ABSTRACT
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.
Subject(s)
Androstadienes/adverse effects , Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Hot Flashes/chemically induced , Musculoskeletal Diseases/chemically induced , Neoadjuvant Therapy , Aged , Aged, 80 and over , Arthralgia/chemically induced , Arthritis/chemically induced , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/diagnostic imaging , Carcinoma, Lobular/metabolism , Disease-Free Survival , Female , Humans , Joint Diseases/chemically induced , Logistic Models , Magnetic Resonance Imaging , Mammography , Mastectomy , Middle Aged , Multivariate Analysis , Myalgia/chemically induced , Odds Ratio , Osteoporosis/chemically induced , Postmenopause , Prognosis , Receptors, Estrogen/metabolism , Treatment Outcome , Ultrasonography, Mammary , Vasomotor SystemABSTRACT
INTRODUCTION: The tumor-associated stroma is of importance for tumor progression and is generally accepted to have a significant influence on patient prognosis. However, little is known regarding specific features of tumor-associated stromal tissues and response to (neoadjuvant) chemotherapy. This study investigated the predictive value of extracellular matrix organization on response to chemotherapy in patients treated in the NEOZOTAC trial. METHODS: Stromal organisation was analyzed via a simple method using image analysis software on hematoxylin and eosin (H&E)-stained slides from primary tumor biopsies collected as part of the NEOZOTAC trial. Heidenhain's AZAN trichrome-stained slides were also analyzed for comparison of collagen evaluation. Sections were stained for phospho-Smad2 (pS2) in order to determine the relationship of TGF-ß signaling with stromal organization. RESULTS: A statistically significant relationship was observed between stroma consisting of organised collagen and pathological response to neoadjuvant chemotherapy (Odds Ratio 0.276, 95%CI 0.124-0.614, P = 0.002). This parameter was also related to ER-status (P = 0.003), clinical tumor -status (P = 0.041), nodal status (P = 0.029) and pS2 status (P = 0.025). Correlation between stromal organisation determined on H&E-stained and AZAN-stained tissue sections was high (Pearson's correlation coefficient = 0.806). CONCLUSION: Intratumoral stromal organisation determined using pre-treatment breast cancer biopsies was related to pathological response to chemotherapy. This parameter might play a role in the management of breast cancer for identifying those patients that are likely to benefit from neoadjuvant chemotherapy.
