Hormone Therapy In Postmenopausal Women Research Articles

Panel: Hormone Therapy Isn't for Chronic Conditions

Combined estrogen and progestin should not be used for the prevention of osteoporosis or other chronic conditions in postmenopausal women, according to recommendations issued by the U.S. Preventive Services Task Force. Hormone therapy currently has Food and Drug Administration approval for use in the prevention of osteoporosis in postmenopausal women. The task force, an independent body of volunteers that advises the Department of Health and Human Services, issued the recommendations as an update of its 2005 statement on hormone therapy for prevention of disease in postmenopausal women. Using the most recent scientific evidence available, including long-term follow-up data from the Women's Health Initiative (WHI) studies of hormone therapy use in postmenopausal women, the task force reached the same conclusions as it had in 2005, advising against combined estrogen and progestin for prevention of chronic conditions, and also against the use of estrogen alone for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy. The task force emphasized that hormone therapy was still indicated for the management of menopausal symptoms, such as hot flashes or vaginal dryness. It additionally made clear that its recommendation against hormone therapy for disease prevention does not apply to women younger than 50 years of age who have undergone surgical menopause. Prior to the WHI studies, a series of government-funded trials that began in the 1990s, with follow-up ending in 2010, showed that hormones had been widely used for the prevention of bone disease in postmenopausal women. Both estrogen and combined estrogen and progestin are known to reduce fracture risk. However, both forms of hormone therapy were shown during the WHI studies to also increase the risk of serious adverse events, to the point where the trials were stopped early. In one randomized, placebo-controlled trial, estrogen alone was associated with a significantly higher risk of stroke, deep vein thrombosis, and gallbladder disease, while combined therapy was associated with an increased risk of stroke, invasive breast cancer, dementia, gallbladder disease, deep vein thrombosis, and pulmonary embolism. Reproductive endocrinologist Jan L. Shifren of the department of obstetrics and gynecology and reproductive biology at Harvard Medical School and director of the menopause program at Massachusetts General Hospital, both in Boston, said in an interview that the task force's updated position largely reflected the current consensus of the Ob/Gyn community, “which is that HT should not be used to prevent the diseases of aging.” The task force was “very careful to point out that they are not saying HT should not be used for the treatment of vasomotor symptoms or vaginal atrophy. It's not that hormones aren't indicated; they're just not indicated for prevention. They remain an appropriate treatment for otherwise healthy, very symptomatic women at the menopause transition,” said Dr. Shifren, who is not a task force member. FDA-approved indications for hormone therapy in postmenopausal women include treatment of menopausal symptoms and prevention of osteoporosis. A black box warning indicates that estrogen with or without progestin should be prescribed at the lowest effective dose and for the shortest time possible. The task force's findings were based on the dosages and formulations used in the WHI trials: oral conjugated equine estrogen (0.625 mg/day plus medroxyprogesterone acetate, 2.5 mg/day) or estrogen 0.625 mg/day alone. Dr. Shifren said that there are some practitioners “who believe that hormone therapy could still be appropriate for the prevention of osteoporosis in people who absolutely cannot tolerate any other therapy. But what I would argue is that it is incredibly rare that there is a patient who can't tolerate one of the very many other FDA-approved treatments for the prevention of osteoporosis.” The task force members declared no relevant financial conflict of interest.

Endocrine Therapy for Postmenopausal Women with Hormone Receptor–Positive her2–Negative Advanced Breast Cancer after Progression or Recurrence on Nonsteroidal Aromatase Inhibitor Therapy: A Canadian Consensus Statement

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

What Is the Optimal Endocrine Therapy for Postmenopausal Women With Hormone Receptor–Positive Early Breast Cancer?

A 56-year-old postmenopausal woman with a recent diagnosis of breast cancer was referred to discuss adjuvant therapy. Annual screening mammogram demonstrated a suspicious mass in the left breast. Ultrasound-guided core needle biopsy revealed an infiltrating ductal carcinoma that was estrogen receptor (ER) positive and progesterone receptor (PR) negative and lacked amplification of human epidermal growth factor receptor 2 (HER2; ie, HER2 negative). She underwent excision and sentinel node evaluation. Pathology demonstrated a 1.9-cm grade 2 invasive cancer without lymphatic vascular invasion; clean margins were obtained, and both sentinel nodes were free of cancer. The 21-gene recurrence score was 16. She has a body mass index (BMI) of 28.5 but is otherwise healthy; levothyroxine is the only prescription medication she takes. She experienced vaginal spotting 2 years earlier because of an endometrial polyp, which was resected. She exercises regularly and takes a calcium supplement with vitamin D. Bone density study performed 6 months earlier was normal other than mild osteopenia in the femoral neck (T score, -1.3). Radiation therapy is planned.

Hormone therapy for postmenopausal women—An unanswered issue

Abstract Menopause is a biological and natural process that occurs as part of aging in women and is secondary to ovarian failure with resultant estrogen deficiency; therefore, menopause should not be considered as a disease. However, there is no doubt that estrogen deficiency induces general psychological and physical changes, and that postmenopausal women will experience many health-related issues and problems, including osteoporotic fractures, coronary heart disease (CHD), and most importantly for the quality of life (QOL) and vasomotor symptoms (VMS) such as hot flashes and night sweats. Hormone therapy (HT) is very effective in the management of postmenopausal women with symptoms. With the large number of patients being treated with HT, especially the combination of estrogen and progestin therapy (EPT) in the Women's Health Initiative (WHI) study, clinicians now recognize the potential adverse effects of EPT. Although this concept is much clearer now, some women might still benefit from short-term HT, especially for young postmenopausal women. In this review, some health issues of postmenopausal women, especially alternative therapies are discussed.

Hormone Therapy in Postmenopausal Women According to the Correlation of Changes in Bone Mineral Density

우리나라는 2005년도 65세 이상의 인구가 9.4%로 저 출산 과 함께 고령 연령의 비율이 크게 증가되고 있는 것이 사회 적인 문제가 되고 있다. 이에 국민 인구가 고령화 되어 가 는 것에 따른 노인 인구 증가에 더 나아가 노인 인구에게 중 요한 건강 문제에 대한 관심이 최근 더욱 부각되고 있다. 노 인성 질환의 대표적인 골다공증은 골의 대사성 질환 중 가 장 흔한 것으로 동일 연령과 성별에서 정상인에 비해 골량 이 현저히 감소된 상태를 말하며, 골다공증은 요통 이외에 는 뚜렷한 자가증상이 없어, 조기 발견이 어렵다. 세계보건기구 (World Health Organization, WHO)는 골다 공증을“골량의 감소와 미세구조의 이상을 특징으로 하는 전신적인 골격계 질환으로, 결과적으로 뼈가 약해져서 부 러지기 쉬운 상태가 되는 질환”으로 정의하고 있으며, 최 근 미국 국립보건원 (National Institutes of Health, NIH)에서 는 이를 축약하여“골강도의 약화로 골절의 위험성이 증가 하게 되는 골격계 질환”으로 규정하였다. 골강도는 골량과 골질에 의해 결정된다. 골량은 주로 골밀도 (bone mineral density, BMD)에 의해 표현되고 골질은 구조, 골 교체율, 무 기질화, 미세 손상 축적 등으로 구성되며, 골밀도는 최대 골 량과 골소실로 정의된다. 그러므로, 골다공증을 진단하기 ISSN 1226-8704 http://dx.doi.org/10.6118/jksm.2013.19.2.101 J Korean Soc Menopause 2013;19:101-105

Should we give up hormone treatment in menopause?

SUMMARY treated with HT protocols including estrogen preparations as well as estrogen/progestogen combinations have been indicated as being exposed to increased risk for breast cancer development. Moreover, HT preparations were demonstrated to be ineffective in protection from cardiovascular diseases and thromboembolic events, in contrast to the prior beliefs. Therefore, today in the light of new data, use of hormone therapy in postmenopausal women seems to lose its relevance. Nevertheless, alternative therapies have been developed to serve for the relief of menopausal disorders. Among them, tibolone, micronized testosterone, dihydroepiandrosterone, selective serotonine noradrenaline re-uptake inhibitors (SNRI), selective estrogen receptor modulators, combined oral contraceptives and fitoestrogens could be preferred. For all that, the most efficacious treatment on menopausal and genitourinary symptoms seems to be HT, yet. Furthermore, HT was indicated to be effective on osteoporosis and reducing postmenopausal bone fractures. HT should be the first choice of treatment in patients with premature ovarian failure and early onset menopause without any familial history of cancer. At the present time, it is advised to use hormone treatment choosing the appropriate preparation with the lowest effective dose with respect to above mentioned indications. If HT was introduced, there are valuable recommendations to keep the duration of therapy less than 5 years. Hormon tedavisi (HT); postmenopozal bir kad›n›n azalan hormon ya da hormonlar›n›n, overlerden salg›lanan duzeylerde olmasa da yerine konulmas› ile hormon yetmezliine bal› geliflen olumsuz durumlar›n ortadan kald›r›lmas›n› hedefleyen tedavi bicimidir. En temel endikasyon hipoostrojenemi ve ona bal› gorulen olumsuz durumlard›r. Vajinal atrofi, idrar inkontinans› gibi genitouriner semptomlar, osteoporoz ve kardiyovaskuler hastal›klar icin yuksek risk varl›¤› HT icin ongorulen dier ana endikasyonlard›r. Ancak, hem ostrojenlerin hem de ostojen/progestajen kombinasyonlar›n›n kullan›ld›¤› HT protokolleri postmenopozal kad›nlarda artm›fl meme kanseri geliflim riski ile ilifliklendirilmektedir. Ayr›ca, HT preparatlar›n›n, duflunuldu¤unun aksine kardiyovaskuler hastal›klar ve tromboembolik olaylarla iliflkili koruyucu etkilerinin bulunmad›¤› gosterilmifltir. Gunumuzde yeni verilerin ›fl›¤› alt›nda, HT'ne eskiden

Conjugated equine estrogen treatment corrected the exacerbated aorta oxidative stress in ovariectomized spontaneously hypertensive rats

ObjectiveThe increased risk of cardiovascular diseases in postmenopausal women has been linked to the decrease in plasma estrogen levels. Preparation of conjugate equine estrogens (CEE) is one of the most routinely used hormone therapy in postmenopausal women. However, studies on the vascular effects of CEE are still sparse and the mechanism of action is not completely elucidated. In this context, we have determined the effects of CEE in the vascular oxidative stress observed in ovariectomyzed (OVX) spontaneously hypertensive rats (SHR). Mechanisms by which CEE interferes with redox-sensitive pathways and endothelial function were also determined. ResultsAortas from OVX rats exhibited increased generation of reactive oxygen species (ROS), NADPH oxidase activity and reduced catalase protein expression, compared to aortas from sham SHR. Endothelium-intact aortic rings from OVX were hyperreactive to NE when compared to Sham aortas. This hyperreactivity was corrected by superoxide dismutase (SOD), catalase, and endothelium removal. Treatment of OVX-SHR with CEE reduced vascular ROS generation, NADPH oxidase activity, enhanced SOD and catalase expression and also corrected the NE-hyperreactivity in aortic rings from OVX-SHR. ConclusionOur study indicates a potential benefit of CEE therapy through a mechanism that involves reduction in oxidative stress, improving endothelial function in OVX hypertensive rats.

Abstract P2-10-02: Clinical validation of the PAM50 risk of recurrence (ROR) score for predicting residual risk of distant-recurrence (DR) after endocrine therapy in postmenopausal women with ER+ early breast cancer (EBC): An ABCSG study

Abstract Aim: To assess the performance of the ROR score in predicting DR for postmenopausal patients with ER+ EBC treated with tamoxifen or tamoxifen followed by anastrozole when the PAM50 test is performed in a routine hospital pathology laboratory. Background: The multi-analyte gene-expression tests (Oncotype DX, MammaPrint) that are currently used in clinical practice to assess prognosis after endocrine therapy in primary ER+ breast cancer are performed in a central referral laboratory. PAM50 is a 50-gene test in development that is designed to be performed in local routine hospital pathology laboratories and has been optimized to separate intrinsic disease subtypes which are used to generate a ROR score. This ROR score has been clinically validated and demonstrated to contain more prognostic information than Oncotype Dx RS in the TransATAC patient population (Dowsett, SABCS, 2011). Methods: 1,251 women from the prospective randomized ABCSG-8 trial were entered into this study: the entry criteria were the availability of their FPET block and informed consent. Three unstained 10 micron sections and 1 H&E slide for each patient were sent to an independent academic pathology laboratory at BCCA where tissue review, manual micro-dissection and RNA extraction were performed. PAM50 analysis was then conducted on 250 ng of the extracted RNA using the NanoString nCounter® technology: both intrinsic subtype and ROR score were calculated. The median follow up of the patients entered into this study is 10 years. 912 are node negative and 339 are node positive. The baseline characteristics of the patients entered showed them to be a representative sample of the overall ABCSG-8 trial population. The primary analysis is designed to test whether the continuous ROR score adds prognostic value over and above the standard clinical variables, using a likelihood ratio test. Results: Results are currently being derived and will be presented in full at SABCS. Discussion: This large clinical trial serves both as a clinical validation study of the PAM 50 test and as a demonstration that a complex multi-analyte gene-expression test can be performed in a routine hospital pathology laboratory while meeting the same quality metrics as a central referral laboratory. The results of the primary analysis, when combined with the results already reported from the Trans ATAC population, yield Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC and form the basis of the design of the clinical utility studies of the PAM 50 test. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-02.

Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients. This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor-positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events). Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003). Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation.

Tratamento pós-menopausa reduz a atividade da catalase e atenua o risco cardiovascular

Menopause can lead to alterations in women's health, with changes in the oxidative status of postmenopausal women in whom information regarding the influence of hormone therapy (HT) on antioxidant enzyme activities is limited. To evaluate the influence of HT on catalase activity; concentrations of lipids and lipoprotein, cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, nitrates, high-sensitivity C-reactive protein and carotid thickness in postmenopausal women. Ninety-four consecutive women were allocated to one of four groups, without HT and with HT. The latter group was subdivided into women using estrogen and those using estrogen plus progestogen therapy. Plasma biochemical parameters and common carotid intima-media thickness measurements were performed. HT antagonized the decrease in catalase activity after menopause, but had no effect on the levels of cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, lipid peroxide, nitrate, high-sensitivity C-reactive protein, or on the common carotid intima-media thickness. Multivariate analysis showed that estrogen-based HT attenuated the relationship between cardiovascular risk factors and the intima-media thickness of the common carotid. This study indicates that HT in postmenopausal women produces beneficial antioxidant and anti-atherosclerotic effects by ameliorating the plasma lipid and lipoprotein profiles, increasing plasma catalase activity and attenuating the association between cardiovascular risk factors and early atherosclerosis.

Tamoxifen Use in Postmenopausal Breast Cancer: CYP2D6 Matters

The question of whether genetic polymorphisms of CYP2D6 can affect treatment outcome in patients with early postmenopausal breast cancer has been a matter of debate. With the recent negative results with regard to CYP2D6 genotyping from the Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen, Alone or in Combination (ATAC) studies, the study investigators suggest that testing for CYP2D6 has no value in clinical practice.1,2 The authors of the accompanying editorial conclude that this matter can be likely laid to rest.3 However, pharmacogenetic experts demanded the retraction of the BIG 1-98 CYP2D6 study4 on the basis of massive departures from Hardy-Weinberg equilibrium (HWE; Table 1), possibly because of the bias that may result when the CYP2D6 genotype is obtained from the tumor (somatic) genome and not the host genome (germline DNA). Various authors in their letters attribute the highly distorted genotype frequencies to allelic imbalance associated with loss of heterozygosity (LOH) in breast tumor tissue,4,5 deviation from the standard genotyping assay protocol,5 or the presence of pseudogenes neighboring the CYP2D6 locus.6 Because the BIG 1-98 and ATAC pharmacogenetic studies may be considered sufficient to settle the issue of the value of CYP2D6 in decision making regarding endocrine therapy in postmenopausal women with breast cancer, we revisit the hypothesis, comment on the complementary evidence, and discuss pros and cons of the validity of CYP2D6 tamoxifen pharmacogenetics.

Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized ‘FIRST’ study

Fulvestrant fIRst-line Study comparing endocrine Treatments is a phase II, randomized, open-label study comparing fulvestrant 500 mg with anastrozole 1 mg as first-line endocrine therapy for postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. At data cut-off, only 36 % of patients had progressed and the median time to progression (TTP) had not been reached for fulvestrant. Here, we report follow-up data for TTP for fulvestrant 500 mg versus anastrozole 1 mg. Key inclusion criteria were postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally advanced or metastatic breast cancer and no prior endocrine therapy. Key exclusion criteria were presence of life-threatening metastases and prior treatment with a non-approved drug. Fulvestrant was administered 500 mg/month plus 500 mg on day 14 of month 1; anastrozole was administered 1 mg/day. TTP was defined by modified Response Evaluation Criteria in Solid Tumors v1.0 before data cut-off for the primary analysis, and investigator opinion after data cut-off. Best overall response to subsequent therapy and serious adverse events are also reported. In total, 205 patients received fulvestrant 500 mg (n = 102) or anastrozole (n = 103). Follow-up analysis was performed when 79.5 % of patients had discontinued study treatment. Median TTP was 23.4 months for fulvestrant versus 13.1 months for anastrozole; a 34 % reduction in risk of progression (hazard ratio 0.66; 95 % confidence interval: 0.47, 0.92; P = 0.01). Best overall response to subsequent therapy and clinical benefit rate for subsequent endocrine therapy was similar between the treatment groups. No new safety concerns for fulvestrant 500 mg were documented. These longer-term, follow-up results confirm efficacy benefit for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for HR+ advanced breast cancer in terms of TTP, and, importantly, show similar best overall response rates to subsequent endocrine therapy.

Hormone therapy in postmenopausal women and risk of endometrial hyperplasia

Reduced circulating estrogen levels around the time of the menopause can induce unacceptable symptoms that affect the health and well-being of women. Hormone therapy (both unopposed estrogen and estrogen/progestogen combinations) is an effective treatment for these symptoms, but is associated with risk of harms. Guidelines recommend that hormone therapy be given at the lowest effective dose and treatment should be reviewed regularly. The aim of this review is to identify the minimum dose(s) of progestogen required to be added to estrogen so that the rate of endometrial hyperplasia is not increased compared to placebo. The objective of this review is to assess which hormone therapy regimens provide effective protection against the development of endometrial hyperplasia or carcinoma. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched January 2012), The Cochrane Library (Issue 1, 2012), MEDLINE (1966 to January 2012), EMBASE (1980 to January 2012), Current Contents (1993 to May 2008), Biological Abstracts (1969 to 2008), Social Sciences Index (1980 to May 2008), PsycINFO (1972 to January 2012) and CINAHL (1982 to May 2008). Attempts were made to identify trials from citation lists of reviews and studies retrieved, and drug companies were contacted for unpublished data. Randomised comparisons of unopposed estrogen therapy, combined continuous estrogen-progestogen therapy, sequential estrogen-progestogen therapy with each other or placebo, administered over a minimum period of 12 months. Incidence of endometrial hyperplasia/carcinoma assessed by a biopsy at the end of treatment was a required outcome. Data on adherence to therapy, rates of additional interventions, and withdrawals owing to adverse events were also extracted. In this update, 46 studies were included. Odds ratios (ORs) were calculated for dichotomous outcomes. The small numbers of studies in each comparison and the clinical heterogeneity precluded meta-analysis for many outcomes. Unopposed estrogen is associated with increased risk of endometrial hyperplasia at all doses, and durations of therapy between one and three years. For women with a uterus the risk of endometrial hyperplasia with hormone therapy comprising low-dose estrogen continuously combined with a minimum of 1 mg norethisterone acetate (NETA) or 1.5 mg medroxyprogesterone acetate (MPA) is not significantly different from placebo at two years (1 mg NETA: OR 0.04; 95% confidence interval (CI) 0 to 2.8; 1.5 mg MPA: no hyperplasia events). Hormone therapy for postmenopausal women with an intact uterus should comprise both estrogen and progestogen to reduce the risk of endometrial hyperplasia.

Effects of oestrogen and testosterone therapy on serum metabolites in postmenopausal women

Metabolite profiles of body fluids or tissue extracts can be regarded as important indicators of physiological or pathological states. Whether hormone-specific alterations of the serum metabolome can be identified using this technique has not been tested yet. The aim of this study was to investigate metabolic responses during hormone therapy in postmenopausal women by a nontargeted metabolomics approach. Sixty naturally postmenopausal women were randomly assigned to treatment with testosterone undecanoate 40 mg every second day; estradiol valerate 2 mg daily; or the combination of both. Serum metabolites were determined by gas chromatography-mass spectrometry (GC-MS) before and after 3 months of treatment. Metabolites affected by the treatment were identified and correlated with changes in insulin sensitivity and lipid profiles. Treatment-dependent and hormone-specific effects on serum metabolites were observed, ranging between 69% reduction and 184% increase, but the metabolites that best explained the differences could not be structurally identified. Effects on annotated metabolites were less associated with clinical parameters as compared to established serum markers for adverse lipid and carbohydrate metabolism, such as cholesterol and triglycerides. However, cystine, lysine and tyrosine were shown to change in correlation with insulin sensitivity and high-density lipoprotein cholesterol levels in response to testosterone, indicating that those responses were somehow related to each other. Oestrogen- and androgen-specific alterations in the serum metabolome could be identified using GC-MS, reflecting hormone-specific effects on whole body metabolism. New knowledge regarding steroid-mediated metabolic responses within different tissues might be obtained using a similar approach on tissue extracts.

A decade of postmenopausal hormone therapy prescribing in the United States

Nearly a decade ago, landmark clinical trials revealed an increase in the risks associated with hormone therapy in postmenopausal women, leading to early changes in prescribing patterns. Long-term prescribing patterns in the United States after these trials are unknown. The objective of this study was to describe changes in hormone therapy prescribing including dose, formulation, patient age, and prescriber specialty from 2000 to 2009. A national pharmacy claims database was used to describe the annual prevalence and incidence rates of hormone therapy prescribing from 2000 to 2009 in women 50 years and older. Throughout the decade, a number of prescribing trends were observed: a continuous decline in hormone therapy overall, an initial drop in new therapy that stabilized after 2003, a decline in oral formulations and increase in vaginal formulations, a decline in standard- and high-dose and an increase in low-dose oral formulations, and an increase in the proportion of women who received hormone therapy from gynecologists. Overall prescribing of hormone therapy continued to decline during the past decade, suggesting a long-term impact of the Women's Health Initiative findings. During this same time, treatment regimens shifted to favor vaginal and lower-dose oral formulations.

Etiology, Assessment, and Management of Aromatase Inhibitor-Related Musculoskeletal Symptoms

Aromatase inhibitors (AIs) are recommended as adjuvant endocrine therapy for postmenopausal women with hormone-responsive breast cancer. With the widespread use of AI adjuvant endocrine therapy, a significant profile of musculoskeletal symptoms has emerged. Moderate to severe musculoskeletal symptoms have led some women to discontinue therapy, compromising the survival benefit. The etiology of AI-related musculoskeletal symptoms is poorly understood, which challenges development of effective management strategies. The purpose of this article is to describe AI-related musculoskeletal symptoms, review possible causes, provide assessment guidelines, and recommend management strategies based on the best available evidence. Little evidence exists for effective management strategies of AI-related musculoskeletal symptoms, and randomized clinical trials are needed to establish effective interventions. A thorough musculoskeletal assessment can help guide clinical decision making for the best individual management approach. Providers need to manage symptoms with the best available evidence to minimize symptom distress and maximize adherence to AI therapy.

PIH25 Clinical and Economic Outcomes Associated with Early Combined Estrogen and Progestogen Hormone Therapy for Post-Menopausal Women

PIH25 Clinical and Economic Outcomes Associated with Early Combined Estrogen and Progestogen Hormone Therapy for Post-Menopausal Women

Neoadjuvant chemotherapy versus neoadjuvant hormonal therapy in postmenopausal women with ER-positive, HER2/neu negative locally advanced breast cancer.

595 Background: Postmenopausal women with large ER+/HER-2 negative tumors frequently receive neoadjuvant chemotherapy (NC), but pathological complete response (pCR) rates are low. Neoadjuvant hormonal therapy (NH) may offer benefit in this setting. Methods: Retrospective review of medical records from University of Miami/Jackson Memorial Hospital from 1998-2011. Primary outcomes: pCR (absence of invasive tumor in breast and lymph nodes at surgery), recurrence free survival (RFS) and tumor size reduction evaluated through comparison of palpable breast mass size at presentation with pathological tumor size in surgical specimen, and categorized as good response (GR) ≥ 30% reduction or no response (NR) < 30%. The Kaplan-Meier method and the log-rank test were used in the analysis of RFS. Results: Data from 151 post-menopausal women with ER+/HER-2 negative BC who received NC (57%) or NH (43%) was analyzed. Median follow-up among alive patients with no evidence of disease was 5.4 years in NC and 2.9 years in NH. Mean age was higher in the NH group (63.3 vs 56.1, p<0.0001). There were no racial or ethnic differences between the groups. Clinical stage was comparable in NC and NH (IIA 5.8% vs 9.2%, IIB 25.6% vs 20%, IIIA 37.2% vs 29.2%, IIIB/IIIC 31.4% vs 41.5%, p=0.775). Tumor histology was predominantly ductal in both groups (NC 85.7% and NH 78.5%, p=0.247). pCR was similar in NC and NH (4.7% vs 0%, p=0.078) along with RFS (median 8.5 yrs vs 6.0 yrs, p=0.946). In the NC group, GR was significantly more frequent (77.9% vs 60%, p=0.017). Among patients in the NH group, having GR was predictive of longer RFS (5-year rate 83.7% vs 50.5%, p=0.014). Breast only pCR occurred at equivalent rates between NC and NH (9.3% vs 3.1%, p=0.189) as did the absence of lymph node metastasis (29.1% vs 26.2%, p=0.606). In the NH cohort 38.5% received no adjuvant chemotherapy. Conclusions: NH provides an effective alternative to NC and, if there is a GR, may preclude the need for chemotherapy in over one third of postmenopausal women with large ER positive/HER-2 negative breast cancer.

Clinical Characteristics of Breast Cancer Detected during Hormone Therapy in Korean Women

Objectives: This study was performed to assess the risk factors, histologic and clinical features of breast cancer in postmenopausal women receiving hormone therapy (HT). Methods: We evaluated 40 breast cancer patients who received HT due to postmenopausal symptoms by reviewing their medical charts at Pusan National University Hospital. Research variables, including patients’ history, type and duration of received HT, moment of cancer debut after starting HT, radiological characteristics of breast cancer stage, histologic type, tumor size, grade, lymph node metastasis, estrogen and progesterone receptor status and 5-year survival were investigated. Results: In the risk factors of breast cancer patients, only one patient had familial history of breast cancer. No patient had smoking history. The average body mass index (BMI) was 23.2 kg/m 2 . Twelve patients (30%) had estrogen only therapy, 13 patients (32.5%) had combined estrogen and progesterone therapy, 10 patients (25%) had tibolone therapy and the others consecutively received combination therapy of the above regimens. The mean duration of treatment was 31 ± 27.9 months (range 0.4-115 months). In the distribution of the cancer debut after starting HT, in 4 cases (10%) was within 1 year, 5 cases (12.5%) within 1-2 years, 10 cases (25%) within 2-3 years, 4 cases (10%) within 3-4 years, 1 case (2.5%) within 4-5 years, and 16 cases (40%) within more than 5 years. The average diameter of tumor size was 1.7 cm. In 92.5% of cases, the tumor was of ductal type. Tumor stage 0 and 1 appeared in 66% and grade I was present in 38% of investigated cases. Hormone receptor-positive breast cancers were 85% and 70% of patients had negative lymph node metastases. The 5-year survival rate was 92%. Conclusion: The breast cancers which emerged during HT in postmenopausal women had hormone receptor-positive tendency. The size and stage of these breast cancers were shown as small and low, and represented low-grade differentiation. Recurrences of disease were uncommon and we found favorable 5-year survival rates and good prognosis.

Adjuvant Hormonal Therapy in Postmenopausal Women with Breast Cancer: Physician’s Choices

The choice of adjuvant hormonal therapy in postmenopausal women with hormone receptor positive breast cancer has remained a matter of controversy and debate. The variety of agents is available, with each claiming to be superior. This clinical survey was undertaken to get an impression of the physician's first choice of therapy in an attempt to find out what questions still need to be answered in the making of “standard of care.” A web-based clinical survey was sent to the cancer physicians around the world, and 182 physicians responded to the survey. Most were medical oncologists in a tertiary care hospital. 36.3% preferred Anastrozole, 35.2% Tamoxifen, and 22.2% Letrozole as their first choice. Data support (67.8%) and safety concerns (30%) were given as the main reasons for the choice, 63.7% switched their therapy, and 24% had to switch because of side effects. 73.6% used 5 years of adjuvant hormonal therapy, 6.6% for 7 years, and 4.4% for 10 years. 61.5% follow their patients 3 times monthly, and 73.2% used laboratory and radiological assessment at each followup. Conclusion. Physicians show disagreement over the choice and duration of hormonal therapy in this patient population. Clinical trials leading to firm recommendations to set standards from which patients benefit the most are needed.