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Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers

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Abstract

Purpose

The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2−) BC is still controversial.

Methods

We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2− BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2− BCs.

Results

A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2− BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2− cases with a high TIL score also tended to achieve pCR (p = 0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2− BC (p = 0.034).

Conclusion

Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2− BC.

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Acknowledgements

We would like to thank Editage (www.editage.jp) for English language editing. This study was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 15K10077).

Funding

We do not have a financial relationship with the organization that sponsored the research.

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Authors and Affiliations

  1. Department of Surgical Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan

    Takahiro Watanabe & Seiichi Hirota

  2. Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Akira I. Hida

  3. Department of Pathology, Matsuyama Red Cross Hospital, 1 Bunkyo, Matsuyama, Ehime, 790-8524, Japan

    Akira I. Hida

  4. Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan

    Natsuko Inoue, Michiko Imamura, Yukie Fujimoto & Yasuo Miyoshi

  5. Department of Medical Informatics, Niigata University Medical and Dental Hospital, Chuo-ku, Niigata, Japan

    Kouhei Akazawa

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  1. Takahiro Watanabe
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  2. Akira I. Hida
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Correspondence to Yasuo Miyoshi.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the ethics committee of the Hyogo College of Medicine (approval number #1886).

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Watanabe, T., Hida, A.I., Inoue, N. et al. Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers. Breast Cancer Res Treat 168, 135–145 (2018). https://doi.org/10.1007/s10549-017-4575-z

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