This finding suggests an insufficient recruitment of critical motor brain areas (especially when the nondominant hand is used), probably as a result of age-related changes in corticocortical connectivity between motor areas. In contrast, both HT groups revealed reduced MAs in sequential finger tapping but an asymmetrical tapping performance related to estradiol levels in simple finger tapping. A similar pattern has previously been found in younger participants. The results suggest that, HT, and E exposure in particular, exerts positive effects on the motor system thereby counteracting an age-related reorganization.

Ankle stiffness in postmenopausal women: influence of hormone therapy and menopause nature

Background Literature suggests that muscle-tendon unit (MTU) stiffness is implicated in human motion performance and injuries. In addition, muscle and joint pains comprise a set of very common climacteric symptoms. Concomitant with such symptoms, physical fragility and mobility limitations are expected, which further affect the functional physical fitness of postmenopausal women. To the authors' knowledge, this is the first study relating MTU stiffness with hormone therapy (HT) and the nature of menopause. The purpose of this study was to investigate the influence of HT and the nature of menopause on triceps-surae MTU stiffness in postmenopausal women.Methods Ninety-three women participated in this study. The data concerning menopause were obtained through medical consultation. MTU stiffness was assessed in vivo using a damped oscillation technique and a load equivalent to 30% of maximal voluntary isometric contraction.Results None of the following pair groups showed statistical differences for MTU stiffness: the HT group (19 426 ± 4148 N/m) and the without-HT group (20 056 ± 3579 N/m); the natural menopause group (19 525 ± 3718 N/m) and the induced menopause group (20 469 ± 4705 N/m). No significant differences were also found between the following pair groups: the natural menopause with-HT group (19 078 ± 3910 N/m) and the without-HT group (20 076 ± 3442 N/m); the induced menopause with-HTgroup (20 756 ± 4932 N/m) and the without-HT group (19 942 ± 4656 N/m).Conclusion The data suggest that MTU stiffness is not related to either the administration of HT in postmenopausal women or to the nature of menopause.

Comparative effects of continuous combined hormone therapy and tibolone on body composition in postmenopausal women

ObjectiveTo compare the effects of tibolone with those of continuous combined hormone replacement therapy (HT) on body composition in postmenopausal women.MethodsOne hundred and fifty postmenopausal women were enrolled in a randomized, controlled trial to compare the effects of tibolone with continuous combined HT on body composition. Patients were randomly allocated into three groups and followed for 9 months. Of the subjects included, 50 women received 2.5 mg tibolone plus one Cal+D tablet (500 mg calcium and 200 IU vitamin D) daily, 50 women received 0.625 mg conjugated equine estrogen and 2.5 mg medroxyprogesterone acetate (CEE/MPA) plus one Cal+D tablet daily, and the rest (50 women) received only one Cal+D tablet and served as a control group. Body composition was evaluated with measurements of body mass index (BMI), weight, waist-to-hip ratio (WHR), fat mass and fat-free mass (FFM) before and after the intervention. Measurements of body fat mass percentage, fat mass, body fat-free mass percentage and fat-free mass (FFM) were assessed by measurement of skin-fold thickness.Results Tibolone significantly increased weight, BMI and FFM and decreased WHR after the treatment in comparison with baseline (p < 0.05). However, only weight and BMI increased significantly in the CEE/MPA group after the treatment (p < 0.05). There were significant increases in weight, BMI and fat mass in the control group after 9 months. In the comparison of the parameters after the treatment between the three groups, tibolone significantly increased FFM compared with the control and CEE/MPA groups (p < 0.01).Conclusions The effect of tibolone on body composition is favorable and therefore tibolone may be regarded as an alternative to continuous combined hormone therapy in postmenopausal women.

Optimal Adjuvant Endocrine Therapy for Early Breast Cancer

Adjuvant endocrine therapy substantially reduces tumor recurrence and mortality in pre- and post-menopausal women with hormone receptor-positive early breast cancer but is ineffective in women with hormone receptor-negative tumors. Tamoxifen has been the standard adjuvant endocrine therapy for both pre- and post-menopausal women with hormone receptor-positive early breast cancer and remains the standard of care for premenopausal women. In addition to tamoxifen, ovarian ablation by surgery or radiotherapy remains an option for selected premenopausal women and trials are evaluating the role of ovarian function suppression using luteinizing hormone-releasing hormone agonists. For postmenopausal women, aromatase inhibitors are more effective than tamoxifen therapy and aromatase inhibitors and tamoxifen are regarded as standards of care. Prolonging adjuvant endocrine therapy in postmenopausal women by the sequencing of aromatase inhibitors and tamoxifen can improve outcomes further. Adjuvant endocrine therapy will probably be used for longer durations in selected postmenopausal women.

Adjuvant Endocrine Therapy for Early Breast Cancer: The Story So Far

Aromatase inhibitors (AIs) have largely replaced tamoxifen as adjuvant hormonal therapy for postmenopausal women with early breast cancer. While tamoxifen is effective in reducing breast cancer recurrence and mortality, recent data indicate two peaks of early, mostly distant metastatic recurrences in patients receiving tamoxifen, and AIs have proven more effective in reducing recurrence. As distant recurrence has been associated with poorer survival and death, reduction in this type of early recurrence event may lead to improved survival over the long term. Recent data from major clinical trials are beginning to bear out this contention.

Adjuvant Endocrine Therapy for Early Breast Cancer: The Story So Far

ABSTRACTAromatase inhibitors (AIs) have largely replaced tamoxifen as adjuvant hormonal therapy for postmenopausal women with early breast cancer. While tamoxifen is effective in reducing breast cancer recurrence and mortality, recent data indicate two peaks of early, mostly distant metastatic recurrences in patients receiving tamoxifen, and AIs have proven more effective in reducing recurrence. As distant recurrence has been associated with poorer survival and death, reduction in this type of early recurrence event may lead to improved survival over the long term. Recent data from major clinical trials are beginning to bear out this contention.

Estrogen and progestogen use in postmenopausal women

To update for both clinicians and the lay public the evidence-based position statement published by The North American Menopause Society (NAMS) in July 2008 regarding its recommendations for menopausal hormone therapy (HT) for postmenopausal women, with consideration for the therapeutic benefit-risk ratio at various times through menopause and beyond. An Advisory Panel of clinicians and researchers expert in the field of women's health was enlisted to review the July 2008 NAMS position statement, evaluate new evidence through an evidence-based analysis, and reach consensus on recommendations. The Panel' s recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. Also participating in the review process were other interested organizations who then endorsed the document. Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered. This paper lists all these areas along with explanatory comments. Areas that vary from the 2008 position statement are noted. A suggested reading list of key references published since the last statement is also provided. Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable for women who initiate HT close to menopause but decreases in older women and with time since menopause in previously untreated women.

Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women.

A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the oestrogen receptor alpha gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT. Subjects Postmenopausal Caucasian women (n = 208) participating in a placebo-controlled randomized trial of 3.2 years of hormone therapy (HT). Plasma triglyceride (TG), remnant lipoprotein cholesterol (RLP-C), and high-density lipoprotein cholesterol (HDL-C) levels and HDL subpopulations were assessed at baseline and at follow up. Single nucleotide polymorphisms (SNPs) in ESR1 and in the ATP binding cassette A1 (ABCA1), cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), lipoprotein lipase (LPL), and scavenger receptor class B type I (SRB1) genes were assessed for their association with baseline plasma levels and HT-related changes in levels of RLP-C and HDL subpopulations. Carriers of the ESR1 PvuII or IVS1-1505 variants had lower plasma TG concentrations and higher plasma HDL-C and alpha-1 and prealpha-1 HDL particle levels at baseline and showed greater increases in HDL-C, apo A-I and alpha-1 particle levels after HT than wild-type carriers. Carriers of the N291S and D9N variants in the LPL gene had significantly higher remnant lipoproteins and lower alpha-2 HDL particle levels at baseline. The CETP TaqIB SNP was a significant determinant of baseline plasma HDL-C and HDL subpopulation profile. Single nucleotide polymorphisms in ESR1, CETP and LPL had significant effects on baseline plasma levels of TG-rich and HDL subpopulations. With the exception of ESR1 SNPs, variation in genes involved in lipid metabolism has a very modest effect on lipoprotein response to HT.

The change of hormone therapy in postmenopausal women in Korea before and after women's health initiative study: 2000~2009

목적: 본 연구의 목적은 Women`s Health Initiative Study (WHI) 발표 전후 2000년부터 2009년까지 10년 동안의 폐경 여성에서 호르몬 사용의 변화와 WHI의 결과가 우리나라의 호르몬 요법 사용에 어떠한 영향을 보였는지 알아보고 이를 통해 앞으로의 폐경 후 호르몬 요법의 전망을 알아보고자 한다. 연구 방법: 이 연구는 International Medical Service HEALTH 회사에서 발표된 약제 통계자료에 기초하였다. 우리나라에서 판매된 호르몬 제제들에 대한 통계자료들은 2000년부터의 자료를 이용하였다. 폐경여성들의 호르몬 제제들의 사용은 연간 호르몬 제제들의 판매액으로 표시하였으며 총 호르몬 제제는 에스트로겐, 에스트로겐/프로게스토겐, 티볼론 제제들의 합으로 표시하였다. 호르몬 제제의 사용 변화를 알기 위해 전년 대비 성장률과 2000년을 기준으로 한 축적성장률을 산출하였다. WHI발표 이후의 사용 변화를 알기 해서 2002년부터 2009년까지 2002년을 기준으로 한 변화를 확인하였다. 결과: 2002년 WHI 발표 이후 우리나라의 총 호르몬 요법 사용은 2002년도의 511억에 비해 2006년에 39%의 감소를 보여 314억까지 감소하였다. 이후 조금씩 상승하여 2009년에는 356억이었다. 반면 티볼론의 사용은 WHI 이후 2년간은 감소하여 2002년 134억에 비해 2004년에는 100억으로 25.4% 감소하였으나 이후 지속적으로 상승하여 2007년에는 134억으로 2002년의 사용량보다 증가하였고, 2009년에는 145억으로 2002년 대비 8.2% 증가하였다. 저용량 호르몬 제제 또한 WHI 이후 지속적으로 증가하여 2002년 8억 대비 2009년에는 71억으로 787.5% 증가하였다. 결론: WHI의 발표 후 폐경 여성들의 호르몬 사용은 2002년에 비해 2003년에 23.9% 감소하였고 저용량 호르몬과 티볼론 사용이 확연히 증가하였다. 앞으로 우리나라 폐경 여성에서 호르몬 사용은 저용량의 호르몬과 티볼론이 대세를 이룰 것으로 생각된다. 또한 호르몬 요법을 시작할 때 환자의 병력, 신체검사를 통한 이득과 위험을 판단한 후 각 개인에 맞는 호르몬 요법을 시행하여야 할 것이다.

Functional Genetic Polymorphisms in the Aromatase GeneCYP19Vary the Response of Breast Cancer Patients to Neoadjuvant Therapy with Aromatase Inhibitors

Aromatase (CYP19) is a critical enzyme in estrogen biosynthesis and aromatase inhibitors (AI) are employed widely for endocrine therapy in postmenopausal women with breast cancer. We hypothesized that single nucleotide polymorphisms (SNPs) in the CYP19 gene may alter the effectiveness of AI therapy in the neoadjuvant setting. Genomic DNA was obtained for sequencing from 52 women pre-AI and post-AI treatment in this setting. Additionally, genomic DNA obtained from 82 samples of breast cancer and 19 samples of normal breast tissue was subjected to resequencing. No differences in CYP19 sequence were observed between tumor and germ-line DNA in the same patient. A total of 48 SNPs were identified including 4 novel SNPs when compared with previous resequencing data. For genotype-phenotype association studies, we determined the levels of aromatase activity, estrone, estradiol, and tumor size in patients pre-AI and post-AI treatment. We defined two tightly linked SNPs (rs6493497 and rs7176005 in the 5'-flanking region of CYP19 exon 1.1) that were significantly associated with a greater change in aromatase activity after AI treatment. In a follow-up study of 200 women with early-stage breast cancer who were treated with adjuvant anastrozole, these same two SNPs were also associated with higher plasma estradiol levels in patients pre-AI and post-AI treatment. Electrophoretic mobility shift and reporter gene assays confirmed likely functional effects of these two SNPs on transcription of CYP19. Our findings indicate that two common genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to aromatase inhibitors.

Central Review of ER, PgR and HER2 in BIG 1-98 Evaluating Letrozole vs. Letrozole Followed by Tamoxifen vs. Tamoxifen Followed by Letrozole as Adjuvant Endocrine Therapy for Postmenopausal Women with Hormone Receptor-Positive Breast Cancer.

Abstract Background: The BIG 1-98 trial, a large international Phase III study, evaluated letrozole (Let) for 5 years (n=1546) vs. Let for 2 years followed by tamoxifen (Tam) for 3 years (L→T; n=1540) and vs. Tam for 2 years followed by Let for 3 years (T→L; n=1548) as initial adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer. Patients with HER2-positive disease did not receive trastuzumab. Efficacy results were presented in SABCS 2008 and showed that neither of the sequential therapy arms significantly improved disease-free survival (DFS) compared with letrozole alone. Centrally-assessed ER, PgR and HER2 have now been evaluated as potential predictive factors for treatment selection.Methods: Tumor blocks for 3975 of the 4634 (86%) patients on these three treatment arms were centrally collected and assessed by the IBCSG Central Pathology Laboratory. The tumors were evaluated for ER and PgR content by immunohistochemistry (IHC), and for HER2 immunoreactivity by IHC and by FISH for IHC 1+ or 2+ tumors. DFS according to centrally-assessed ER, PgR and HER2 status was analyzed using multivariable Cox modeling. STEPP methodology was used to explore patterns of DFS differences according to quantitative values of receptor levels (% staining cells).Results: Upon central review, 3885 tumors were confirmed to express ER and are the focus of this analysis. PgR expression did not predict differential treatment effects among the 3 treatment arms. With only 240 (6.2%) HER2-positive tumors, there was a suggestion of differential treatment benefit relative to HER2 status, in particular of a benefit of Let for 5 yrs over Tam→Let in HER2-positive tumors.Discussion: Given the caveat of a low prevalence of HER2-positive tumors and absence of HER2-directed therapy in the BIG 1-98 trial population, there is a suggestion that Let for 5 years may be a better option than a sequence of Tam and Let among women with HER2-positive tumors. Thus it may be better to initiate and continue treatment of endocrine-responsive, HER2+ tumors with Let rather than a sequence of Tam and Let. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 76.

Joint Disorders Frequency and Structural Changes during Anastrozole Adjuvant Treatment in Early Breast Cancer: A Prospective Trial (D5392L00013).

Abstract Background:Aromatase inhibitors (AIs) are standard adjuvant endocrine-therapy in postmenopausal women with hormone-sensitive breast cancer. However, main side effects reported are musculoskeletal symptoms. The pathogenic and anatomic features of AI-induced arthralgia have not been clearly defined. The objective of the study was to describe the joint symptoms and structural joint changes in women received adjuvant anastrozoleMethods: Postmenopausal women with hormone receptor positive early breast cancer were enrolled in this open, multicentre trial. Anastrozole was administrated 1mg/day p.o. All of them were naïve of AI and tamoxifen treatment. Patients were followed one year with clinical examination every 3 months, ultrasound (US) examination every 6 months, measurements of inflammation biomarkers and cartilage biomarkers of degradation U-CTX-II (urinary C-terminal crosslinked telopeptide of type II collagen) every 6 months and X-rays at baseline and 12 monthsResults: From June 2006 to December 2007, one hundred and fourteen patients (114) were included and 106, with a median age of 61.5 (49-79) years, were followed-up for 1 year.Overall, 33% of patients were previously treated by chemotherapy, (anthracyclines 97%, taxanes 63 %) and 40.6% were receiving hormone replacement therapy (HRT) at tumour diagnosis. The prevalences of arthralgia were 40.6, 59.1 and 60.6 % at baseline, 6 months and 12 months respectively.Among the 63 (59.4%) patients without arthralgia at baseline, 37 patients presented with arthralgia during treatment (26 between baseline and M6, 11 between M6 and M12) with median time to onset of 4 months.In univariate logistic analysis, significant determinant factors of joint disorders at 12 months were previous osteoarthritis and personal history of arthralgia but not the previous HRT or previous adjuvant chemotherapy with taxanes. In multivariate analysis, none of those factors were significant.Clinical examination by rheumatologist and US examination did not show any significant changes of the number of synovitis and tenosynovitis over 12 months.There were no significant changes of the U-CTX-II levels and of joint damages assessed by radiographs. Inflammation biomarkers did not significantly change over 12 months.Conclusion: This prospective study with a systematic rheumatologist follow up of the patients showed that arthralgia occurs early after the beginning of anastrozole therapy (first 6 months); and suggest that joint disorders were not associated with any cartilage degradation after 1 year of treatment. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 801.

Low-dose hormone therapy in postmenopausal women in China

Objective To review the experience of menopausal symptoms and low-dose hormone therapy (HT) in postmenopausal women in China.Design Literature review and critical summaries of available prospective, clinical trials (randomized, controlled trials, RCTs).Results Chinese women experience menopausal symptoms less frequently compared with women in developed countries, and the prevalence of menopausal symptoms is less in women of southern China than in women of northern China. The majority of postmenopausal Chinese women lack knowledge about HT, and the usage rate of HT is low in these women compared to that in women of developed countries. Some RCTs investigated the efficacy and safety of low- or ultra-low-dose HT, including conjugated equine estrogen, estradiol valerate, transdermal estradiol, nylestriol alone or in combination with progesterone, and tibolone in postmenopausal Chinese women. These RCTs reported that low- or ultra-low-dose HT relieved menopausal symptoms and prevented bone loss as well as standard-dose HT and was less likely to induce side-effects, including irregular vaginal bleeding and breast tenderness; there may be dose-dependent effects of HT. No study evaluated the effects of low-dose HT on cardiovascular events or breast mammographic density/risk of breast cancer.Conclusions More RCTs are required to confirm efficacy and to assess the safety of low- or ultra-low-dose HT for a long-term period in a large group of postmenopausal women.

Progress in tailoring adjuvant endocrine therapy for postmenopausal women with early breast cancer

Clinical trials have shown that a variety of aromatase inhibitor strategies modestly reduce the risk of breast cancer recurrence over 5 years of tamoxifen for postmenopausal women with endocrine-sensitive disease. This review will discuss the use of predictive biomarkers to tailor postmenopausal endocrine therapy. In spite of early promise, recent studies suggest that quantitative evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression do not identify a subgroup of patients with differential benefit from an aromatase inhibitor over tamoxifen therapy. Estrogen receptor-positive tumors with increased proliferation, evaluated by Ki-67, may be selectively responsive to aromatase inhibitor therapy. Growing evidence suggests that inherited polymorphisms in tamoxifen-metabolizing enzymes identify a subgroup of patients with poor outcome under tamoxifen therapy that might best be treated with an aromatase inhibitor. The emergence of early treatment-related side effects on either aromatase inhibitor or tamoxifen, such as hot flashes and anthralgias, has been linked to a decreased risk of recurrence, although additional validation is needed. There are no robust clinically available tools that can be used to reliably identify patients that are likely to be selectively responsive to an aromatase inhibitor over tamoxifen alone. The decision to use an aromatase inhibitor in clinical practice should be primarily guided by consideration of recurrence risk and contraindications to tamoxifen.