Search

Purpose In the adjuvant setting, specific adverse events (AEs) such as vasomotor symptoms (VMS) and musculoskeletal AEs are associated with relapse-free survival in aromatase inhibitor (AI)-treated patients. In the neoadjuvant setting, specific AEs may be associated with tumor response to AIs as well. Methods Between 2007 and 2012, 107 patients participated in the prospective TEAMIIA trial, a prospective, phase II trial investigating 6 months of neoadjuvant exemestane in patients with strongly ER-positive breast cancer. Radiological response (≥30% decrease in tumor size) was studied in relation to VMSs and MSAEs. Pearson's Chi-Square tests and multivariate logistic regression analyses were used to evaluate of statistical significance (p < 0.05). Results Out of 102 patients 26 patients (25.4%) experienced at least one episode of VMS and 27 patients (26.4%) experienced MSAE. Out of 240 reported adverse events, 71 were specific AEs (40 MSAEs, 31 VMSs). Radiological response was greater in patients who reported VMSs compared to patients who did not (70.8% vs. 49.3%, multivariate OR 2.91, 95% C.I. 1.03–8.26, P = 0.045). No significant advantage towards better response was observed in patients who experienced MSAEs (60.0% vs. 53.3%, univariate OR 1.33, 95% C.I. 0.53–3.38, P = 0.545). Conclusion VMSs are associated with tumor response to neoadjuvant exemestane and may be useful for predicting treatment outcomes of AI treatment at an early stage in patients treated with neoadjuvant AIs. [ABSTRACT FROM AUTHOR]

Background In 2007 the St. Gallen consensus panel defined three endocrine response classes: highly endocrine responsive (ER-H), incomplete endocrine responsive (ER-I) and non-endocrine responsive tumours (ER-N). However, it is uncertain whether ER-I tumours are less responsive than ER-H tumours. We investigated whether recurrence rates vary over time between response classes. Additionally, we investigated the most predictive response class definition for tamoxifen benefit. Patients and methods We recollected tumours from 646 patients who participated in a randomized trial of adjuvant tamoxifen vs. observation. Estrogen receptor (ER), progesterone receptor (PgR), HER2 status and tumour grade were revised centrally. St. Gallen classes were evaluated for recurrence free interval (RFI). Change in hazards over time was assessed. Subsequently, 6 alternative response class definitions were compared to optimize the cut-off for PgR and ER. Results Schoenfeld residuals indicate a failure of proportional hazards between the endocrine response groups (p = 0.0001). The HR for recurrence risk shifted over time with the ER-H group initially being at lower risk (HR ER-H vs. ER-I 0.5), but after six years the recurrence risk increased (HR 1.9). The cut-off values for ER and PgR that statistically best discriminated RFI in the first 4 years for lymph node positive patients were ER ≥ 50% and PgR ≥ 75%. Conclusion We demonstrated a marked variability in endocrine therapy benefit. Patients with ER-H tumours have a larger benefit during adjuvant tamoxifen and in the first years after accomplishing of the therapy, but suffer from late recurrences. This might have implications for optimal treatment duration. [ABSTRACT FROM AUTHOR]

Abstract: Background: Breast cancer patients with node positive disease can have an excellent outcome with tamoxifen only. It is unclear whether analysing both the 70-gene signature and hormone receptors provides superior prediction of outcome in tamoxifen-treated patients than either alone. Methods: Three series were evaluated: 121 patients (81% node positive) received adjuvant tamoxifen, 151 patients did not receive tamoxifen (10% node positive) and 92 patients received tamoxifen for metastatic disease. The 70-gene signature was analysed using MammaPrint™. Oestrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry was evaluated following St. Gallen Consensus (Highly Endocrine Responsive: ER and PR ≥ 50%, Incompletely Endocrine Responsive: ER and/or PR low or either one absent). Results: In patients treated with adjuvant tamoxifen, both the 70-gene signature (adjusted for Endocrine Response Categories HR 2.17, 95%CI 1.01–4.66) as well as the Endocrine Response Categories (adjusted for 70-gene signature HR 6.35, 95%CI 1.90–21.3) were associated with breast-cancer-specific-survival (BCSS). Also in patients treated with tamoxifen for metastatic disease, combined analysis of the 70-gene signature and ER/PR revealed additional value (multivariate Cox regression, p = 0.013). In patients who did not receive tamoxifen, only the 70-gene signature was associated with outcome. Conclusion: In the series analysed, the 70-gene signature was mainly a prognostic factor, while ER and PR levels were mainly associated with outcome after tamoxifen. Combination of these three factors may improve outcome prediction in tamoxifen-treated patients. [Copyright &y& Elsevier]