br Fig e The proportions of included patients administered

Fig. 2 e The proportions of included patients administered adjuvant systemic treatments. (A) CHT regimens in patients with luminal A subtype disease. (B) CHT regimens in patients with luminal B subtype disease. (C) ET period for all included patients. (D) ET regimens for all patients. (Color version of figure is available online.)
risk factors in the CHT/ET group than in the ET-alone group (Supplementary Fig. 2A-C).
Discussion
Our study assessed IHC and clinicopathological features to evaluate whether patients with early-stage HR-positive BC with negative Trehalose 6-phosphate node involvement could benefit from CHT. Although the tumors in the CHT/ET group had more aggressive biological behaviors compared with those of the ET-alone group, there were no significant differences in DFS and OS between the two groups, and the DFS rate in the CHT/ET group was slightly better than that in the ET-alone group. Therefore, CHT improved the DFS of some patients. Subgroup analysis to identify these benefitting patients revealed that PR 20%, HER2 overexpression, stage T1c, and histologic grade 3 BC may benefit from CHT. To determine whether these four risk factors were 
independent, we divided the patients into five groups ac-cording to the numbers of risk factors and found no sig-nificant differences in DFS rates in those with 0 or 1 of these four risk factors. However, patients with at least two risk factors may benefit from CHT. Therefore, these four parameters combined may predict the benefit of CHT. In other words, young patients with HR-positive and stage pT1N0 BC may be exempt from CHT (i.e., ET alone is enough) if they have up to one of the four risk factors (PR 20%, HER2 overexpression, stage T1c, or histological grade 3) because CHT does not improve their OS or DFS; otherwise, CHT should be required.
HR-positive BC is divided into luminal A and luminal B types. The results of the DBCG77B study showed no signifi-cant differences in the 10-y DFS and 25-y OS rates of patients with luminal A BC regardless of CHT administra-tion.16,18 These findings indicate that early-stage luminal A type BC patients do not benefit from CHT. The latest anal-ysis of the results of the Danish study also showed that
Fig. 3 e KaplaneMeier curves showing the overall (A) and disease-free (B) survival with respect to adjuvant chemotherapy. (Color version of figure is available online.)
Fig. 4 e Subgroup analysis of the treatment benefit in breast cancer patients treated with CHT/ET or ET alone. (Color version of figure is available online.)
Fig. 5 e (A) KaplaneMeier curves of the disease-free survival in relation to CHT in HER2 overexpression, (B) histological classification 3, (C) T1c, and (D) PR£ 20%. (Color version of figure is available online.)
premenopausal luminal A BC patients do not benefit from CHT (hazard ratio ¼ 1.07, P < 0.05), even if they have lymph node involvement.19 However, a former study defined luminal A type BC as ER-positive, with a PR-positivity rate higher than 10%. Furthermore, the common limitation of the two studies was that the CHT regimens were cyclo-phosphamide or cyclophosphamide, methotrexate, and 5-fluorouracil only and did not contain anthracycline or tax-ane, which are routinely used today. Therefore, the direct significance of these studies is limited. In the present study, we also observed no benefit for patients with luminal A BC who underwent CHT. However, luminal A patients with PR-positivity rates lower than 20% BC could benefit from CHT if they also had a diameter of T1c or histological grade 3. PR is considered a part of the post-ER pathway, and the presence of PR is believed to reflect the functionality of the ER. Thus, the PR status could predict the benefit of CHT to a certain extent.20 In ER-positive BC, PR status is also used as a positive prognostic marker of