A randomized, triple negative breast cancer enrolling trial to confirm molecular profiling improves survival (ARTEMIS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS590-TPS590 ◽  
Author(s):  
Clinton Yam ◽  
Kenneth R. Hess ◽  
Jennifer Keating Litton ◽  
Wei Tse Yang ◽  
Helen Piwnica-Worms ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Triple Negative Breast Cancer ◽  
Primary Tumor ◽  
Triple Negative ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Type I ◽  
Free Survival

TPS590 Background: Following neoadjuvant chemotherapy (NACT), patients (pts) with triple negative breast cancer (TNBC) achieving pathologic complete response/residual cancer burden-0 (pCR/RCB-0) or minimal residual disease (RCB-I) have an improved relapse free survival when compared to pts with more extensive residual disease (RCB-II/III) (Symmans et al, JCO 2017). Pts with chemo-resistant TNBC have a poor prognosis as there are currently no FDA-approved targeted agents available for TNBC. We previously reported the ability of a novel gene expression signature (GES) to predict sensitivity to NACT (Hatzis et al, JAMA 2011). Here we seek to prospectively validate the use of this GES in combination with imaging to predict response to NACT and establish the clinical impact of selecting pts predicted to have non-responsive disease (NRD) for enrollment in clinical trials of targeted therapy. Methods: All pts will undergo a biopsy of the primary tumor for molecular characterization (MC) and will be randomized 2:1 to know their MC results (intervention arm) or not (control arm). A maximum of 360 pts will be enrolled and randomized using a group sequential design with one-sided O’Brien-Fleming boundaries, with two equally spaced binding interim tests for futility and superiority and one final test, having an overall Type I error of 0.05 and power of 0.80 to detect an improvement in pCR/RCB-I from 50% to 64%. Secondary endpoints include rates of clinical trial enrollment, disease free survival and integrated biomarker analyses. All pts will receive 4 cycles of anthracycline-based NACT with imaging done every 2 cycles to assess response. After completion or progression on anthracycline-based NACT, pts predicted to have NRD based on MC/imaging (intervention arm) or imaging alone (control arm) will be offered enrollment on a clinical trial. Pts are eligible if they have stage I-III TNBC with a primary tumor that is ≥1.5cm. Pts with contraindications to anthracyclines and/or taxanes are excluded. Enrollment began in November 2015. 105 pts have been enrolled to date with 71 and 34 pts randomized to the intervention and control arms, respectively. Clinical trial information: NCT02276443.

Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer

2021 ◽  
Author(s):  
Jie-Yu Zhou ◽  
Kang-Kang Lu ◽  
Wei-Da Fu ◽  
Hao Shi ◽  
Jun-Wei Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Discriminative Ability ◽  
Free Survival ◽  
Disease Free

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

scholarly journals Targeted-Gene Sequencing to Catch Triple Negative Breast Cancer Heterogeneity before and after Neoadjuvant Chemotherapy

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1753 ◽  
Author(s):  
Serena Di Cosimo ◽  
Valentina Appierto ◽  
Marco Silvestri ◽  
Giancarlo Pruneri ◽  
Andrea Vingiani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Primary Tumor ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
Gene Sequencing ◽  
Tumor Biopsy ◽  
Recurrent Mutations ◽  
Targeted Gene Sequencing

Triple negative breast cancer (TNBC) patients not attaining pathological Complete Response (pCR) after neo-adjuvant chemotherapy (NAC) have poor prognosis. We characterized 19 patients for somatic mutations in primary tumor biopsy and residual disease (RD) at surgery by 409 cancer-related gene sequencing (IonAmpliSeqTM Comprehensive Cancer Panel). A median of four (range 1–66) genes was mutated in each primary tumor biopsy, and the most common mutated gene was TP53 followed by a long tail of low frequency mutations. There were no recurrent mutations significantly associated with pCR. However, half of patients with RD had primary tumor biopsy with mutations in genes related to the immune system compared with none of those achieving pCR. Overall, the number of mutations showed a downward trend in post- as compared to pre-NAC samples. PIK3CA was the most common altered gene after NAC. The mutational profile of TNBC during treatment as inferred from patterns of mutant allele frequencies in matched pre-and post-NAC samples showed that RD harbored alterations of cell cycle progression, PI3K/Akt/mTOR, and EGFR tyrosine kinase inhibitor-resistance pathways. Our findings support the use of targeted-gene sequencing for TNBC therapeutic development, as patients without pCR may present mutations of immune-related pathways in their primary tumor biopsy, or actionable targets in the RD.

scholarly journals BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study

2018 ◽  
Vol 36 (22) ◽  
pp. 2281-2287 ◽  
Author(s):  
Peter A. Fasching ◽  
Sibylle Loibl ◽  
Chunling Hu ◽  
Steven N. Hart ◽  
Hermela Shimelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Strong Predictor ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Brca1 And Brca2 ◽  
Mutation Carriers

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

Vitamin D status and survival in patients with triple negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18210-e18210
Author(s):  
John Khoury ◽  
Sruthi Jinna ◽  
Ali Sahlieh ◽  
Rebecca Chacko ◽  
David Macari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Postmenopausal Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Stage I ◽  
Free Survival ◽  
Disease Free

e18210 Background: Although many studies have investigated the association of blood 25OH-vitamin D (vit-D) levels with breast cancer prognosis, the results have been mixed. It has been suggested that low vit-D concentrations were associated with advanced tumor stage and triple-negative (TNBC) subtype. We retrospectively investigated associations of serum vit-D levels with triple negative breast cancer outcome. Methods: Out of 797 cases of TNBC diagnosed at William Beaumont Hospital between 2006-2017, 163 patients had vit-D level available within 1 year prior to diagnosis. Analyses of vit-D levels was classified by 3 cut points (deficient, < 20.0 ng/mL; insufficient, 20.0-29.9 ng/mL; sufficient, ≥30.0 ng/mL). Primary outcomes are disease free survival (DFS) and overall survival (OS). SPSS statistics 25 software was used to analyze the data. Results: Median age of diagnosis of TNBC was 60. Of these patients 43.6% were diagnosed with stage I, 37.4% at stage II, 4.9% at stage III and 4.9% at stage IV. 47.2% of the patients had sufficient vit-D level prior to diagnosis, 28.2% with insufficient vit-D level and 24.5% with deficient vit-D. Vit-D deficiency was more prevalent in premenopausal than in postmenopausal women (33.3%, 41% and 25.6% in premenopausal women for deficient, insufficient and sufficient levels respectively vs 21.8%, 24.2% and 54% in postmenopausal women). Rates of Vit-D deficiency were not different between early disease and advanced disease (24.3% of patient with stage I-II vs 25% in patients with stage III-IV). Median OS and disease-free survival were not statistically different among the 3 different categories. 5-year OS was 91%, 91% and 85% for deficient, insufficient and sufficient levels respectively. 5-year DFS was 93%, 95% and 95% for deficient, insufficient and sufficient levels respectively. Multivariate COX regression analysis demonstrated that age and stage were associated with mortality, whereas vit-D level was not. Conclusions: The results from this study show that adequate vit-D level do not have an impact on OS and DFS in patients with triple negative breast cancer. Premenopausal women are more likely to have inadequate vit-D level. Identification and treatment of vitamin D deficiency is still important for musculoskeletal health and possibly extraskeletal health in general population and breast cancer survivors specifically.

scholarly journals Survival Study of Triple-Negative and Non–Triple-Negative Breast Cancer in a Brazilian Cohort

2018 ◽  
Vol 12 ◽  
pp. 117955491879056 ◽  
Author(s):  
Homero Gonçalves ◽  
Maximiliano Ribeiro Guerra ◽  
Jane Rocha Duarte Cintra ◽  
Vívian Assis Fayer ◽  
Igor Vilela Brum ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Lymph Node Involvement ◽  
Free Survival ◽  
Node Involvement ◽  
Brazilian Cohort ◽  
Disease Free

Objective: To analyze the clinical, pathological, and sociodemographic aspects between triple-negative breast cancer (TNBC) and non-TNBC in a Brazilian cohort and identify potential prognostic factors. Methods: This hospital-based retrospective cohort study included 447 women with breast cancer treated at referral centers in Southeastern Brazil. Overall and disease-free survival were compared; prognostic factors were evaluated. Results: Triple-negative breast cancer corresponded to 19.5% of breast cancer diagnosis and was more prevalent among nonwhite and less educated women. The patients with TNBC tended to present with stage III cancer, high p53 expression, lymphocytic infiltration, and multifocality and treated with radical surgery and chemotherapy. The 5-year overall and disease-free survival were 62.1% and 57.5% for TNBC and 80.8% and 75.3% for non-TNBC, respectively ( P < .001). The TNBC recurrence was associated with multicentricity, whereas lymph node involvement increased the risk of both recurrence and death. Non-TNBC worse clinical course was associated with nonwhite ethnicity, lower education level, lymph node involvement, and advanced stage. Conclusions: Triple-negative breast cancer exhibited a more aggressive behavior, earlier and more frequent recurrence, and worse survival compared with non-TNBC. While biological and social variables were associated with poorer prognosis in non-TNBC, only lymph node involvement and multicentricity were correlated with worse clinical outcomes in TNBC.

scholarly journals Stromal PD-L1 Expression Is Associated With Better Disease-Free Survival in Triple-Negative Breast Cancer

2016 ◽  
Vol 146 (4) ◽  
pp. 496-502 ◽  
Author(s):  
Xiaoxian Li ◽  
Ceyda Sonmez Wetherilt ◽  
Uma Krishnamurti ◽  
Jing Yang ◽  
Yamin Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free
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