Prognostic significance of the skeletal muscle index and systemic inflammatory index in patients with lymph node-positive breast cancer after radical mastectomy.

BACKGROUND: The role of skeletal muscle index (SMI) and systemic inflammation index (SII) for patients with lymph node-positive breast cancer remain controversial. This retrospective study aims to evaluate the individual and synergistic value of SMI and SII in outcomes prediction in this population. METHODS: Lymph node-positive breast cancer patients who received mastectomy between January 2011 and February 2013 were included in this retrospective study. We used abdominal computed tomography (CT) to measure skeletal muscle mass at the third lumbar (L3) level. The optimal cut-off values of SMI and SII were determined through maximizing the Youden index on the receiver operating characteristic (ROC) curves. Kaplan-Meier method was used to assess the correlation between SMI, SII, and overall survival (OS). The prognostic value of SMI and SII were analyzed with the multivariable Cox proportional hazards model. RESULTS: Of 97 patients included in our study (mean age: 46 [range: 27-73] years; median follow-up: 62.5 months), 71 had low SMI (sarcopenia), 59 had low SII, and 56 had low SMI + SII. Kaplan-Meier survival curves showed that both high SMI (P = 0.021, 5-year OS: 84.0% vs. 94.1%) and high SII (P = 0.043, 5-year OS: 81.0% vs. 97.3%) were associated with worse OS. Additionally, patients with either low SMI or low SII had significantly better OS (P = 0.0059, 5-year OS: 100.0% vs. 84.6%) than those with high SMI + SII. Multivariable analysis confirmed the predictive values of high SMI (P = 0.024, hazard ratio [HR]: 9.87) and high SII (P = 0.048, HR: 6.87) for poor OS. Moreover, high SMI + SII was significantly associated with poor survival (P = 0.016, HR: 16.36). CONCLUSIONS: In this retrospective analysis, both SMI and SII independently predicted the prognosis of patients with lymph node-positive breast cancer. SMI + SII might be a stronger prognostic factor than either alone based on our findings, but should be further verified in a larger study.

The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer.

BACKGROUND: The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. METHODS: Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. RESULTS: Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642-0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3-4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1-2N1 disease (P = 0.191). CONCLUSIONS: Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3-4N1 and T1-4N2-3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1-2N1 TNBC.

Erratum to prognostic value of skeletal muscle index and monocyte-to-lymphocyte ratio for lymph node-positive breast cancer patients after mastectomy.

[This corrects the article DOI: 10.21037/atm.2019.11.37.].

The preoperative systemic inflammation response index (SIRI) independently predicts survival in postmenopausal women with breast cancer.

The recently developed preoperative systemic inflammation response index (SIRI) was reported as a useful biomarker that could predict survival in certain types of malignant tumors. However, the prognostic value of preoperative SIRI in postmenopausal breast cancer remains unclear. This study aimed to explore the relationship between SIRI and survival in postmenopausal patients with breast cancer. A total of 390 postmenopausal patients with breast cancer who underwent a mastectomy at Sun Yat-sen University Cancer Center were retrospectively studied. SIRI was based on peripheral neutrophil, monocyte, and lymphocyte counts, calculated as: neutrophil count × monocyte count/lymphocyte count. The best cut-off value for SIRI was determined using receiver operating characteristic curve analysis. Patients were divided into 2 groups:Low SIRI < 0.54 and high SIRI > 0.54. High SIRI was significantly related to progesterone receptor status. Kaplan-Meier survival analysis showed that T stage, N stage, clinical stage, carcinoembryonic antigen, estrogen receptor, progesterone receptor, endocrinotherapy, and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI could also independently predict OS. Preoperative SIRI may be a reliable predictor of OS in postmenopausal patients with operable breast cancer to provide personalized prognostication and to assist in the formulation of a clinical treatment strategy.

Prognostic significance of the skeletal muscle index and an inflammation biomarker in patients with breast cancer who underwent postoperative adjuvant radiotherapy.

BACKGROUND: Given the growing evidence that sarcopenia and inflammation influence the survival of patients with cancer, we evaluated the prognostic significance of the skeletal muscle index (SMI) combined with an inflammation marker in patients with breast cancer who underwent postoperative adjuvant radiotherapy. METHODS: We conducted a retrospective analysis of 301 patients with breast cancer who received postoperative adjuvant radiotherapy between 2010 and 2012. The SMI was measured using preradiotherapy computed tomography (CT) simulation images at the level of the fourth thoracic vertebra (T4). Receiver operating characteristic curve analyses were used to determine the optimal cutoff values for the SMI and inflammatory marker. Patients were divided into 2 groups (high SMI and low SMI), based on the SMI cutoff of 10.57 cm2/m2. RESULTS: Patients in the high-SMI group had a median overall survival (OS) of 62.4 months, which was significantly shorter than those in the low-SMI group, with a median OS of 68.5 months (P = 0.025). Patients in the high-SMI group had a median recurrence-free survival (RFS) of 62.3 months, which was shorter but not significantly than the median RFS of 65.2 months of the low-SMI group (P = 0.159). Univariate and multivariate survival analyses revealed SMI was an independent predictor of OS (P = 0.044). The SMI-MLR combination was found to be an independent predictor of OS (P = 0.006) and RFS (P = 0.009). CONCLUSIONS: The current findings support the SMI as a promising indicator for predicting clinical outcomes in patients with breast cancer receiving postoperative adjuvant radiotherapy. A high SMI accompanied by systemic inflammation was significantly associated with reduced OS and RFS.

Prognostic impact of the pretreatment albumin to alkaline phosphatase ratio for nonmetastatic breast cancer patients.

Introduction: Albumin and alkaline phosphatase have been previously demonstrated as independent prognostic factors for various types of cancer. Here, we aimed to explore the potential value of pretreatment albumin to alkaline phosphatase ratio (AAPR) on overall survival (OS) in nonmetastatic breast cancer patients. Methods: A total of 746 nonmetastatic breast cancer patients were enrolled in this study. Receiver characteristic curve was used to analyze the AAPR threshold. Survival analysis was conducted using the Kaplan-Meier method and compared with the log-rank test. Both univariate and multivariate analyses were performed using Cox proportional hazards regression methodology. Results: The optimal cutoff value of AAPR in predicting OS in nonmetastatic breast cancer patients was 0.525. Increased pretreatment AAPR level was related to age at diagnosis (≥60 years vs <60 years, P=0.000), tumor size (T≤2 cm vs T>2 cm, P=0.034), estrogen receptor (positive vs negative, P=0.022), progesterone receptor (positive vs negative, P=0.025), carcino-embryonic antigen (abnormal vs normal, P=0.016), surgery (lumpectomy vs mastectomy, P=0.002), chemotherapy (yes vs no, P=0.004), radiotherapy (yes vs no, P=0.013), endocrine therapy (yes vs no, P=0.027) but not with lymph node involvement, HER-2 status or CA-153. The 5-year OS rate was 80.16% for the low AAPR group and 92.66% for the high AAPR group. Kaplan-Meier analysis indicated that patients with low-AAPR levels had shorter OS than patients with high-AAPR levels (P=0.001). N classification (P<0.05), Ki-67 (HR=3.603, 95% CI=1.046-12.414, P=0.042) and AAPR (HR=0.447, 95% CI=0.205-0.976, P=0.043) were related to OS in multivariate analyses, respectively. Conclusion: AAPR is an independent prognostic factor for OS in nonmetastatic breast cancer patients. Further prospective studies are required to confirm our findings.

21-Gene Recurrence Score Assay Could Not Predict Benefit of Post-mastectomy Radiotherapy in T1-2 N1mic ER-Positive HER2-Negative Breast Cancer.

Introduction: It is still controversial whether post-mastectomy radiotherapy (PMRT) is necessary for women with T1-2 N1mic ER-positive HER2-negative breast cancer. The 21-gene recurrence score (RS) assay has been validated in T1-2 N1 breast cancer to be prognostic of locoregional recurrence (LRR) and overall survival (OS). This study aims to evaluate the predict value of 21-gene recurrence score assay for the benefit of PMRT in T1-2 N1mic ER-positive HER2-negative breast cancer. Methods: A population-based cohort study was performed on women with T1-2 N1mic ER-positive HER2-negative breast cancer who underwent mastectomy and were evaluated using the 21-gene RS in the Surveillance, Epidemiology, and End Results (SEER) registry between 2004 and 2015. Clinical characteristics as well as OS and breast cancer-specific survival (BCSS) were compared between patients with and without PMRT in patients with a Low-, Intermediate-, and High-RS. Multivariate COX regression analysis was performed to investigate if the 21-gene RS assay could predict benefit of PMRT in this group of breast cancer patients. Results: A total of 1571 patients met the criteria of our study and were enrolled, including 970 patients in the Low-Risk group (score <18), 508 in the Intermediate-Risk group (score 18-30), and 93 patients in the High-Risk group (score >30). In the High-Risk group, there were more patients with age ≥50 (87.0 vs. 64.3%, P = 0.040) and received chemotherapy with a borderline significance (91.3 vs. 72.9%, P = 0.066) in the PMRT subgroup than in the no PMRT subgroup. In all three groups, OS was comparable between the PMRT subgroup and the no PMRT subgroup. Furthermore, multivariate analysis did not show any OS benefit for PMRT based on the 21-gene recurrence score. Conclusion: This study showed that the 21-gene RS assay was not able to predict the benefit of PMRT for OS in women with T1-2 N1mic ER-positive HER2-negative breast cancer. However, further prospective larger sample-size trials are warranted to determine if a benefit exists.

Noninferior Outcome After Breast-Conserving Treatment Compared to Mastectomy in Breast Cancer Patients With Four or More Positive Lymph Nodes.

Introduction: We conducted a non-inferiority analysis using real-world data to compare the survival outcomes of stage T1-2N2-3 (tumor size ≤5 cm and four or more node metastases) breast cancer after breast-conserving surgery (BCS) and mastectomy (MAST). Methods: The study included patients with stage T1-2N2-3 invasive breast carcinoma from the Surveillance, Epidemiology, and End Results program, who underwent BCS or MAST between 2004 and 2012, along with both radiotherapy and chemotherapy. The statistical analyses used included the chi-squared test, multivariate Cox proportional hazards models, and propensity score matching (PSM). Results: The study population comprised 13,263 patients, including 4,787 (36.1%) and 8,476 (63.9%) patients who were treated with BCS and MAST, respectively. Patients with younger age and advanced stage were more likely to have received MAST. The probability of receiving MAST increased over the years, while the probability of BCS decreased (p < 0.001). The 5-year breast cancer-specific survival (BCSS) was 86.1% in the BCS cohort compared to 83.1% in the MAST cohort (p < 0.001). Surgical procedure was an independent prognostic factor for BCSS. Patients who received MAST had worse BCSS than those treated with BCS (hazard ratio = 1.179, 95% confidence interval = 1.087-1.278, p < 0.001). These results remained significant after stratification by age, tumor grade, T stage, N stage as well as marital status. Similar results were obtained after PSM. Conclusions: BCS resulted in noninferior outcome than MAST in patients with T1-2/N2-3 invasive breast carcinoma. BCS may therefore be an optimal treatment option when both treatment options are feasible and appropriate.

Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases.

PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). Methods Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed. RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs. CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

Prognostic value of skeletal muscle index and monocyte-to-lymphocyte ratio for lymph node-positive breast cancer patients after mastectomy.

BACKGROUND: We aimed to assess the prognostic value of the skeletal muscle index (SMI) and monocyte-to-lymphocyte ratio (MLR) in lymph node-positive breast cancer patients after mastectomy. METHODS: We enrolled female lymph node-positive breast cancer patients who had undergone mastectomy between January 2011 and December 2013 with lymph node metastasis. Skeletal muscle tissue was measured using computed tomography (CT), and the patients were grouped based on the receiver operating characteristic curves to obtain the cut-off point for SMI; similarly, the optimal cutoff point for the MLR was obtained. Survival analysis was chiefly performed to determine overall survival (OS) among the patients. RESULTS: The median age of the 97 included patients was 46 years (range, 27-73 years), whereas the median follow-up duration was 62.5 months. Of these patients, 71 exhibited low SMI and 66 exhibited high MLR. Kaplan-Meier curves indicated that low SMI (5-year OS, 97.2% vs. 84.6%; log-rank P=0.021) and low MLR (5-year OS, 98.5% vs. 83.9%; log-rank P=0.004) were associated with better OS. Moreover, patients with both high SMI and MLR (high SMLR) had significantly worse OS (5-year OS, 66.7% vs. 96.6%; log-rank P<0.001), relative to the low SMLR group. Multivariate analysis indicated that patients with low SMI had a lower overall dying risk, relative to those with high SMI [hazard ration (HR), 0.188; P=0.038], whereas patients with high MLR had a higher risk of death as compared to those with low MLR (HR, 7.152; P=0.021). Furthermore, SMLR was an independent prognostic factor of poor OS (HR, 13.272; P=0.001). CONCLUSIONS: Low SMI and low MLR are both associated with better OS in lymph node-positive breast cancer patients after mastectomy. SMI combined with MLR (SMLR) may be powerful prognosis factor for OS among these patients.

The Value of Prognostic Nutritional Index (PNI) in Predicting Survival and Guiding Radiotherapy of Patients With T1-2N1 Breast Cancer.

Background: To investigate the significance of the prognostic nutrition index (PNI) as a predictor of survival and guide for treating T1-2N1 breast cancer. Methods: Patients with T1-2N1 breast cancer (N = 380) who underwent a mastectomy at our center were studied. PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm3). The cutoff for the PNI was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the PNI and the clinicopathologic characteristics were analyzed using Pearson's χ2 test. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Results: Subgroup analyses of patients with low PNI value (≤52.0) and high PNI value (>52.0) showed that a high PNI was significantly associated with HER2 status, the neutrophil-lymphocyte ratio (NLR), the monocyte-lymphocyte ratio (MLR), and KI 67 status. The OS of patients with a high PNI was significantly better than that of patients with a low PNI. We then conducted subgroup analyses based on PNI and radiotherapy. Among patients who received radiotherapy, the OS of those with a high PNI was significantly better than that of patients with a low PNI. Among patients with a high PNI, the OS of those who received radiotherapy was better than that of the patients who did not receive radiotherapy. However, among the patients with a low PNI, the OS of those who received radiation was worse than that of patients who did not receive radiotherapy. The Kaplan-Meier survival analysis and the multivariate analysis of patients with T1-2N1 breast cancer who received radiotherapy showed PNI independently predicted OS. Conclusions: The preoperative PNI may be a reliable predictor of OS of patients with operable T1-2N1 breast cancer, with the capacity to provide a personalized prognosis and facilitate the development of clinical treatment strategies. However, radiotherapy did not achieve satisfactory outcomes in patients with PNI ≤52.0; thus, further studies on treatment optimization are needed.