Pretreatment Absolute Lymphocyte Count and Neutrophil-to-lymphocyte Ratio Are Prognostic Factors for Stage III Breast Cancer

Yamanouchi, Kaoru; Maeda, Shuichi; Takei, Daiki; Koga, Yasushi; Yamashita, Masaru; Hamada, Takashi; Hirayama, Takanori; Yoneda, Akira; Tokunaga, Takayuki; Takeshita, Hiroaki; Kuroki, Tamotsu

doi:10.21873/anticanres.15151

Cited by 11 publications

(10 citation statements)

References 36 publications

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“…1,2 Local immune cell responses to breast tumors are well characterized and are associated with cancer progression and survival. [3][4][5][6][7] Peripheral blood leukocyte profiles measured after diagnosis may also be associated with prognosis, [8][9][10] but whether leukocyte subtypes are altered before diagnosis remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Prediagnostic Immune Cell Profiles and Breast Cancer

Kresovich

O’Brien

et al. 2020

JAMA Netw Open

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IMPORTANCE Higher overall leukocyte counts in women may be associated with increased risk of breast cancer, but the association of specific leukocyte subtypes with breast cancer risk remains unknown. OBJECTIVE To determine associations between circulating leukocyte subtypes and risk of breast cancer. DESIGN, SETTING, AND PARTICIPANTS Between 2003 and 2009, the Sister Study enrolled 50 884 women who had a sister previously diagnosed with breast cancer but were themselves breast cancer free. A case-cohort subsample was selected in July 2014 from the full Sister Study cohort. Blood samples were obtained at baseline, and women were followed up through October 2016. Data analysis was performed in April 2019. MAIN OUTCOMES AND MEASURES The main outcome was the development of breast cancer in women. Whole-blood DNA methylation was measured, and methylation values were deconvoluted using the Houseman method to estimate proportions of 6 leukocyte subtypes (B cells, natural killer cells, CD8 + and CD4 + T cells, monocytes, and granulocytes). Leukocyte subtype proportions were dichotomized at their population median value, and Cox proportional hazard models were used to estimate associations with breast cancer. RESULTS Among 2774 non-Hispanic white women included in the analysis (mean [SD] age at enrollment, 56.6 [8.8] years), 1295 women were randomly selected from the full cohort (of whom 91 developed breast cancer) along with an additional 1479 women who developed breast cancer during follow-up (mean [SD] time to diagnosis, 3.9 [2.2] years). Circulating proportions of B cells were positively associated with later breast cancer (hazard ratio [HR], 1.17; 95% CI, 1.01-1.36; P = .04). Among women who were premenopausal at blood collection, the association between B cells and breast cancer was significant (HR, 1.38; 95% CI, 1.05-1.82; P = .02), and an inverse association for circulating proportions of monocytes was found (HR, 0.75; 95% CI, 0.57-0.99; P = .05). Among all women, associations between leukocyte subtypes and breast cancer were time dependent: higher monocyte proportions were associated with decreased near-term risk (within 1 year of blood collection, HR, 0.62; 95% CI, 0.43-0.89; P = .01), whereas higher B cell proportions were associated with increased risk 4 or more years after blood collection (HR, 1.38; 95% CI, 1.15-1.67; P = .001). CONCLUSIONS AND RELEVANCE Circulating leukocyte profiles may be altered before clinical diagnoses of breast cancer and may be time-dependent markers for breast cancer risk, particularly among premenopausal women.

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Section: Introductionmentioning

confidence: 99%

Prediagnostic Immune Cell Profiles and Breast Cancer

Kresovich

O’Brien

et al. 2020

JAMA Netw Open

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“…It has long been established that immune cells play a fundamental role in controlling the initiation and progression of cancer 4 , 5 and that lymphocytes are the main source of adaptive antitumor immune responses. 4 In line with these findings, the peripheral absolute lymphocyte count (ALC) was reported to have an important prognostic role in many cancers, including gastric cancer, 6 pancreatic cancer, 7 breast cancer, 8 and CRC. 9 , 10 However, it is notable that ALC is limited due to its low efficacy in predicting the outcome of CRC.…”

Section: Introductionmentioning

confidence: 81%

Preoperative Absolute Lymphocyte Count to Carcinoembryonic Antigen Ratio Is a Superior Predictor of Survival in Stage I to III Colorectal Cancer

Zhou

Cheng

Zhang

et al. 2022

Clin Med Insights Oncol

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Background: Preoperative absolute lymphocyte count (ALC) and carcinoembryonic antigen (CEA) are useful prognostic indicators in colorectal cancer (CRC); however, the role of the ALC-to-CEA ratio (LCR) has been less addressed. Methods: A total of 189 stage I to III CRC patients who underwent radical resection were enrolled retrospectively. The significance of the LCR in predicting disease-free survival (DFS) and overall survival (OS) was calculated and compared with other markers based on ALC. The DFS and OS differences among the low- and high-LCR subgroups and risk factors for the outcome were estimated by Kaplan–Meier analysis and the Cox proportional hazards model, respectively. Results: Taking 0.28 as the cutoff point, the LCR has a sensitivity and a specificity of 75.60% and 77.00%, respectively, in predicting OS. The prognostic efficacy of LCR was significantly superior to that of other markers based on ALC for predicting DFS and OS. A total of 34.92% (66/189) of patients displayed a low LCR (<0.28), and these patients were more likely to present poor cell differentiation ( P = .03), tumor deposits ( P < .01) and advanced T ( P < .01) and liver metastasis ( P = .02). Patients with a low LCR had significantly worse DFS (Log Rank = 34.98, P < .01) and OS (Log Rank = 43.17, P < .01) than those with a high LCR. The LCR was an independent prognostic factor for both DFS (hazard ratio (HR) = 0.35, 95% confidence interval (CI): 0.20-0.62, P < .01) and OS (HR = 0.18, 95% CI: 0.08-0.37, P < .01). Conclusions: The LCR is a superior predictor of survival in stage I to III CRC, and patients with a low LCR have an inferior outcome; however, additional studies are required to validate its prognostic role.

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“…NLR is an established prognostic predictor in various human cancers (9). For breast cancer, a systematic review conducted by Corbeau et al (10) revealed that the majority of studies showed negative prognostic correlation between all survival outcomes (DFS, BCSS and OS) and a high NLR (11)(12)(13), including in cohorts of patients receiving NAC (14,15). TIL is a predictor of response to NAC (16), and a robust prognostic factor for both treatment-naive and post-neoadjuvant chemotherapy breast cancers (17)(18)(19), and is recognized as an important histologic feature for breast cancer classi cation in the latest World Health Organization classi cation of tumours of the breast (20).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-lymphocyte ratio reflects tumor infiltrating lymphocytes, tumor associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy

Tsang

et al. 2023

Preprint

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Introduction The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumor microenvironment, tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aims to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Methods A cohort of breast cancer patients receiving NAC with subsequent was retrieved. Clinical data were reviewed. Histologic slides and CD8 immunohistochemistry from biopsy (pre-chemotherapy) and excision (post-chemotherapy) specimens were assessed for TILs and TAMs. Results Totally 146 patients were included. There was significant positive correlation between pre-chemotherapy and post-surgery NLR at a cutoff of 2.6 (median pre-chemotherapy NLR) (p<.001). NLR pre-chemotherapy was associated positively with necrosis on biopsy (p=.027) and excision (p=.021) and TAMs on excision (p=.049). NLR one-year post-surgery was associated with high tumor stage (p=.050) and low histologic grade (p=.008). TIL count was lower in NLR-high cases at nearly all time points, by histologic assessment and CD8 immunostaining (p<.050). In multivariate analysis, post-surgery NLR is an independent predictor for overall survival (OS) (HR=9.524, p<.001), breast cancer specific survival (BCSS) (HR=10.059, p=.001) and disease-free survival (DFS) (HR=2.824, p=.016). Conclusion The association between NLR with tumor necrosis, TAM and TIL illustrates an interaction between the circulating and local immune microenvironment. Late NLR is a strong indicator of outcome and may be useful for prognostication and disease monitoring.

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Pretreatment Absolute Lymphocyte Count and Neutrophil-to-lymphocyte Ratio Are Prognostic Factors for Stage III Breast Cancer

Cited by 11 publications

References 36 publications

Prediagnostic Immune Cell Profiles and Breast Cancer

Prediagnostic Immune Cell Profiles and Breast Cancer

Preoperative Absolute Lymphocyte Count to Carcinoembryonic Antigen Ratio Is a Superior Predictor of Survival in Stage I to III Colorectal Cancer

Neutrophil-lymphocyte ratio reflects tumor infiltrating lymphocytes, tumor associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy

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