Adjuvant Hormonal Therapy In Patients Research Articles

Impact of web application support versus standard management on adherence with adjuvant hormone therapy in patients treated for breast cancer: the WEBAPPAC study

BackgroundNon-metastatic breast cancer treatment is mainly based on surgery, with or without chemotherapy, radiotherapy and/or hormone therapy. To reduce the risk of hormone receptor positive (HR+) disease recurrence, hormone therapy is prescribed for at least 5 years. It may induce adverse drug reactions (ADRs) as joint pain, sexual dysfunction, weight increase, fatigue, mood disorders and vasomotor symptoms. Around 30–40% of patients withhold hormone therapy within 5 years after initiation. Based on encouraging results of mobile health in patient follow-up, we developed a web-application addressed for breast cancer patients initiating adjuvant hormonal therapy and aimed to assess its impact on hormone therapy adherence, ADRs management, and health-related quality of life.MethodsThe WEBAPPAC trial is a randomized, open-label, prospective, single-center phase 3 study aiming to assess the interest of a web-application support as compared to standard management among breast cancer patients initiating hormone therapy. The main endpoint is the proportion of patients with hormone therapy adherence failure within 18 months after treatment start, in each arm. Eligible patients will be 1:1 randomized between the WEBAPPAC web-application support (experimental arm,) or standard support (control arm), with stratification on type of hormone therapy (Aromatase inhibitor or Tamoxifen). We plan to enroll 438 patients overall. Failure to hormone therapy will be assessed using the Morisky 8-item self-questionnaire (MMSA8), patient adherence logbook, and medical consultations. Secondary outcomes include hormone therapy adherence at 6 months, pain (Visual Analogue Scale and Brief Pain Inventory), quality of life (EORTC QLQ-C30 and BR23 self-questionnaires), anxiety and depression (Hospital and Depression Scale), and return to work and/or daily activities. The user experience with the WEBAPPAC web-application will be assessed using the System Usability Scale (SUS) questionnaire.DiscussionHormone therapy discontinuation or adherence failure in breast cancer patients may be indirectly related to an increased risk of recurrence. A better control of medication adherence, through the detection of side effects and some proposed actions trying to reduce them, appears therefore essential to limit the risk of disease recurrence. The WEBAPPAC web-application thus aims better monitoring and allowing higher level of responsiveness in case of ADRs, thus improving treatment adherence.Trial registrationNCT04554927, registered September 18, 2020.Protocol versionVersion 2.1 dated from December 21, 2021.

224P Adherence to adjuvant hormonal therapy in patients with localized breast cancer

Hormonal therapies are the cornerstone of systemic adjuvant treatment of estrogen receptor (ER)-positive breast cancer. The full benefit of this treatment is obtained with long-term adherence. However, discontinuation of hormonal therapy is common. Factors associated with non-compliance to therapy are complex and worth of detailed evaluation.

Adherence and Beliefs to Adjuvant Hormonal Therapy in Patients with Breast Cancer: A Cross-Sectional Study (Conference Paper) #

Breast cancer is the most common cancer among women over the world. To reducing reoccurrence and mortality rates, adjuvant hormonal therapy (AHT) is used for a long period. The major barrier to the effectiveness of the treatment is adherence. Adherence to medicines among patients is challenging. Patient beliefs in medications can be positively or negatively correlated to adherence. Objectives: To investigate the extent of adherence and factors affecting adherence, as well as to investigate the association between beliefs and adherence in women with breast cancer taking AHT. Method: A cross-sectional study included 124 Iraqi women with breast cancer recruited from Middle Euphrates Cancer Center. Morisky medication adherence scale (MMAS) and beliefs about medication questionnaires (BMQ) are used to assess adherence and beliefs respectively. Result: 25% of women were fully adherent (MMAS = 8). 83.06% of all women developed side effects from medications received. Side effects and unemployed women were significantly associated with non-adherence. Additionally, there is no significant association between beliefs in medications and adherence. conclusion The enormous percent of poor adherence caused by side effects suggests the need for interventions by educating patients about the importance of their treatment and how to overcome side effects.

The role of the clinical pharmacist in guiding adjuvant hormonal therapy in patients with breast cancer.

Breast cancer is the most prevalent type of cancer among women, affecting about 2.1 million worldwide and is responsible for the highest number of cancer-related deaths among women. Approximately 80% of breast cancers express on the surface of hormone receptor cells, such as progesterone and estrogen. In these cases, Adjuvant Hormonal Therapy (AHT) is indicated for a period of five to ten years and consists of taking a daily oral pill. The two most used drugs in AHT are tamoxifen and Aromatase Inhibitors. One of the issues most faced by individuals who are subjected to long periods of treatment is the lack of medication adherence and, consequently, therapeutic inefficiency. It is believed that the monitoring by the pharmacist can contribute to the reduction of errors inherent to the medication, making the treatment more effective and improving the patient's quality of life. The present study aimed to know the perception of patients who live with breast cancer and who do AHT in relation to the educational performance of the clinical pharmacist. This is a qualitative, descriptive and exploratory study, carried out from March to October 2020, with 15 women undergoing treatment at the oncology unit of a tertiary-care hospital in south of Brazil. The data were obtained through a semi-structured interview using an instrument composed of two parts, one referring to the characterization of the participants and the other with the guiding question of the research: "How do you perceive the role of the pharmacist in relation to the guidelines for the use of adjuvant hormonal therapy?". The method of theoretical saturation was used to perform the sample closure and the thematic analysis was used to analyze the data. The participants were between 32 and 74 years old, seven were on tamoxifen therapy and eight on anastrozole, ten were on the first year of treatment, two on the second and three on the third year. The themes that emerged were: pharmacist-patient interaction as a safety factor in hormone therapy; role of the pharmacist in the development of strategies for self-management of the patients during hormone therapy; and, challenges for the pharmacist in relation to hormone therapy through continued guidance. It was evident that the pharmacist's educational action encouraged the participants to carry out the treatment in a more confident and assertive manner according to their particularities and beliefs.

Effect of adjuvant hormone therapy in patients with prostate cancer: A meta-analysis of randomized controlled trials.

To summarize the evidence regarding the treatment effect of adjuvant hormone therapy (AHT) in patients with prostate cancer (PCa). AHT following radiotherapy, chemotherapy, or surgery is widely used in patients with PCa. However, the treatment effect is inconsistent in individual trials. The electronic databases including PubMed, EmBase, and Cochrane Library were searched to identify randomized controlled trials (RCTs) in September 2016. RCTs that evaluated the effects of AHT in patients with PCa were included. Hazard ratio (HR) and relative risks (RR) were used to measure the treatment effects of AHT using a random effects model. The analyses were further stratified by factors that could affect the treatment efficacy. A total of 14,594 potential studies were identified, and 27 RCTs were included. Compared with the control group, patients who received AHT were associated with a significant improvement in overall survival (OS) (HR: 0.78; 95% confidence interval [CI]: 0.71-0.85; P <.001), disease-free survival (DFS) (HR: 0.50; 95% CI: 0.39-0.65; P <.001), total mortality (RR: 0.90; 95% CI: 0.85-0.96; P = .001), recurrence (RR: 0.70; 95% CI: 0.60-0.81; P <.001), and disease-specific mortality (RR: 0.70; 95% CI: 0.56-0.87; P <.001). However, no significant difference was observed between AHT and control for response rate (RR: 1.75; 95% CI: 0.91-3.37; P = .095). The findings of this meta-analysis confirmed that patients who received AHT had a significant improvement in OS, DFS, total mortality, recurrence, and disease-specific mortality. Further, large-scale RCTs are required to evaluate the treatment effect in specific subpopulations.

Individual approach to choosing an appropriate regimen of adjuvant hormone therapy in patients with early-stage breast cancer

Adjuvant hormone therapy is considered the gold standard of therapy for hormone receptor-positive operable breast cancer. The approach to adjuvant hormone therapy in premenopausal patients has changed significantly in recent years. This change was caused by clinical trials, which have confirmed the advantage of adding ovarian suppression to tamoxifen or aromatase inhibitors monotherapy. Individual approach to choosing an appropriate regimen of adjuvant hormone therapy in premenopausal patients with breast cancer should be based on the assessment of risks for relapse, expected effectiveness of treatment and evaluation of drug safety.

Abstract 3772: Cyclin E as a prognostic marker and predictor of response to neoadjuvant chemotherapy and adjuvant hormonal therapy in patients with stage II-III breast cancer

Abstract Purpose: While we know that many cytotoxic chemotherapeutic agents act to modulate the cell cycle, the role of cyclin E as a predictive marker of response to chemotherapy is unknown. Given that the cell cycle is compromised in tumors that overexpress cyclin E, we hypothesized that cyclin E overexpression would predict decreased response to neoadjuvant chemotherapy and increased risk of relapse in the subset of patients with pathologic complete response (pCR). Experimental Design: 286 women with a diagnosis of clinical stage II-III invasive breast cancer that had received neoadjuvant chemotherapy with paclitaxel (or docetaxel) and FAC, FEC or AC followed by surgery were enrolled into this study. Histological sections from the pre- and post-therapy tissue sections of the patient samples were analyzed for cyclin E using immunohistochemistry (IHC). In breast cancers, high levels of cyclin E result in the expression of its low molecular weight isoforms (LMW-E) which are predominantly cytoplasmic due to the loss of the nuclear localization signal. LMW-E expression can be measured by cytoplasmic staining of cyclin E on IHC. The expression of cyclin E was correlated with response to treatment using multivariable logistic regression. Clinical-Pathological factors, disease-free (DFS), recurrence-free (RFS), and overall survival (OS) rates were also evaluated. Results: A complete pCR was obtained in 79 of 286 cases (31%). Patients with high pretreatment cytoplasmic cyclin E expression on IHC had a decreased pCR rate as compared to those patients with low cytoplasmic cyclin E levels (32.3% vs 67.7%). On multivariable logistic regression analysis, the strongest predictors of poor response to therapy (failure to attain pathologic complete response) were the cytoplasmic cyclin E expression and negative Her-2 status (p&amp;lt;0.0001, OR: 9.0 and p&amp;lt;0.0001, OR: 6.5 respectively). Patients with high cytoplasmic cyclin E expression were significantly correlated with poor DFS, RFS and OS in both pretreatment and posttreatment groups. Conclusions: Cytoplasmic cyclin E expression is a strong predictive factor for pCR in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Routine clinical assessment of cyclin E could be used to identify patients at high risk for poor response to neoadjuvant therapy or recurrence and stratified for more personalized therapy. Citation Format: Cansu Karakas, Ashleigh Francis, Min Yi, Aysegul Sahin, Khandan Keyomarsi, Kelly Hunt. Cyclin E as a prognostic marker and predictor of response to neoadjuvant chemotherapy and adjuvant hormonal therapy in patients with stage II-III breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3772. doi:10.1158/1538-7445.AM2015-3772

Predictors of Discontinuation of Adjuvant Hormone Therapy in Patients With Breast Cancer.

To identify predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer. We conducted a record-linkage study based on data from Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and self-reported questionnaire. Women diagnosed with breast cancer between 2005 and 2008 in Stockholm, Sweden, were prospectively followed for 5 years until 2013, starting from their first prescription of tamoxifen or aromatase inhibitors (N = 3,395). Family history of ovarian cancer (hazard ratio [HR], 1.55; 95% CI, 1.19 to 2.02); younger (< 40 years; HR, 1.39; 95% CI, 1.08 to 1.78) and older (≥ 65 years; HR, 1.15; 95% CI, 1.03 to 1.28) age; higher Charlson comorbidity index (≥ 2 v 0; HR, 1.35; 95% CI, 1.03 to 1.76); and use of analgesics (HR, 1.33; 95% CI, 1.16 to 1.52), hypnotics/sedatives (HR, 1.24; 95% CI, 1.07 to 1.43), GI drugs (HR, 1.25; 95% CI, 1.08 to 1.43), and hormone replacement therapy (HR, 1.27; 95% CI, 1.08 to 1.49) were identified as baseline predictors for hormonal treatment discontinuation. Use of analgesics (HR, 1.22; 95% CI, 1.08 to 1.37), hypnotics/sedatives (HR, 1.21; 95% CI, 1.07 to 1.37), antidepressants (HR, 1.22; 95% CI, 1.06 to 1.40), or GI drugs (HR, 1.27; 95% CI, 1.13 to 1.43), and switching therapy between tamoxifen and aromatase inhibitors (HR, 1.50; 95% CI, 1.23 to 1.83) during the first year of hormonal treatment were associated with increased risk of discontinuation during the next 4 years. Predictors identified in our study can be used in developing targeted intervention to prevent adjuvant hormone therapy discontinuation and subsequently to improve breast cancer outcomes.

Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

FDG Avidity at PET/CT During Adjuvant Hormonal Therapy in Patients With Breast Cancer

We aim to retrospectively evaluate the impact of hormone therapy (HT) on FDG avidity of metastatic lesions in patients with breast cancer (BC) undergoing PET/CT. Three hundred eight patients with BC were scanned with PET/CT at 2 Italian institutions (mean time from diagnosis 4 yrs, range: 1-24 yrs). Main indications for PET/CT were elevation of tumor markers (34.4%) and clinical or radiological suspicion of relapse (65.6%). The diagnostic accuracy of FDG PET/CT was computed according to the standard method. Student t test was used to assess the mean differences between the study groups, whereas categorical data were compared with chi-square test. Significance was set at P <0.05. Two hundred sixty-four patients with positive estrogen receptor and who had received adjuvant HT were included in the analysis. At the time of PET/CT scan, HT was ongoing in 176 patients (66.7%) and 88 (33.3%) had completed adjuvant HT. Ninety-eight (55.7%) patients on HT and 59 (67%) off HT had a positive PET/CT; therefore, the scan resulted negative in the remaining 107 patients, 78 and 29 on and off HT, 44.3% and 33%, respectively (P < 0.001). At a median follow-up of 7 months (range 1-48 mos), disease recurrence was confirmed in either clinical or radiological examinations in 126 (47.7%) patients; 72 (40.9%) versus 54 (61.4%) patients on and off HT, respectively (P < 0.005). True-positive PET/CT results were found in 82% and 91% of patients on and off HT, respectively, whereas it failed to identify disease relapse in 13 (18%) and 5 (9%) patients on and off HT, respectively. In our series, FDG PET/CT shows a similar diagnostic accuracy in detecting disease relapse between patients with BC on adjuvant HT versus those who have completed therapy. These preliminary results suggest that the glucose metabolism is not altered by hormonal suppression at the time of the scan.

Reply to K. Lin et al

We thank Lin et al for their interest and for their thoughtful comments on our article. They question the validity of our analysis, indicating a potential bias because of the exclusion of patients who discontinued hormonal therapy as a result of disease progression and death from causes other than prostate cancer. We agree with their point, and we did address the limitations of our hypothesis-generating analysis, including this issue, in our article. To overcome the specific limitation mentioned by Lin et al and to address the issue of bias, we performed a landmark analysis looking only at those patients who survived beyond 5 years in all three groups. The results of this analysis have been published in a previous correspondence to Journal of Clinical Oncology. Briefly, of the total of 189 patients who received less than 5 years of hormonal therapy in the original analysis, 145 (77%) were alive for at least 5 years. There were no significant changes in the distribution of pretreatment characteristics for the smaller, landmark subset of patients compared with the original 189-patient cohort. The 5-year landmark analysis continues to show a trend for an overall survival difference favoring more than 5 years hormonal duration (11-year survival, 64% v 50%), although this difference is no longer statistically significant (P .2), perhaps because of the smaller sample. There are, however, still statistically significant differences among the three hormonal therapy duration groups with respect to disease-free survival (P .0009), local failure (P .02), and distant metastases (P .002), favoring the longer hormonal therapy duration. The optimal duration of adjuvant hormonal therapy for patients with high-risk prostate cancer remains undetermined. As stated by Lin et al, a recent randomized trial shows a detrimental effect on survival for a shorter course of hormonal therapy. Whether treatment duration beyond 5 years will be associated with a significant improvement in survival remains to be established, and only a properly designed randomized trial will unequivocally answer this provocative question.

Impact of the Duration of Adjuvant Hormonal Therapy in Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy: A Secondary Analysis of RTOG 85-31

Impact of the Duration of Adjuvant Hormonal Therapy in Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy: A Secondary Analysis of RTOG 85-31

Impact of the Duration of Adjuvant Hormonal Therapy in Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy: A Secondary Analysis of RTOG 85-31

Radiation Therapy Oncology Group 85-31 was a randomized trial of androgen suppression for life for patients with locally advanced prostate cancer. However, not all patients continued on the protocol-mandated long-term hormonal therapy despite no evidence of recurrence. We correlated duration of adjuvant hormonal therapy and outcomes among patients who prematurely discontinued hormonal therapy. The protocol mandated pelvic radiotherapy followed by goserelin given indefinitely or until disease progression. There were 189 analyzable patients. Patients were divided in groups based on the tertile of hormonal therapy duration (HTD) as follows: < or = 1 year, more than 1 year and < or = 5 years, and more than 5 years. Overall survival (OS), disease-free survival (DFS), cause-specific mortality, local failure (LF), and distant metastasis (DM) were studied. Kaplan-Meier estimation and Cox proportional hazards regression model were used for OS and DFS, and Fine and Gray's regression model was used for the other outcomes. The median follow-up for surviving patients is 9.6 years. The median duration of adjuvant hormonal therapy was 2.2 years. The HTD more than 5 years group is significantly associated with an improved survival and DFS and fewer DMs than other HTD groups. After adjustment for age, radical prostatectomy, nodal status, Gleason score, and stage variables, the HTD more than 5 years group remains significantly associated with better OS and DFS than other HTD groups. In this hypothesis-generating analysis, prolonged HTD of more than 5 years seems significantly associated with improvements in most outcomes. Given these data, decreasing HTD to < or = 5 years may have a detrimental effect on patients with locally advanced prostate cancer. Only a randomized trial will conclusively clarify this issue.

Is Adjuvant Hormonal Therapy Necessary to Japanese Patients with Locally Advanced Prostate Cancer Treated by 3D-CRT?

It is recommended to give adjuvant hormonal therapy for patients with locally advanced prostate cancer based on some randomized trials. However, in those studies, timing of initiating salvage hormonal therapy after PSA or clinical failure was not clearly indicated, although it was suggested that it could affect the survival outcome. Furthermore, there were marked racial differences in clinical outcome after hormonal therapy between Japanese-American men and Caucasian men. Therefore, we evaluated the outcome of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) for Japanese patients with locally advanced prostate cancer, to estimate if AHT could have a possibility of improving survival as reported.

Adjuvant Hormonal Therapy for Stage I Endometrial Cancer

What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer? There is little consensus on the role of adjuvant treatment for patients with stage i endometrial cancer. Although the use of hormonal therapy has been established in advanced disease, less agreement has emerged concerning the benefits of adjuvant hormonal therapy for patients with early-stage disease. The objective of the present evidence series was to review the existing literature on the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer. REPORTS WERE SOUGHT THAT INCLUDED AT LEAST ONE OF THE FOLLOWING OUTCOMES: overall survival, disease-free survival, recurrence (local, or distant, or both), adverse effects, and quality of life. Because of the potential for long-term adverse effects with adjuvant hormonal treatment in this patient population, especially with regard to thromboembolic or cardiovascular events, the rates of non-cancer-related death were also of interest. The medline, embase, and Cochrane Library databases were systematically searched for randomized controlled trials, practice guidelines, systematic reviews, and meta-analyses. The resulting evidence informed the development of the clinical practice guideline. The systematic review with meta-analyses and practice guideline were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (DSG). Nine randomized trials and one published meta-analysis comparing adjuvant hormonal therapy with no adjuvant therapy in women with stage i endometrial cancer constituted the evidence base. One trial reported a statistically significant survival benefit with adjuvant progestogen as compared with no further treatment (97% vs. 69%, p < 0.001). In that trial, the treatment group had a higher number of patients with less myometrial invasion, and a lower number of patients with advanced-stage disease. These differences in baseline characteristics between the randomized groups were considered to be clinically important. In addition, the results of that trial were not consistent with those of other trials, and the trial was a source of statistical heterogeneity when data were pooled across trials. In two of the nine randomized trials, statistically significant recurrence-free benefits were detected with adjuvant hormonal therapy as compared with no further therapy. In one trial, the difference between the rates of recurrence was 16%; however, the methodologic concerns related to that that trial limited its relevance. In the other trial, the difference between the rates of recurrence was 5%. In that trial, patients were at a high risk of recurrence. None of the remaining seven randomized trials reported any significant difference in recurrence rates between treatment groups. The meta-analysis identified in the literature detected no statistically significant recurrence-free or overall survival benefit associated with adjuvant hormonal therapy as compared with no adjuvant therapy [odds ratio (or): 1.05; 95% confidence interval (ci): 0.88 to 1.24). Those results are consistent with the results of the meta-analysis in the present report, which included an additional two trials (or: 1.10; 95% ci: 0.91 to 1.34). This clinical recommendation applies to women with newly diagnosed stage i endometrial cancer. The available evidence does not demonstrate any benefit for adjuvant hormonal therapy. The use of hormonal therapy is not recommended as adjuvant treatment for patients with stage i endometrial cancer.

The impact of the duration of adjuvant hormonal therapy in patients with unfavorable prognosis prostate cancer treated with radiotherapy: Secondary analysis of RTOG 85–31

5062 Background: RTOG 85–31 was a Phase III trial of androgen suppression for life as an adjuvant to radiotherapy. However not all patients continued on the protocol-mandated long-term hormonal therapy despite no evidence of recurrent disease. This analysis correlates duration of adjuvant hormonal therapy and outcomes among patients who prematurely discontinued long-term hormonal therapy. Methods: The protocol mandated pelvic radiotherapy (60–66 Gy) followed by goserelin 3.6 mg monthly given indefinitely or until disease progression. To avoid potential bias due to early progression/death, only patients who were alive with no evidence of disease at the time of cessation of hormonal therapy were included. There were 377 analyzable patients. Patients were divided in groups based on the hormonal therapy duration (HTD), as follows: = 1 year (27.3%), 1&lt; and =2 years (11.4%), 2&lt; and =4 years (13.3%), 4&lt; and =6 years (10.6%) and &gt; 6 years (37.4%). End-points were overall survival, disease-free survival, disease-free survival with PSA &lt;1.5 ng/mL, disease-specific survival, local failure and distant failure. Cox-proportional hazards regression model was used to test the outcomes among the 5 groups. Results: The median follow-up time of surviving patients is 11.27 years. Pretreatment characteristics by hormone duration groups were well balanced except for age. The median duration of adjuvant hormonal therapy was 3.59 years. For each outcome, there are statistically significant differences among the 5 HTD groups in all outcomes without adjusting for other covariates. Pairwise comparisons show that HTD &gt; 6 year group is significantly associated with having an improved survival and fewer failure events than all other HTD groups (HR &lt; 1, p-value &lt;0.0001). Adjusted for age and stratification variables, the HTD&gt;6 year group remains the only group significantly associated with having fewer failure events in all outcomes. Conclusions: Prolonged HTD of &gt; 6 years is significantly associated with improvements in all end-points studied. Based on these data, decreasing HTD to &lt; 6 years may have a detrimental effect in patients with unfavorable prostate cancer. No significant financial relationships to disclose.

The Emerging Role of Aromatase Inhibitors in the Adjuvant Management of Breast Cancer

Adjuvant hormonal therapy for patients with endocrine sensitive breast cancer has been dominated for several decades by the gold standard tamoxifen. Promising data on third generation aromatase inhibitors (AI), anastrozole, letrozole and exemestane, in metastatic setting led to the development of these agents in early breast cancer. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting remain discussed. Various approaches have been evaluated ranging from: 1. Front line 5 year use of AI instead of tamoxifen for newly diagnosed patients, to 2. Switching to AI after 2 or 3 years of tamoxifen for patients presently on tamoxifen (total of 5 years), or 3. Continuing with an AI after completion of 5 years of adjuvant tamoxifen. However, it is unclear today whether one of these AI strategies is superior to the other ones. The overall therapeutic index of AIs appears superior to that of tamoxifen with proven improved efficacy and better toxicity profile. AIs are all less toxic than tamoxifen in terms of thromboembolic disease and gynaecological complications while musculoskeletal disorders and joint pains are more frequent seen with AIs. This review will explore the results from the available adjuvant AIs trials and will define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer.

BICALUTAMIDE 150 MG IN ADDITION TO STANDARD CARE IN PATIENTS WITH LOCALIZED OR LOCALLY ADVANCED PROSTATE CANCER: RESULTS FROM THE SECOND ANALYSIS OF THE EARLY PROSTATE CANCER PROGRAM AT MEDIAN FOLLOWUP OF 5.4 YEARS

We evaluated the efficacy and tolerability of 150 mg bicalutamide daily given in addition to standard care, in patients with localized or locally advanced prostate cancer. The bicalutamide Early Prostate Cancer program consists of 3 randomized, double blind, placebo controlled trials prospectively designed for combined analysis. A total of 8,113 men with T1b-T4, M0, any N (N0 in 1 trial) prostate cancer were randomized to bicalutamide 150 mg/day (4,052) or placebo (4,061) in addition to standard care (radical prostatectomy, radiotherapy or watchful waiting). Primary end points were objective progression-free survival (PFS) and overall survival. At median 5.4 years of followup (21.6% progression events) bicalutamide significantly improved PFS in the overall population. This result was driven by positive results in trials 24 and 25, with the North American trial (trial 23) showing no difference. Patients with locally advanced disease gained most benefit from bicalutamide in terms of PFS, irrespective of underlying therapy. Overall survival was similar in the bicalutamide and placebo groups, across the program and in each trial. Among watchful waiting patients survival appeared to be improved with bicalutamide in those with locally advanced disease, whereas survival appeared to be reduced with bicalutamide in those with localized disease. The most common adverse events with bicalutamide were gynecomastia and breast pain. Other adverse events occurred with a similarly low incidence in the 2 treatment groups. This analysis confirms that bicalutamide provides benefit in patients with locally advanced disease. The current data suggest that early or adjuvant hormonal therapy for patients at low risk of disease progression, such as those with localized disease, is not appropriate.

The benefits of adjuvant hormonal therapy in patients with early breast cancer 35 years old or younger

Background: Endocrine therapy is the preferred first-line therapy in patients with nonaggressive, receptor-positive, metastatic breast cancer. Endocrine therapies in these patients are as effective as chemotherapy in terms of survival and tumor response. In addition, hormonal therapies produce fewer and less severe adverse effects than does chemotherapy. Classes of endocrine therapy currently on the market include selective estrogen receptor modulators (SERMs), aromatase inhibitors, and progestins. For several decades, tamoxifen has been considered the gold standard of therapy. However, despite its proven efficacy, a high proportion of patients do not respond. Therefore, a need exists for alternative therapies or for agents to use following tamoxifen failure.Objective: This review article highlights the various endocrine options available for patients with advanced breast cancer and discusses new agents on the horizon.Conclusions: Although more studies are needed to determine the optimal sequence of hormonal therapy and the ideal agent within each class, the availability of new and multiple options is encouraging for women with advanced breast cancer.

Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413: Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK, Han S, Thomas CR Jr, Shipley WS; Radiation Therapy Oncology Group 9413, University of California-San Francisco, San Francisco, CA.

Purpose This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. Materials and methods Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) less than or equal 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause. Results With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT ( P = .022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT ( P = .56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% vs. 44% vs. 49% vs. 50%, respectively; P = .008). No survival advantage has yet been seen. Conclusion WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.