Abstract
BackgroundIt has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer.MethodsA total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed.ResultsThe pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1–2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy.ConclusionsThis retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.
Highlights
It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer
Systemic treatment for triple-negative breast cancer (TNBC) has been restricted mainly to conventional chemotherapy in the past [8,9,10, 14, 17], but new targeted therapies such as immune-checkpoint inhibitors [18] and poly-adenosine diphosphate ribose polymerase (PARP) inhibitors [19, 20] have been under investigation in clinical trials, which are suitable for subgroups of TNBC patients with a germline BRCA1/2 mutation or a homologous recombination deficiency (HRD) in the tumor [7, 14, 21, 22]
TNBC is associated with an increased deoxyribonucleic acid (DNA)-repair defect in the tumor cells, which is caused either by germline mutations in genes such as BRCA1/2, PALB2, and others [23, 24] or by a somatic HRD, which can be exploited by systemic therapies [21]
Summary
Patient selection Patients selected for this study were treated for invasive TNBC with neoadjuvant chemotherapy at the University Breast Center of Franconia at Erlangen University Hospital between 2008 and 2013. The cut-off point for high proliferation determined by Ki-67 staining was regarded as more than 35% positively stained cells, in accordance with a biological analysis presented previously. This cut-off value of Ki-67 was chosen because it distinguished the response to chemotherapy best in TNBC [46]. Tumors with a 2+ staining score were tested for gene copy numbers of HER2 by chromogene in-situ hybridization. All analyses were carried out using the R system for statistical computing (version 3.3.2, 2016; R Core Team, Vienna, Austria)
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