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Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5% (Q1–Q3 range (IQR), 0–10). We found that sTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02–1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33–17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC.

Introduction and objectives Up to 30% of early breast cancer (BC) patients treated with neoadjuvant chemotherapy will have systemic relapse during the follow-up. The integration of clinical, analytical and molecular parameters associated to tumor biology or host immune response could help to better stratify the prognosis of these patients. The aim of this study was to analyze the prognostic ability of immune-related and proliferation markers in combination with clinical parameters in patients with early BC treated with neoadjuvant chemotherapy. Methods and materials Retrospective and single-center cohort of BC patients treated with neoadjuvant chemotherapy between 2001 and 2010. We analyzed the following pre-treatment biological markers: neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and CD3+-tumor-infiltrating lymphocytes (TIL), interferon-gamma and interleukin-10 in tumor samples by using a tissue microarray. Gene expression of AURKA, MYBL2, MKI67 and CTNNB1 in RNA from tumor samples was also evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis was performed using Cox regression. The predictive capacity of the regression models was evaluated using AIC (Akaike Information Criterion) index, ROC curves and Harrell's C statistics. 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-positive (12% HER2-positive), 11% HER2-positive and 22% triple-negative. Pathological complete response (pCR): 16.5%. Median follow-up: 12 years. In the univariate analysis, NLR (HR 1.23, 95% CI 1.11-1.36; p Table 1.Analysis of prognostic capacity with the consecutive addition of biomarkersAICAUC ROC (95% CI)pHarrell's C-index (95% CI)pModel 1: ypTN2740,76 (0,58-0,94)Ref*0,74 (0,57-0,91)Ref*Model 2: ypTN + NLR1870,78 (0,61-0,95)0,830,80 (0,67-0,93)0,53Model 3: ypTN + NLR + TIL850,85 (0,73-0,98)0,300,83 (0,73-0,94)0,30Model 4: ypTN + NLR + TIL + + AURKA + MYBL2570,91 (0,80-1)0,110,89 (0,81-0,97)0,13*Ref: model 1 was the reference category that was used for comparison of AUC and C-index.AIC: Akaike Information Criterion. AUC ROC: Area Under the ROC Curve. ROC: Receiver Operating Characteristic. Citation Format: Esmeralda Garcia-Torralba, Beatriz Álvarez-Abril, Carlos Bravo-Pérez, Esther Navarro Manzano, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa García-Garre, Gema Marín Zafra, Francisco Ayala de la Peña, Elena García-Martínez. Development of prognostic models based on clinical, immune-related and proliferation factors in early breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-03.

Introduction. There are still 30-40% of patients with early breast cancer (BC) that relapse after neoadjuvant chemotherapy (NAC). New prognostic biomarkers are needed. Current evidence shows that both markers of antitumor local and systemic immune response, such as tumor infiltrating lymphocytes (TIL) and neutrophil-to-lymphocyte ratio (NLR) have prognostic value in early BC. Most works have evaluated baseline levels, but their variation after NAC might be related to treatment resistance and should be explored.The aim of this study was to simultaneously investigate the prognostic significance of the pre-post-NAC variation of TIL and NLR in patients with early BC.Methods. Retrospective, single-center cohort of 121 patients with early BC treated with NAC between 2001 and 2010. Pre- and post-NAC TIL (CD3+) were assessed by tumor tissue microarrays performed in both diagnostic core-needle biopsy and surgical excision specimens, respectively. Pre- and post-NAC NLR were calculated based on blood tests collected within 1 month of cancer diagnosis and at the moment of surgery, respectively. The change on TIL and NLR after NAC was estimated by calculating the absolute difference of post- and pre- values of these parameters (Δpost-pre). We examined the association between the absolute difference of TIL and NLR (both divided into deciles) and survival outcomes by Cox regression. To represent in Kaplan-Meier curves the combined effect of the change of TIL and NLR in OS, we divided patients into 4 groups, depending on the sign of Δpost-pre values of TIL and NLR: 1) no TIL nor NLR increment after NAC (ΔTIL & ΔNRLpost-pre≤0); 2) no TIL but NLR increment (ΔTILpost-pre≤0, ΔNRLpost-pre>0); 3) TIL but no NLR increment (ΔTILpost-pre>0, ΔNRLpost-pre≤0); and 4) TIL and NLR increment following NAC (ΔTIL & ΔNRLpost-pre>0).Results. 47 (40%) out of 121 patients had pre- and post-NAC values of both NLR and TIL. Patients’ baseline characteristics are shown in Table 1. The median follow-up of this group was 11.5 years (IQR: 10.5 - 12.5 years). At the final follow-up date, overall survival (OS) was 87.2 %. In the univariable analysis, the increase in TIL and NLR after NAC among deciles showed a negative prognostic value for OS (TIL: HR 1.54, 95%CI 1.05-2.26, p=0.026; HR 1.32 95%CI 0.98-1.79, p=0.070). In the multivariable analysis, adjusted by cancer staging after NAC, both the increase of TIL and NLR after NAC among deciles add independent predictive value (TIL: HR 1.53, 95%CI 1.00-2.34, p=0.049; RNL: HR 1.42 95%CI 0.95-2.12, p=0.09).The subpopulation of patients with no TIL increment after NAC (Groups 1&2, N=23) showed the best prognosis, with no deaths at 10 years. Among patients with TIL increment (Groups 3&4, N=22), those with no NLR increment (Group 3, N=5) showed an intermediate prognosis (20% deaths at 10 years), whereas patients with concurrent NLR increment (Group 4, N=17) had the lowest OS (29.4% deaths at 10 years). Differences observed between groups were statistically significant (Log Rank p=0.042).Conclusion. The integrated characterization of TIL and NLR variations after NAC identifies different prognostic subgroups in early BC patients. In our cohort, both the increment of TIL and/or NLR after NAC are associated to a worse prognosis. Future validation of these findings in large, multicenter cohorts might allow treatment optimization by means of new strategies such as immunotherapy. Table 1.Patients’ baseline characteristicsN=47Age (median, range)56 (21, 78)Menstrual statusPostmenopausal25 (53,2%)Premenopausal22 (46,8%)Histologic subtypeInvasive ductal carcinoma42 (91,5%)Other subtypes4 (8,5%)Histologic gradeGrade 12 (4,3%)Grade 218 (38,3%)Grade 323 (48,9%)Unknown4 (8,6%)cTcT221 (44,7%)cT324 (51,1%)cT4a-d2 (4,2%)cNcN018 (38,3%)cN114 (29,8%)cN26 (12,8%)cN39 (19,1%)Molecular subtypeHR+ HER2-22 (46,8%)HER2+ HR+8 (17,0%)HER2+ HR-6 (12,8%)Triple negative10 (21,3%)Breast surgeryConservative26 (55,3%)Mastectomy21 (44,7%)Axillary surgerySentinel lymph node biopsy12 (25,5%)Axillary lymph node dissection35 (74,5%)Relapse typeMetastasis7 (14,9%)Local/contralateral1 (0,83%)Deaths6 (12,8%) Citation Format: Esmeralda Garcia-Torralba, Beatriz Álvarez-Abril, Carlos Bravo-Pérez, Esther Navarro Manzano, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa García-Garre, Gema Marín Zafra, Francisco Ayala de la Peña, Elena García-Martínez. Prognostic significance of changes in tumor infiltrating lymphocytes and neutrophil-to-lymphocyte ratio after neoadjuvant chemotherapy in early breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-11.

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 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 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.

Background: HER2DX (Prat et al. EBiomedicine 2022) is a 27-gene prognostic (risk-score) and predictive (pathological complete response [pCR]-score) assay in early-stage HER2+ breast cancer based on clinical data and the expression of 4 gene signatures (immune, proliferation, luminal differentiation and HER2 amplicon). Here, we aim to evaluate, for the first time, the ability of HER2DX to predict pCR following neoadjuvant TCH or TCHP in HER2+ disease. Methods: Standardized HER2DX was performed in a central lab on baseline pre-treatment FFPE tumor biopsies from the GOM-HGUGM-2018-05 study in Spain, a consecutive retrospective series of patients (pts) with newly diagnosed stage I-III HER2+ breast cancer eligible for neoadjuvant therapy. Pts received standard 6 cycles of docetaxel, carboplatin and trastuzumab (TCH) or TCH with pertuzumab (TCHP) regimens. Primary aim was to test the ability of HER2DX pCR score to predict pCR (ypT0/is ypN0). Secondary objectives were to test the ability of HER2DX pCR score to predict pCR independently of clinical-pathological variables and the PAM50 subtype (HER2-enriched versus not), and to evaluate the association of HER2DX pCR score with the HER2DX risk-score. Logistic regression and receiver-operator curve (ROC) analysis were assessed. Statistical analyses were performed in R code 4.0.5. Results: HER2DX was evaluated in 155 pts (97%) enrolled in the study with available RNA (as of June 2022). Mean age of pts was 50 (range 22-74) and 55.2% of pts (n=85) were pre-menopausal. Clinical T2-4 disease represented 77.4% of cases (n=120), clinical node-positive disease (cN1-3) represented 63.9% of cases (n=99), and 68.0% of tumors (n=105) were hormone receptor-positive. The overall pCR rate was 57.4% (95% confidence interval [CI] 50-65): 52.2% (95% CI 40-64) with TCH (n=67) and 61.4% (95% CI 50-72) with TCHP (n=88). The proportion of HER2DX low-, medium- and high-pCR groups was 34.2%, 34.8% and 31.0%, respectively. HER2DX pCR score (as a continuous variable from 0 to 100) was significantly associated with pCR (odd ratio [OR]=1.03, p=5.91e-07). The pCR rates in HER2DX pCR-high and pCR-low groups were 75.0% and 28.0% (OR=7.6, 95% CI 3.2-19.1, p=7.14e-06), respectively. In pts treated with TCHP, the pCR rates in HER2DX pCR-high and pCR-low groups were 85.7% and 27.3% (OR=16.0, 95% CI 4.3-59.01, p=3.2e-05), respectively. The AUC ROC of HER2DX pCR score (as a continuous variable) and pCR status was 0.746 (in all pts) and 0.812 (in pts treated with TCHP). HER2DX pCR score was significantly associated with pCR independently of hormone receptor status, Ki67, age, menopausal status, pertuzumab use, clinical stage and PAM50 HER2-enriched subtype. The proportion of HER2DX low- and high-risk of relapse disease was 32.0% and 68.0%, respectively. The correlation of HER2DX pCR score and HER2DX risk-score was weak (coefficient=-0.17), as previously described. Proportion of cases according to both HER2DX scores and absolute difference of pCR rates between TCHP and TCH in each combined group is shown in Table. Conclusion: The HER2DX genomic test predicts pCR following neoadjuvant TCH or TCHP regimens independently of clinical-pathological variables and intrinsic subtype. The combination of both HER2DX scores might help better tailor systemic therapy in patients with newly diagnosed stage I-III HER2+ breast cancer. Citation Format: Coralia Bueno-Muiño, Isabel Echavarria, Sara López-Tarruella, Roche-Molina Marta, María del Monte-Millán, Tatiana Massarrah, Yolanda Jerez Gilarranz, Blanca Herrero, Salvador Gámez, Iván Márquez-Rodas, María Cebollero-Presmanes, Nevado Santos Manuel, Pilar de la Morena Barrio, Francisco Ayala de la Peña, José Ángel García-Sáenz, Fernando Moreno Antón, Álvaro Rodríguez Lescure, Teresa Quintanar, Diego Malón-Giménez, Laura Rodriguez-Lajusticia, Ana Isabel Ballesteros García, Dulce Bañón Torres, Lucía Villarejo, Nerea Lobato, Ainhoa Arias, Inmaculada Ocaña, Enrique Álvarez, Laia Paré, Mercedes Marín-Aguilera, Patricia Galván, Fara Brasó-Maristany, Ana Vivancos, Patricia Villagrasa, Joel S Parker, Charles M. Perou, Aleix Prat, Miguel Martín. Independent validation of the HER2DX genomic test in HER2-positive breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab +/- pertuzumab (TCH/TCHP): a correlative analysis from a multicenter academic study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-46.

Background: Endocrine resistance is a major cause of therapeutic failure in metastatic breast cancer (MBC). The information provided by DNA sequencing of plasma cell free DNA (cfDNA) and by the analysis of circulating tumor cells (CTC) may be useful to determine the occurrence and type of endocrine resistance. However, different levels of concordance between cfDNA and CTC, and also between liquid biopsy and tissue biopsy, have been reported. Thus, the best strategy for performing DNA sequencing in the setting of therapeutic decisions for luminal MBC patients is not well defined. The purpose of this study was to determine the concordance between DNA sequencing data from CTC, cfDNA, metastasis, and primary tumor in endocrine-resistant luminal MBC.Methods: Using the same panel (10 genes) we performed simultaneous sequencing of cfDNA, CTC, metastases and primary tumor in 38 patients with luminal MBC. CTC isolation was performed with an Epcam-based immunomagnetic system. Concordance of DNA sequencing data of the different types of sample was analyzed and correlated with clinical data. Results: CTC were detected in 21% of the patients. The rate of detection of genetic alterations was 87.5% for CTC, 61.5% for cfDNA, 63.2% for metastasis and 67.7% for primary tumor, and involved mainly TP53, PIK3CA, ESR1 and AKT1. A higher number of mutations was found in cfDNA of MBC patients with progressive disease (p=0.02) and the same trend was observed for endocrine resistance (p=0.08), especially for PIK3CA, ESR1 and AKT1 mutations. Global concordance was low to intermediate between CTC and cfDNA, but significantly higher between CTC and metastasis. Concordance also varied according to the specific genetic alteration, with no ESR1 mutations detected in CTC and with a low concordance for PIK3CA and AKT1 mutations between CTC and cfDNA samples.Conclusions: DNA sequencing of different types of tumor samples (cfDNA, CTC, metastasis and primary tumor) may provide different rates of genomic alterations detection in luminal endocrine-resistant MBC. A moderate to low concordance, with discordances depending both on the clinical situation and on the sequenced gene, support the complementarity of the different samples, with cfDNA and metastatic tissue as the preferred sources of tumor DNA.

Resumen Se resumen en este trabajo las comunicaciones mas relevantes y con mayor impacto clinico presentadas en el Simposio Internacional de Cancer de Mama, celebrado en San Antonio en diciembre de 2015. Desde el punto de vista translacional, las principales aportaciones han sido las referidas a la dinamica clonal y a la heterogeneidad tumoral, asi como a la posibilidad de estudiar mutaciones emergentes relacionadas con resistencia mediante biopsia liquida y tecnicas de secuenciacion masiva, como demuestran los datos de los ensayos BELLE-2 y BOLERO-2. Desde el punto de vista clinico, los resultados finales del estudio BCIRG-006 y los intermedios del estudio ExteNET en cancer de mama HER2 modifican el panorama de la adyuvancia en este grupo de pacientes. Los resultados del estudio ABCSG-18 con denosumab adyuvante en enfermedad luminal apoyan los resultados previos con bifosfonatos. En enfermedad triple negativa, se han aportado datos interesantes acerca de la utilizacion de carboplatino y nab-paclitaxel en esquemas neoadyuvantes. El estudio CREATE-X con capecitabina adyuvante plantea la posibilidad de mejorar el pronostico de las pacientes que no alcanzan respuesta completa tras neoadyuvancia, especialmente en el grupo triple negativo. La posibilidad de reducir la intensidad del tratamiento en algunos subgrupos de pacientes, las controversias sobre la irradiacion nodal y el manejo quirurgico de la axila, y los datos iniciales sobre inmunoterapia completan este resumen.

Purpose Although diabetes mellitus (DM) is recognized as a risk factor for chemotherapy-induced neurotoxicity, its true impact on intensity and time course of peripheral neuropathy is still unclear. The goal was to analyze the relevance of preexisting DM to weekly paclitaxel-induced peripheral neuropathy (PIPN). Methods We performed a retrospective case-control study (1:2) including a total of 129 patients with breast cancer (43 with DM and 86 controls) treated with single-agent weekly paclitaxel (wP). Results Compared with controls, patients with DM treated with wP experienced PIPN more frequently (74.4% vs 58.4%; P=.016) and with higher severity (grade 2-3: 51.2% vs 27.7%; P=.014). A significant delay in PIPN resolution was observed in women with DM (P=.001) and, in a multivariate analysis, DM was the only independent predictor for delayed recovery (hazard ratio [HR], 0.16; 95% CI, 0.05-0.55; P=.003). After 2 years, 68.7% of patients with DM (vs 29.2% of women without DM) still experienced PIPN, which was functionally significant (grade 2-3) in 18.2%. Conclusions Significantly more dose delays and reductions because of PIPN occurred in patients with DM. Preexisting DM associates with long-lasting significant PIPN in patients treated with wP. Benefits and risks of long-term significant PIPN should be carefully balanced in patients with DM before starting wP chemotherapy.