Background: Obesity is associated with an increased risk of breast cancer (BC) recurrence and decreased survival, also in case of adjuvant endocrine therapy. It is still not clear whether the activity of aromatase inhibitors and tamoxifen (T) given as adjuvant therapy is affected by body mass index (BMI), although both drugs are widely prescribed. In this analysis, we explored the outcome of TEAM patients (pts) treated with exemestane (E) versus T (2.75 yrs), and with E versus T followed by E (T/E) (5 yrs) in relation to BMI. Patients and Methods: The TEAM trial is a randomized, international phase III study in postmenopausal hormone sensitive early BC pts comparing the activity and safety of adjuvant E (25 mg daily) or the sequence of T (20 mg daily) followed by E (T/E), both regimens given for five years. WHO BMI definitions were used: normal 18.5-24.9 kg/m2, overweight 25-30 kg/m2, obese >30 kg/m2. Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method; results were compared by using the log-rank test and Cox proportional hazard modelling adjusted for country. Results: Weight and height was known in 4741 pts. Mean BMI was 26.9 kg/m2 (SD 4.9); 39% had a normal BMI, 36.9% overweight, and 23.3% of pts was obese. Underweight pts (n=41, 0.9%) were excluded from further analysis. At 2.75 yrs (E vs T) disease relapse in normal weight, overweight and obese pts using E was observed in 8.1%, 6.8% and 7.5% respectively (p=0.57), and in 9.1%, 8.8%, and 12.5%, respectively (p=0.06) of pts using T. The hazard ratio (HR for risk of relapse on E vs T) in the three subgroups was 0.91 (95%CI 0.66-1.24), 0.78 (95%CI 0.55-1.089), and 0.57 (95%CI 0.39-0.84, p=0.004), respectively. At a median follow-up of 5.1 years, disease relapse in normal weight, overweight and obese pts using E occurred in 14.8%, 15.1% and 15.1%, respectively; and in pts using T in 17.0%, 16.9%, and 18.3%, respectively. Regarding DFS, the HR in normal weight, overweight, and obese pts was 0.87 (95%CI 0.69-1.10), 0.88 (95%CI 0.70-1.11), and 0.75 (95%CI 0.56-1.01, p=0.058), respectively, and with respect to OS 0.87 (95%CI 0.65-1.15, p= 0.32), 0.89 (95%CI 0.67-1.18, p= 0.43), and 0.71 (95% CI 0.51-1.01, p= 0.053), respectively. Conclusions: After 2.75 years more disease events were observed in obese women using tamoxifen, which was not seen in obese exemestane users, whereas at 5 years these differences in disease recurrences disappeared in this group. In contrast to recent reports, there seems to be a difference regarding the influence of a high BMI on recurrence rate between tamoxifen and the aromatase inhibitor exemestane. Further research on this topic is warranted. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-3.
Rationale Understanding and effectively addressing the factors that affect patient compliance with adjuvant aromatase inhibitors (AI) is required in order for patients to obtain maximum benefit from treatment. The CARIATIDE study sought to determine whether the provision of educational materials (EM) could improve compliance and persistence with adjuvant AI. At 1-y follow-up (FU), there was no improvement in overall compliance with AI therapy, compliance with initial AI or persistence rates when EM were provided. Final results from the 2-y FU are presented here. Methods This 2-y, global observational study (NCT00681122) randomized 2758 patients, across 18 countries, to Group A: Standard Therapy or Group B: Standard Therapy + EM. The EM were developed in collaboration with patient advocates, and consisted of a range of information on breast cancer-related topics. Compliance rate with adjuvant AI medication was the primary endpoint. Secondary endpoints included persistence rate after 1 and 2y, and reasons for, and time to, discontinuation of AI therapy. Compliance rate was defined as the proportion of patients being ‘compliant’ with the adjuvant AI medication; switching from AI therapy to tamoxifen would result in a non-compliance score at time of switching. For compliance with initial adjuvant AI medication, switching to another AI or hormone therapy would result in a non-compliance score. A patient was considered a ‘persistent’ user if they did not switch AI medication, AI medication was uninterrupted and there was no discontinuation of the AI medication during the second year. Patients’ compliance and behavior were evaluated using compliance questionnaires, EM feedback and validated questionnaires (EORTC IN-PATSAT32, GHQ-12, FACT-ES). Results Of the 2758 patients randomized at study initiation, 2242 were available for analysis at 2-y FU. The results confirmed those obtained at 1-y FU. No statistically significant difference in compliance with AI therapy was observed between Group A and Group B (82% and 82%, respectively, p=0.9926). Compliance with initial AI was 81% in Group A and 80% in Group B (p=0.5541), with persistence rates of 90% and 88%, respectively (p=0.2425). Of the proportion of patients who had compliance data for both years (Group A n=1118; Group B n=1111) 72% were compliant for the whole 2-y FU period. Across the full 2-y FU, AI treatment discontinuation rates of 8% and 9% were observed in Group A and B, respectively, with discontinuation most frequently attributed to AI-related side effects. Analysis showed that no specific baseline demographic characteristics were associated with compliance behavior. Compliance rates differed widely between countries. Conclusions At 2-y FU, EM were not found to improve overall patient compliance, compliance with initial AI, or persistence with therapy. In total, 72% of patients were compliant across the full 2-y FU. AI-related side effects remained the most frequent cause of AI treatment discontinuation across the full FU period. The 2-y CARIATIDE data confirm the 1-y findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-16-02.
Background: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included prospectively planned biomarker studies to identify predictive biomarkers for patients receiving endocrine therapy. Quantitative IHC data for ER/PgR, HER1, HER2, HER3 and FISH analysis of HER2 in all cases was available for the current analysis relative to outcome of estrogen receptor-positive (ER+) early breast cancer patients treated with exemestane versus tamoxifen. Patients & Methods: Pathology blocks from 4598 TEAM patients were collected and tissue microarrays constructed. Quantitative analysis of receptors (HER1/2/3) by conventional IHC, and FISH (for HER2 only) were analysed relative to disease-free survival and treatment on an intent to treat basis using survival data for the first 2.75 years of the TEAM trial. Results: Of 4595 eligible cases samples received, 16 were excluded, and 4010 had complete biomarker data for all markers (HER1/HER2 & HER3) for the final biomarker analysis, 3.5% were HER1 positive, 13% HER2 positive & 21% HER3 positive. 1248 (31%) cases were HER1or2or3 positive (HER1-3+ve). HER1-3 positivity was associated with poor outcome (HR=1.6 95%CI=1.3-2.0). In HER1-3 negative patients the hazard ratio (for risk of relapse on exemestane versus tamoxifen in the first 2.75 years) was 0.68 (95% CI = 0.52-0.89), for the HER1-3 positive cases the hazard ratio was 1.14 (95% CI = 0.83-1.56) with a significant treatment by marker interaction (HR=1.68 95%CI=1.1-2.5; p=0.0014 in multivariate analysis). Trends for similar effects were seen for HER1 negative (-ve) vs HER1 positive (+ve) (HRs 0.80, 95%CI=0.65-0.99 vs 1.63 95%CI=0.74-3.59), HER2-ve vs HER2+ve (HRs 0.71, 95%CI=0.57- 0.9 vs 1.69 95%CI=108-2.63) and HER3-ve vs HER3+ve (HRs 0.78 95%CI=0.62-0.99 vs 1.04 95%CI=0.67-1.62) breast cancers. Conclusion: Preferential exemestane versus tamoxifen treatment benefit was seen in HER1/2/3 negative cases, whilst HER1/2/3 positive cases had a poor prognosis in this endocrine treated population (suggesting a degree of resistance to endocrine therapy), and no evidence of additional benefit from AIs versus tamoxifen. These three Type I receptor tyrosine kinases appear to identify breast cancers with relative resistance to all forms of endocrine therapy. This prospectively planned and powered treatment by marker analysis provides high level scientific evidence which may assist clinicians and patients in determining optimal AI schedules for women with early breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-4.
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