Years Of Adjuvant Hormonal Therapy Research Articles

Abstract PS5-20: Protein interactome dysregulation analysis reveals putative therapeutic targets for BCI(H/I)-low breast cancers patients

Abstract Background: Hormone receptor-positive (HR+) breast cancer (BC) is a disease of late recurrence. HR+ BC patients who are disease free after five years of adjuvant hormonal therapy, have an ongoing risk of disease recurrence and death for at least 15 years from diagnosis. Multiple trials have demonstrated consistent absolute benefits with extending adjuvant endocrine therapy to 10 years in HR+ patients. In several extended endocrine therapy trials, we have shown that HR+ patients with BCI(HoxB13/IL17BR) [BCI(H/I)]-high biomarker expression benefit from extended endocrine therapy, while those with low BCI(H/I)-low expression do not benefit from such therapy. Currently, there are limited therapeutic options for BCI(H/I)-low patients who are at high risk for late disease recurrence. Previous cell line-based, global scale protein-protein interaction (PPI) dysregulation mapping studies have identified therapeutic pathways within cellular circuits carrying the perturbed protein-protein interaction. To identify exploitable therapeutic vulnerabilities in BCI(H/I)-low BC patients, we performed comparative multiplexed quantitative mass spectrometry-based interactome dysregulation analysis of BCI(H/I)-low with BCI(H/I)-high BC samples and correlated interactome perturbations with drug responses. Methods: 21 BCI(H/I)-high and 23 BCI(H/I)-low frozen tumor samples from ER+ BC patients were identified in the MGH BC tissue repository, and proteomes were mapped using TMT-11 reagents, and the Synchronous Precursor Selection supported MS2/MS3 method on an Orbitrap Fusion and an Orbitrap Lumos. Dysregulations of PPIs were mapped through using bivariate outlier testing on each identified protein pair based on mapping Mahalanobis distances. . Protein identifiers (IDs) were converted to their appropriate gene IDs and gene set enrichment analysis (GSEA) was performed. Using previously established PPI data from 41 human breast cancer cell lines, we performed comparative PPI dysregulation GSEA and leading edge GSEA of the BCI(H/I)-high and -low samples. To identify therapeutic target candidates for BCI(H/I)-low patients, tumor interactome dysregulations were correlated with drug response dysregulations determined in drug screen of 195 cancer therapeutics against 41 breast cancer cell lines. Results: Across 44 samples, we have quantified more than 11,608 proteins with an average of 7,890 proteins per sample. Protein concentration co-regulation analysis resulted in identifying more than 11,908 protein-protein associations (ρ >0.65, FDRq <0.0001). PPI dysregulation analysis revealed an average of more than 1596 dysregulated PPIs per tumor sample. GSEA of the 21 BCI(H/I)-high proteome samples revealed a positive association with the Bowie tamoxifen response, and the α- and γ-interferon response C2 gene sets, while the 23 BCI-H/I-Low samples revealed a positive association (p=0.03, FDRq=0.052) with the hedgehog signaling and the early estrogen Hallmark gene sets. Protein-protein interaction GSEA identified 85 significant gene sets (p <0.016, FDRq <0.25) that were more frequently dysregulated in the BCI-H/I-low samples as compared with the BCI(H/I)-high samples. Dysregulated pathways in BCI-H/I-low samples included cell cycle regulation, anaphase promoting complex-mediated degradation of mitotic proteins, and ERK and RAS signaling. Correlation of the BCI(H/I)-low interactome perturbations with cell line model drug responses to a library of 195 therapeutics revealed a significant correlation with PI3K inhibitor drug response. Conclusion: Quantitative mass spectrometry-based protein-protein interaction dysregulation identified the PI3K- pathway as a putative exploitable therapeutic vulnerability in BCI(H/I)-low HR+ BC patients at risk for late disease recurrence. Citation Format: Dennis Sgroi, Johannes Kreuzer, Robert Morris, Xcanda Herrera Lopez, Wayland Chiu, Wilhelm Haas. Protein interactome dysregulation analysis reveals putative therapeutic targets for BCI(H/I)-low breast cancers patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-20.

Abstract B016: Predictors of nonadherence to adjuvant hormonal therapy among breast cancer patients

Abstract Purpose: This study aimed to investigate the predictive factors associated with nonadherence to adjuvant hormonal therapy (AHT) by year among patients with receptor-positive breast cancer. Background: AHT is used to treat and manage hormone receptor-positive breast cancers, which comprise 70% of all breast cancers. Low adherence to these medications has been shown to increase the risk of death by approximately 20%. Despite the known benefits for reducing mortality and reoccurrence, adherence to AHT medications has proven to be a major challenge for patients. Previous studies have linked several demographic and clinical characteristics as predictors of adherence. Methods: Women diagnosed with receptor-positive breast cancer between the years 2002 to 2010 were identified through the South Carolina Central Cancer Registry, which was linked to administrative databases, the South Carolina Medicaid Program, and a private payor plan. We identified 1,095 patients with breast cancer who met our eligibility criteria and filled at least two AHT medications. The medication possession ratio (MPR), the ratio of number of pills for each AHT and the number of days between each AHT refill, was derived using automated pharmacy records to identify AHT prescriptions and the dates of each refill. The average MPR was calculated for each year over a 3-year period. Regression models and t-tests were used to assess factors associated with nonadherence of AHT for each of the 3 years. Results: The average adherence rate for AHT was 0.93, 0.90, and 0.90 following year 1, year 2, and year 3, respectively. For each of the 3 years, African Americans had a significantly lower adherence to AHT compared to European Americans. In addition, women under the age of 50 years had a significantly lower MPR for each year compared to women 50 and older (p = <.01). Insurance type also had a significant impact on compliance over the 3-year period (p = <.01). Women were more likely to be adherent to aromatase Inhibitors (AIs) compared to selective estrogen receptor modulators (SERMs) across all 3 years. Interestingly, geographic location (urban versus rural) did not affect adherence until the third year of treatment (0.91 ± 0.17 vs. 0.87 ± 0.20, p = 0.02, respectively). Treatment factors such as radiation and chemotherapy did not appear to impact AHT adherence. However, upon further investigation, following year 1 of treatment, women taking both AHT and chemotherapy simultaneously, as opposed to only taking AHT, had a significantly lower adherence rate (0.86 ± 0.19 vs. 0.92 ± 0.14, p = <.01, respectively). Conclusion: Demographic characteristics such as age, race, and insurance type appeared to impact AHT adherence across the initial three years of AHT. However, there are other factors that should be considered at different timepoints during treatment, such as geographic location and treatment regimen. This study provides important insight into probable factors and characteristics that can be used to provide targeted interventions for improving AHT adherence. Citation Format: Samantha C. Truman, Oluwole Babatunde, Christian Alvarado, Sue P. Heiney, Joshua E. Sellner, Kelly E. Reiss, Swann Arp Adams. Predictors of nonadherence to adjuvant hormonal therapy among breast cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B016.

Gastrointestinal metastatic breast cancer unmasked by anticoagulation

BackgroundCancer is a leading cause of provoked venous thromboembolism (VTE) and requires use of anticoagulation. As the incidence of lobular breast carcinoma increases, more breast cancer patients experience gastrointestinal metastatic disease which often manifests with gastrointestinal bleeding. Herein we discuss the challenges associated with the diagnosis and management of breast cancer metastatic to the GI tract revealed by need for anticoagulation due to concurrent cancer-associated VTE. CaseA 72 year old woman with a past medical history of ER+ PR+ HER2- Stage IIIa left lobular breast carcinoma previously treated with neoadjuvant chemotherapy, bilateral mastectomies and radiation followed by adjuvant hormonal therapy with letrozole. After 2 years of adjuvant hormonal therapy, she was diagnosed with unprovoked VTE. She was started on rivaroxaban for indefinite anticoagulation. After 5 months she presented with complaints of melena and weakness and a hemoglobin of 7.1 g/dL and platelets of 110 x 109/L. Esophagoduodenoscopy was performed which showed acute gastritis with random gastric biopsies noted to be positive for metastatic lobular breast carcinoma. Due to GI bleeding, rivaroxaban was held, however the patient developed an acute proximal right femoral vein VTE. A second trial of anticoagulation with heparin did not reveal continued bleeding, so she was discharged on apixaban. Unfortunately, despite starting chemotherapy with ibrance and faslodex she developed worsening melena resulting in the need to the place an IVC filter and cessation of anticoagulation. DiscussionAs lobular breast cancer can spread along serosal surfaces, new onset of GI bleeding in patients with history of lobular breast cancer should increase suspicion for GI metastatic disease. Use of anticoagulation may unmask bleeding in such patients. The increased risk of GI bleeding in cancer patients must be considered when selecting anticoagulation for the management of cancer-associated VTE. Management of cancer associated thrombosis is complex and hemostasis strategies for of mucosal bleeding from metastatic lobular breast cancer may require tailored approaches that compensate for the malignant cause. Furthermore, a thorough assessment of platelet counts and other coagulation factors should be considered as a minority of patients with metastatic disease can present with consumptive coagulopathy.

Abstract OT1-12-01: Exploration of factors associated with imminent risk of late recurrence in hormone receptor positive breast cancer

Abstract Research objectives: To conduct a prospective observational study of patient and tumor-related factors in women with high risk hormone receptor (HR)+/HER2- breast cancer (BC) following at least 5 years of adjuvant hormonal therapy, in order to identify risk factors for imminent recurrence. Rationale: Many of the life-threatening BC recurrences in women with HR+HER2- BC take place more than 5 years post-diagnosis, often after completion of adjuvant hormonal therapy. The identification of a biomarker(s) for late BC recurrence could lead to interventional trials to evaluate preventive therapies. We will evaluate whether the presence of blood-based biomarkers [(i) Circulating Tumor Cells (CTCs), (ii) circulating tumor DNA (ctDNA), (iii) tumor markers (CA 15-3, CEA)] and patient factors may predict BC recurrence. Trial design: A prospective cohort of eligible women with previously treated HR+HER2- BC who have not experienced a distant recurrence will be enrolled; patient and circulating factors will be measured annually until distant recurrence or study completion. Host factors (including BMI, lifestyle, medical illness, surgery, trauma and stress, as well as circulating PlGF, VEGF-1 and inflammatory markers) that may contribute to exit of BC cells from dormancy will also be assessed. The primary outcome is distant BC recurrence. Any BC event, including loco-regional recurrence, new breast or other primary cancer will be evaluated as a secondary endpoint. Outcomes will be ascertained by regular self-report (via annual telephone calls) and/or physician report and confirmed by medical record review. Key eligibility criteria: i) Diagnosis of ER and/or PR positive (either or both 10% positive), HER2 negative invasive BC, ii) predicted >1.5-2% annual risk of recurrence (T2, T3 or T4 with any N+;T1 N2+; T2N0 or T1 N1 cancers with high risk genomic scores), iii) receipt of adjuvant endocrine therapy for at least 4 years, with discontinuation planned in the next 12 months or completion of endocrine therapy within the last 5 years, iv) prior adjuvant chemotherapy, targeted therapy and bone targeted therapies are allowed provided they have been completed. Specific aims: 1) Determine if the presence of (i) CTCs, (ii) ctDNA, (iii) CA15-3 and CEA are associated with imminent risk (within 1-2 years) of distant recurrence in the study population. 2) Identify host factors associated with these blood-based biomarkers, as well as clinical outcomes. Statistical methods: A matched case control design (matching for time since completion of adjuvant hormone therapy, baseline T, N and grade) will be used to investigate associations of key study variables with imminent risk of distant recurrence within the next 1-2 years. Measurements of patients who do versus do not recur will be compared over the 1-2 years prior to relapse. Each variable will be allocated one third of a study-wide type one error of 0.05 (2-sided). ROC analyses and multivariable modelling will be used to optimize sensitivity, specificity, PPV and NPV. Available questionnaire data will be summarized at all time-points to generate descriptive survivorship data. Accrual: Starting in August 2018, we plan to recruit 1,000 patients over 2 years at selected Canadian cancer centres. Citation Format: Jerzak KJ, Cescon DW, Chia SK, Bratman S, Ennis M, Stambolic V, Chang M, Dowling R, Goodwin PJ. Exploration of factors associated with imminent risk of late recurrence in hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-12-01.

Abstract P5-08-10: The breast cancer index as a tool in decision making for adjuvant hormonal therapy in early luminal breast cancer: Initiation, withdrawal and continuance

Abstract Background: Most women with newly diagnosed breast cancer are of luminal type and will be offered 5-10 years of adjuvant endocrine therapy. Many women will not have a survival benefit from this therapy and 30% or more will struggle with side effects and quality of life issues. Breast Cancer Index (BCI) is a genomic biomarker for early-stage, ER+ breast cancer and has been validated to assess risk of late (5-10 yr) distant recurrence and predict likelihood of benefit from extended (>5y) endocrine therapy utilizing the HoxB13/IL17BR(H/I) ratio. H/I has also been shown to predict benefit from endocrine therapy in the early adjuvant setting. The objective of this study was to characterize the impact of BCI on endocrine therapy decision-making for early-stage breast cancer patients. Methods: Data was collected retrospectively from patients with early-stage luminal breast cancer treated at Breastlink who underwent BCI testing between 10/2014-5/2015. The impact of BCI test results were analyzed for 3 indications: 1) initiation of endocrine therapy for patients considering no adjuvant treatment; 2) patients 6 mo-4y post diagnosis struggling with side effects and desiring to discontinue endocrine therapy; and 3) patients beyond 4 years of adjuvant hormonal therapy deciding whether to extend therapy for an additional 5 years. Results: One hundred patients underwent BCI testing with median age 53 (range 35-77). The BCI assay was utilized in 14 cases at diagnosis, 54 cases at 6 mo-4y during therapy, and 32 cases at >4y post-diagnosis. In patients tested at time of diagnosis, 10/11 that were low risk for late recurrence and low likelihood of benefit from endocrine therapy chose not to initiate therapy, and 2/2 patients were high risk/high likelihood to benefit initiated therapy. One patient, a 72 year-old with low risk and high likelihood to benefit, declined therapy. In patients tested between 6 mo-4y on therapy, 30/30 patients were low risk and low likelihood of benefit chose to stop endocrine therapy, and 11/11 patients were high risk and high likelihood of benefit chose to continue. Of 7 patients that were low risk but high likelihood of benefit, 5 continued therapy. All 6 patients that were high risk but low likelihood of benefit chose to stop therapy. Of 32 patients tested after 4 years of adjuvant therapy, 13/13 were low risk and low likelihood of benefit chose to stop endocrine therapy at 5 years, and 8/8 were high risk and high likelihood of benefit chose to extend therapy to 10 years. All 5 patients that were high risk but low likelihood of benefit elected to stop, and 3/6 patients that were low risk but high likelihood to benefit extended therapy. In total, endocrine therapy treatment decision making aligned with predictive (H/I) results in 93/100 patients. Conclusion: The BCI test was instrumental in assisting almost all women in their decision to receive or maintain adjuvant hormonal therapy and 67% of women discontinued or declined hormonal therapy based on test results. All patients with high risk and high predictive benefit on BCI assay chose to pursue adjuvant endocrine therapy. Oncologists can use BCI in their algorithms of delivering personalized cancer care. Citation Format: Link JS, Buck LJ, Kapoor NS. The breast cancer index as a tool in decision making for adjuvant hormonal therapy in early luminal breast cancer: Initiation, withdrawal and continuance. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-10.

Women's experiences of hormonal therapy for breast cancer: exploring influences on medication-taking behaviour.

Five to 10 years of adjuvant hormonal therapy is recommended to prevent breast cancer recurrence. This study investigated modifiable influences on adjuvant hormonal therapy medication-taking behaviour (MTB) in women with stage I-III breast cancer. Semi-structured face-to-face interviews among women with stage I-III breast cancer prescribed adjuvant hormonal therapy purposively sampled by their MTB at two cancer centres. Thematic analysis was conducted based on the Framework approach, with the Theoretical Domains Framework (TDF) informing the analysis framework; the TDF is an integrative framework consisting of 14 domains of behavioural change to inform intervention design. Thirty-one women participated in interviews (14 adherent/persistent; 7 non-adherent/persistent; 10 non-persistent). Three domains identified both barriers and enablers to hormonal therapy MTB across the three MTB strata: beliefs about consequences, intentions and goals and behaviour regulation, but their influence was different across the strata. Other domains influenced individual MTB strata. Key enablers for adherent/persistent women were identified within the domain beliefs about consequences (breast cancer recurrence), intentions and goals (high-priority), beliefs about capabilities (side effects) and behaviour regulation (managing medication). Barriers were identified within the domain behaviour regulation (no routine), memory, attention and decision processes (forgetting) and environmental context and resources (stressors) for non-adherent/persistent women and intentions and goals (quality of life), behaviour regulation (temporal self-regulation), reinforcement, beliefs about consequences (non-necessity) and social influences (clinical support) for non-persistent women. This study identified modifiable influences on hormonal therapy MTB. Targeting these influences in clinical practice may improve MTB and hence survival in this population.

Compliance With Hormonal Therapy in Elderly Women With Early Breast Cancer Who Were Not Treated With Adjuvant Radiation Following Lumpectomy

Several recent studies have suggested that adjuvant radiation therapy (RT) can be omitted in select elderly women with early stage, hormone receptor-positive breast cancer who consent to be treated with 5 years of adjuvant hormonal therapy (HT). The purpose of this study was to determine compliance with and adherence to adjuvant HT for elderly women with breast cancer following breast conserving surgery (BCS) who were not treated with adjuvant RT.

Five or more years of adjuvant endocrine therapy in breast cancer: a meta-analysis of published randomised trials

Five years of adjuvant hormonal therapy is the standard of care in early breast cancer (BC) expressing oestrogen receptors (ER+). Prolonged duration of adjuvant endocrine therapy is implemented to prevent recurrence and death; in particular, its carryover effect may prevent very late events. This meta-analysis compares the efficacy of 5years of hormonal therapy alone with that of additional years of hormonal therapy, in patients with early BC. Randomised trials comparing 5years versus more than 5years of hormonal therapy in BC were identified by electronic searches of PubMed, EMBASE, ISI Web of Science and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using the fixed- or random-effects models. The primary endpoints were overall survival (OS), BC-specific survival (BCSS) and relapse-free survival (RFS) reported as odds ratios (ORs) and 95% confidence interval (CI). Eight trials, including 29,138 patients, were identified. Overall, in ER+ BCs, extended endocrine therapy beyond 5years of tamoxifen significantly improved OS (OR, 0.89; 95% CI 0.80-0.99; P=0.03), BCSS (OR, 0.78; 95% CI 0.69-0.9; P=0.0003) and RFS (OR 0.72; 95% CI 0.56-0.92; P=0.01) compared with 5years of hormonal therapy alone. Loco-regional and distant relapses were reduced by 36 and 13%, respectively. Compared with 5years of tamoxifen, additional adjuvant endocrine therapy reduced risk of death and relapse of ER+ BC by ~10 and 30%, respectively. This strategy should be considered in patients free of disease after 5years of hormonal therapy.

IN24 Pregnancy after breast cancer

With the rising trend of delaying childbearing and considerable progress in managing early breast cancer, more young breast cancer patients are inquiring into the feasibility and safety of subsequent pregnancy. For more than three decades, several studies have tried to address this question, however they all sufferedmajor limitations. This includes lack of statistical power, issues related to selection bias, limited information on systemic therapy, and lack of information on outcome according to ER status. The later remains a highly clinically relevant point, as there are concerns that pregnancy could be detrimental in patients with endocrine sensitive disease. All these factors combined resulted in poor counseling of womenwith history of breast cancer desiring subsequent pregnancy. It has been shown that up to 30% of patients who become pregnant following breast cancer diagnosis are advised by their treating physicians to proceed for an abortion. This highlights that there is a general conception that pregnancy adversely impacts the prognosis of these patients and also that abortion could partly reduce such risk. Recently we conducted a large multicenter study in an attempt to address the limitations highlighted earlier. This study included 1,207patients inwhich 333becamepregnant following breast cancer diagnosis and the rest served as a comparative group. All patients had known ER status and the study was powered to examine the differences in disease free survival (DFS) in the ER-positive cohort. At a median follow-up of 5 years following pregnancy, no difference in DFS was observed between patients who became pregnant and the control group irrespective of the ER status with a trend of a better overall survival in the pregnant group. Furthermore, induction of abortion was not found to be associated with disease outcome. In view of the currently available evidence, women with history of breast cancer should not be denied the opportunity to become subsequently pregnant irrespective of the characteristics of their disease. Patients should be informed that they can consider becoming pregnant after completion of their adjuvant therapy. This remains rather challenging for some patients particularly those who require five years of adjuvant hormonal therapy. In such patients, stopping hormonal therapy earlier could potentially have detrimental effect on breast cancer outcome and hence they should be informed about that; although the exact impact of such approach on their absolute risk of relapse and/or death remains unknown. In patients who become pregnant, abortion does not appear to have an impact on breast cancer outcome and hence, it should not be promoted for therapeutic reasons. Prior therapies (chemotherapy, radiation and targeted therapy) do not appear to have an impact on subsequent pregnancy course and/or fetal outcome. However, breastfeeding from the previously affected breast could be compromised secondary to fibrosis from prior breast conserving surgery and radiotherapy. Around 40–50% of patients fail to breastfeed from the ipsilateral breast; however, exclusive breastfeeding from the contralateral breast remains feasible. Very scarce data is available on the effect of subsequent breastfeeding on disease outcome. However, in the absence of data suggesting a detrimental effect, breastfeeding should not be discouraged. IN25 Pregnancy registry and trial project O. Pagani*. Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland

Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

BackgroundPatients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.Methods/DesignThis is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (125I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with 125I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during 125I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.DiscussionTo our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.Trial registrationUMIN000003992

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

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

Abstract PD08-03: Competing Causes of Mortality vs. Breast Cancer Mortality at 5-Years among 9766 Postmenopausal Women with Hormone Receptor Positive Early Breast Cancer Treated on the TEAM Study of Adjuvant Hormonal Therapy

Abstract Background: The TEAM (Tamoxifen Exemestane Adjuvant Multinational) trial is a contemporary multinational study of the effects of 5 years of adjuvant hormonal therapy, either exemestane (E) or tamoxifen switching to E (TàE). Five-year results were presented at SABCS 2009 showing no difference in outcome between E vs TàE (Rea D, SABCS Abstract 11), thus giving us the opportunity to analyze the causes of mortality in the entire population of 9766 women. Methods: Postmenopausal women with hormone receptor positive (HR+) early breast cancer (BC) were randomized to E or TàE for 5 years after completion of surgery, adjuvant chemotherapy (when indicated), and radiation therapy based on local guidelines. All data were collected and analyzed at the Central Data Center in Leiden. The primary outcome of DFS as well as safety and other secondary outcomes were analyzed in 2009 after 1285 events had occurred to trigger the analysis. Results: Between 2001 and January 2006, 9766 women were randomized; 100% were HR+, 50% had node negative disease, 68% received adjuvant radiotherapy, and 36% received adjuvant chemotherapy. The median follow-up was 5.1 years with over 60% of women having been followed for 5 or more years. Among 961 deaths, 568 (59%) were caused by BC and 393 (41%) by causes other than BC. The cumulative incidence of death from BC vs. other causes at 5-years for all women and by nodal status is as follows (see table): There was a general relationship with non-breast cancer deaths and increasing age at diagnosis (≥70 years), as expected. Non-breast cancer causes of mortality included second malignancy (105); cardiac (71), cerebral (33), or pulmonary (28) events; miscellaneous other causes (105); and unknown (51). Conclusions: Among 9766 postmenopausal women with HR+ BC treated with contemporary hormonal strategies following standard primary treatment, the probability of death from causes other than BC was nearly as high as the probability of dying from BC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-03.

Adjuvant treatment of breast cancer in postmenopausal women: role of exemestane

Adjuvant hormonal therapy significantly reduces the risk of recurrence and death following surgery for estrogen receptor (ER)-positive early breast cancer. Previously, the gold standard hormonal therapy was tamoxifen, a selective modulator of the ER. However, large clinical trials conducted over the past decade have defined the efficacy of an alternative class of hormonal agent, namely the third-generation aromatase inhibitors (AIs): exemestane, letrozole, and anastrozole. On the basis of the pivotal International Exemestane Study (IES), exemestane, a steroidal third-generation AI, was licensed for the adjuvant treatment of postmenopausal women with ER-positive early breast cancer following 2-3 years of tamoxifen to complete a total of 5 years of adjuvant hormonal therapy. Here, we consider recent data to emerge primarily from the IES and Tamoxifen Exemestane Adjuvant Multicenter trials and consider their implications for the role of exemestane in the adjuvant treatment of breast cancer.

Duration of adjuvant endocrine therapy of breast cancer: how much is enough?

To describe the current status regarding the duration of adjuvant tamoxifen and/or aromatase inhibitors in women with early-stage hormone receptor positive breast cancer. Women with early-stage breast cancers that express estrogen and/or progesterone receptors benefit from adjuvant hormonal therapy with antiestrogen drugs. Five years of tamoxifen is the standard to which other approaches have been compared. In premenopausal women, a total of 5 years of adjuvant hormonal therapy using tamoxifen is the preferred approach. In postmenopausal women, aromatase inhibitors alone or in sequence after tamoxifen for 5 years has become the standard of care. The use of antiestrogen therapy for longer than 5 years has been studied in several trials. There is a suggestion that there may be improved disease-free survival in some subgroups, but the clinical significance and magnitude of this benefit remains an open question. Some particularly high-risk subgroups may be candidates for extended adjuvant therapy. In addition to the efficacy of adjuvant hormonal therapy, careful attention must be paid to compliance with the prescribed medication, management of side effects, and evaluation of costs. There are many approaches to the adjuvant hormonal therapy of breast cancer supported by large trials. No one approach is uniquely superior to others. Longer follow-up may lead to more specific recommendations. Adjuvant hormonal therapy for women with hormone receptor positive breast cancer plays a critical role in the management of early stage hormone receptor positive breast cancer.

Selection Bias Is Not a Good Reason for Advising More Than 5 Years of Adjuvant Hormonal Therapy for All Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy

Selection Bias Is Not a Good Reason for Advising More Than 5 Years of Adjuvant Hormonal Therapy for All Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy

Adjuvant Aromatase Inhibitors Following Tamoxifen for Early-Stage Breast Cancer in Postmenopausal Women: What Do We Really Know?

Adjuvant hormonal therapy in the treatment of women with early-stage, hormone receptor (HR)—positive breast cancer is now considered the standard of care. Adjuvant tamoxifen decreases the risk of breast cancer recurrence and death in women with early-stage breast cancer when taken for 5 years. The benefits of tamoxifen are counterbalanced by toxicities including an increased risk of endometrial cancer and thromboembolic events. The selective aromatase inhibitors (AIs)—including anastrozole, letrozole, and exemestane—are challenging the role of tamoxifen as the adjuvant hormonal therapy of choice in postmenopausal women. Results of the Arimidex and Tamoxifen Alone or in Combination trial favor the use of anastrozole over tamoxifen as initial adjuvant hormonal therapy, with improvement in disease-free survival (DFS) and a favorable toxicity profile. The results of 2 large adjuvant trials using AIs sequentially with tamoxifen in postmenopausal women with early-stage, HR-positive breast cancer have been reported. The MA-17 study randomized women to placebo or letrozole for 5 years after completion of 4.5–6 years of initial tamoxifen. The Intergroup Exemestane Study (IES) randomized women following 2–3 years of adjuvant tamoxifen to continue to receive tamoxifen or switch to exemestane for a total of 5 years of adjuvant hormonal therapy. The MA-17 and IES trials demonstrated superior DFS with the AI and corroborated the smaller GROCTA-4B and Italian Tamoxifen Arimidex trials, which studied sequential therapy with aminoglutethamide or anastrozole. There is now substantial medical evidence supporting the use of AIs in postmenopausal women with early-stage, HR-positive breast cancer.