Vol.:(0123456789) 1 3 Breast Cancer Research and Treatment https://doi.org/10.1007/s10549-017-4630-9 LETTER TO THE EDITOR Is Ki67 still a powerful ally in predicting the clinical beneft of anthracyclines  for the adjuvant treatment of early breast cancer? Sara Bravaccini 1  · Andrea Rocca 1  · Giuseppe Bronte 1 Received: 28 November 2017 / Accepted: 18 December 2017 © Springer Science+Business Media, LLC, part of Springer Nature 2018 Curigliano and Criscitiello analyzed the clinical beneft of anthracyclines in addition to taxanes in the adjuvant treat- ment of early breast cancer [1]. The authors stated that there are still no defnitive markers of sensitivity to anthracyclines. Some authors studied the role of conventional and other new biological markers to predict response to anthracyclines in diferent subsets of breast cancer patients. Viale and col- leagues reported that among 1521 patients with endocrine- responsive tumors, a high Ki67 labeling index did not predict the relative efcacy of chemoendocrine therapy compared with endocrine therapy alone [2]. Neither Ki67 nor TOP2A expression or gene alterations showed a clear predictive value for beneft from the addition of the anthra- cycline. Our team demonstrated that epirubicin-containing regimens are superior to cyclophosphamide-methotrexate- fuorouracil (CMF) alone in patients with highly prolifer- ating (Ki67 > 20%), triple negative or triple unfavorable tumors (ER-, PgR-, Ki67 > 20%) [3]. Moreover, we found that the advantage in terms of disease-free survival (DFS) and overall survival (OS) of an anthracycline based adjuvant treatment was evident in patients with high Ki67 at cut-of values of 10, 14, and 20% (Table 1). This means that an anthracycline-based treatment is necessary in patients with more aggressive disease. Unfortunately, the combination of anthracycline with a taxane was not analyzed in our study. Curigliano and Criscitiello reported that the data on the use of TOP2A gene amplifcation to select patients for treat- ment with anthracyclines are still controversial [1]. Since TOP2A gene amplifcation is a proliferative marker and has not been shown to be a real predictive marker, perhaps Ki67 could represent a more suitable biomarker. It’s determina- tion is inexpensive and easy to perform and, despite some reproducibility and standardization issues, seems easy to be analyzed/interpreted in all laboratories. The assessment of TOP2A amplifcation requires more complicated tools (i.e., reagents, instruments) and a higher level of expertise of the pathologist. Assessment of TOP2A amplification by fluorescent in situ hybridization does not allow a new or centralized reading by the same or a second observer after a certain  time period. Moreover, the role of chromosome 17 polisomy is still unclear. Although a defnitive Ki67 cut-of has not been estab- lished, it could nevertheless be a suitable candidate as a predictive marker in the comparison between taxane only and an anthracycline-taxane combination. * Sara Bravaccini sara.bravaccini@irst.emr.it 1 Istituto Scientifco Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola (FC), Italy