Published in:
01-04-2018 | Letter to the Editor
Is Ki67 still a powerful ally in predicting the clinical benefit of anthracyclines for the adjuvant treatment of early breast cancer?
Published in: Breast Cancer Research and Treatment | Issue 3/2018
Login to get accessExcerpt
Curigliano and Criscitiello analyzed the clinical benefit of anthracyclines in addition to taxanes in the adjuvant treatment of early breast cancer [1]. The authors stated that there are still no definitive markers of sensitivity to anthracyclines. Some authors studied the role of conventional and other new biological markers to predict response to anthracyclines in different subsets of breast cancer patients. Viale and colleagues reported that among 1521 patients with endocrine-responsive tumors, a high Ki67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone [2]. Neither Ki67 nor TOP2A expression or gene alterations showed a clear predictive value for benefit from the addition of the anthracycline. Our team demonstrated that epirubicin-containing regimens are superior to cyclophosphamide-methotrexate-fluorouracil (CMF) alone in patients with highly proliferating (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-off values of 10, 14, and 20% (Table 1). This means that an anthracycline-based treatment is necessary in patients with more aggressive disease.
Table 1
Hazard ratio (HR) for DFS and OS comparing epirubicin (EPI) followed by CMF and CMF followed by EPI with CMF alone in relation to Ki67 levels
|
EPI → CMF + CMF → EPI
|
CMF
|
HR (95% CI)
|
p*
|
|
|---|---|---|---|---|
|
% 5-year DFS (95% CI)
|
% 5-year DFS (95% CI)
|
|||
|
Ki67
|
||||
|
≤ 10%
|
87 (78–96)
|
82 (64–100)
|
0.62 (0.20–1.88)
|
0.398
|
|
> 10%
|
82 (79–86)
|
74 (66–82)
|
0.67 (0.46–0.99)
|
0.044
|
|
≤ 14%
|
89 (81–97)
|
86 (72–100)
|
0.70 (0.23–2.13)
|
0.532
|
|
> 14%
|
82 (78–86)
|
73 (65–82)
|
0.65 (0.44–0.95)
|
0.028
|
|
< 20%
|
89 (84–95)
|
85 (75–95)
|
0.55 (0.26–1.16)
|
0.116
|
|
> 20%
|
82 (78–86)
|
68 (60–77)
|
0.53 (0.36–0.79)
|
0.002
|
|
EPI → CMF + CMF → EPI
|
CMF
|
HR (95% CI)
|
p*
|
|
|---|---|---|---|---|
|
% 5-year OS (95% CI)
|
% 5-year OS (95% CI)
|
|||
|
Ki67
|
||||
|
≤ 10%
|
96 (90–100)
|
94 (83–100)
|
0.67 (0.11–4.08)
|
0.665
|
|
> 10%
|
92 (89–95)
|
88 (82–94)
|
0.58 (0.34–0.98)
|
0.040
|
|
≤ 14%
|
96 (91–100)
|
95 (87–100)
|
0.76 (0.13–4.62)
|
0.769
|
|
> 14%
|
92 (89–95)
|
87 (81–93)
|
0.56 (0.33–0.94)
|
0.030
|
|
< 20%
|
97 (94–100)
|
96 (90–100)
|
0.33 (0.09–1.24)
|
0.100
|
|
> 20%
|
92 (89–95)
|
83 (76–90)
|
0.45 (0.27–0.77)
|
0.003
|