Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer

Abstract

Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC. Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts. A total of 1,463 stage I-III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95% confidence interval (CI), 0.16-0.35] and BCM (HR = 0.19; CI, 0.11-0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis ( = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy. Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment. .

Roles of neutrophil/lymphocyte ratio in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy

“…NLR is a routinely available marker of the systemic inflammatory response, and there is no significant difference of NLR value in distinct breast cancer subtype [16]. The presence of higher NLR in the blood has been recognized as a poor prognostic factor among triplenegative BC patients [10,11]. Meanwhile, a metaanalysis suggested that NLR was a good prognostic marker for HER2-positive BC and triple-negative BC, but not for luminal A and luminal B subtype BC [17].…”

“…Nevertheless, there are no authorized biomarkers reflecting systemic immune status [8]. Some studies indicated that low pretreatment neutrophil/lymphocyte ratio (NLR) was predictive factor of better DFS outcome in BC, especially in triplenegative BC patients [10][11][12]. In the HER2-positive subtype, few studies have explored the relationship between NLR and DFS of patients with or without trastuzumab treatment.…”

Roles of neutrophil/lymphocyte ratio in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy

“…NLR is a routinely available marker of the systemic inflammatory response, and there is no significant difference of NLR value in distinct breast cancer subtype [16]. The presence of higher NLR in the blood has been recognized as a poor prognostic factor among triple-negative BC patients [10,11].…”

Roles of neutrophil/lymphocyte ratio in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy

“…NLR is a routinely available marker of the systemic inflammatory response, and there is no significant difference of NLR value in distinct breast cancer subtype [31]. The presence of higher NLR in the blood has been identified as a poor prognostic factor among triple negative BC patients [1,4].…”

“…Nevertheless, there are no authorized biomarkers reflecting systemic immune status [18]. Some studies indicated that low pretreatment neutrophil/lymphocyte ratio (NLR) was predictive factor of better DFS outcome in BC, especially in triple-negative BC patients [1,4,13]. In the HER2-positive subtype, few studies have explored the relationship between NLR and DFS of patients with or without trastuzumab treatment.…”