Neoadjuvant And Adjuvant Chemotherapy For Early Triple-negative Breast Cancer

Survival outcomes for dose-dense paclitaxel plus carboplatin neoadjuvant versus standard adjuvant chemotherapy in stage Ⅱ to Ⅲtriple-negative breast cancer:A prospective cohort study with propensity-matched analysis[Background]There is a scarcity of data exploring the long-term benefits of platinumbased(anthracycline-free)neoadjuvant chemotherapy(NACT)for triple-negative breast cancer(TNBC).[Methods]The prospective cohort study was conducted at Cancer Hospital,Chinese Academy of Medical Sciences.Patients with TNBC in stage Ⅱ-Ⅲ were enrolled to receive NACT of dose-dense paclitaxel(175mg/m2)plus carboplatin(AUC 4.0)biweekly(ddPCb)for 6 cycles,and matched patients during the same period who received standard adjuvant chemotherapy for survival comparison.The primary endpoint was recurrence-free survival(RFS).The secondary endpoints included overal survival(OS),pathologic complete response(pCR)rates in the neoadjuvant group,and chemotherapy-related toxicities.[Results]From January 2014 to July 2021,264 patients were included in the primary nonmatched analysis(neoadjuvant 99,adjuvant 165).Compared with patients in the adjuvant group,patients who received NACT had larger tumors(T3:55.2%vs 1.2%),higher degrees of nodal burden(N2-3:55.6%vs 28.4%),and more advanced disease(stage Ⅲ:62.7%vs 29.0%)(P<0.001).Almost all(96.4%)patients in the adjuvant group received epirubicin plus cyclophosphamide followed by paclitaxel(EC-P).Within a median followup of 44.9 months,the 4-year RFS(82.6%vs 75.4%)and OS(86.6%vs 80.5%)were higher for patients in the neoadjuvant group without statistical difference.Receipt of NACT was associated with better RFS after adjustment in the multivariate analysis(hazard ratio[HR],0.38;95%confidence interval[CI],0.17-0.88;P-0.023).A total of 134 patients(67 pairs)were matched and the matching covariates were acceptably balanced.In the matched cohort,the 4-year RFS(84.9%vs 60.9%;HR,0.32;95%CI,0.15-0.69;P=0.003)and OS(88.0%vs 65.9%;HR,0.30;95%Cl,0.12-0.75;P=0.010)were significantly superior for platinum-based neoadjuvant than standard adjuvant chemotherapy.Multivariate survival analysis confirmed that patients who received NACT had significantly improved RFS(HR,0.27;95%CI,0.10-0.72;P=0.009).The pCR rate was 40.9%in the neoadjuvant group,and the 4-year RFS for patients who achieved pCR was significantly better(97.1%vs 76.3%;HR,0.11;95%CI,0.02-0.88;P=0.037).Compared with standard chemotherapy,ddPCb was related to less neutropenia(55.6%vs 74.5%)and more thrombocytopenia(32.3%vs 9.1%).[Conclusions]These results support the consideration of platinum-based NACT for promising survival benefits for TNBC in stage Ⅱ-Ⅲ,and the ddPCb regimen is emerging as an innovative and well-tolerated option.Randomized data and predictive biomarkers for platinum-based chemotherapy are needed to be further investigated.Intratumoral and stromal immunocyte subsets changes and roles induced by neoadjuvant chemotherapy in triple-negative breast cancer:A quantitative analysis in a prospective cohort of paclitaxel plus carboplatin[Background]The immune microenvironment of triple-negative breast cancer(TNBC)and its modulation by neoadjuvant chemotherapy(NACT)remain to be fully characterized.Our current study aims to evaluate NACT induced immunocyte subsets changes and assess the prognostic value of specific immune biomarkers for TNBC in the prospective cohort of paclitaxel plus carboplatin.[Methods]Tumor samples from the NACT cohort were obtained.Bioptic pre-NACT specimens and surgical post-NACT specimens(in residual disease)were evaluated for intratumoral(It)and stromal(Str)immunocytes by immunohistochemistry for detection of CD3,CD4,CD8,CD 19,and CD68.The density(number of positive cells/mm2)of each subset in It or Str was quantitated separately.Pathologic complete response(pCR)and recurrence-free survival(RFS)were analyzed.[Results]A total of 72 cases had available cancer samples in breast,and 28 had paired specimens pre-and post-NACT.The degree of immunocyte infiltration in Str was much higher than that in It,with the density of CD3 highest and the CD 19 lowest.Compared with pre-NACT specimens,the positivity density of residual disease decreased in It,while increased in Str.The differences were significant in Str-CD3 and It-CD8(P<0.05).In the 28 paired specimens,the changes of Str-CD3,It-CD4,Str-CD8,Str-CD19 were statistically significant.Higher pre-NACT positivity density of Str-CD3,Str-CD4,StrCD8 correlated with increased pCR rates,and It-CD8 moderate and strong positivity density was a predictor of pCR as well(P<0.05).Higher pre-NACT positivity density of Str-CD3,Str-CD4,Str-CD8,Str-CD19 meant a lower risk of recurrence(P<0.05).Restricted cubic spline was used to identify the best values of cut-off.The high infiltration for Str-CD3,Str-CD4,Str-CD8,Str-CD19 was defined as positivity density more than 3380,2340,1700,and 1400,respectively.Patients with high infiltration had better RFS,and the hazard ratios(HRs)were 0.18(95%confidence interval[CI],0.04-0.83;P=0.027),0.38(95%CI,0.10-1.40;P=0.146),0.35(95%CI,0.10-1.30;P=0.118),0.09(95%CI,0.01-0.69;P=0.021).It-CD19 positive in pre-NACT tissue was related to significantly better RFS(HR,0.19;95%CI,0.04-0.86;P=0.031).The correlation between the density of immunocyte subsets in residual disease and prognosis was weakened,and patients with high It-CD3 density(>25)of moderate and strong positivity had a lower risk of recurrence(HR,0.25;95%CI,0.07-0.94;P=0.039).[Conclusions]The study supports that NACT induces significant immunocyte changes in TNBC.Compared with pre-NACT,the positivity density of residual disease decreased in It,while increased in Str.Obvious correlation was found between the immunocyte subsets in pre-NACT tissues and prognosis.Further studies with larger samples are needed to provide effective biomarkers.Adjuvant chemotherapy decision-making and clinical assessments for triple-negative breast cancer with residual disease after neoadjuvant chemotherapy:Real-world data in a single center[Background]Triple-negative breast cancer(TNBC)patients with residual disease(RD)after neoadjuvant chemotherapy(NACT)have a poor prognosis with limited data regarding adjuvant therapy and no criteria for clinical prognosis assessment.The current study aimed to analyze factors affecting adjuvant chemotherapy decision-making in the real-world practice,and identify prognostic factors to achieve clinical risk stratification.[Methods]Patients with TNBC who had invasive RD after NACT from July 2008 to September 2021 were retrospectively included.The characteristics of the patients who received adjuvant chemotherapy and did not were compared.Multivariate Cox proportional hazards model was used to identify the influencing factors of recurrence-free survival(RFS).The Neo-Bioscore(NB)scores were performed for patients included and the assessment methods were evaluated by ROC curve.[Results]A total of 194 patients were included,and 121(62.4%)received adjuvant chemotherapy.Patients with adjuvant chemotherapy had larger tumor pre-and-post NACT(cT4:11.0%vs 17.4%;ypT2 and above:27.8%vs 51.6%),received anthracyclines and(or)taxane regimens more frequently in NACT(27.4%vs 44.6%),had fewer cycles and worse response in NACT(<6 cycles:15.1%vs 38.8%;Miller-Payne 1-2:21.1%vs 40.9%)(P<0.05).Among the 121 patients who received adjuvant chemotherapy,21 supplemented the remainder of NACT,10 extended the regimen in NACT,and 88 received regimens different from NACT.Within a median follow-up of 44.5 months,the 5-year RFS and overall survival(OS)rates were 65.7%and 75.5%.After adjustment for confounding factors,a lower risk of recurrence was observed among patients receiving adjuvant chemotherapy without statistical significance.In the multivariate model,lymph node status after NACT(ypN)was demonstrated to be an independent predictor for RFS.Compared with ypNO,the hazard ratios(HRs)of ypN1-3 were 2.62(95%confidence interval[CI]1.07-6.41),2.91(95%CI,1.00-8.43),8.43(95%CI,3.02-23.55).The continuous number of positive lymph nodes after NACT was prognostic,with higher accuracy than NB scores(area under the ROC:0.75 vs 0.67).According to the best values of cut-off,patients with>2 positive lymph nodes postoperatively or NB scores>5 had worse RFS and OS significantly.[Conclusions]In the real-world practice,adjuvant chemotherapy decision-making for TNBC with RD after NACT differred by tumor size before and after NACT,regimens and efficacy of NACT.Postoperative lymph node status was an independent factor for RFS,and patients with>2 positive lymph nodes or NB>5 had poorer prognosis.Prospective randomized studies with an appropriate method for risk stratification are needed to detetmine the value of intensive adjuvant therapy.Chemotherapy decision-making and survival outcomes in older women with early triple-negative breast cancer:Evidence from real-world practice[Background]Data regarding chemotherapy options and benefits in older women with early triple-negative breast cancer(TNBC)are limited.Our study aimed to assess the effects of adjuvant chemotherapy on recurrence-free survival(RFS),breast cancer-specific survival(BCSS),and overall survival(OS)rates in elderly TNBC patients.[Methods]Patients aged>65 years diagnosed with stage Ⅰ-Ⅲ TNBC(except T1aN0)at the Cancer Hospital,Chinese Academy of Medical Sciences between 2010 and 2016 were retrospectively included.Survival outcomes influenced by chemotherapy and other singlefactor were estimated by the Kaplan-Meier method.Multivariate Cox regression was performed to minimize bias.[Results]A total of 177 patients were included with a median age of 69 years(range,6586),almost all had a Charlson Comorbidity Index of 0-2,and 127(71.8%)received chemotherapy.Patients who received chemotherapy were younger,had more advancedstage disease(especially a higher lymph node burden),had better ECOG performance status,and received radiation therapy more frequently(P<0.05).Among the 127 patients who were administered chemotherapy,45(35%)received taxane plus carboplatin,36(28%)received anthracycline-and-taxane-based regimens,and 23(18%)received taxane-based regimens.The regimen options differed based on patient age and tumour stage(P<0.05).Nearly 80%of the patients completed ≥6 cycles of chemotherapy,and half had their dosage decreased.After adjustment for confounding factors,patients who received ≥6 cycles of chemotherapy were found to have improved RFS rates(hazard ratio[HR],0.28;95%confidence interval[CI],0.09-0.87;P=0.027),and receipt of chemotherapy(≥1 cycle)was associated with better BCSS(HR,0.19;95%CI,0.04-0.97;P=0.046)and OS(HR,0.26;95%CI,0.08-0.87;P=0.029)rates.Subgroup analysis showed that improvements in RFS with>6 cycles of chemotherapy were increasing with staging.[Conclusions]These results support the considering the risk for recurrence and performing individualized assessments when determining the appropriate chemotherapy approach for older women with early TNBC.