Adverse Effects Of Hormone Therapy Research Articles

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer

PurposeSide effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL).MethodsPatients aged ≥ 70 years with stage I–III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time.ResultsOverall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = − 4.37; 95% CI − 7.96 to − 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = − 11.10; 95% CI − 18.80 to − 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement.ConclusionA large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.

Evaluation of an electronic consultation service for transgender care

BackgroundAccess to transgender care in Canada is poor. Although primary care providers are ideally positioned to initiate care, many feel uncomfortable providing transgender care. This study aimed to explore the impact of an electronic consultation (eConsult) service between primary care providers and transgender care specialists on access to care and to explore the content of clinical questions that were asked.MethodsThis was a retrospective mixed methods analysis of 62 eConsults submitted between January 2017 and December 2018 by primary care providers to specialists in transgender care in a health region in eastern Ontario, Canada. A descriptive analysis was conducted to assess the average response time and the total time spent by the specialist for the eConsults. An inductive and deductive content analysis was carried out to identify common themes of clinical questions being asked to transgender specialists. A post-eConsult survey completed by primary care providers was assessed to gain insight into avoided face-to-face referrals and overall provider satisfaction.ResultsThe median specialist response time was 1.2 days (range: 1 h to 5 days) and the average time spent by specialists per eConsult was 18 min (range: 10 to 40 min). The qualitative analysis identified six major themes: 1) interpretation/management of abnormal bloodwork, 2) change in management due to lack of desired effect/hormone levels not a target, 3) initiation of hormone therapy/initial work up, 4) management of adverse effects of hormone therapy, 5) transition related surgery counseling and post-op complications, and 6) management of patients with comorbidities. Approximately one-third of eConsults resulted in an avoided face-to-face referral and 95% of primary care providers rated the value of their eConsult as a 5 (excellent value) or 4.ConclusionsThis study demonstrated that a transgender eConsult service has potential to significantly improve access to care for transgender patients. Given the importance that timely access has on improving mental health and reducing suicide attempts, eConsult has the potential to make a substantial clinical impact on this population. Identified themes of eConsult questions provides insight into potential gaps in knowledge amongst primary care providers that could help inform future continuing education events.

The impact of xenoestrogens on effectiveness of treatment for hormone-dependent breast cancer – current state of knowledge and perspectives for research

Breast cancer is the most common cancer occurring in women and causing the highest number of deaths among them. The role of xenoestrogens has been the subject of many studies in the pathogenesis of breast cancer. Less is known about the impact of xenoestrogens on the effectiveness of hormone therapy used to treat breast cancer, and thus possible drug-xenostrogen interactions. The aim of this review is to summarize the current state of knowledge and present perspectives for further research on the impact of xenoestrogens on the effectiveness of drugs used in the treatment of hormone-dependent breast cancer. Phytoestrogens, in particular flavonoid genistein, are the best studied group of xenoestrogens in terms of interaction with drugs used in the treatment of breast cancer, due to their frequent use, including their use in alleviating the adverse effects of hormone therapy. Analyzing the current state of knowledge, it seems that phytoestrogens intake should be avoided during conventional anti-cancer treatment. Of the other xenoestrogens, bisphenol A (BPA) is one of the best-tested compounds for interactions with drugs used to treat breast cancer. It has been shown that bisphenol A could reduced therapeutic effect of active tamoxifen metabolite and cytostatics used in breast cancer treatment. Confirmation in clinical trials of the results obtained in vitro and in vivo tests, would enable the creation of specific recommendations for patients undergoing breast cancer treatment, especially hormone therapy. An area requiring further research is the analysis of the effects of xenoestrogens other than phytoestrogens, e.g. metalloestrogens, on the effects of drugs used in the treatment of breast cancer.

Abstract P2-18-01: Single modality adjuvant therapy with radiation (RT) alone or endocrine therapy (ET) alone in women ≥65 years with early stage, hormone receptor positive breast cancer treated with breast-conserving surgery: A population-based analysis

Abstract Purpose: Current guidelines recommend for women (≥65 years at diagnosis) with early stage (T1N0), hormone receptor (HR+) breast cancer (BC) treated with breast-conserving surgery (BCS) that treatment with 5 years of endocrine therapy (ET) alone with omission of radiation (RT) is acceptable. Population studies however report that many women continue to receive RT. The use of RT may reflect preferences due to the convenience of modern RT and/or concerns of the adverse effects of ET. Adjuvant treatment with RT alone may be an attractive option, but further data on the outcomes and morbidity following mono adjuvant therapy with either RT alone or ET alone is needed. We established a contemporary population-based cohort of women ≥65 years with HR+ T1N0 BC treated by BCS. We report the risk of local recurrence, any secondary breast events and adverse treatment-related effects following single modality adjuvant therapy with RT or ET alone. Methods: We identified all women aged ≥65 years at diagnosis with HR+ T1N0 BC diagnosed in Ontario from 2010-2016, treated with BCS and adjuvant RT alone or ET alone (tamoxifen or aromatase inhibitors (AI)). The administration of ET was ascertained from the Ontario Drug Benefit database. Cases were coded as having received either tamoxifen or AI according to the first prescription. Cases with Her2+ BC or those who did not undergo nodal surgery were excluded. Outcomes were ascertained using deterministic linkages of administrative databases. Propensity-weighted scores (PS) were calculated using baseline factors (diagnosis year, age, Charlson comorbidity score, nodal surgery type, grade, socioeconomic status, HR category). Kaplan Meier curves and PS-adjusted multivariable Cox regression were used to evaluate risks of ipsilateral LR, any in-breast event (ipsilateral or contralateral), and adverse treatment-related outcomes (venous thromboembolism (VTE), osteoporotic fracture, vaginal bleeding requiring hysteroscopy or curettage, ischemic heart events, second malignancy. Results: The cohort includes 1054 that received BCS + adjuvant RT and 497 that received BCS + adjuvant ET alone (N= 201 tamoxifen; N=296 AI). Median follow-up time was 5 years. LR occurred in 0.9% (n=10) after RT alone and 2.8% (n=14) after ET alone (p=0.005). Rates of any in-breast event were 3.2% and 3.4%, respectively (p=0.8). Adjusting for PS, treatment with ET alone was associated with an increased risk of LR (HR= 2.79, 95% CI: 1.20, 6.49, p=0.02), no difference in the risk of any in-breast event (HR=0.96, 95% CI: 0.53, 1.77, p=0.9) and a higher risk of VTE (HR=1.8, 95% CI: 1.0, 3.2, p=.05) compared to those treated with RT alone. Women treated with tamoxifen alone had a 5-fold increased risk of vaginal bleeding (HR=4.7, 95%CI: 2.2, 10.0, p<0.0001) and a 2-fold increased risk of VTE (HR=1.9, 95% CI: 0.97, 3.75, p=0.06) compared to those treated with AI alone or RT alone. There were no significant differences in the risks of any or osteoporotic fracture, ischemic heart events, or second malignancies across treatment groups (Table 1). Conclusions: Women ≥65 years with HR+ EBC treated with single modality adjuvant therapy with RT or ET alone experience low risks of recurrence and morbidity. In this population-based study, RT alone compared to ET alone was associated with a lower risk of LR and less adverse events. Table 1. 5-year rates of adverse eventp-valueAny Fracture0.3• RT only11.9• tamoxifen9.5• aromatase inhibitor13.3Osteoporotic Fracture0.1• RT only5.8• tamoxifen2.8• aromatase inhibitor7.3Hysteroscopy/Curettage<.0001• RT only2.1• tamoxifen7.9• aromatase inhibitor0.5Thrombosis/Pulmonary Embolism0.1• RT only3.2• tamoxifen6.2• aromatase inhibitor3.8Ischemic Heart Disease0.3• RT only4.5• tamoxifen1.4• aromatase inhibitor4.2Other Cancer0.7• RT only6.7• tamoxifen7.7• aromatase inhibitor6.4 Citation Format: Mira Goldberg, Rinku Sutradhar, Lawrence Paszat, Timothy Whelan, Sumei Gu, Cindy Fong, Eileen Rakovitch. Single modality adjuvant therapy with radiation (RT) alone or endocrine therapy (ET) alone in women ≥65 years with early stage, hormone receptor positive breast cancer treated with breast-conserving surgery: A population-based analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-18-01.

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019

BackgroundInnovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence. ObjectiveTo present the results from the APCCC 2019. Design, setting, and participantsSimilar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process. Results and limitationsPanellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material. ConclusionsThese voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials. Patient summaryThe Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.

Position statement on the hormonal management of adult transgender and gender diverse individuals

Rising demand for gender-affirming hormone therapy mandates a need for more formalised care of transgender and gender diverse (TGD) individuals in Australia. Estimates suggest that 0.1-2.0% of the population are TGD, yet medical education in transgender health is lacking. We aim to provide general practitioners, physicians and other medical professionals with specific Australian recommendations for the hormonal and related management of adult TGD individuals. Hormonal therapy is effective at aligning physical characteristics with gender identity and in addition to respectful care, may improve mental health symptoms. Masculinising hormone therapy options include transdermal or intramuscular testosterone at standard doses. Feminising hormone therapy options include transdermal or oral estradiol. Additional anti-androgen therapy with cyproterone acetate or spironolactone is typically required. Treatment should be adjusted to clinical response. For biochemical monitoring, target estradiol and testosterone levels in the reference range of the affirmed gender. Monitoring is suggested for adverse effects of hormone therapy. Preferred names in use and pronouns should be used during consultations and reflected in medical records. While being TGD is not a mental health disorder, individualised mental health support to monitor mood during medical transition is recommended. Gender-affirming hormone therapy is effective and, in the short term, relatively safe with appropriate monitoring. Further research is needed to guide clinical care and understand long term effects of hormonal therapies. We provide the first guidelines for medical practitioners to aid the provision of gender-affirming care for Australian adult TGD individuals.

Switching endocrine therapy in breast cancer as a strategy for musculoskeletal symptoms, tolerance, and adherence.

192 Background: Adverse effects of endocrine therapy (ET), especially musculoskeletal symptoms (MSS), represent the major cause of treatment discontinuation in breast cancer (BC) patients, resulting in increased risk of recurrence. Aromatase inhibitors (AI), the mainstay of ET, are associated with a high incidence of MSS such as arthralgia and myalgia. The hypothesis of whether switching ET subclass improves adherence and symptoms was tested. Methods: We conducted a retrospective single site chart review of female patients with nonmetastatic BC, who were seen at Cancer Clinic from January to June of 2017. All patients received AI as a first choice of adjuvant ET; those with disease recurrence while on ET were excluded. We collected data on baseline health, adherence and discontinuation rate, as well as whether switching to a different ET agent (another AI or tamoxifen) was attempted. The subsequent compliance and symptomatology after switching were assessed. Results: 483 eligible patients were identified and divided into 4 groups based upon adherence: 354 (73.3%) were found to be compliant with AI without interruption, 109 (22.5%) switched to a different ET and remained compliant (≥ 1 switch), 16 (3.3%) eventually discontinued ET despite attempting ≥ 1 switch, and 5 patients (1.0%) stopped treatment without a switch. On comparison of the different groups, patients who permanently discontinued ET were more likely to be elderly and have preexisting musculoskeletal condition. MSS was found to be the single most common cause for AI intolerance (105 patients, 81.4%). The median time to switch was 6.3 months (0.3-63.9). Among the compliant switchers, most needed only 1 switch (79) but there were patients who required 2 or 3 switches (23 and 6, respectively). Majority of patients switched from anastrozole to exemestane (84, 51.8%). Significant improvement in symptoms after the switch was reported by 73.3% of patients. Conclusions: Switching between different ET subclasses is an effective treatment strategy to alleviate side effects and enhance adherence to ET. A higher compliance rate of 95.8% was observed in our study compared to a national average estimated at < 80%.

Abstract 601: Cognitive sequelae of adjuvant endocrine therapy in older women treated for early-stage breast cancer

Abstract Background: Approximately 75% of women with BC have hormone receptor-positive (HR+) disease and are treated with anti-estrogen endocrine therapy (ET) in the adjuvant setting. Consistent with estrogens' well-established roles in neuroprotection and cognitive functioning, accumulating evidence suggests ET has adverse effects on cognition. However, there is a paucity of data regarding the cognitive effects of ET in older women, despite the fact that they are at greater risk of BC, HR+ disease, and cognitive impairment than their younger counterparts. Purpose: We conducted a prospective study to examine the cognitive effects of ET in older BC patients with a specific focus on verbal memory, the cognitive domain known to be most sensitive to the effects of estrogen deprivation. Methods: Forty-two chemotherapy-naïve non-demented HR+ BC patients aged 60+ underwent neuropsychological assessment before starting ET, and again after one year of treatment. This within-subjects design allowed us to control for pre-treatment effects of BC on cognition. The neuropsychological battery consisted of standardized measures assessing cognitive functioning across six domains: verbal memory, visual memory, processing speed, executive function, language function, and perceptual reasoning. Raw neuropsychological test scores were converted to age-adjusted z-scores to control for the effects of age on cognition. Change in mean-level performance from pre-treatment to post-treatment within each domain was examined using paired t-tests. Results: Participants exhibited significant decline from baseline pre-treatment performance in verbal memory over the year (t = 2.60, p = 0.01). This corresponds to a small to moderate effect size (d = 0.40). Performance on other domains did not change significantly over the year (all p > 0.05). Conclusions & Implications: Our findings suggest specific adverse effects of ET on verbal memory, which is consistent with previous evidence that performance on verbal memory measures is highly sensitive to the effects of estrogen deprivation. This finding is of considerable clinical relevance given that multiple large-scale studies have found performance within this domain to be an early predictor of cognitive impairment and dementia. Moreover, that significant verbal memory decline occurred after just one year of treatment is particularly concerning given that patients are currently treated with these agents for at least five years, with extended treatment durations of up to 10 years becoming increasingly common. In light of the frequency with which ET is prescribed to older women, it is critical that the potential longer-term effects of ET on cognitive functioning are examined in future larger-scale studies. Our findings should be interpreted with caution because we did not include untreated HR+ BC controls, which are not feasible to recruit given current prescribing guidelines. Citation Format: Emily A. Underwood, Kathleen I. Pritchard, Katarzyna Jerzak, Gerald Lebovic, Christine Elser, Paula Rochon, Mary C. Tierney. Cognitive sequelae of adjuvant endocrine therapy in older women treated for early-stage breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 601.

(OA26) Significance of Hormone Therapy & Bisphosphonate Use on Vertebral Compression Fracture (VCF) Incidence Following Spine Stereotactic Body Radiation Therapy (SBRT) for Breast Cancer Metastases

Spinal metastases are increasingly being treated with SBRT. Though effective, a potential toxicity of SBRT is VCF. Breast cancer (BC) is one of the most common primary sites to metastasize to the spine, & due to factors such as HT use, these patients may be at higher risk for VCF following SBRT. Our study aimed to determine the rate of SBRT induced VCF (S-VCF) in BC patients, & to understand if there is a significant relationship between hormone therapy (HT) & bisphosphonate (Bp) use on this risk. 335 vertebral bodies (VB) (n=131 patients) were treated with spine SBRT for BC metastases at a single institution between 06/2001 & 12/2014. EMRs were retrospectively reviewed in this IRB approved study, & data on the use of Bp, Selective Estrogen Receptor Modulators (SERMs), & Aromatase Inhibitors (AIs) were recorded. Development of a new VCF, progression of an existing VCF & requirement of stabilization surgery after SBRT were the primary endpoints of this study. These were evaluated using CT & MRI. Only VCF development/progression occurring in VB treated with SBRT were considered. VBs with concurrent tumor progression, or surgery prior to SBRT were not included. Statistical significance of VCF incidence, & the use of Bp & HT concurrent with, within 6 m, 1 yr, & 2 yrs of SBRT, was evaluated using the Chi-Square Test for Independence, & Fisher’s Exact Test. Follow up was available for 91 patients (69%) & 233 VB. Median survival post SBRT was 21 m. 58.8% of patients were Caucasian, 33.6% African American, & 7.6% were of other ethnicities. Bone density was low in 59% of patients. Median SBRT dose was 18 Gy/1 fx. Median tumor volume was 35.83 cc. Median follow-up was 15.6 m. 33 VCFs in 20 patients were observed. 48% were new, 24% progressed, & 27% were VB that required surgical stabilization after SBRT. The overall S-VCF rate was 14%. 70 patients (192 VB), 50 patients (146 VB), & 78 (221 VB) were exposed to AIs, SERMs, & Bp, with S-VCF rates of 14.6%, 14%, & 13% respectively. The following were found to be statistically significant in relation to S-VCF: SERM use concurrent (p= .003), within 6 m of (p= .028), & within 2 yrs of (p= .021) SBRT. Also significant was Bp use within 1 yr of SBRT (p< .0001). AI use was not found to be statistically significant for any of the time frames evaluated in our study. Rate of developing a VCF in our cohort was 14%. The overall rate of S-VCF in BC patients is not considerably higher than rates previously reported in non-histology specific series. We will further analyze our cohort to better understand the protective or adverse effects of HT & Bp use in BC patients receiving spine SBRT. To the best of our knowledge, this is the only reported series analyzing S-VCF in BC with an emphasis on the relation of Bp & HT use.

Bidirectional Text Messaging to Monitor Endocrine Therapy Adherence and Patient-Reported Outcomes in Breast Cancer.

Up to 40% of patients with breast cancer may not adhere to adjuvant endocrine therapy. Therapy-related adverse effects (AEs) are important contributors to nonadherence. We developed a bidirectional text-message application, BETA-Text, that simultaneously tracks adherence, records symptoms, and alerts the clinical team. We piloted our intervention in 100 patients. The intervention consisted of text messages to which patients responded for 3 months: daily, evaluating adherence; weekly, evaluating medication-related AEs; and monthly, regarding barriers to adherence. Concerning responses prompted a telephone call from a clinic nurse. The primary objective was to assess patient acceptance of this intervention using self-reported surveys. To compare participants with the general population at our institution, we assessed 100 consecutively treated patients as historical controls using medical record review. We approached 141 consecutive patients, 100 (71%) of whom agreed to participate and 89 of whom completed the intervention. A majority of patients reported that the intervention was easy to use (98%) and helpful in taking their medication (96%). Four patients discontinued therapy before 3 months, and 93% of patients who continued therapy took ≥ 80% of their medication. The frequency of AEs reported by participants via text was higher than that reported in clinical trials: hot flashes (72%), arthralgias (53%), and vaginal symptoms (35%). Approximately 39% of patients reported one or more severe AE that prompted an alert to the provider team to call the patient. A daily bidirectional text-messaging system can monitor adherence and identify AEs and other barriers to adherence in real time without inconveniencing patients. AEs of endocrine therapy, as detected using this texting approach, are more prevalent than reported in clinical trials.

Effect of acupuncture on hot flush and menopause symptoms in breast cancer- A systematic review and meta-analysis.

BackgroundMany breast cancer patients suffer from hot flush and medical menopause as side effects of treatment. Some patients undergo acupuncture, rather than hormone therapy, to relieve these symptoms, but the efficacy of acupuncture is uncertain. This meta-analysis evaluated the efficacy of acupuncture on hot flush and menopause symptoms in women with breast cancer.MethodsA literature search was performed, following the PRISMA Statement and without language restrictions, of 7 databases from inception through March 2017. All selected studies were randomized clinical trials (RCTs) that examined the effect of needle acupuncture on hot flush and menopause symptoms in patients with breast cancer. The methodological quality of these trials was assessed using Cochrane criteria, and meta-analysis software (RevMan 5.2) was used to analyze the data.ResultsWe examined 844 breast cancer patients (average age: 58 years-old) from 13 RCTs. The trials had medium-to-high quality, based on the modified Jadad scale. The meta-analysis showed that acupuncture had no significant effect on the frequency and the severity of hot flush (p = 0.34; p = 0.33), but significantly ameliorated menopause symptoms (p = 0.009). None of the studies reported severe adverse events.ConclusionsAcupuncture significantly alleviated menopause symptoms, but had no effect on hot flush. Breast cancer patients concerned about the adverse effects of hormone therapy should consider acupuncture. Further large-scale studies that also measure biomarkers or cytokines may help to elucidate the mechanism by which acupuncture alleviates menopause symptoms in patients with breast cancer.

Experience with androgen deprivation therapy for prostate cancer in Japan and future perspectives.

Novel anti-androgens and androgen biosynthesis inhibitors have been developed to treat castration-resistant prostate cancer. However, knowledge of androgen deprivation therapy (ADT) has not been developed in the criticism, including information regarding the adverse effects of hormonal therapy. We hypothesize that there are ethnic differences in the efficacy and adverse effects of ADT; therefore, this review summarizes the experience of ADT, mainly in Japan. A risk stratification instrument, the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, was developed based on the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. It revealed that clinical outcomes were substantially better for males treated with ADT in Japan compared with those in the United States. Moreover, there were small survival differences in patients with localized and locally advanced cancer who received local therapy and primary ADT in another Japanese cohort study. In terms of adverse effects, including bone loss and cardiovascular risk, ADT appears to be better tolerated in Japanese populations than in Western cohorts. An ongoing randomized controlled trial of a trimodality treatment comprising brachytherapy, external beam radiation therapy, and neoadjuvant with or without adjuvant ADT in patients with localized high-risk prostate cancer will provide novel insights regarding adjuvant ADT. As a future perspective, the optimal selection of the type of primary ADT, including combining androgen blockade and novel hormonal compounds, adjusted according to each patient's clinicopathological background, may provide better clinical outcomes in patients with advanced prostate cancer.

Knowledge and personal use of menopausal hormone therapy among Chinese obstetrician-gynecologists

Obstetrician-gynecologists' (ob-gyns) knowledge of the benefits and risks of-and attitude toward-menopausal hormone therapy (HT) have evolved since the publication of the Heart and Estrogen/progestin Replacement Study and the Women's Health Initiative. The survey investigated Chinese ob-gyns' perception and personal use of-and attitude toward-HT. A total of 2,000 self-administered questionnaires were sent to female ob-gyns who attended gynecological endocrinology workshops in 15 provinces and cities in China from February to May 2013. A total of 904 eligible questionnaires were collected (response rate, 45.2%). Most of the respondents knew that HT could relieve menopausal symptoms (97.7%) and prevent osteoporosis (93.5%). Most (69.4%) of the respondents thought that HT would increase the risk of breast cancer, and 52.9% thought that HT would increase the risk of endometrial cancer. The most common concern regarding adverse effects of HT was risk of breast cancer, followed by risk of endometrial cancer, risk of venous thrombosis, and weight gain. One hundred twenty-three of 324 symptomatic respondents (38.0%) reported HT use, and a further 28 respondents (8.6%) had tried transdermal and vaginal estrogen creams. These findings show better knowledge of HT among Chinese ob-gyns compared with the general Chinese population. However, HT use is relatively low, and ob-gyns seem to be overconcerned with the risks of HT. HT education must be promoted among Chinese ob-gyns to enhance the proper use of HT in the general population.

Le cancer bronchique féminin

In France, the incidence of lung cancer in women is growing exponentially, making it the second cancer in terms of mortality.Among women patients, more adenocarcinoma, a more frequent non-smoking status, and a better overall prognosis compared to cancer in males are to be seen. Nevertheless, tobacco remains the main risk factor for women, who also appear to be more sensitive to its oncological action.Women are more likely to have « hormone-induced » cancer; studies show adverse effects of hormonal therapy and some benefit of anti- oestrogen treatment. On the other hand, the main oncogenes are occurring more frequently in women, and interactions between EGFR and oestrogen are the source of several recent studies on possibilities for new therapies.These differences in terms of genetic and hormone sensitivity presage several lines of research in order to better understand the oncogenesis of this cancer and to adapt therapies in the age of personalized treatments.

Adverse effects of endocrine therapy in breast cancer: single institute experience.

Aim of the studyThe main purpose of this study is to assess the known adverse effects of adjuvant endocrine therapy for non-metastatic breast cancer patients and to present our single center experience with light of literature.Material and methodsThe breast cancer patients treated with adjuvant radiotherapy in Medical School of Ege University between January 2007 and December 2009 were evaluated for this trial after obtaining their acceptance. Vital findings, bone mineral densitometry, endometrium thickness measured with trans-vaginal ultrasonography, biochemical results including liver function tests and blood lipid profile (total cholesterol, HDL, LDL, VLDL, triglyceride) were recorded for each controls. Socio-demographic data, financial statuses, medical history, co-morbid diseases were obtained from first controls. Patients were followed without any local recurrence and distant metastases until June 2011.ResultsEndometrium thickness was not seen in AI using patients. As compared with tamoxifen group, lack of thickness in AI group was statistically significant (p = 0.000). When compared the values before AI, the number of patients who had osteoporosis was gradually increasing. The decrease was seen in the number of patients with osteopenia. The number of patients with normal lipid profile was gradually increasing up to the second evaluation for tamoxifen group (p = 0.000). On the other hand, the number of patients with hyperlipidemia was increasing for AIs group in follow-up period statistically (p = 0.006).ConclusionsWith the aid of careful patient follow and effective disease management strategies, the negative effect over the QoL can be minimized and also the greatest benefit from endocrine therapy can be obtained.

Cutaneous adverse effects of hormonal adjuvant therapy for breast cancer: A case of localised urticarial vasculitis following anastrozole therapy and a review of the literature

Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used to treat women with breast cancer in both the adjuvant and recurrent disease setting. Cutaneous adverse reactions to these drugs have been rarely reported in the literature. We report an unusual case of urticarial vasculitis following the aromatase inhibitor anastrozole that localised to the unilateral trunk and mastectomy scar, and review the literature on the cutaneous adverse effects of hormonal therapy for breast cancer.

Estrogens and cardiovascular disease risk revisited: the Women's Health Initiative.

In 2002 and 2004, the Women's Health Initiative found no evidence that hormone therapy with estrogen or estrogen with progestin (E + P) protected against cardiovascular disease (CVD). Since then, further analyses have been performed. This review summarizes current analyses on the effects of hormone therapy on CVD and CVD risk factors. The negative effects of hormone therapy vary by the type of CVD event. Estrogen alone and E + P show consistent effects on CVD, but E + P has more impact on coronary heart disease (CHD) and venous thromboembolism. Women of all ethnicities, including those who are obese, have diabetes, or are taking daily aspirin or statins remain at risk for adverse effects from hormone therapy. Although younger women or more recently menopausal women taking hormone therapy may be at relatively lower risk for CHD and myocardial infarction, they remain at risk for stroke, venous thromboembolism and peripheral artery disease. Adverse effects are enhanced in older women with menopausal symptoms. Although hormone therapy lowers LDL cholesterol and lipoprotein (a) and raises high-density lipoprotein cholesterol, it has adverse effects on triglyceride, lipoprotein composition, and inflammatory and hemostatic markers. Baseline metabolic syndrome and high LDL cholesterol increase the CHD risk with hormone therapy. Analyses of discontinuation data in the estrogen-alone and E + P trials suggest that the adverse effects of hormone therapy on CVD are reversible. Recent analyses do not justify postmenopausal hormone therapy for CVD prevention. Further research on the role of hormone therapy-induced changes in CVD risk factors along with genetic studies may increase understanding and aid in developing safer therapies for menopausal symptoms.

Predictors of patient-reported toxicities from endocrine therapy: Importance of illness perceptions, treatment beliefs, and fear of recurrence.

542 Background: Numerous studies have documented the toxicities of endocrine therapy (ET) for early breast cancer (EBC) and their deleterious impact on quality of life and adherence. However, little is known about the factors that underlie patient's susceptibility to report toxicities. The identification of risk factors for toxicities from ET is important as it would allow early targeting of symptom management interventions for women more vulnerable to adverse effects of ET. This prospective study aims to examine the impact of pre-treatment perceptions of EBC, ET beliefs and fear of breast cancer (BC) recurrence (FBCR) on toxicities reported after 6 months of ET. Methods: Women diagnosed with EBC completed a survey prior to initiating endocrine therapy, then at 3, 6 and 12 months. Standardized self-report instruments were used to assess EBC perceptions, ET beliefs, FBCR and toxicities. Clinical and treatment variables were also evaluated. Univariate analyses and mulitivariate regression were conducted to identify factors associated (p&lt;0.1) with side effects at 6 months. Results: Since 9/2010, 173 patients have consented and 84 (mean age = 60 y) have completed the questionnaires at baseline and after 6 months of ET. Controlling for age, none of the clinical or treatment variables (stage of disease, type of surgery, receipt of chemotherapy and radiation therapy) were significant univariate predictors of toxicities. In multiple regression, stronger perceptions that BC has serious consequences on their lives (β=0.218, p&lt;0.05), greater concerns about the adverse effects of ET (β=0.215, p&lt;0.05) and higher levels of FBCR (β=0.316, p&lt;0.01) at baseline were associated with higher levels of reported toxicities. Conclusions: Baseline psychological factors predicted level of patient-reported toxicities to a larger extent than clinical/treatment factors. How patients perceived their illness, their beliefs about ET side effects and their fear of cancer recurrence are strongly associated with side effects experienced after 6 months of ET. These results could facilitate the identification of a subgroup of patients for early interventions to improve symptom management.

Tissue Selective Estrogen Complexes (TSECs) and the Future of Menopausal Therapy

As women age and enter menopause, the decline of ovarian function and the consequent decrease in the circulating levels of estrogens leads to the manifestation of a number of undesirable physiological alterations such as osteoporosis, altered lipid profile, vasomotor instability, vaginal atrophy, and an increased incidence of cardiovascular, metabolic, and neural disorders. Hormone replacement therapy traditionally consisted of the administration of estrogens in conjunction with progestins. The estrogens were thought to be effective in reversing or inhibiting the adverse changes that occur in menopause. Progestins were added solely to inhibit the adverse endometrial effects, including hyperplasia and cancer, observed with estrogen administration alone. However, progestin administration has also been reported to be associated with an increased risk of breast cancer. The controversy surrounding the benefits and risks associated with hormone replacement therapy and the goal of developing a successful therapy devoid of unwanted side effects emphasized the need for alternatives to progestins, which are likely to be responsible for most of the adverse effects of hormone therapy. Appropriately, the discovery of a new class of compounds, the tissue selective estrogen complexes (TSECs) that pair selective estrogen receptor modulators (SERMs) with one or more estrogens to achieve unique estrogen receptor properties that are tissue specific, seems to be the perfect finding for this quest. The SERMs are able to activate or inhibit the activity of estrogen receptors, depending on the tissue targeted, due to their ability to recruit specific comodulator proteins. Since there are known SERMs with concomitant antagonist activity in the uterus and mammary glands and agonist activity in bone and most likely liver, their clinical use to treat menopausal undesired health effects seems appropriate. Unfortunately, SERMs alone cannot counteract the vasomotor instability that comes with decreased ovarian function and therefore do not completely fulfill the therapeutic needs. Thus, the introduction of a new concept for treatment based on the combined use of estrogens and SERMs, the TSECs, allows the achievement of a more favorable clinical profile than either therapy alone. The appropriate pairing of an estrogen and an SERM allows endometrial protection with effective action for other menopausal indications, by exploring the beneficial effects of estrogens while blocking its undesired actions through the SERMs. Although not just any estrogen/SERM combination will provide the anticipated outcome, recent work has shown that a TSEC containing bazedoxifene and conjugated estrogens was able to prevent bone loss and to reduce total cholesterol without uterine stimulation, while its clinical trials demonstrated its efficacy in preventing vasomotor instability. These exciting results suggest that TSECS will be on the forefront of menopausal therapy by defeating its detrimental symptoms, constituting a novel and promising approach for hormone replacement therapy.

Physical activity and body composition, body physique, and quality of life in premenopausal breast cancer patients during endocrine therapy – a feasibility study

Endocrine therapy (ET) is a common method of treatment in breast cancer patients; however, its negative impact on body composition, body physique (physical body shape/measurements), and quality of life (QoL) remains controversial. Previous studies have shown physical exercise can have a positive effect on QoL in breast cancer patients, especially premenopausal subjects. Objective. In this feasibility study, we sought to assess the impact that physical exercise had on body composition and QoL in premenopausal breast cancer patients undergoing ET, and to determine the appropriateness of further testing of this intervention in this patient group. Material and methods. This study involved 41 premenopausal female breast cancer patients before and after six, 12, and 18 months of ET. Aerobic training began in the 6th month and resistance training was added in the 12th month. Body composition was evaluated using dual-energy x-ray absorptiometry (DXA) scans, body physique was evaluated using anthropometric measurement techniques, and QoL was evaluated using questionnaires from the European Organization for Research and Treatment of Cancer. Results. The initial period of ET with no exercise resulted in a reduction in fat-free body mass (FFBM), an increase in fat body mass (FBM), and a decline in QoL scores. Adding aerobic training resulted in a reduction of FBM and percentage of android fat, and improved QoL scores. The introduction of resistance training further reduced percentage of android and gynoid fat, increased FFBM, and further improved QoL scores. Conclusion. ET negatively impacts body composition, body physique, and QoL of premenopausal breast cancer patients. This feasibility study shows that physical activity may improve QoL and reduce adverse effects of ET on body composition and body physique, indicating appropriateness for further investigation on the use of exercise programs in premenopausal breast cancer patients to improve the outcomes of therapy.