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Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy.

ABSTRACT: Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that is characterized by poor prognosis, strong tumor invasion and a high pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). The pCR rate is a prognostic factor for TNBC. We aimed to evaluate the relationship between pCR and TNBC after NAC and originally tried to identify factors related to achieving pCR for TNBC using a meta-analysis.We systematically searched the literature for pCR and breast cancer after NAC and carefully identified eligibility criteria. The association between pCR and breast cancer subtypes was estimated using Review Manager, while pCR rates for TNBC and non-TNBC were determined using Meta-Analyst.This analysis included a total of 9,460 cases from 27 studies. The summary odds ratio estimating the relationship between pCR and breast cancer subtypes (TNBC vs non-TNBC) was 3.02 (95% confidence interval (CI), 2.66 to 3.42). The TNBC pCR rate was 28.9% (95% CI, 27.0 to 30.8%) and the non-TNBC was 12.5% (95% CI, 11.7 to 13.4%). From subgroup analyses, we identified the factors associated with the highest pCR rates for TNBC.TNBC has a higher pCR rate than non-TNBC. In the NAC setting, these factors of platinum-containing, more than six cycles, four kinds of drugs, 16 weeks' treatment duration and sequential chemotherapy may contribute to increasing the pCR rate.

SUBMITTER: Wu K

PROVIDER: S-EPMC4011773 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy.

Wu Kunpeng K Yang Qiaozhu Q Liu Yi Y Wu Aibing A Yang Zhixiong Z

World journal of surgical oncology 20140415

<h4>Background</h4>Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that is characterized by poor prognosis, strong tumor invasion and a high pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). The pCR rate is a prognostic factor for TNBC. We aimed to evaluate the relationship between pCR and TNBC after NAC and originally tried to identify factors related to achieving pCR for TNBC using a meta-analysis.<h4>Methods</h4>We systematically searched the lit ...[more]

PMID: 24731479

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Project description:BackgroundTo investigate the association of axillary pathologic complete response (pCR) rate among breast cancer patients with pCR after neoadjuvant chemotherapy (NCT).MethodsThe retrospective clinical data of 1,903 patients who were treated with NCT between March, 2010 and December, 2018, were collected from one Chinese database and analyzed. The correlations between clinicopathological characteristics and breast pCR with axillary pCR were calculated by χ2 test. Binary logistic regression analysis was used for multivariate analysis. The relative risk of positive axillary nodes after NCT in patients with and without breast pCR was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by initial N stage and tumor subtype.ResultsThe rate of axillary pCR was increased in the cases with initial cN0, Ki67 high expression, HR+HER2+/HR-HER2+/TN subtypes, and breast pCR. After NCT, the relative risk of nodal disease burden was 4.81 in patients without breast pCR compared with patients with breast pCR. The relative risk of positive nodal status in patients with cN0, cN1, cN2, and cN3 disease without vs. with breast pCR was 6.45, 4.88, 5.69 and 6.24, respectively. The relative risk of positive nodal status in patients with HR+HER2-, HR+HER2+, HR-HER2+, and TN disease was 4.02, 4.50, 3.82 and 4.18, respectively. Of cN0 patients with breast pCR, only 4 out of 44 (9%) with HER2-positive disease had 1 or 2 axillary lymph node metastases at final surgical pathology compared to 30 out of 98 (31%) of those without breast pCR. There was no evidence of positive nodal residue among all 21 patients (100%) with TN disease compared to 65% (36 of 55) of patients without breast pCR.ConclusionsNodal status is strongly correlated with breast pCR after NCT. Patients with initial cN0/1 TN/HER2 positive disease who achieve breast pCR at surgery have a low risk of nodal metastasis. These results suggest that the failure rate of missing positive lymph nodes among those patients was very low and that it is safe for such patients to undergo sentinel lymph node biopsy (SLNB) after NCT. This study also provides a theoretical basis for clinical trials focused on the avoidance of axillary surgery in selected patients.

Project description:ImportanceA recent publication reported that of 527 patients with clinically node-negative (cN0) cT1/cT2 triple-negative breast cancer (TNBC) or ERBB2-positive disease treated with neoadjuvant chemotherapy (NAC), 100% of those who achieved a breast pathologic complete response (pCR) had pathologic node negativity (pN0). Eliminating axillary surgery in these patients has been suggested as safe based on these results.ObjectiveTo evaluate nodal positivity rates in patients with cT1/cT2 N0 ERBB2-positive disease and TNBC with a breast pCR after NAC using the National Cancer Database (NCDB), which included academic and community settings.Design, setting, and participantsThis retrospective study reviewed data from the NCDB from January 1, 2010, through December 31, 2015. Participants included patients with cN0/cN1 cT1/cT2 breast cancer who received NAC followed by surgery. Pathologic nodal positivity rates by breast pCR were compared in cN0 and cN1 disease, within each tumor subtype (ERBB2-positive, TNBC, and hormone receptor-positive/ERBB2-negative). Data were analyzed from September 13, 2017, through January 30, 2018.ExposuresNeoadjuvant chemotherapy followed by surgery.Main outcomes and measuresThe pathologic nodal positivity rate after NAC (ypN) specifically in patients with cT1/cT2 cN0 ERBB2-positive disease or TNBC who achieve a breast pCR after NAC.ResultsA total of 30 821 patients with cT1/cT2 cN0/cN1 breast cancer treated with NAC and surgical resection (99.6% female; mean [SD] age, 52.0 [11.5] years) were identified. Of 6802 patients with cN0 ERBB2-positive disease, 3062 (45.0%) achieved breast pCR and of those, 49 (1.6%; 95% CI, 1.2%-2.1%) were ypN positive. In 6222 patients with cN0 TNBC, 2315 (37.2%) achieved breast pCR, and of those, 36 (1.6%; 95% CI, 1.1%-2.1%) were pathologic node positive after NAC. Rates of ypN positivity were higher in patients with cN0 and residual disease in the breast; 632 of 3740 (16.9%) with ERBB2-positive disease and 492 of 3907 (12.6%) with TNBC with residual disease in the breast were node positive (P < .001). Among 4164 patients with cN1 ERBB2-positive disease, 1801 (43.3%) achieved breast pCR, with 223 of those (12.4%) being ypN positive. In 3293 patients with TNBC, 1229 (37.3%) achieved breast pCR, with 173 of these (14.1%) being ypN postive. Breast pCR rates were lower in hormone receptor-positive/ERBB2-negative disease (646 of 5069 [12.7%] for cN0; 711 of 5271 [13.5%] for cN1) and ypN positivity rates were 26 of 646 (4.0%) in cN0 vs 217 of 711 (30.5%) in cN1 disease with breast pCR and 1464 of 4423 (33.1%) in cN0 disease vs 3775 of 4560 (82.8%) in cN1 disease with residual disease in the breast.Conclusions and relevanceIn this study, the highest rates of breast pCR were seen in ERBB2-positive disease and TNBC. In patients with cN0 ERBB2-positive disease or TNBC with breast pCR, the nodal positivity rate was less than 2%, which supports consideration of omission of axillary surgery in this subset of patients.

Project description:Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy.This was an institutional review board-approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservation or mastectomy), and adjuvant radiation therapy between 1997 and 2015. Medical records were reviewed for clinical stage, tumor grade and subtype, neoadjuvant chemotherapy regimen, type of surgery, pathologic stage, use of radiation therapy, date and location of recurrence, and date of death. Molecular subtypes were defined using immunohistochemistry and histologic grade. ypT0 and ypN0 were defined as no residual invasive disease in breast or nodes, respectively. LRR was defined as any failure within the breast, chest wall, or regional lymph nodes. Statistical analysis was performed; LRR and DFS rates over 30 months were determined from Kaplan-Meier plots.Ninety-four patients with TNBC were analyzed, of whom 72 received radiation therapy. This subgroup was isolated for further investigation. Median follow-up was 32.5 months in this group. The pathologic complete response (pCR) rate was 36%, and presence or absence of disease in breast and/or nodes was significantly predictive of LRR. In TNBC patients who received radiation therapy, 30-month LRR was 22% in 41 patients with ypT+ versus 0% in 31 patients with ypT0 (P = .003), 23% in 31 patients with ypN+ versus 5% in 41 patients with ypN0 (P = .016), and 20% in 46 patients with residual disease in breast or nodes versus 0% in 26 patients with pCR (P = .015). The difference in the rate of LRR between those who underwent lumpectomy versus mastectomy did not reach significance (8% vs 17%, respectively). Furthermore, patients with residual disease had a higher rate of DFS events (hazard ratio, 3.58; 95% confidence interval, 1.37-9.41; P = .006). The difference in DFS was not significantly associated with the type of surgery received.Patients with TNBC treated with neoadjuvant chemotherapy who have residual disease in the breast or lymph nodes at the time of surgery have significantly higher rates of locoregional failure and lower DFS compared with those with a pCR despite the use of adjuvant radiation therapy. Strategies to intensify therapy for patients with residual disease warrant further investigation.

Project description:ImportanceAdding carboplatin to standard neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) likely benefits a subset of patients; however, determinants of benefit are poorly understood.ObjectiveTo define the association of molecular subtype, tumor proliferation, and immunophenotype with benefit of carboplatin added to NAC for patients with stages II to III TNBC.Design, setting, and participantsThis was a prespecified secondary analysis of a phase 3, double-blind, randomized clinical trial (BrighTNess) that enrolled 634 women across 145 centers in 15 countries. Women with clinical stages II to III TNBC who had undergone pretreatment biopsy were eligible to participate. Whole transcriptome RNA sequencing was performed on the biopsy specimens. The prespecified end point was association of pathologic complete response (pCR) with gene expression-based molecular subtype, with secondary end points investigating established signatures (proliferation, immune) and exploratory analyses of immunophenotype. Data were collected from April 2014 to March 2016. The study analyses were performed from January 2018 to March 2019.InterventionsNeoadjuvant chemotherapy with paclitaxel followed by doxorubicin and cyclophosphamide, or this same regimen with carboplatin or carboplatin plus veliparib.Main outcomes and measuresAssociation of gene expression-based molecular subtype (PAM50 and TNBC subtypes) with pCR.ResultsOf the 634 women (median age, 51 [range, 22-78] years) enrolled in BrighTNess, 482 (76%) patients had evaluable RNA sequencing data, with similar baseline characteristics relative to the overall intention-to-treat population. Pathologic complete response was significantly more frequent in PAM50 basal-like vs nonbasal-like cancers overall (202 of 386 [52.3%] vs 34 of 96 [35.4%]; P = .003). Carboplatin benefit was not significantly different in basal-like vs nonbasal-like subgroups (P = .80 for interaction). In multivariable analysis, proliferation (hazard ratio, 0.36; 95% CI, 0.21-0.61; P < .001) and immune (hazard ratio, 0.62; 95% CI, 0.49-0.79; P < .001) signatures were independently associated with pCR. Tumors above the median for proliferation and immune signatures had the highest pCR rate (84 of 125; 67%), while those below the median for both signatures had the lowest pCR rate (42 of 125; 34%). Exploratory gene expression immune analyses suggested that tumors with higher inferred CD8+ T-cell infiltration may receive greater benefit with addition of carboplatin.Conclusions and relevanceIn this secondary analysis of a randomized clinical trial, triple-negative breast cancer subtyping revealed high pCR rates in basal-like and immunomodulatory subsets. Analysis of biological processes related to basal-like and immunomodulatory phenotypes identified tumor cell proliferation and immune scores as independent factors associated with achieving pCR; the benefit of carboplatin on pCR was seen across all molecular subtypes. Further validation of immunophenotype with existing biomarkers may help to escalate or de-escalate therapy for patients with TNBC.Trial registrationClinicalTrials.gov Identifier: NCT02032277.

Project description:BackgroundThe persistence of residual tumour after neoadjuvant chemotherapy (NAC) in localised triple-negative breast cancer (TNBC) is known to have a negative prognostic value. However, different degrees of expression of some immunohistochemical markers may correlate with different prognoses.MethodsThe expression of biomarkers with a known prognostic value, i.e., cytokeratin 5/6 (CK5/6), androgen receptor (AR), epidermal growth factor receptor (EGFR) proliferation-related nuclear antigen Ki-67, human epidermal growth factor receptor 2 (HER2), protein 53 (p53), forkhead box protein 3 (FOXP3), and cluster differentiation 8 (CD8), was analysed by immunohistochemistry in 111 samples after NAC in non-metastatic TNBC patients addressed to Georges-François Leclerc Cancer Centre Dijon, France. Clinical and pathological variables were retrospectively collected. Cox regression was used to identify immunohistochemical (IHC) and clinicopathological predictors of event-free survival (EFS) (relapse or death).ResultsMedian age was 50.4 years (range 25.6-88.3), 55.9% (n = 62) were non-menopausal, 70 (63.1%) had stage IIA-IIB disease. NAC was mostly sequential anthracycline-taxanes (72.1%), and surgical intervention was principally conservative (51.3%). We found 65.7% ypT1, 47.2% lymph node involvement (ypN+), and 29.4% lymphovascular invasion (LVI). Most residual tumours were EGFR >110 (H-score) (60.5%, n = 66), AR ≥4% (53.2%, n = 58), p53-positive mutated (52.7%, n = 58), CD8 ≥26 (58.1%, n = 61), FOXP3 ≥7 (51.4%, n = 54), more than half in the stroma, and 52.3% (n = 58) HER2 score 0. After a median follow-up of 80.8 months, 48.6% had relapsed. Median EFS was 62.3 months (95% CI, 37.2-not reached (NR)). Factors independently associated with poor EFS were AR-low (p = 0.002), ypN+ (p < 0.001), and LVI (p = 0.001). Factors associated with lower overall survival (OS) were EGFR-low (p = 0.041), Ki-67 high (p = 0.024), and ypN+ (p < 0.001).ConclusionPost-NAC residual disease in TNBC showed biomarkers specific to a basal-like subtype and markers of lymphocyte infiltration mostly present in the stroma. Prognostic markers for EFS were AR, LVI, and ypN and warrant further validation in a prognostic model.

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Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy.

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Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy.

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