Abstract P1-07-01: HLA class I expression is associated with tumor-infiltrating lymphocytes and response and survival after neoadjuvant chemotherapy in hormone receptor-positive, HER2-negative breast cancer

2018 ◽  
Author(s):  
BV Sinn ◽  
K Weber ◽  
C Denkert ◽  
PA Fasching ◽  
WD Schmitt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Hla Class I ◽  
Class I ◽  
Hormone Receptor Positive ◽  
Infiltrating Lymphocytes

scholarly journals Prediction of Distant Metastatic Recurrence By Tumor-Infiltrating Lymphocytes in Hormone Receptor-Positive Breast Cancer

2021 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Rika Kouhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Distant Metastases ◽  
University Hospital ◽  
Metastatic Recurrence ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Infiltrating Lymphocytes

Abstract Background: Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2- breast cancer.Methods: Four-hundred and seventy-one patients with HR+/HER2- breast cancer underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy) at the Osaka City University Hospital from April 2007 to October 2015. Needle biopsy specimens were obtained from all patients to evaluate tumor morphology and examine TILs. Morphological assessment was conducted using conventional hematoxylin and eosin staining.Results: Breast cancer recurrence was observed in 42 patients. In patients with no TIL density, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2- breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144).Conclusions: Our findings indicate that TILs may predict distant metastatic recurrence in stages I–II of HR+/HER2- breast cancer.

Prediction of distant metastatic recurrence by tumor-infiltrating lymphocytes in hormone receptor-positive breast cancer

2021 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Rika Kouhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Distant Metastases ◽  
University Hospital ◽  
Metastatic Recurrence ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Infiltrating Lymphocytes

Abstract Background: Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2- breast cancer.Methods: Four-hundred and seventy-one patients with HR+/HER2- breast cancer underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy) at the Osaka City University Hospital from April 2007 to October 2015. Needle biopsy specimens were obtained from all patients to evaluate tumor morphology and examine TILs. Morphological assessment was conducted using conventional hematoxylin and eosin staining.Results: Breast cancer recurrence was observed in 42 patients. In patients with no TIL density, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2- breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144).Conclusions: Our findings indicate that TILs may predict distant metastatic recurrence in stages I–II of HR+/HER2- breast cancer.

scholarly journals Prediction of distant metastatic recurrence by tumor-infiltrating lymphocytes in hormone receptor-positive breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Rika Kouhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Distant Metastases ◽  
Breast Cancer Patients ◽  
Metastatic Recurrence ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Infiltrating Lymphocytes

Abstract Background Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2− breast cancer. Methods In stages I–II of HR+/HER2− breast cancer patients who underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy), forty-two patients relapsed after surgery. TILs were evaluated using needle biopsy specimens for the diagnosis of breast cancer. Morphological assessment was conducted using conventional hematoxylin and eosin staining. Results Six patients had no TILs density. In them, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2− breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144). Conclusions Our findings indicate that TILs may predict distant metastatic recurrence in stages I–II of HR+/HER2− breast cancer in patients who do not undergo chemotherapy.

scholarly journals Outcome Prediction after Neoadjuvant Chemotherapy (NAC) for Breast Cancer, using Tumor-Infiltrating Lymphocytes within Fibrotic Foci of Tumor Stroma (FF-TILs)

2021 ◽  
Author(s):  
Yuka Asano ◽  
Shinichiro Kashiwagi ◽  
Rika Kouhashi ◽  
Akimichi Yabumoto ◽  
Koji Takada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Multivariable Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Hormone Receptor Positive ◽  
Close Relationship ◽  
Infiltrating Lymphocytes

Abstract Background: Tumor-infiltrating lymphocytes (TILs), which are indicators for monitoring an immune response, are generally mononuclear immunocytes that aggregate with tumors and are thought to have a close relationship with cancer cells. On the other hand, a fibrotic focus (FF) within the stroma of a tumor is a histological formation that plays an important role in the cancer microenvironment with regard to proliferation and development. Here, we focus on TILs that exist within the FF and we have performed pathological evaluations.Methods: Of the 320 patients were treated with neoadjuvant chemotherapy (NAC), 239 subjects who were able to evaluate FF-TILs were targeted. Lymphocytes that infiltrate the FF are FF-TILs.Results: The disease-free survival (DFS) period after NAC for the high-FF-TIL group was found to be significantly longer than that for the low-FF-TIL group for all cases (p < 0.001) and for all subtypes of triple-negative breast cancer (TNBC) (p = 0.001), human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p = 0.010), and hormone receptor-positive breast cancer (HRBC) (p = 0.003). In multivariable analysis as well, high-FF-TIL group classification was an independent factor for recurrence after NAC for all cases (p < 0.001, hazard ratio (HR) = 0.198) and all subtypes of TNBC (p = 0.006, HR = 0.172), HER2BC (p = 0.025, HR = 0.135), and HRBC (p = 0.007, HR = 0.228).Conclusions: It is suggested that FF-TILs are a useful factor for predicting recurrence of breast cancer after NAC.Article headings: NAC for breast cancer by evaluation of FF-TILs

scholarly journals Prediction of Distant Metastatic Recurrence by Tumor-Infiltrating Lymphocytes in Hormone Receptor-Positive Breast Cancer

2020 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Tamami Morisaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Distant Metastases ◽  
University Hospital ◽  
Metastatic Recurrence ◽  
Cancer Subtypes ◽  
Hormone Receptor Positive ◽  
Infiltrating Lymphocytes

Abstract Background: Breast cancer subtypes are known to have different sites of metastatic recurrence. Distant metastases are often seen during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer (HER2BC) and triple-negative breast cancer (TNBC) while being relatively rare in those with hormone receptor-positive and HER2-negative breast cancer (HR+HER2-BC). Tumor-infiltrating lymphocytes (TILs) can serve as an index to monitor tumor immune microenvironment and possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+HER2-BC.Methods: Four-hundred and seventy-one patients with HR+HER2-BC underwent surgery as the first treatment and received adjuvant endocrine therapy except adjuvant chemotherapy at the Osaka City University Hospital from April 2007 to October 2015. To evaluate tumor morphology and examine TILs, needle biopsy specimens were used. Morphological assessment was conducted using conventional hematoxylin and eosin staining.Results: Forty-two patients had a recurrence of breast cancer. In patients with no TIL density, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+HER2-BC without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144).Conclusions: We concluded that TILs may be able to predict distant metastatic recurrence in stages I–II of HR+HER2-BC.

scholarly journals Human leucocyte antigen class I in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Bruno Valentin Sinn ◽  
Karsten E. Weber ◽  
Wolfgang Daniel Schmitt ◽  
Peter A. Fasching ◽  
William Fraser Symmans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Immune Cell ◽  
Hla Class I ◽  
Class I ◽  
Endocrine Treatment ◽  
Hormone Receptor Positive ◽  
Tumor Immunogenicity

Abstract Background Clinical application of cancer immunotherapy requires a better understanding of tumor immunogenicity and the tumor microenvironment. HLA class I molecules present antigens to CD8+ cytotoxic cells. Their loss or downregulation is frequently found in tumors resulting in reduced T cell responses and worse prognosis. Methods We evaluated HLA class I heavy chain expression by immunohistochemistry in 863 biopsies (GeparTrio trial). Patients received neoadjuvant chemotherapy and adjuvant endocrine treatment if tumors were hormone receptor-positive (HR+). In parallel, the expression of HLA-A was analyzed using a microarray cohort of 320 breast cancer patients from the MD Anderson Cancer Center. We evaluated its association with clinical outcome, tumor-infiltrating lymphocytes (TILs), and immune cell metagenes. Results In HR+/HER2− breast cancer, HLA class I heavy chain expression was associated with increased TILs and better response to chemotherapy (7% vs. 14% pCR rate, P = 0.029), but worse disease-free survival (hazard ratio (HR) 1.6 (1.1–2.4); P = 0.024). The effect was significant in a multivariate model adjusted for clinical and pathological variables (HR 1.7 (1.1–2.6); P = 0.016) and was confirmed by analysis of HLA-A in a microarray cohort. HLA-A was correlated to most immune cell metagenes. There was no association with response or survival in triple-negative or HER2+ disease. Conclusions The study confirms the negative prognostic role of lymphocytes in HR+ breast cancer and points at a complex interaction between chemotherapy, endocrine treatment, and tumor immunogenicity. The results point at a subtype-specific and potentially treatment-specific role of tumor-immunological processes in breast cancer with different implications in triple-negative and hormone receptor-positive disease.

scholarly journals The Immunology of Hormone Receptor Positive Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jonathan Goldberg ◽  
Ricardo G. Pastorello ◽  
Tuulia Vallius ◽  
Janae Davis ◽  
Yvonne Xiaoyong Cui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Hormone Receptor ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Hla Class I ◽  
Breast Tumors ◽  
Immune Checkpoint Blockade ◽  
Response To Therapy ◽  
Hormone Receptor Positive

Immune checkpoint blockade (ICB) has revolutionized the treatment of cancer patients. The main focus of ICB has been on reinvigorating the adaptive immune response, namely, activating cytotoxic T cells. ICB has demonstrated only modest benefit against advanced breast cancer, as breast tumors typically establish an immune suppressive tumor microenvironment (TME). Triple-negative breast cancer (TNBC) is associated with infiltration of tumor infiltrating lymphocytes (TILs) and patients with TNBC have shown clinical responses to ICB. In contrast, hormone receptor positive (HR+) breast cancer is characterized by low TIL infiltration and minimal response to ICB. Here we review how HR+ breast tumors establish a TME devoid of TILs, have low HLA class I expression, and recruit immune cells, other than T cells, which impact response to therapy. In addition, we review emerging technologies that have been employed to characterize components of the TME to reveal that tumor associated macrophages (TAMs) are abundant in HR+ cancer, are highly immune-suppressive, associated with tumor progression, chemotherapy and ICB-resistance, metastasis and poor survival. We reveal novel therapeutic targets and possible combinations with ICB to enhance anti-tumor immune responses, which may have great potential in HR+ breast cancer.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

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