Survival In Triple-negative Breast Cancer Patients Research Articles

Distant metastasis in triple-negative breast cancer

Triple-negative breast cancer (TNBC) relapses more frequently than hormone receptor-positive subtypes and is often associated with poor outcomes. This retrospective study reviewed the pattern of distant metastasis with regard to survival in patients with TNBC. A total of 205 TNBC patients were analyzed. TNBC patients with lung metastases had the longest median post-metastatic OS (with 95% confidence interval) of 16.6 (10.3-22.9) months, followed by the bone, 16.3 (11.7-20.8) months, the liver, 8.9 (3.5-14.4) months, the pleura, 7.5 (2.8-12.3) months, and the brain, 4.3 (0.6-8.0) months. Kaplan-Meier plots indicated that TNBC patients with metastatic spread to brain, liver, and pleural had poorer post-metastatic OS rate than patients with lung metastases (p = 0.001, 0.004, and 0.029, respectively). Moreover, brain and liver metastases correlated significantly with poorer post-metastatic OS as compared to bone metastasis (p = 0.004 and 0.011, respectively). Route of first metastasis correlated significantly with survival of TNBC patients with brain metastases being the poorest survival indicator, followed by metastases to liver, pleura, bone, and lung.

Analysis of pattern, time, and risk factors influencing recurrence in triple-negative breast cancer patients.

e11553 Background: The aim of the study was to assess the rate, pattern and time of recurrence in patients with triple-negative breast cancer (TNBC) treated in one institution. The second goal was to evaluate factors influencing recurrence and overall survival in this group of patients. Methods: 2534 consecutive breast cancer patients were diagnosed at the Cancer Center and Institute of Oncology in Warsaw, Poland, between January 2005 and December 2006. Out of 2534 patients, 228 (9%) were TNBC (ER/PR/HER2-negative). The clinicopathological characteristics were determined using descriptive statistics. The overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The univariate and multivariate analyses were developed to identify factors influencing recurrence and survival in TNBC patients. Results: Most of the patients were diagnosed with stage II or III breast cancer (47% and 34%, respectively), the median age at diagnosis was 54.5 years. The most common histological type was ductal cancer (81%). 31% of patients were treated with neoadjuvant chemotherapy and 49% with adjuvant chemotherapy – almost all consisted of anthracyclines. 6 years of observation revealed that the metastatic disease occurred in 35% of all TNBC patients: 15% in the brain, 14% in the lungs, 11% in the bones, 8% in the liver and 14% had locoregional relapse. The highest risk of recurrence was during the first 3 years after primary treatment and then during the next two years of observation it did not change. Median DFS and OS were not reached at the time of analysis, 6-year DFS and OS were 68% and 62%, respectively.Factors influencing recurrence were: tumor size and systemic adjuvant chemotherapy while factors influencing overall survival were: tumor size, nodal status, adjuvant/neoadjuvant treatment and metastases in the brain, liver and bones. Conclusions: Characteristic pattern of recurrence in time was revealed. The tumor size was responsible for recurrence despite lack of involvement of lymph nodes. Aggressive adjuvant/neoadjuvant treatment ordered in all clinical stages of TNBC (including N0) was factor responsible for avoiding local and distant relapse and prolonging overall survival.

MiR-34b is associated with clinical outcome in triple-negative breast cancer patients

BackgroundBreast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC) represents the major phenotype of basal-like molecular subtype of breast cancer, characterized by higher incidence in young women and a very poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs playing significant role in the pathogenesis of many cancers including breast cancer. Therefore, miRNAs are also potential prognostic and/or predictive biomarkers in triple-negative breast cancer patients.MethodsThirty-nine TNBC patients with available formalin-fixed paraffin-embedded (FFPE) tissues were enrolled in the study. MiR-34a, miR-34b, and miR-34c were analyzed using qRT-PCR and correlated to clinico-pathological features of TNBC patients.ResultsExpression levels of miR-34b significantly correlate with disease free survival (DFS) (p = 0.0020, log-rank test) and overall survival (OS) (p = 0.0008, log-rank test) of TNBC patients. No other significant associations between miR-34a, miR-34b, and miR-34c with available clinical pathological data were observed.ConclusionsMiR-34b expression negatively correlates with disease free survival and overall survival in TNBC patients. Thus, miR-34b may present a new promising prognostic biomarker in TNBC patients, but independent validations are necessary.

Abstract 5482: Theranostic nanoparticles for targeted therapy of triple negative breast cancer and for monitoring therapeutic response by MRI

Abstract Clinical Significance: Among 1 million cases of newly diagnosed breast cancer worldwide each year, over 170,000 cases will have a distinct type of triple-negative breast cancer (TNBC), which lacks expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (Her-2/neu). The patients with TNBC are usually detected at the late stage, have an aggressive tumor type, an increased likelihood of local and distant recurrence, and a poorer prognosis compared to women with other types of breast cancer. TNBC patients usually receive neoadjuvant therapy to reduce local and distant recurrence. However, more than 50% of TNBC patients are resistant to conventional chemotherapy. Therefore, novel methods for effective therapy are an urgent need for improving survival of the TNBC patients. Methods: We have developed a targeted therapy for TNBC by systemic delivery of biodegradable theranostic magnetic iron oxide nanoparticles (IONPs) that combine targeted drug delivery and non-invasive tumor imaging capabilities. These theranostic IONPs are targeted to urokinase plasminogen activator receptor (uPAR) by conjugating to the amino-terminal fragment (ATF) of the high affinity receptor binding domain of uPA. Results: 1). Our results from analysis of the gene expressing profile of a cohort of 143 breast cancer tissues revealed that uPAR, a potential cell surface target for the development of targeted therapeutics in TNBC, is highly expressed in the TNBC tissues compared to the luminal type of breast cancer (p < 0.0001). The major advantage of targeting uPAR is that the receptor is highly expressed in tumor cells and angiogenic endothelial cells, which facilitates transporting nanoparticles across the endothelium lining tumor vessels. Internalization of ATF-nanoparticle complexes by tumor cells further increases intracellular drug concentration; 2). We demonstrated that systemic delivery of uPAR-targeted theranostic IONPs carrying a chemotherapy drug, doxorubicin, significantly inhibited the growth of primary tumors through anti-tumor and anti-angiogenesis effects, and delayed local and distant recurrence for 8 weeks as compared mice-treated with free doxorubicin in a TNBC-like 4T1 mouse mammary tumor model. The improved therapeutic effect using these targeted theranostic nanoparticles has also been demonstrated in a human breast cancer xenograft model; 3). Targeting theranostic nanoparticles into tumors allow for monitoring intratumoral drug delivery and therapeutic response in the tumors by MRI; and 4). Targeted delivery of doxorubicin using theranostic IONPs reduces systemic toxicity of the drug in normal organs, such as heart and liver. Conclusion: uPAR-targeted theranostic nanoparticles have potential for targeted therapy, timely assessment of therapeutic response of a given therapy, and ultimately, increased survival of TNBC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5482.

Triple-negative breast cancer: Epidemiology, characteristics, and survival in a Lebanese cohort

e22228 Background: Breast cancer (BC) is the most common malignancy in women in Lebanon. Triple negative (TN) phenotype is known to be associated with an increased likelihood of recurrence and death. The purpose of this study is to determine the incidence, characteristics and survival of TN BC patients in a Medical Oncology department in a University Hospital in Lebanon. Methods: We retrospectively reviewed the pathology of all women with breast cancer that were seen in our institution between 1997 and 2008. TN BC patients (pts) were defined as those that were negative for all 3 receptors (estrogen, progesterone and HER2neu on immunohistochemistry). Pts' characteristics and survival of TN women were analyzed. Results: Of the 1599 breast cancer pts, 155 (9.7%) had a triple negative phenotype. Median age was 52 years. A positive family history of breast/ovarian cancer was found in 15 pts (10%). Pathology studies showed: invasive ductal carcinoma component in 138 pts (89%), pure medullary carcinoma in 7 pts (5%), pure invasive lobular carcinoma in 6 pts (4%), pure mucinous carcinoma in 3 pts (2%) and epidermoid carcinoma in 1 pt (1%). A grade III was found in 98 of specimens (63%). Twenty-six pts (17%) presented with stage I, 73 (47%) with stage II, 37 (24%) with stage III and 19 (12%) with stage IV. Twelve percent had inflammatory breast cancer. After a median follow up of 17 months (mths), 43 pts had relapsed (5 stage I, 18 stage II and 20 stage III). The most common sites of relapse were brain (in 20 % of cases), lungs (in 20% of cases) and bone (in 11% of cases). Five- year disease free survival and 5-year overall survival were respectively 75% and 88% for stage I, 58% and 72% for stage II and 40% and 63% for stage III. Adjuvant therapy was administered to 96% of pts among which a taxane-based regimen was used in 38% of cases . Median survival for stage IV was 19 mths with a first line taxane-based regimen used in 50% of cases. Conclusions: The incidence of TN BC in Lebanon is similar to that described in the literature. It has an aggressive course. Focus on understanding the biology of this particular BC subtype is essential for determining targets for future therapeutic options. No significant financial relationships to disclose.