br HR positive BC is divided into luminal A and
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 BAY-598 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
disease outcome.21 A lower PR-positivity rate is an indicator of poor prognosis in BC; therefore, CHT is necessary for these patients.22-24
The other type of HR-positive BC, luminal B, is defined as ER or PR positive, HER2 overexpressing, and high Ki67 status. HER2 overexpression is correlated with more aggressive tumor growth, a poorer prognosis, and a reduced OS.25 Ac-cording to the National Comprehensive Cancer Network, patients with HER2-overexpressing BC, especially with a tumor diameter greater than 0.5 cm, require CHT and anti-HER2 therapy.6,26 However, in the present study, the boundary of tumor diameter was 1 cm, indicating that only patients with a tumor diameter larger than 1 cm and with HER2 overexpression should undergo CHT. The results of the present study provide more accurate CHT indications for patients with HER2-positive BC with a tumor diameter be-tween 0.5 and 1 cm. Patients may be exempt from CHT except for those with a histological grade 3 or with a PR positivity below 20%.
Fig. 6 e Kaplan-Meier curves of the disease-free survival in relation to CHT with respect to the number of patient risk factors.
(A) No risk factors. (B) One risk factors. (C) Two risk factors. (D) Three or four risk factors. (Color version of figure is available online.)
A subgroup of luminal B BC shows high expression levels of Ki67, indicating a large number of mitotic cells. Many studies have suggested Ki67 as an independent pre-dictor of BC prognosis. Ki67 is also apparently correlated to the differentiation, infiltration, and lymphatic metastasis of BC.27-30 However, these studies could only conclude that Ki67 is related to prognosis and is not an indicator of the potential benefit of CHT. Although only early-stage BC was included in our study, Ki67 was not related to prognosis and patients with high levels of Ki67 did not benefit from CHT. Therefore, Ki67 level should not be considered an indicator for CHT.
Histological grade 3 refers to very low tumor cell nucleus stage and cell, indicating that the cancer will metastasize easily and there will be a need for systemic CHT.31 In our study, we also observed that patients with histological grade 3 could benefit from CHT. Since the 2015 St. Gallen IEC, histo-logical grade 3 has been considered a high-risk factor for relapse in HR-positive BC patients. CHT is recommended for these patients,31 which is concordant with our findings. However, to a certain degree, histological grade 3 was not enough to show the potential benefit of CHT in our study, in contrast to the 2015 St. Gallen IEC. We should also consider other risk factors for patients with histological grade 3 when choosing indications for CHT.
As HR-positive BC had a better prognosis, especially among early-stage patients with negative lymph node involvement, the follow-up period of our study (median: 56 mo) was rela-tively short. Another limitation was that the CHT and ET regimens in our study had no uniform standard. Therefore, more prospective randomized controlled studies and subse-quent extensive analyses are warranted.