Dataset Information

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy.

ABSTRACT: Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines and/or taxanes +/- carboplatin. We explored the clinicopathological characteristics of Lehmann subtypes and their association with the pathologic complete response (pCR) to different treatments. The global pCR rate was 37%, and it was unevenly distributed within Lehmann's subtypes. Basal-like 1 (BL1) tumors exhibited the highest pCR to carboplatin containing regimens (80% vs 23%, p=0.027) and were the most proliferative (Ki-67>50% of 88.2% vs. 63.7%, p=0.02). Luminal-androgen receptor (LAR) patients achieved the lowest pCR to all treatments (14.3% vs 42.7%, p=0.045 when excluding mesenchymal stem-like (MSL) samples) and were the group with the lowest proliferation (Ki-67?50% of 71% vs 27%, p=0.002). In our cohort, only tumors with LAR phenotype presented non-basal-like intrinsic subtypes (HER2-enriched and luminal A). TNBC patients present tumors with a high genetic diversity ranging from highly proliferative tumors, likely responsive to platinum-based therapies, to a subset of chemoresistant tumors with low proliferation and luminal characteristics.

SUBMITTER: Santonja A

PROVIDER: S-EPMC5995183 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy.

Santonja Angela A Sánchez-Muñoz Alfonso A Lluch Ana A Chica-Parrado Maria Rosario MR Albanell Joan J Chacón José Ignacio JI Antolín Silvia S Jerez José Manuel JM de la Haba Juan J de Luque Vanessa V Fernández-De Sousa Cristina Elisabeth CE Vicioso Luis L Plata Yéssica Y Ramírez-Tortosa César Luis CL Álvarez Martina M Llácer Casilda C Zarcos-Pedrinaci Irene I Carrasco Eva E Caballero Rosalía R Martín Miguel M Alba Emilio E

Oncotarget 20180529 41

Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines a ...[more]

PMID: 29899867

Similar Datasets

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: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.

Dataset Information

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy.

Publications

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets