Use of Tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer.
BACKGROUND
Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.


METHODS
TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively.


RESULTS
Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).


CONCLUSIONS
The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Shinichiro
S
Kashiwagi
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Yuka
Y
Asano
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Wataru
W
Goto
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Koji
K
Takada
Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Katsuyuki
K
Takahashi
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Satoru
S
Noda
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Tsutomu
T
Takashima
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Naoyoshi
N
Onoda
Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Shuhei
S
Tomita
Department of Diagnostic Pathology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Masahiko
M
Ohsawa
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Kosei
K
Hirakawa
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Masaichi
M
Ohira
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005663:Furans / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D000095662:Polyether Polyketides
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides