Neoadjuvant Chemotherapy In Triple-negative Breast Cancer Patients Research Articles

Clinical verification of the relationship between serum lipid metabolism and immune activity in breast cancer patients treated with neoadjuvant chemotherapy

BackgroundLipid metabolism has been recently reported to affect the prognosis and tumor immune activity in cancer patients. However, the effect of lipid metabolism on chemosensitivity in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) remains unclear.MethodsWe examined 327 patients with breast cancer who were treated with NAC followed by curative surgery. The correlations between the serum levels of total cholesterol (TC) and triglyceride (TG) and the clinicopathological features, including the efficacy of NAC, neutrophil-to-lymphocyte ratio (NLR), and absolute lymphocyte count (ALC), were evaluated retrospectively.ResultsSerum TG levels were increased after NAC in all the subtypes, and the rate of change was the highest, especially in triple-negative breast cancer (TNBC) (21.0% → 48.1%). In addition, only TNBC patients with an objective response (OR) had significantly higher TG levels after NAC than those without (P = 0.049). Patients with a high ALC before NAC had significantly higher TG levels after NAC than patients with all breast cancer (P = 0.001), HER2-enriched breast cancer (P = 0.021), and TNBC (P = 0.008). Patients with a low NLR before NAC had significantly higher TG levels after NAC only among patients with TNBC (P = 0.025). In patients with human epidermal growth factor receptor 2-enriched breast cancer, the group with normal TC levels before NAC had significantly better OS than those with high TC levels (P = 0.013, log-rank test), and in patients with TNBC, the group with high TC levels after NAC had significantly better OS than those with normal TC levels (P = 0.014, log-rank test).ConclusionsGood systemic immune activity and chemosensitivity may be associated with lipid metabolism regulated by NAC in TNBC patients.

Artificial intelligence (AI)–powered spatial analysis of tumor-infiltrating lymphocytes (TIL) for prediction of response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC).

595 Background: Stromal TIL are a well-recognized prognostic and predictive biomarker in breast cancer. There is a need for tools assisting visual assessment of TIL, to improve reproducibility as well as for convenience. This study aims to assess the clinical significance of AI-powered spatial TIL analysis in the prediction of pathologic complete response (pCR) after NAC in TNBC patients. Methods: H&E stained slides and clinical outcomes data were obtained from stage I – III TNBC patients treated with NAC in two centers in Korea. For spatial TIL analysis, we used Lunit SCOPE IO, an AI-powered H&E Whole-Slide Image (WSI) analyzer, which identifies and quantifies TIL within the cancer or stroma area. Lunit SCOPE IO was developed with a 13.5 x 109 micrometer2 area and 6.2 x 106 TIL from 17,849 H&E WSI of multiple cancer types, annotated by 104 board-certified pathologists. iTIL score and sTIL score were defined as area occupied by TIL in the intratumoral area (%) and the surrounding stroma (%), respectively. Immune phenotype (IP) of each slide was defined from spatial TIL calculation, as inflamed (high TIL density in tumor area), immune-excluded (high TIL density in stroma), or desert (low TIL density overall). Results: A total of 954 TNBC patients treated from 2006 to 2019 were included in this analysis. pCR (ypT0N0) was confirmed in 261 (27.4%) patients. The neoadjuvant regimens used were mostly anthracycline (97.8%) and taxane (75.1%) -based, with 116 (12.1%) patients receiving additional platinum and 41 (4.3%) patients treated as part of immune checkpoint inhibitor or PARP inhibitor clinical trials. The median iTIL score and sTIL score were 4.3% (IQR 3.2 – 5.8) and 8.1% (IQR 6.3 – 13.4), respectively. The mean iTIL score was significantly higher in patients who achieved pCR after NAC (5.8% vs. 4.5%, p < 0.001), and a similar difference was observed with sTIL score (12.1%.1 vs. 9.4%, p < 0.001). iTIL score was found to remain as an independent predictor of pCR along with cT stage and Ki-67 in the multivariable analysis (adjusted odds ratio 1.211 (95% CI 1.125 – 1.304) per 1 point (%) change in the score, p <0.001). By IP groups, 291 (30.5%) patients were classified as inflamed, 502 (52.6%) as excluded, and 161 (16.9%) as desert phenotype. The patients with inflamed phenotype were more likely to achieve pCR (44.7%) than other phenotypes (19.8%, p < 0.001). Conclusions: AI-powered spatial TIL analysis could assess TIL densities in the cancer area and surrounding stroma of TNBC, and TIL density scores and IP classification could predict pCR after NAC.

Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis

PurposeSome studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients.MethodsAfter searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations.ResultsSix RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50–0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3–4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001).ConclusionsPD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.

Association between systemic immune-inflammation index and neoadjuvant chemotherapy efficacy as well as prognosis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with a relatively poor prognosis. Neoadjuvant chemotherapy (NAC) is the main treatment method. Due to the heterogeneity of the tumor, the chemotherapy response of TNBC patients is significantly different. Inflammation is closely related to the occurrence and development of cancer. The systemic immune-inflammation index (SII) is an indicator that can comprehensively reflect the state of systemic inflammation. This study aims to explore the association between SII and the NAC efficacy as well as the prognosis in TNBC. The data of TNBC patients who underwent NAC and systemic treatment in Xiangya Hospital of Central South University from January 2015 to June 2019 were collected. According to the inclusion and exclusion criteria, 231 TNBC patients were finally included. The pre-NAC SII was calculated according to the blood routine results of the patients at 1 week before chemotherapy, and the patients were divided into a pre-NAC low SII group (SII<412, 115 cases) and a pre-NAC high SII group (SII≥412, 116 cases). The SII after chemotherapy was calculated according to the blood routine results of the patients at 2 to 3 months after the end of chemotherapy, and the patients were divided into a low SII group after chemotherapy (SII<474, 115 cases) and a high SII group after chemotherapy (SII≥474, 116 cases). Pearson's chi-square test was used to analyze the relationship between SII and other clinical characteristics of TNBC patients, and the relationship between the NAC efficacy and clinical characteristics of TNBC patients. Binary logistic regression analysis was used to find independent factors that affect the efficacy of NAC in TNBC patients. Kaplan-Meier curve analysis was used to analyze factors affecting the prognosis of TNBC patients. Cox regression model was used to find independent factors affecting the prognosis of TNBC patients. Before NAC, the differences in SII between groups with different ages and tumor sizes were significant (P=0.007 and P=0.002, respectively); after chemotherapy, there were no significant differences in SII between different ages, tumor sizes, histological grades, lymph node staging, and Ki-67 groups (all P>0.05). There were 115 patients with low SII before NAC, with a pathological complete response (pCR) rate of 15.7%; there were 116 patients with high SII before NAC, with a pCR rate of 6.0%. Patients with low SII before NAC had a higher pCR rate than patients with high SII before NAC, and the difference was statistically significant (P=0.019).There were 156 patients with lymph node staging pN0, with a pCR rate of 14.7%; and there were 75 patients with lymph node staging pN1-pN2, with a pCR rate of 2.7%. Patients with lymph node staging pN0 had a higher pCR rate than those with lymph node staging pN1-pN2, and the difference was significant (P=0.006). During the follow-up, 34 patients had local recurrence or distant metastasis. The Kaplan-Meier survival curve showed that the 3-year disease-free survival (DFS) rates for patients with low SII before NAC and high SII before NAC were 87.8% and 82.8%, respectively, and the former was significantly higher than the latter (P=0.005); the 3-year DFS rates for patients with tumor sizes of T1-T2 and T3 were 89.0% and 67.5%, respectively, and the former was significantly higher than the latter (P=0.001); the 3-year DFS rates for patients with lymph node staging of pN0 and pN1-pN2 were 87.8% and 82.8%, respectively, and the former was significantly higher than the latter (P=0.009). Cox analysis showed that SII before NAC and tumor size were independent influencing factors of patients' DFS (P=0.038, P=0.010, respectively). SII has important clinical significance in predicting the efficacy and prognosis of NAC in TNBC patients, and it has the potential to be a biomarker.

Abstract P6-02-03: Quantitative apparent diffusion coefficient (ADC) radiomics of tumor and peritumoral regions as potential predictors of treatment response to neoadjuvant chemotherapy (NACT) in triple negative breast cancer (TNBC) patients

Abstract Background and Purpose: TNBC is comprised of biologically aggressive tumors with diverse clinical behavior and response to chemotherapy. Prediction of disease response to NACT is critical to the development of personalized medicine in TNBC. We evaluated first-order radiomic features from quantitative ADC maps of the tumor and peritumoral region as discriminators of response to NACT in TNBC patients. Materials and Methods: This IRB-approved prospective study (ARTEMIS trial, NCT02276443) included 34 patients with biopsy proven stage I-III TNBC who underwent evaluation of treatment response by multi-parametric MRI. Patients had a baseline MRI (BL) and a second MRI after 4 cycles (C4) of their treatment. After completion of NACT, all patients underwent surgery and were classified as pathologic complete response (pCR) or non-pCR. Both MRI exams included T2W series, a dynamic contrast enhanced series (DCE), a conventional diffusion weighted imaging (DWI) series, and a reduced field of view (rFOV) DWI series. Tumor volumes were contoured by an experienced breast radiologist on ADC maps with reference to b1000 DWI images. Regions with necrosis or clip artifacts were excluded from the contour. Peritumoral regions were defined as a 5 mm rim of tissue surrounding the tumor based on DCE series, T2-weighted images with fat suppression and ADC maps. Thirteen first-order radiomic features, including mean, minimum, maximum, percentiles, kurtosis and skewness at a single measurement and the difference between BL and C4 were compared between pCR and non-pCR using Receiver Operating Characteristic (ROC) curve and Wilcoxon rank sum test. Results: The kurtosis of tumor at C4 by conventional DWI was significantly higher in non-pCR than in pCR patients (AUC=0.785, p=0.0097). The change in kurtosis from BL to C4 by conventional DWI was also significantly higher in non-pCR than in pCR patients (AUC=0.73, p=0.043). The skewness of tumor at C4 by rFOV DWI scan was significantly lower in pCR than non-pCR patients (AUC=0.73, p=0.023). The 10th percentile of the peritumoral region’s ADC was significantly different between pCR and non-pCR (mean=1.19, SD is ± 0.27 10-3 mm2/s vs mean=1.34, SD ± 0.27 10-3 mm2/s respectively, AUC=0.70, p=0.048). The kurtosis and 25th percentile of the ADC of peritumoral region were borderline significantly different between pCR and non-pCR (AUC=0.69, p=0.067; AUC=0.69, p= 0.073 respectively). Conclusion: ADC first-order radiomic features from tumor and peritumoral region in TNBC may be useful for predicting treatment response to NACT. Larger study is necessary and is currently in progress to validate these findings. Citation Format: Beatriz E. Adrada, Abeer H. Abdelhafez, Benjamin C. Musall, Kenneth R. Hess, Jong Bum Son, Mark D. Pagel, Ken-Pin Hwang, Rosalind P. Candelaria, Lumarie Santiago, Gary J. Whitman, Huong Le-Petross, Tanya W. Moseley, Elsa Arribas, Deanna L. Lane, Marion E. Scoggins, David A. Spak, Jessica W.T. Leung, Senthil Damodaran, Bora Lim, Vicente Valeo, Jason B White, Alastair M. Thompson, Jennifer K. Litton, Stacy L. Moulder, Jingfei Ma, Wei T. Yang, Gaiane M Rauch. Quantitative apparent diffusion coefficient (ADC) radiomics of tumor and peritumoral regions as potential predictors of treatment response to neoadjuvant chemotherapy (NACT) in triple negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-02-03.

A Nomogram to Predict the Pathologic Complete Response of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Based on Simple Laboratory Indicators.

Triple-negative breast cancer (TNBC) patients who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better prognoses. This study aimed to develop an intuitive nomogram based on simple laboratory indexes to predict the pCR of standard NAC in TNBC patients. A total of 80 TNBC patients who received eight cycles of thrice-weekly standard NAC (anthracycline and cyclophosphamide followed by taxane) and subsequently underwent surgery in Zhejiang Cancer Hospital were retrospectively enrolled, and data on their pretreatment clinical features and multiple simple laboratory indexes were collected. The optimal cut-off values of the laboratory indexes were determined by the Youden index using receiver operating characteristic (ROC) curve analyses. Forward stepwise logistic regression (likelihood ratio) analysis was applied to identify predictive factors for a pCR of NAC. A nomogram was then developed according to the logistic model, and internally validated using the bootstrap resampling method. pCR was achieved in 39 (48.8%) patients after NAC. Multivariate analysis identified four independent indicators: clinical tumor stage, lymphocyte to monocyte ratio, fibrinogen level, and D-dimer level. The nomogram established based on these factors showed its discriminatory ability, with an area under the curve (AUC) of 0.803 (95% confidence interval 0.706-0.899) and a bias-corrected AUC of 0.771. The calibration curve and Hosmer-Lemeshow test showed that the predictive ability of the nomogram was a good fit to actual observation. The nomogram proposed in the present study exhibited a sufficient discriminatory ability for predicting pCR of NAC in TNBC patients.

Impact of Topoisomerase IIα, PTEN, ABCC1/MRP1, and KI67 on triple-negative breast cancer patients treated with neoadjuvant chemotherapy.

Triple-negative breast cancer (TNBC) patients with residual disease following neoadjuvant chemotherapy (NAC) harbor higher risk of relapse, and eventual demise compared to those who achieve pathologic complete response. Therefore, in this study, we assessed a panel of molecules involved in key pathways of drug resistance and tumor progression before and after NAC in TNBC patients, in order to clarify the underlying mechanisms. We studied 148 TNBC Japanese patients treated with anthracycline/taxane-based NAC. KI67, Topoisomerase IIα (TopoIIα), PTEN, p53, Bcl2, vimentin, ABCG2/BCRP1, ABCB1/MDR1, and ABCC1/MRP1 were immunolocalized in surgical pathology materials before and after NAC. The status of vimentin and increasing labeling index (LI) of TopoIIα and KI67 in biopsy specimens were significantly associated with those who responded to NAC treatment. The abundance of p53 (p = 0.003), ABCC1/MRP1 (p = 0.033), ABCB1/MDR1 (p = 0.022), and a loss of PTEN (p < 0.0001) in surgery specimens following treatment were associated with pathologic parameters. TopoIIα, PTEN, and ABCC1/MRP1 status predicted pathologic response. In addition, the status of PTEN, ABCC1/MRP1, ABCB1/MDR1, Bcl2, and vimentin in surgical specimens was also significantly associated with adverse clinicopathological factors in surgery specimens, suggesting that these alterations could be responsible for tumor relapse in TNBC patients. KI67, TopoIIα, PTEN, and ABCC1/MRP1 status could predict treatment response and/or eventual clinical outcomes. These results could also provide an insight into the mechanisms of drug resistance and relapse of TNBC patients receiving NAC.

Relevance between TOP2A, EGFR gene expression and efficacy of docetaxel plus epirubicin as neoadjuvant chemotherapy in triple negative breast cancer patients

To retrospectively analyze the relevance between DNA topoisomerase Ⅱ alpha (TOP2A), epidermal growth factor receptor (EGFR) gene expression and efficacy of docetaxel plus epirubicin as neoadjuvant chemotherapy in triple negative breast cancer (TNBC) patients. A total of 53 women with triple negative breast cancer who underwent docetaxel plus epirubicin as neoadjuvant chemotherapy were included in this study. The gene detection was done in the samples before chemotherapy by DNA chip technology. The relevance between TOP2A, EGFR gene expression and efficacy, pathological complete response (pCR) rate of neoadjuvant chemotherapy were retrospectively analyzed. The high expression rate of TOP2A in all the TNBC patients was 35.8% (19/53), while the rate of EGFR was 39.6% (21/53). The overall pCR rate of TNBC patients who underwent docetaxel plus epirubicin as neoadjuvant chemotherapy was 18.9% (10/53). The pCR rate was 31.6% (6/19) in TNBC patients whose TOP2A expression was high, compared to 11.8% (4/34) in whose was low (P>0.05). The pCR rate was 28.6% (6/21) in TNBC patients whose EGFR expression was high, compared to 12.5% (4/32) in whose was low (P>0.05). The pCR rate was 75.0% (6/8) in TNBC patients whose TOP2A, EGFR expression were both high, and was significantly higher than that in all the TNBC patients (P<0.01). Efficacy of docetaxel plus epirubicin as neoadjuvant chemotherapy in TNBC patients can be predicted by detecting TOP2A, EGFR gene expression. The result may contribute to the development of more individualized neoadjuvant chemotherapy.

Abstract P3-11-13: Change of Ki-67 after long course of neoadjuvant chemotherapy as prognostic factors in patients with stage II, III triple negative breast cancer

Abstract Background: Triple negative breast cancer (TNBC) shows poor prognosis despite their higher response rate to neoadjuvant chemotherapy (NAC). Response to NAC such as pathologic complete response (pCR) is a well-known useful prognostic marker for relapse and overall survival. Pre-chemotherapy baseline higher Ki-67 is a positive predictive marker for higher pCR rate but a negative prognostic marker for relapse free survival (RFS) and overall survival (OS). After short course of NAC, Ki-67 index changed in response to the treatment. The purpose of this study is to investigate the prognostic role of Ki-67 index change between before and after the long course of NAC in TNBC patients. Patients and Methods: Patients with clinical stage II or III breast cancer treated with NAC at Seoul National University Hospital were enrolled and their clinicopathological findings including Ki-67 index were reviewed retrospectively. The definition of Ki-67 threshold of high was ≥14% in current study. TNBC definition was adopted from 2011 St Gallen Consensus Panel. Results: From Jan 2009 to Dec 2010, a total of 183 patients received NAC. Among them, 46 (25.1%) were TNBC. The pCR rate (19.6% vs 9.5%, P=0.069) and the objective response rate (complete response + partial response) (76.1% vs 70.8%, P=0.153) were higher in TNBC group than in non-TNBC group. The RFS was not different between the two groups (3 year 77.3% vs 75.4%, P=0.877). The change of Ki-67 index from high (≥14%) to low (&amp;lt;14%) was significantly associated with longer RFS in only in TNBC group. As for TNBC patients with high Ki-67 index at diagnosis, RFS of those whose Ki-67 index changed to low after NAC were significantly longer than that of whose Ki-67 index remained high (3 year RFS 87.2% vs 54.5%, P=0.036). In non-TNBC group, change of Ki-67 index was not significantly associated with RFS (P=0.245). The initial Ki-67 index itself (high vs. low) was not associated with RFS in both TNBC and non-TNBC group (P=0.726 and P=0.523 respectively). Conclusion : The change of Ki-67 index from high to low is associated with longer RFS in TNBC. Ki-67 index change between before and after the NAC can be used for further discrimination of TNBC as a prognostic marker. Citation Format: Yaewon Yang, Tae-Yong Kim, Seock-Ah Im, Bhumsuk Keam, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Hyeong-Gon Moon, Wonshik Han, In Ae Park, Dong-Young Noh. Change of Ki-67 after long course of neoadjuvant chemotherapy as prognostic factors in patients with stage II, III triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-13.

Early assessment with 18F-fluorodeoxyglucose positron emission tomography/computed tomography can help predict the outcome of neoadjuvant chemotherapy in triple negative breast cancer

BackgroundIn patients with triple-negative breast cancer (TNBC), pathology complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This prospective study was designed and powered to investigate the ability of interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) to predict pathology outcomes to NAC early during treatment. Patients and methodsConsecutive TNBC women underwent 18FDG-PET/CT at baseline and after two courses of NAC. Maximum standardised uptake value (SUVmax) in the primary tumour and lymph nodes at each examination and the evolution (ΔSUVmax) between the two scans were measured. NAC was continued irrespective of PET results. Correlations between PET parameters and pathology response, and between PET parameters and event-free survival (EFS), were examined. ResultsFifty patients without distant metastases were enroled. At completion of NAC, surgery showed pCR in 19 patients, while 31 had residual tumour. Mean follow-up was 30.3months. Thirteen patients, all with residual tumour, experienced relapse. Of all assessed clinical, biological and PET parameters, ΔSUVmax in the primary tumour was the most predictive of pathology results (p<0.0001; Mann–Whitney-U test) and EFS (p=0.02; log rank test). A threshold of 42% decrease in SUV was identified because it offered the best accuracy in predicting EFS. There were 32 metabolic responders (⩾42% decrease in SUVmax) and 18 non-responders. Within responders, the pCR rate was 59% and the 3-year EFS 77.5%. In non-responders, the pCR rate was 0% and the 3-year EFS 47.1%. ConclusionInterim 18FDG can early predict the inefficacy of NAC in TNBC patients. It shows promise as a potential contributory biomarker in these patients.

Pathological tumor response to neoadjuvant chemotherapy using anthracycline and taxanes in patients with triple-negative breast cancer

Although triple-negative breast cancer (TNBC) is associated with a poor prognosis, recent reports have indicated that a higher proportion of TNBC patients shows a pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) than is the case for non-TNBC patients. The aim of this study was to identify markers that predict pCR to NAC in TNBC patients, and to clarify prognostic factors that affect the outcome of TNBC patients with residual disease (RD) after NAC. Among 44 TNBC patients who received anthracycline- and taxane-based combination NAC, we analyzed the relationship between pathological response and clinicopathological characteristics, including immunohistochemical parameters (cytokeratin 5/6, epidermal growth factor receptor, Ki-67, p53, breast cancer susceptibility protein 1 and topoisomerase IIα). We also assessed the prognostic impact on patients with RD by analyzing the correlation between disease-free survival (DFS) and clinicopathological parameters. Sixteen patients (36%) achieved a pCR and log-rank test showed that these patients had a significantly more favorable outcome than patients with RD (DFS, P=0.00184; overall survival, P=0.0080). Among the clinicopathological parameters examined, none was correlated with pathological response, with the exception of p53. Patients with immunohistochemical overexpression of p53 more frequently achieved a pCR than those without p53 overexpression (P=0.0484). In the patients with RD, the Cox proportional hazards model showed that the presence of lymphovascular invasion was significantly associated with shorter DFS (hazard ratio, 13.333; 95% CI 1.587-111.111; P=0.0171). p53 overexpression may be a key predictor of a favorable response to NAC. Since patients with RD, particularly those positive for lymphovascular invasion, had an extremely poor outcome, novel therapeutic approaches for these patients are warranted.