Exploration Of Prognostic Factors In Triple-Negative Breast Cancer With High Risk Of Recurrence And Progression

Background and objective:Triple-negative breast cancer(TNBC)patients with residual disease after neoadjuvant chemotherapy(NAC)have a high rate of early recurrence/metastasis and present a poor prognosis.Valid factors to evaluate the prognosis are still lacking.We performed this study to explore prognostic factors focusing on genetic alterations and clinicopathology features in non-pathologic complete response(pCR)TNBC patients to provide value for clinical practice and scientific research.Methods:Patients initially diagnosed with early-stage TNBC,treated with NAC,and who had residual disease after primary tumor surgery at the China National Cancer Center during 2016 and 2020 were enrolled.Genomic analyses were performed by targeted sequencing for each tumor sample.Clinicopathological features and molecular biological features of patients were summarized based on NAC regimens,and differences in category variables were compared using the Wilcoxon test or Fisher’s exact test.The cumulative disease-free survival(DFS)was estimated using the Kaplan-Meier analysis and compared between groups using the log-rank test.Univariable and multivariable cox regression analyses were conducted to screen potential prognostic factors of the patients.Results:Fifty-seven patients were included in our study.Genomic analyses showed that TP53(41/57,72%),PIK3CA(12/57,21%),MET(7/57,12%),and PTEN(7/57,12%)alternations commonly occurred.Patients harboring the PIK3CA mutation showed worse DFS than patients with wild-type PIK3CA.The three-year DFS rate was 40.0%compared with 72.3%(P=0.028).NAC with a platinum-based regimen resulted in a significantly improved DFS than an anthracycline-based regimen.The three-year DFS rate increased from 54.5%to 74.5%.In addition,patients with clinical stage Ⅲ disease had significantly shorter DFS than those with clinical stage Ⅰ and Ⅱ(P<0.001).The clinical TNM(cTNM)stage and PIK3CA status were independent prognostic factors of DFS.A prognostic stratification indicated that patients with clinical stages Ⅰ&Ⅱ possessed the best DFS(a three-year DFS rate of 96%),followed by those with clinical stage Ⅲ&wild-type PIK3CA(a three-year DFS rate of 53.7%).In contrast,patients with clinical stage Ⅲ&the PIK3CA mutation had the worst DFS(a three-year DFS rate of 0).Conclusions:In TNBC patients with residual disease after NAC,a comprehensive evaluation combining the cTNM staging and PIK3CA status present better prognostic value.Background and objective:non-Pathologic complete response(pCR)triple-negative breast cancer(TNBC)has an inferior prognosis,with higher invasiveness and recurrence/metastasis rates.Valid factors to evaluate the prognosis are still lacking.Homologous recombination deficiency has been shown to predict response to platinum and PARP inhibitors,but its prognostic role is unclear.We performed this study to explore the prognostic value of HRD in non-pCR TNBC patients after neoadjuvant chemotherapy(NAC).Methods:Patients with early-stage TNBC who received NAC and surgery for the primary tumor at the National C ancer Center of China from 2016 to 2020 were screened,and their postoperative pathology showed residual disease.Genomic analyses were performed by targeted sequencing for each tumor sample.HRD status was assessed by combing HRD scores and tumor BRCA1/2 mutation status.Positive-HRD status was defined as tumor BRCA1/2 pathogenic mutation/suspect pathogenic mutation and/or an HRD score≥42.Clinicopathological features of patients were summarized based on HRD status,and differences in category variables were compared using the Wilcoxon test or Fisher’s exact test.The cumulative disease-free survival(DFS)was estimated using the Kaplan-Meier analysis and compared between groups using the log-rank test.Cox regression analyses were conducted to screen potential prognostic factors of the patients.Results:Thirty-seven patients were included in our study.In total,16 patients(43.2%)had negative-HRD status,and 21 patients(56.8%)had positive-HRD status.Patients with positive-HRD status were more common in younger,premenopausal women.The median age was 40 in HRD-positive patients,compared with 51.5 in HRD-negative patients(P=0.002).MYC gene mutations were more common in HRD-positive patients,and the incidences of MYC gene mutations in HRD-positive and negative patients were 29%and 0%,respectively.We discovered that patients with positive-HRD status had worse DFS than those with negative-HRD status.The 3-year DFS rate was 66.7%compared with 81.3%,and the median DFS was 45.7 and not reached for the HRD-positive and HRDnegative groups,respectively.Besides,the prognostic effect of HRD status in non-pCR TNBC appeared to be more pronounced in patients other than ypN3 status(P=0.038).Similar results were obtained in the different NAC groups.Conclusions:In patients with non-pCR TNBC after NAC,HRD might be a promising prognostic biomarker for DFS.This finding warrants further exploration.Background and objective:Although triple-negative breast cancer(TNBC)is sensitive to initial chemotherapy,it has a short remission period and is more likely to produce chemotherapy resistance.Early recurrence and metastasis often occur within two years after diagnosis,and the prognosis is inferior.This study was to investigate the clinicopathological features and prognosis between early and late relapsed/metastatic TNBC to guide clinical diagnosis,and treatment.Methods:A total of 471 patients with relapsed/metastatic TNBC at 21 cancer centers from 2012 to 2014 were finally included.Patients were divided into an early relapsed/metastatic group and a late relapsed/metastatic group according to the metastatic-free interval(MFI)with a boundary of 24 months.The clinicopathological features,recurrence/metastasis,first-line treatment,and prognosis were compared between the two groups.Differences in category variables were compared using the chi-square test or Fisher’s exact test.The cumulative progression-free survival(PFS)was estimated using the Kaplan-Meier analysis and compared between groups using the log-rank test.The relationship between PFS and clinical features was analyzed by the COX regression model.Results:271 patients(57.5%)were in the early relapsed/metastatic group.Most patients were grade Ⅲ,ki-67>20%,and clinical stage Ⅲ at primary diagnosis.Two hundred patients(42.5%)were in the late relapsed/metastatic group,and more patients were present with bone metastasis and receiving paclitaxel-based regimens as first-line treatment.In terms of the first-line treatment regimen,62.5%of patients in the early relapsed/metastatic group received a non-paclitaxel regimen,among which the most common regimen was platinum combined with gemcitabine(56,21.6%),followed by capecitabine combined with vinorelbine(38,8.4%)and platinum combined with vinorelbine(37,8.2%).More than half of the patients in the late relapsed/metastatic group received a paclitaxelcontaining regimen,among which paclitaxel combined with platinum was the most commonly used regimen(36,18.6%),followed by paclitaxel combined with capecitabine(18,9.3%)and paclitaxel combined with anthracycline(18,9.3%).The objective response rate(ORR)of the total population was 39.2%,and the ORR of patients in the early and late relapsed/metastatic groups was 36.0%and 43.5%,respectively.The median PFS of the enrolled patients was five months,and the PFS of the early relapsed/metastatic group was significantly worse than that of the late relapsed/metastatic group,with the median PFS of 4 months and six months,respectively.COX multivariate regression analysis showed that the clinical TNM stage(cTNM)was an independent prognostic factor for PFS in the early relapsed/metastatic group(P=0.03).Age at first diagnosis was an independent prognostic factor of PFS in the late relapsed/metastatic group(P=0.049).Conclusions:This multicenter real-world study showed that the patients with early relapse/metastasis had more invasive biological characteristics,poor therapeutic effects,and worse prognoses.On the contrary,the late relapsed/metastatic population presented the characteristics of an inert tumor,with a high reutilization rate of paclitaxel chemotherapy and a relatively good prognosis.