Treatment Of Postmenopausal Women Research Articles

Cognitive functioning during long-term tamoxifen treatment in postmenopausal women with breast cancer.

Endocrine therapy is widely used-often for many years-in women with breast cancer. Yet little is known about cognitive functioning after long-term use of tamoxifen. We examine cognitive sequelae, approximately 3 years after diagnosis, in postmenopausal women with breast cancer who were treated with adjuvant tamoxifen. Data from participants who underwent surgical operation with or without radiotherapy, participants who received adjuvant tamoxifen, and healthy controls were collected. Neuropsychological tests were administered, and participants completed questionnaires on health-related quality of life (Quality of Life Questionnaire Core 30 and Breast Cancer-Specific Quality-of-Life Questionnaire), menopausal symptoms (Functional Assessment of Cancer Therapy-Breast endocrine symptom subscale), and anxiety and depression (Hopkins Symptom Checklist). In total, 107 women participated (adjuvant tamoxifen group, n = 20; surgical operation/radiotherapy group, n = 43; healthy control group, n = 44). Women in the adjuvant tamoxifen group had received tamoxifen for a mean (SD) of 31.5 (18.6) months (range, 15-79 mo) and performed worse on verbal memory than the surgical operation/radiotherapy group (P < 0.05) and the healthy control group (P < 0.05). Participants in the adjuvant tamoxifen group performed worse on measures of fluency than healthy controls (P < 0.05). Furthermore, women in the adjuvant tamoxifen group reported worse cognitive functioning (P < 0.05) than women in the surgical operation/radiotherapy group or the healthy control group. Our results provide insights into cognitive functioning in women who receive long-term adjuvant tamoxifen treatment. By adding the surgical operation/radiotherapy group, we could control for the mental and physical influences of the diagnosis and treatment of breast cancer. Cognitive domains that rely on verbal abilities (verbal memory and fluency) seem to be at risk for deterioration after treatment with tamoxifen.

Treatment patterns and duration in post-menopausal women with HR+/HER2− metastatic breast cancer in the US: a retrospective chart review in community oncology practices (2004–2010)

Background:Clinical guidelines prefer endocrine therapy (ET) as initial treatment for post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2−) metastatic breast cancer (mBC). Chemotherapy (CT) should be reserved for patients who develop symptomatic visceral disease or have no clinical benefit after three sequential ET regimens. It is unclear if real-world clinical practice reflects these guidelines.Objective:To describe treatment patterns and treatment durations by lines of therapy for ET and CT among post-menopausal HR+/HER2− mBC patients.Methods:Charts were reviewed from a network of community-based oncology practices of eligible patients who had progressed after initiating adjuvant or first-line treatment for mBC between 1 January 2004 and 30 September 2010. Extracted chart data included demographics, treatment histories, and outcomes. Treatment duration was estimated using Kaplan–Meier estimators.Results:A total of 144 patients were studied. Patients received a median of two lines of ET, and <10% had three or more lines of ET before receiving CT. From first line to second line, the median treatment duration was 11.6 to 4.9 months for ET overall; 13.8 to 10.5 months for anastrozole; 18.6 to 7.0 months for letrozole; and 5.1 to 2.9 months for fulvestrant. For CT, the median duration was 5.1 months in the first line and 3.7 months and below in subsequent lines.Conclusion:During the study period (1 January 2004 – 30 September 2012), most patients received <3 lines of ET before receiving CT. The drop in median duration of ET from first to second line suggests that single agent ETs might not be as effective beyond the first line. A key limitation of this study was the small sample size. In addition, more research is needed to further investigate the short treatment duration of fulvestrant across early lines of therapy (which could indicate lack of efficacy).

Menopausal hormone treatment in postmenopausal women: risks and benefits.

Our objectives in this review were to examine the relevant menopausal hormone treatment (MHT) trials in postmenopausal women during the past 3 decades, provide an insight analysis of these studies from a clinical point of view, determine the efficacy and applicability of hormone therapy in the prevention of cardiovascular diseases, and provide suggestions on the use of MHT as a cardiovascular disease prophylaxis based on the available data. MHT may have a more complicated role in cardiovascular protection, and there is a need for further research to elucidate the dose and type of estrogen, its route of administration, the time of MHT initiation, and the preventive role of MHT in women's health.

Commentary on "menopausal hormone treatment in postmenopausal women: risks and benefits".

Commentary on "menopausal hormone treatment in postmenopausal women: risks and benefits".

Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline

To update practice guidelines for the therapeutic use of androgens in women. A Task Force appointed by the Endocrine Society, American Congress of Obestricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), European Society of Endocrinology (ESE), and International Menopause Society (IMS) consisting of six experts, a methodologist, and a medical writer. The Task Force commissioned two systematic reviews of published data and considered several other existing meta-analyses and trials. The GRADE methodology was used; the strength of a recommendation is indicated by a number "1" (strong recommendation, we recommend) or "2" (weak recommendation, we suggest). Multiple e-mail communications and conference calls determined consensus. Committees of the Endocrine Society, ASRM, ACOG, ESE, and IMS reviewed and commented on the drafts of the guidelines. We continue to recommend against making a diagnosis of androgen deficiency syndrome in healthy women because there is a lack of a well-defined syndrome, and data correlating androgen levels with specific signs or symptoms are unavailable. We recommend against the general use of T for the following indications: infertility; sexual dysfunction other than hypoactive sexual desire disorder; cognitive, cardiovascular, metabolic, or bone health; or general well-being. We recommend against the routine use of dehydroepiandrosterone due to limited data concerning its effectiveness and safety in normal women or those with adrenal insufficiency. We recommend against the routine prescription of T or dehydroepiandrosterone for the treatment of women with low androgen levels due to hypopituitarism, adrenal insufficiency, surgical menopause, pharmacological glucocorticoid administration, or other conditions associated with low androgen levels because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk. Evidence supports the short-term efficacy and safety of high physiological doses of T treatment of postmenopausal women with sexual dysfunction due to hypoactive sexual desire disorder. Importantly, endogenous T levels did not predict response to therapy. At present, physiological T preparations for use in women are not available in many countries including the United States, and long-term safety data are lacking. We recommend that any woman receiving T therapy be monitored for signs and symptoms of androgen excess. We outline areas for future research. Ongoing improvement in androgen assays will allow a redefinition of normal ranges across the lifespan; this may help to clarify the impact of varying concentrations of plasma androgens on the biology, physiology, and psychology in women and lead to indications for therapeutic interventions.

Oral health after breast cancer treatment in postmenopausal women

OBJECTIVE:Oral health can affect a patient's general health and quality of life. Given the increase in breast cancer survival rates, investigations of factors influencing the quality of life of survivors have gained importance. Therefore, the objective of our study was to characterize oral health in postmenopausal breast cancer survivors.METHODS:We conducted a matched case-control study. Forty-eight women who survived breast cancer (age 62.1±9.1 years) and 48 healthy controls (age 61.8±8.6 years) were included. For each case and control, a complete oral evaluation chart was completed.RESULTS:The prevalence of chronic periodontal disease was 98% in breast cancer survivors and 87% in controls. The breast cancer survivors had a median of 16 remaining teeth, whereas controls had a median of 22 remaining teeth (p = 0.03). The percentage of sites with gingival bleeding was 16.05% (0-100%) in breast cancer survivors and 0% (0-72%) in controls (p = 0.04).CONCLUSION:Chronic periodontal disease and tooth loss were highly prevalent in postmenopausal breast cancer survivors. To improve survivors' quality of life, a preventive oral health evaluation should be available prior to cancer treatment.

Exemestane metabolites: Synthesis, stereochemical elucidation, biochemical activity and anti-proliferative effects in a hormone-dependent breast cancer cell line

Exemestane is a third-generation steroidal aromatase inhibitor that has been used in clinic for hormone-dependent breast cancer treatment in post-menopausal women. It is known that exemestane undergoes a complex metabolization, giving rise to some already identified metabolites, the 17β-hydroxy-6-methylenandrosta-1,4-dien-3-one (17-βHE) and the 6-(hydroxymethyl)androsta-1,4,6-triene-3,17-dione (6-HME). In this study, four metabolites of exemestane have been analyzed, three of them were synthesized (6β-spirooxiranandrosta-1,4-diene-3,17-dione (2), 1α,2α-epoxy-6-methylenandrost-4-ene-3,17-dione (3) and 17-βHE (4)) while one was acquired, the 6-HME (6). The stereochemistry of the epoxide group of 2 and 3 has been unequivocally elucidated for the first time on the basis of NOESY experiments. New structure–activity relationships (SAR) have been established through the observation that the substitution of the double bonds by epoxide groups led to less potent derivatives in microsomes. However, the reduction of the C-17 carbonyl group to a hydroxyl group originating 17-βHE (4) resulted in a significant increase in activity in MCF-7aro cells when compared to exemestane (IC50 0.25 μM vs 0.90 μM, respectively). All the studied metabolites reduced MCF-7aro cells viability in a dose and time-dependent manner, and metabolite 3 was the most potent one. Altogether our results showed that not only exemestane but also its main metabolites are potent aromatase inhibitors and reduce breast cancer cells viability. This suggests that exemestane efficacy may also be due to the active metabolites that result from its metabolic transformation. Our results emphasize the importance of performing further studies to expand our understanding of exemestane actions in breast cancer cells.

Naringenin modulates skeletal muscle differentiation via estrogen receptor α and β signal pathway regulation.

Several experiments sustain healthful benefits of the flavanone naringenin (Nar) against chronic diseases including its protective effects against estrogen-related cancers. These experiments encourage Nar use in replacing estrogen treatment in post-menopausal women avoiding the serious side effects ascribed to this hormone. However, at the present, scarce data are available on the impact of Nar on E2-regulated cell functions. This study was aimed at determining the impact of Nar on the estrogen receptor (ERα and β)-dependent signals important for 17β-estradiol (E2) effect in muscle cells (rat L6 myoblasts, mouse C2C12 myoblasts, and mouse skeletal muscle satellite cells). Dietary relevant concentration of Nar delays the appearance of skeletal muscle differentiation markers (i.e., GLUT4 translocation, myogenin, and both fetal and slow MHC isoforms) and impairs E2 effects specifically hampering ERα ability to activate AKT. Intriguingly, Nar effects are specific for E2-initiating signals because IGF-I-induced AKT activation, and myoblast differentiation markers were not affected by Nar treatment. Only 7days after Nar stimulation, early myoblast differentiation markers (i.e., myogenin, and fetal MHC) start to be accumulated in myoblasts. On the other hand, Nar stimulation activates, via ERβ, the phosphorylation of p38/MAPK involved in reducing the reactive oxygen species formation in skeletal muscle cells. As a whole, data reported here strongly sustain that although Nar action mechanisms include the impairment of ERα signals which drive muscle cells to differentiation, the effects triggered by Nar in the presence of ERβ could balance this negative effect avoiding the toxic effects produced by oxidative stress .

A systematic review on the use of daily subcutaneous administration of teriparatide for treatment of patients with osteoporosis at high risk for fracture in Asia.

This systematic review aimed to examine the evidence for teriparatide in Asia for osteoporosis with a high fracture risk and for exploratory (unapproved) bone-related indications. MEDLINE (1946+), EMBASE (1966+), and ClinicalTrials.gov (2008+) were searched (16 August 2013); all studies of daily subcutaneous teriparatide 20μg for bone-related conditions from China, Hong Kong, Japan, Republic of Korea, Philippines, Singapore, and Taiwan were included. Evidence on efficacy/safety was retrieved primarily from randomized controlled trials (10 publications) of postmenopausal women from Japan and China. In these studies, teriparatide was well tolerated; subjects had significantly greater increases in lumbar spine bone mineral density (BMD) from baseline compared with placebo, antiresorptive agents, or elcatonin/calcitonin; bone turnover markers increased from baseline and were sustained at elevated levels during teriparatide treatment. Few studies reported fracture risk, pain, or quality of life; one study showed a lower incidence of new-onset vertebral fracture with teriparatide versus antiresorptive agents. Nonrandomized studies (nine publications, one unpublished trial) conducted mainly in Taiwan, Japan, and the Republic of Korea provided supporting data for efficacy. The exploratory (unapproved) use of teriparatide (17 publications) for fracture healing and osteonecrosis of the jaw was described primarily in case reports. The clinical effectiveness of teriparatide for treatment of postmenopausal women with osteoporosis who are at high risk of fracture in Asia is focused primarily on improvements in BMD and tolerability. Recommended additional studies may include assessment of fracture risk and the effect of teriparatide on pain, quality of life, and mortality in Asia.

The role of teriparatide in sequential and combination therapy of osteoporosis.

Osteoporosis is complicated by the occurrence of fragility fractures. Over past years, various treatment options have become available, mostly potent antiresorptive agents such as bisphosphonates and denosumab. However, antiresorptive therapy cannot fully and rapidly restore bone mass and structure that has been lost because of increased remodelling. Alternatively recombinant human parathyroid hormone (rhPTH) analogues do increase the formation of new bone material. The bone formation stimulated by intermittent PTH analogues not only increases bone mineral density (BMD) and bone mass but also improves the microarchitecture of the skeleton, thereby reducing incidence of vertebral and nonvertebral fractures. Teriparatide, a recombinant human PTH fragment available in Switzerland, is reimbursed as second-line treatment in postmenopausal women and men with increased fracture risk, specifically in patients with incident fractures under antiresorptive therapy or patients with glucocorticoid-induced osteoporosis and intolerance to antiresorptives. This position paper focuses on practical aspects in the management of patients on teriparatide treatment. Potential first-line indications for osteoanabolic treatment as well as the benefits and limitations of sequential and combination therapy with antiresorptive drugs are discussed.

SAT0463 Effect of Eight Years of Denosumab Treatment in Postmenopausal Women with Osteoporosis: Five-Year Results from the Freedom Extension

BackgroundDenosumab (DMAb) is an approved therapy for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. The effects of DMAb treatment for up to 10 years are...

Phase II, randomized, placebo-controlled study of BYL719 or buparlisib (BKM120) with letrozole for neoadjuvant treatment of postmenopausal women with HR+/HER2−, PIK3CA mutant or wild-type, breast cancer (BC).

TPS655^ Background: The PI3K/AKT/mTOR pathway is frequently activated in BC, with mutations in PIK3CA particularly common in hormone receptor-positive (HR+) tumors. In preclinical studies of HR+ BC...

Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor-associated musculoskeletal symptoms: a study protocol for a multicenter, randomized, controlled clinical trial.

BackgroundAromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. One of the main adverse effects of AIs is musculoskeletal symptoms, which leads to a lower quality of life and poor adherence to AI treatment. To date, no effective management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has been developed.Methods/designTo determine whether the traditional Chinese medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled and treated with traditional Chinese medicine or placebo for 12 weeks. The primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands, which will be obtained at baseline and at 4, 8, 12 and 24 weeks.DiscussionThe results of this study will provide a new strategy to help relieve AIMSS.Trial registrationISCTN: ISRCTN06129599 (assigned 14 August 2013).

Cost-effectiveness analysis of extended adjuvant endocrine therapy in the treatment of post-menopausal women with hormone receptor positive breast cancer.

Five years of Tamoxifen (Standard TAM) is a common treatment option for early-stage, hormone receptor positive (HR+) breast cancer (BC). Extending Standard TAM by 5 additional years (Extended TAM) can improve survival and BC recurrences. In postmenopausal women, the use of extended aromatase inhibitors (Extended AI) after Standard TAM is an alternative to Extended TAM. This study examines the cost-effectiveness (CE) of extending Standard TAM with Extended TAM vs. Extended AI in postmenopausal HR+ early-stage BC patients. Three treatments were assessed: (1) Standard TAM; (2) Extended TAM; (3) Extended AI through a Markov model using a Canadian health system perspective, lifetime time-horizon, quality adjusted life years (QALYs), and a 5% discount rate for future costs and utilities. Incremental cost-effectiveness ratios (ICERs) were calculated, and the impact of parameter uncertainty was assessed through probabilistic sensitivity analyses (SA) using conventional CE thresholds. The estimated total per person costs in 2012 Canadian dollars [$1.00 CAD=$0.99 US 2012] were the least for Extended TAM ($8,623 CAD) and most for Extended AI ($9,432 CAD). Extended AI was the most effective regimen, while Standard TAM was the least. Extended AI was cost-effective at conventional thresholds vs. Extended TAM (ICER: $3,402 CAD/QALY) which was robust to the SA. This study suggests that Extended AI and Extended TAM result in improved QALYs and lower healthcare costs vs Standard TAM. Extended AI results in the greatest improvement in QALYs and is the most cost-effective treatment alternative despite its higher drug costs.

Inhibition of sclerostin in the management of osteoporosis: results of a phase 2 clinical trial meet expectations.

Inhibition of sclerostin in the management of osteoporosis: results of a phase 2 clinical trial meet expectations.

The impact of educational materials on compliance and persistence rates with adjuvant aromatase inhibitor treatment: First-year results from the Compliance of ARomatase Inhibitors AssessmenT In Daily practice through Educational approach (CARIATIDE) study

The CARIATIDE study was designed to assess the impact of educational materials (EMs) on compliance and persistence rates with aromatase inhibitor (AI) treatment in postmenopausal women with hormone-receptor-positive early breast cancer. Patients were randomized to standard AI treatment (Group A; N = 1379) or standard AI treatment plus EMs containing information on a range of breast-cancer-related topics (Group B; N = 1379). Standardized questionnaires assessed investigator-perceived levels of care and evaluated patient compliance and behavior. At 1 year, there was no significant difference in compliance between Group A and Group B (81% vs. 82%, p = 0.4524). However, higher compliance in patients receiving EMs was observed in Sweden/Finland (p = 0.0246). Compliance with initial AI and persistence rate were not significantly altered by EM. Other factors associated with improved compliance, irrespective of EMs, e.g. administration of chemotherapy were identified.

Population pharmacokinetic/pharmacodynamic evaluation of low-dose drospirenone with 17β-estradiol in postmenopausal women with moderate to severe vasomotor symptoms

This study aims to characterize the pharmacokinetics/pharmacodynamics of drospirenone and estradiol in the treatment of postmenopausal women with moderate to severe vasomotor symptoms and to explore the relationship between the serum exposures of estradiol and drospirenone and efficacy, measured by reductions in moderate to severe hot flushes. Participants in a 12-week, double-blind, randomized, placebo-controlled study of daily drospirenone/estradiol in two low-dose combinations (0.25 mg/0.5 mg and 0.5 mg/0.5 mg), estradiol (0.3 mg), or placebo provided infrequent serum samples for pharmacokinetic analysis of estradiol and drospirenone, with additional frequent sampling during 24 hours in a study subset. Estradiol steady-state serum concentrations were described by a one-compartmental model with first-order elimination and zero-order absorption. The pharmacokinetics of drospirenone was described by a linear open two-compartment model with first-order elimination kinetics from the central compartment and delayed first-order absorption kinetics. A total of 1,516 serum estradiol concentrations and 736 serum drospirenone concentrations (n = 251) from 383 women were evaluated. Baseline estradiol concentrations increased with rising body mass index, and apparent clearance of estradiol at steady state was 39% higher in smokers versus nonsmokers. The serum exposures of both estradiol and drospirenone affected efficacy, as analyzed by a generalized linear model. Smoking had a negative effect on the efficacy of hormone therapy. The efficacy of low-dose drospirenone/estradiol for reducing vasomotor symptoms correlates with the serum exposure of estradiol and, for the first time, the serum exposure of drospirenone. Smoking adversely affects the clearance of estradiol and the efficacy of treatment.

A randomized, double-blind, placebo-controlled study of the lowest effective dose of drospirenone with 17β-estradiol for moderate to severe vasomotor symptoms in postmenopausal women

This study aims to investigate the efficacy and safety of daily drospirenone/17β-estradiol in two low-dose combinations (0.25 mg/0.5 mg and 0.5 mg/0.5 mg, respectively) versus 17β-estradiol (0.3 mg) or placebo in postmenopausal women with moderate to severe vasomotor symptoms. Seven hundred thirty-five postmenopausal women aged 40 years or older who experienced a minimum of 7 to 8 moderate to severe hot flushes per day, or 50 to 60 moderate to severe hot flushes per week, participated in a 12-week, double-blind, randomized, placebo-controlled study. The primary efficacy variables were mean changes from baseline to weeks 4 and 12 in the weekly frequency and weekly mean daily severity of moderate to severe hot flushes recorded daily by the participants on diary cards. All active treatments were significantly more effective than placebo for the primary efficacy variables for drospirenone/17β-estradiol (P < 0.0001), and for 17β-estradiol (P < 0.01) at 4 and 12 weeks. Efficacy was greater for both low-dose drospirenone/17β-estradiol combinations versus the lower-dose 17β-estradiol. Change in vaginal pH and vaginal maturation index showed significant improvements (with P values versus placebo of <0.0001 and P ≤ 0.0028, respectively), and exploratory analysis of the Clinical Global Impressions scale score indicated an overall satisfaction of women with active treatments. All active treatments were generally well tolerated with low rates of adverse event-related dropouts, and the safety profile of drospirenone/17β-estradiol in both low-dose combinations was consistent with previous studies. Drospirenone 0.25 mg/17β-estradiol 0.5 mg is concluded to be the lowest dose with demonstrated efficacy in the treatment of postmenopausal women with moderate to severe vasomotor symptoms.

Fulvestrant: a guide to its use in hormone receptor-positive metastatic breast cancer in postmenopausal women in the EU

Fulvestrant (Faslodex®), an estrogen receptor antagonist, is indicated for the treatment of postmenopausal women with estrogen receptor-positive, locally advanced or metastatic breast cancer for disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on therapy with an anti-estrogen. In this patient population, a fulvestrant 500 mg regimen is more effective in prolonging the time to disease progression than a fulvestrant 250 mg regimen and is generally well tolerated.

Abstract P1-14-01: Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior non-steroidal aromatase inhibitor treatment in postmenopausal women with hormone receptor-positive metastatic breast cancer (Hi-FAIR ex study)

Abstract (Background) After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is uncertain which of endocrine therapy is the most appropriate. (Methods) A randomized, open-label, multicenter phase II study was conducted to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, with exemestane 25 mg (EXE), a steroidal aromatase inhibitor. After disease progressed with assigned drug, the patients were subsequently treated with the other drug if patients were suitable for continuation with endocrine treatment. The primary endpoint was clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and antitumor effect of subsequent endocrine treatment. To prove a probability of 90% that TOR120 was superior to EXE, 41 patients were required for each group. To account for dropouts and protocol violation, we planned to recruit 90 patients (45 in each group). (Results) Initially, a total of 91women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM. When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there was no statistical difference between TOR120 (n = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%, p = 0.14), ORR (10.8% vs. 2.2%, p = 0.083), and OS (Hazard ratio (HR) 0.60, p = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (HR 0.61, p = 0.045). Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women with TOR120 was stopped after a few days because of nausea, general fatigue, hot flash and night sweating. Twenty-four patients received subsequent TOR120 after failure of initial EXE treatment. Of these patients, ORR and CBR were 4.2% (1/24) and 33.3% (8/24), respectively. In 23 patients who received EXE after TOR120, ORR and CBR were 17.4% (4/23) and 30.4% (7/23), respectively. (Conclusion) TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could be equal to or potentially be more beneficial than EXE. In addition, about one third of patients who progress on either TOR120 or EXE could obtain clinical benefit from subsequent EXE or TOR120. Trial registration number: UMIN000001841. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-14-01.