Rare triple-negative breast cancers (TNBC): An NCDB analysis.

e19253 Background: The literature on rare triple negative breast cancer (TNBC) histology types is sparse; herein we present the clinical demographic and treatment patterns as well as overall survival (OS) for rare (< 10%) types of breast cancers that typically present as TNBCs: Medullary carcinoma (MedC), Adenoid cystic carcinoma (ACC), and Metaplastic breast cancer (MetC). Methods: Records of patients with a confirmed diagnosis of MedC, ACC, and MetC between 2010 and 2016 in the National Cancer Database (NCDB) were analyzed. Patients with an unknown stage were excluded. Univariate analyses and multivariable Cox-regression models were performed in SAS v. 9.4. Results: A total of 8,479 records were analyzed. MetC was the most commonly diagnosed histologic type in our cohort with 6,867 (81%) patients versus 255 (3.0%) MedC patients and 1,357 (16%) ACC patients. MedC presented earlier in life, with a median age of 53 years versus 62 years for ACC patients, and 63 years for MetC patients. The proportion of TNBC varied by histology type for MedC (70.4%), ACC (77.0%), and MetC (79.0 %). Patients with ACC were less likely to receive radiotherapy (52.4%) and chemotherapy (12.9%) compared to MedC (61.2%, 74.5%) and MetC (49.7%, 68.6%) respectively. On Cox multivariate regression, age ≥60 (HR 4.7), stage ≥3 [compared to patients with stage 0&1] (HR 5.7), and not receiving radiotherapy (HR 2.0) or chemotherapy (HR 1.25) conferred worse overall survival for MedC. Similarly, among patients with ACC, age ≥60 (HR 3.5), stage ≥3 (HR 5.3), and lymph node involvement (HR 4.8) were adverse prognostic indicators as well as not receiving radiation therapy (HR 1.47). Among MetC, lung metastasis (HR 2.6), stage ≥3 (HR 4.5), but also not receiving chemotherapy (HR 1.8) or radiation therapy (HR 1.47) was associated with worse survival outcomes. All p-values for cox regression is <0.0001. The 5-year OS was 92.6% for patients with MedC, 92.0% for ACC patients, 69.3% for MetC patients; all p-values <0.0001. Conclusions: This analysis describes rare types of TNBCs: MedC (most common), ACC, and MetC. We noted heterogeneity among these 3 rare types of TNBC, with the worst 5-year OS noted for MetC. Poor prognostic factors for MetC include advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and would potentially inform the optimal management of these breast carcinomas.

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Prognostic Biomarkers on a Competitive Endogenous RNA Network Reveals Overall Survival in Triple-Negative Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.681946 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wenxing Qin ◽

Feng Qi ◽

Jia Li ◽

Ping Li ◽

Yuan-Sheng Zang

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Prognostic Model ◽

Triple Negative ◽

Cox Regression ◽

Critical Role ◽

Differentially Expressed ◽

Cerna Network ◽

Competitive Endogenous Rna

The objective of this study was to construct a competitive endogenous RNA (ceRNA) regulatory network using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with triple-negative breast cancer (TNBC) and to construct a prognostic model for predicting overall survival (OS) in patients with TNBC. Differentially expressed lncRNAs, miRNAs, and mRNAs in TNBC patients from the TCGA and Metabric databases were examined. A prognostic model based on prognostic scores (PSs) was established for predicting OS in TNBC patients, and the performance of the model was assessed by a recipient that operated on a distinctive curve. A total of 874 differentially expressed RNAs (DERs) were screened, among which 6 lncRNAs, 295 miRNAs and 573 mRNAs were utilized to construct targeted and coexpression ceRNA regulatory networks. Eight differentially expressed genes (DEGs) associated with survival prognosis, DBX2, MYH7, TARDBP, POU4F1, ABCB11, LHFPL5, TRHDE and TIMP4, were identified by multivariate Cox regression and then used to establish a prognostic model. Our study shows that the ceRNA network has a critical role in maintaining the aggressiveness of TNBC and provides comprehensive molecular-level insight for predicting individual mortality hazards for TNBC patients. Our data suggest that these prognostic mRNAs from the ceRNA network are promising therapeutic targets for clinical intervention.

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Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation

Cancers ◽

10.3390/cancers11020127 ◽

2019 ◽

Vol 11 (2) ◽

pp. 127 ◽

Cited By ~ 10

Author(s):

Yueh-Chun Lee ◽

Wen-Ling Wang ◽

Wei-Chao Chang ◽

Yu-Hao Huang ◽

Guan-Ci Hong ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Cancer Patients ◽

Triple Negative ◽

Mass Spectrometry Analysis ◽

Radiation Response ◽

Stem Cell Population ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Poor Prognostic Factor

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

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SEER-Medicare study of early-stage triple-negative breast cancer: Real-world treatment patterns, survival, and expenditures 2010 to 2016.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12512 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12512-e12512

Author(s):

Jan Sieluk ◽

Amin Haiderali ◽

Min Huang ◽

Lingfeng Yang ◽

Konstantinos Tryfonidis ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Elderly Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Patient Characteristics ◽

Breast Cancers ◽

The Us ◽

Poor Outcomes

e12512 Background: In the US, triple-negative breast cancer (TNBC) represents about 10–20% of breast cancers. Current information about the clinical and economic burden of early-stage TNBC in elderly patients is lacking. Methods: We used the SEER-Medicare database to identify patients with continuous Medicare Parts A/B enrollment, ≥66 years old, newly diagnosed between 2010 - 2015 (followed until 2016) with stage II-III TNBC, who initiated systemic neoadjuvant and/or adjuvant (including chemotherapy and radiation) therapy. Overall survival (OS) and event-free survival (EFS) from diagnosis were estimated using Kaplan-Meier (KM). Healthcare costs were determined during neoadjuvant and adjuvant periods. Results: Of 1569 patients ( > 99% women), 94 (6%) received neoadjuvant therapy, 1162 (74%) received adjuvant therapy, and 313 (20%) received both (neo/adj; Table). Age and race/ethnicity distributions were comparable in the three cohorts. Primary tumor T stage was T1c/T2 for 43%, 83%, and 58% in neoadjuvant, adjuvant, and neo/adj, respectively, and T3 for 14%, 10%, and 15%, respectively. The most common systemic regimens in both neoadjuvant and adjuvant periods were a taxane +/- anthracycline; 21% and 67% of patients in adjuvant and neo/adj cohorts received radiation therapy after surgery. Most claims were for outpatient treatment; hospitalizations were uncommon. The total mean expenditures per patient per month were US$10,620 and $24,408 during neoadjuvant and adjuvant periods, respectively. Conclusions: This study provides insights into patient characteristics, as well as clinical and economic outcomes for elderly patients with early-stage TNBC, treated from 2010-2016 in the US, highlighting the high monetary burden of TNBC and poor outcomes associated with stage III patients. [Table: see text]

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An 8-lncRNA Signature Predicts Survival of Triple-Negative Breast Cancer Patients Without Germline BRCA1/2 Mutation

10.21203/rs.3.rs-60544/v1 ◽

2020 ◽

Author(s):

Minling Liu ◽

Wei Dai ◽

Mengyuan Zhu ◽

Xueying Li ◽

Shan Huang ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cox Regression ◽

Validation Cohort ◽

Functional Enrichment ◽

Biological Behavior ◽

Risk Scores ◽

Training Cohort

Abstract Background: Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment.Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm.Results:We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P=0.00018 and P =0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion.Conclusions: We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.

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The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer

BMC Cancer ◽

10.1186/s12885-020-07639-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Lei Zhang ◽

Ru Tang ◽

Jia-Peng Deng ◽

Wen-Wen Zhang ◽

Huan-Xin Lin ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Cox Regression ◽

Population Based ◽

Breast Cancers ◽

Cancer Specific Survival ◽

Postmastectomy Radiotherapy ◽

Pathological Staging ◽

Node Positive ◽

Advanced Tumor

Abstract Background The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. Methods Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. Results Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642–0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3–4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1–2N1 disease (P = 0.191). Conclusions Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3–4N1 and T1-4N2–3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1–2N1 TNBC.

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An 8-lncRNA signature predicts the survival of triple-negative breast cancer patients without germline BRCA1/2 mutation

Medical Research ◽

10.6913/mrhk.202109_3(3).0003 ◽

2021 ◽

Vol 3 (3) ◽

pp. 15-32

Author(s):

Minling LIU ◽

Wei DAI ◽

Mengyuan ZHU ◽

Xueying LI ◽

Min WEI ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cox Regression ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Training Cohort ◽

Cox Regression Analysis ◽

Platinum Based Chemotherapy

Purpose: TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment. Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort. Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The qPCR assay was performed to confirm the expressions and clinicopathological correlations of two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm. Results: We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. Patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores (P=0.00018 and P =0.0068 respectively). 30 paired specimens of TNBC without gBRCAm in our center showed that two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed, and significantly associated with tumor grade and invasion. Conclusion: We constructed a novel 8-lncRNA signature which significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8 lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targets which function needed further exploration.

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Construction and Validation of a Prognostic Risk Model for Triple Negative Breast Cancer Based on Autophagy-Related Genes

10.21203/rs.3.rs-1141994/v1 ◽

2021 ◽

Author(s):

Cheng Yan ◽

Qingling Liu ◽

Ruoling Jia

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Regression Analysis ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Risk Model ◽

Cox Regression ◽

Risk Group ◽

Lasso Regression ◽

Cox Regression Analysis

Abstract Background: Autophagy plays an important role in triple negative breast cancer (TNBC). However, the prognostic value of autophagy-related genes (ARGs) in TNBC remains unknown. In this study, we established a survival model to evaluate the prognosis of TNBC patients using ARGs signature.Methods: A total of 222 autophagy-related genes were downloaded from The Human Autophagy Database. The RNA-sequencing data and corresponding clinical data of TNBC were obtained from the TCGA database. Differential gene expression of ARGs (DE-ARGs) between normal samples and TNBC samples was determined by the EdgeR software package. Then, univariate Cox, Lasso, and multivariate Cox regression analyses were performed. According to the Lasso regression results based on univariate Cox, we identified a prognostic signature for overall-survival (OS), which was further validated by using GEO cohort. We also found an independent prognostic marker that can predict the clinicopathological features of TNBC. Furthermore, a nomogram was drawn to predict the survival probability of TNBC patients, which could help in clinical decision for TNBC treatment. Finally, we validated the requirement of a ARG in our model for TNBC cell survival and metastasis.Results: There are 43 differentially expressed ARGs (DE-ARGs) were identified between normal and tumor samples. A risk model for OS using CDKN1A, CTSD, CTSL, EIF4EBP1, TMEM74 and VAMP3 by Lasso regression analysis was established based on univariate Cox regression analysis. Overall survival of TNBC patients was significantly shorter in the high-risk group than in the low-risk group for both the training and validation cohorts. Using the Kaplan-Meier curves and ROC curves, we demonstrated the accuracy of the prognostic model. Multivariate Cox regression analysis was used to verify risk score as independent predictor. Then a nomogram was proposed to predict 1-, 3-, and 5-year survival for TNBC patients. The calibration curves showed great accuracy of the model for survival prediction. Finally, we found that depletion of EIF4EBP1, one of ARGs in our model, significantly reduced cell proliferation and metastasis of TNBC cells. Conclusion: An autophagy-related prognosis model in TNBCs was constructed using ARGs signature containing CDKN1A, CTSD, CTSL, EIF4EBP1, TMEM74 and VAMP3. It could serve as an independent prognostic biomarker in TNBC.

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TCOF1 upregulation in triple-negative breast cancer promotes stemness and tumour growth and correlates with poor prognosis

British Journal of Cancer ◽

10.1038/s41416-021-01596-3 ◽

2021 ◽

Author(s):

Jianyang Hu ◽

Yuni Lai ◽

Hao Huang ◽

Saravanan Ramakrishnan ◽

Yilin Pan ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Poor Prognosis ◽

Triple Negative ◽

Cox Regression ◽

Critical Role ◽

Rna Seq ◽

Data Set ◽

Super Enhancer

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis. By performing multiomic profiling, we recently uncovered super-enhancer heterogeneity between breast cancer subtypes. Our data also revealed TCOF1 as a putative TNBC-specific super-enhancer-regulated gene. TCOF1 plays a critical role in craniofacial development but its function in cancer remains unclear. Methods Overall survival and multivariant Cox regression analyses were conducted using the METABRIC data set. The effect of TCOF1 knockout on TNBC growth and stemness was evaluated by in vitro and in vivo assays. RNA-seq and rescue experiments were performed to explore the underlying mechanisms. Results TCOF1 is frequently upregulated in TNBC and its elevated expression correlates with shorter overall survival. TCOF1 depletion significantly inhibits the growth and stemness of basal-like TNBC, but not of mesenchymal-like cells, highlighting the distinct molecular dependency in different TNBC subgroups. RNA-seq uncovers several stem cell molecules regulated by TCOF1. We further demonstrate that KIT is a downstream effector of TCOF1 in mediating TNBC stemness. TCOF1 expression in TNBC is regulated by the predicted super-enhancer. Conclusions TCOF1 depletion potently attenuates the growth and stemness of basal-like TNBC. Expression of TCOF1 may serve as a TNBC prognostic marker and a therapeutic target.

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NCOG-05. MANAGEMENT OF BRAIN METASTASIS IN TRIPLE NEGATIVE BREAST CANCER

Neuro-Oncology ◽

10.1093/neuonc/noaa215.544 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii130-ii130

Author(s):

Ravi Medikonda ◽

Siddhartha Srivastava ◽

Timothy Kim ◽

Yuanxuan Xia ◽

Mira Patel ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Brain Metastasis ◽

Brain Metastases ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Whole Brain ◽

Whole Brain Radiation ◽

Brain Radiation

Abstract Brain metastasis is common in patients with breast cancer, and those with triple negative status have an even higher risk. Stereotactic radiosurgery (SRS) is preferred to whole brain radiation therapy (WBRT) in most patients. However, triple negative status is currently not considered when determining optimal radiation therapy. Given the aggressive nature of triple negative breast cancer, we evaluated a role for WBRT for all patients in this cohort. We conducted a single-institution retrospective cohort study to determine whether triple negative patients with brain metastases have a higher burden of intracranial disease and whether type of initial radiation therapy affects overall survival for this cohort of patients. 85 patients met the inclusion criteria for this study. 25% of patients had triple negative breast cancer, of which 91% received SRS and 53% of patients received WBRT. The average number of new brain metastases from time of initial brain imaging to radiation therapy was 0.67 (St.Dev:1.1) in the non-triple negative status patients and 2.6 (St. Dev:3.7) in the triple negative status patients (p=0.001). Using a cox proportional hazards model, it was found that whole brain radiotherapy does not significantly affect overall survival in patients with triple negative breast cancer (p = 0.96). Our findings highlight the highly aggressive intracranial nature of triple negative breast cancer. Indeed, the rate of increase in brain metastases is significantly higher for triple negative patients compared to non-triple negative patients. As a result, we evaluated whether triple negative patients would benefit from whole brain radiation regardless of findings on initial brain imaging. Despite 53% of patients receiving WBRT, our investigation found that there is no additional benefit to WBRT in triple negative breast cancer patients. These results suggest a need to re-evaluate the role of WBRT in the management of triple negative breast cancer.

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Survival of patients with locally advanced triple-negative breast cancer after neoadjuvant platinum-containing chemotherapy: Experience of a single institute.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.274 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 274-274

Author(s):

E. A. Ibrahim

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Pathological Complete Response ◽

Locally Advanced ◽

Complete Response ◽

Biological Entity ◽

Breast Cancers

274 Background: Primary systemic chemotherapy is a standard approach to treating women with locally advanced breast cancers, with higher survival rates reported among patients who attain a pathologic complete response. Triple-negative breast cancer is a special biological entity that remains major challenge to oncologist. Around 12%-20% of breast cancers are triple negative. The current phase II study was conducted to evaluate the pathological complete response (pCR) using cis-platinum containing regimen as neoadjuvant chemotherapy in locally advanced triple negative breast cancer. Methods: Eighteen women with stage III triple negative breast cancer who were recruited between July 2007 and February 2010 at King Fahad Specialist Hospital, Dammam, Saudi Arabia. Neoadjuvant chemotherapy consisted of 4 cycles of AC or FEC 100, followed by 4 cycles consisted of docetaxel-cisplatin every 3 weeks. Primary end point was pathological complete response. Results: Median age: 49 y (24-70); premenopausal: 16; 25% were below 35 years of age; Median tumor size: 9 cm (3.5-19); Grade III: 15; Stage IIIA: 3, IIIB:14, IIIC:1; all but 2 had positive nodes at diagnosis (89%). Clinical evaluation of response by RECIST criteria pre surgery: OR: 17/18 (94%), CR: 9 (50%); PR: 8 (44%).The second sequence with D-Cis-T doubled the rate of clinical CR obtained with AC/FEC. One patient was not operated due to disease progression. Pathological assessment, revealed that 8 (47%) pts had no residual invasive carcinoma in the breast; 3 (18%) had residual occasional scattered tumor cells less than 5 mm (pT1a); 10 (59%) had negative nodes; 8 achieved CpR and 2 nCpR. Patients with residual invasive component and/or nodal involvement had high baseline Ki 67 level. After a median follow up of 24 months, cumulative overall survival at 24 months is 88.9% for whole group. Cumulative overall survival in relation to response was 100% for patients who achieved pCR while overall cumulative survival rate for patients without pCR was 83.3% without statistical significance. Conclusions: This cisplatin based neoadjuvant chemotherapy regimen was well tolerated and achieved a high rate of pCR/npCR.

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