The prognostic impact of neutrophil-lymphocyte ratio (NLR) in metastatic breast cancer (MBC) has been previously evaluated in early and metastatic mixed breast cancer cohorts or without considering other relevant prognostic factors. Our aim was to determine whether NLR prognostic and predictive value in MBC was dependent on other clinical variables. We studied a consecutive retrospective cohort of patients with MBC from a single centre, with any type of first line systemic treatment. The association of NLR at diagnosis of metastasis with progression free survival (PFS) and overall survival (OS) was evaluated using Cox univariate and multivariate proportional hazard models. In the full cohort, that included 263 MBC patients, a higher than the median (>2.32) NLR was significantly associated with OS in the univariate analysis (HR 1.36, 95% CI 1.00–1.83), but the association was non-significant (HR 1.12, 95% CI 0.80–1.56) when other clinical covariates (performance status, stage at diagnosis, CNS involvement, visceral disease and visceral crisis) were included in the multivariate analysis. No significant association was observed for PFS. In conclusion, MBC patients with higher baseline NLR had worse overall survival, but the prognostic impact of NLR is likely derived from its association with other relevant clinical prognostic factors.
Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.
Physicians must be mindful of the importance of emotional support and individual characteristics when communicating treatment options, benefits, and adverse effects of each alternative to oncological patients.
e12524 Background: Nodal micrometastatic disease (ypN1mic) after neoadjuvant chemotherapy (nCT) for breast cancer (BC) is considered an indication for axillary lymph node disection. While pN1mic prognostic impact has been extensively studied, the prognostic impact of ypN1mic disease is uncertain and these patients are usually grouped together with nodal macrometastatic disease. Since outcomes may be difficult to evaluate in the setting of BC residual disease, our aim was to compare the prognostic meaning of ypN1mic with that of ypN0 when a pCR is obtained in the breast. Methods: We retrospectively analyzed a series of 454 BC consecutive patients treated between 2010 and 2018 with neoadjuvant chemotherapy (nCT) based on anthracyclines and taxanes (plus antiHER2 treatment when appropriate). Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients with pre-nCT sentinel lymph node biopsy or without post-nCT pathologic evaluation were excluded. Disease free (DFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox regression models. Results: 454 BC patients were included, with 106 (24%) pCR. Median follow-up was 39 months. 99 (21.8%) patients obtained a pCR both in breast and axilla (ypT0/Tis ypN0), with 4 recurrences (4%) while only 7 (1.5%) patients had isolated nodal micrometastatic disease (ypT0/Tis ypN1mic), with 2 recurrences (28%). Median DFS was not reached for the ypN0 group and was 28 months (95%CI: 21.6-34.4 months) for the ypN1mic group (HR: 16.55, 95%cI: 2.68-102.37; p = 0.003). No differences were observed for OS (p = 0.77), although 2/2 ypN1mi showed distant recurrence (2/4 for ypN0 patients). Baseline clinical and pathologic characteristics were comparable between both groups, with no differences in performance status (p = 0.45), clinical nodal stage (p = 0.48), HER2 (p = 0.32), estrogen receptors (p = 0.93), grade (p = 0.34), presence of carcinoma in situ (0.60) or clinical complete response (p = 0.42). Clinical characteristics of patients with recurrence were also similar (100%: clinically positive nodes, negative estrogen receptors, no clinical complete response). Conclusions: Residual nodal micrometastatic disease after nCT seems to be associated with a higher risk of recurrence. Although longer follow-up and larger series are needed to confirm our data, these results support the escalation of post-nCT treatment even in patients with ypN1mic and breast pCR.
e12559 Background: MicroRNAs are involved in cancer biology through their role in regulation of protein expression. The miR-200 family plays a dual role in breast cancer (BC), both regulating epithelial to mesenchymal transition and promoting metastatic colonization. Plasma levels of miR-200 have been previously evaluated as prognostic factors in early and metastatic BC (MBC) but its role as a potential diagnostic marker is less well established. The aim of this study was to determine the potential diagnostic value of miR-200c-3p plasmatic levels in women with locally advanced and metastatic BC. Methods: We included 73 BC patients and 14 controls. Plasma samples were obtained at diagnosis, before treatment. RNA from plasma samples was extracted with NucleoSpin miRNA plasma (Macherey-Nagel). We analyzed expression levels of miR-200c-3p, which were relativized (2-ΔΔCT method) to miR-16. Non-parametric statistical tests were used to determine the association of miR-200c levels with clinical variables. Receiver-operating curves (ROC) were constructed and diagnostic ability evaluated. Kaplan-Meier curves and Cox models were used for survival analyses. Results: 73 BC patients were included: 36 locally advanced BC (LABC) and 37 MBC (7 recurrences and 30 MBC at initial diagnosis [MBCID]). Plasma miR-200c levels were significantly higher in MBC than in controls (p = 0.001) and in LABC (p = 0.001). We found differences neither for age nor for estrogen receptors, HER2, tumor subtype or histology. Overall and disease free survival did not differ by miR-200c levels in any of the groups. Among MBC patients, higher levels were observed in MBCID (p = 0.023). In the group of women with an initial diagnosis of BC (n = 65), high miR-200c levels (over 1st tertile) identified metastatic disease with a sensitivity of 90.0% (95%CI: 72.3-97.4%) and a specificity of 51.4% (95%CI: 34.3-68.3%); negative predictive value: 85.7%; positive predictive value: 61.4%; ROC AUC: 0.79. Conclusions: MiR-200c plasma levels are higher in BC patients with metastatic disease at diagnosis, and might be clinically useful to identify them. Further research on miR200c biological role in MBC and validation in larger populations with sequential samples are warranted.
Introduction and objectives: Tumor infiltrating lymphocytes (TILs) and neutrophil-to-lymphocyte ratio (NLR) play a prognostic role in early stage breast cancer (BC). There is no evidence about the combined effect of both factors. Our objective was to evaluate the integrated clinical significance of TILs and NLR in patients with early BC treated with neoadjuvant therapy. Materials and methods: Retrospective, single-center analysis of a cohort of patients with early BC treated with neoadjuvant chemotherapy between 2001-2010. Pre-treatment TILs (CD3+-TIL count) was evaluated using a tumor tissue microarray. NLR was calculated within one month of cancer diagnosis. TILs (logarithmic transformed) and NLR were analyzed as continuous variables. Survival analysis was performed using multivariable Cox regression models. Results:A total of 121 patients were included. Median age: 56 years. Cancer stage at diagnosis: 16% IIA, 28% IIB, 33% IIIA, 7% IIIB and 16% IIIC. Molecular subtype: 64% hormone receptor(HR)-positive (12% HER2-positive), 11% HER2-positive HR-negative and 22% triple-negative. Pathological complete response (pCR): 16.5%. Median follow-up: 12 years. Pre-treatment TIL analysis was available in 71 patients (59%) and NLR in 101 (83%). There was no correlation between both variables (Spearman's Rho: 0.03, p = 0.98). In the univariate analysis, the NLR showed a negative prognostic value for overall survival (OS) (HR 1.23, 95%CI 1.11-1.36; p <0.001, C-index: 0.64 95%CI 0.52-0.77, p = 0.69). The effect was opposite for TILs (HR: 0.76 95%CI 0.61-0.95, p = 0.02; C-index: 0.69 95%CI 0.57-0.81, p = 0.69). The linear approximation was adequate, and there was no suspicion of non-proportionality of the hazards. In the multivariate analysis, including or not cancer staging after neoadjuvant therapy, NLR remained as an independent variable (HR 1.18, 95%CI 1.04-1.33; p = 0.01) and a statistic trend for TILs was also observed (HR 0.83, 95%CI 0.65-1.07; p = 0.16). Given the limited sample size, the multivariate analysis did not provide clear evidence of an additive effect. Nevertheless, the combined analysis of both parameters showed a better fit with respect to the two variables separately (Akaike Information Criterion for the combined model, for TILs and for NLR: 106, 133 and 214, respectively). Conclusion:The integrated characterization of TILs and NLR identifies different prognostic subgroups in early BC patients receiving neoadjuvant chemotherapy. Future validation of these findings in large, multicenter cohorts might allow treatment optimization by means of new strategies such as immunotherapy. Citation Format: Esmeralda García-Torralba, Francisco Ayala de la Peña, Beatriz Alvarez-Abril, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa Garcia Garre, Gema Marin Zafra, Alberto Carmona-Bayonas, Elena Garcia Martinez. Prognostic significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with breast cancer receivingneoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-45.
Introduction and objectives Pathologic complete response (pCR, ypT0/Tis ypN0) after neoadjuvant chemotherapy (nCT) in early breast cancer (BC) is associated with higher survival rate. Controversy about the prognostic significance of low-volume or micrometastatic axillary residual disease (ypN1mi-RD) exists. Essentially, it is considered equivalent to high-volume nodal disease (ypN1/ypN2-RD) for the indication of lymphadenectomy after nCT. Clarifying ypN1mi-RD prognostic value would be useful for planning adjuvant therapy. Thus, our objective was to assess the prognostic significance of ypN1mi-RD in the context of primary breast tumor pCR. Material and methodsRetrospective, single-center analysis of a cohort of early BC patients treated with nCT between 2010 and 2018 who achieved breast pCR (ypT0/Tis) combined with axillary pCR (ypN0) or ypN1mi-RD or ypN1/ypN2-RD. Cases with pre-nCT sentinel lymph node biopsy were excluded. 5-year disease-free survival (DFS) and overall survival (OS) were analyzed using Cox regression models.ResultsAmong 470 early BC patients treated with nCT, 134 (28.5%) had in-breast pCR, of whom: 97 (20.6%) were ypN0; 7 (1.5%) were ypN1mic; 10 (2.1%) were ypN1 and 5 (1.1%) were ypN2. Clinicopathological characteristics of the groups are shown in the Table. Median follow-up: 33 months. Eight patients relapsed, 4 of 97 with nodal pCR and 4 of 22 with axillary residual disease: 2/7 ypN1mic; 1/10 ypN1 and 1/5 ypN2. Patients who relapsed predominantly presented pre-nCT clinical lymph node involvement, hormone receptor negativity, ki67<20% and absence of complete clinical response (100%). Globally, patients with axillary residual disease had lower DFS rates (95% vs. 69%, p = 0.03), with no apparent differences between ypN1-RD vs. ypN2-RD in the subgroup analysis (75% vs. 80%, respectively). ypN1mic-RD patients showed the poorest DFS (33%, p <0.01). In the multivariable analysis, ypN1mic-RD had worse DFS than nodal pCR (HR 13.98, 95%CI 1.95-100.24, p = 0.01), but no differences were observed between the low and high-volume residual axillary disease categories (HR 0.24, 95%CI 0.03-1.74, p = 0.16). Due to the low rate of events, no differences in terms of OS were observed (p = 0.77).Conclusion In the context of in-breast pCR after nCT for early BC, ypN1mic-RD not only presented a higher risk of relapse than nodal pCR, but also was not associated with a better prognosis than that observed for ypN1/ypN2-RD. Micrometastatic axillary residual disease behaves as an independent adverse prognostic factor, comparable to high-volume axillary residual disease, and might be considered as a factor for the indication of post-nCT adjuvant treatment. Table. Clinicopathologic characteristics of the cohort of early BC patients treated with nCT betweenypT0/TisypT0/TisypN1mic-RDypN1/N2-RDpCR(N=7)(N=15)(N=97)Age (median, range)49 (25-83)47 (40-77)47 (25-80)Menstrual statusPostmenopausal3 (42,8%)4 (26,7%)42 (43,3%)Premenopausal4 (57,1%)11 (73,3%)55 (56,7%)ECOGECOG 05 (71,4%)13 (86,7%)78 (80,4%)ECOG 12 (28,5%)2 (13,3%)19 (19,6%)Histologic subtypeInvasive ductal carcinoma7(100,0%)14 (93,3%)95 (97,9%)Other subtypes0 (0,0%)1 (6,7%)2 (2,0%)Histologic gradeGrade 10 (0,0%)0 (0,0%)1 (1,0%)Grade 23 (42,9%)5 (33,3%)17 (17,5%)Grade 34 (57,1%)8 (53,3%)67 (69,1%)Unknown0 (0,0%)2 (13,3%)0 (0,0%)cTcT11 (14,2%)4 (26,7%)8 (8,2%)cT24 (57,1%)5 (33,3%)63 (64,9%)cT32 (28,6%)6 (40,0%)24 (24,7%)cT4a-d0 (0,0%)0 (0,0%)2 (2,1%)cNcN01 (14,3%)0 (0,0%)27 (27,8%)cN13 (42,9%)5 (33,3%)34 (35,1%)cN21 (14,3%)6 (40,0%)24 (24,7%)cN32 (28,6%)4 (26,7%)11 (11,3%)Molecular subtypeHR+ HER2-1 (14,3%)8 (53,3%)11 (11,3%)HR+ HER2+3 (42,9%)1 (6,7%)30 (30,9%)HR- HER2+2 (28,6%)3 (20,0%)21 (21,6%)TNBC1 (14,3%)3 (20,0%)35 (36,1%)Breast surgeryConservative7 (100%)10 (66,7%)67 (69,1%)Mastectomy0 (0,0%)5 (33,3%)30 (30,9%)Nodal surgerySLN biopsy0 (0,0%)0 (0,0%)22 (22,7%)ALND7 (100,0%)15 (100,0%)75 (77,3%)ypTypT05 (71,4%)7 (46,7%)80 (82,5%)ypTis2 (28,6%)8 (53,3%)17 (17,5%)Relapse typeMetastatic2 (28,6%)2 (28,6%)2 (2,1%)Local/contralateral0 (0,0%)0 (0,0%)2 (2,1%)Deaths0 (0,0%)1 (6,7%)1 (1,0%)BC: breast cancer. HR: hormone receptor. nCT: neoadjuvant chemotherapy. pCR: pathologic complete response. SLN: sentinel lymph node. TN: triple negative. ypN1mic-RD: micrometastatic axillary residual disease. ypN1/N2-RD: high-volume axillary residual disease. Citation Format: Esmeralda García-Torralba, Maria Esperanza Guirao Garcia, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elena Garcia Martinez, Elisa Garcia Garre, Gema Marin Zafra, Beatriz Alvarez Abril, Esther Navarro Manzano, Francisco Ayala de la Peña. Prognostic significance of residual micrometastatic axillary involvement with complete pathologic breast response after neoadjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-54.
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