Triple-negative Cancer Patients Research Articles

Optimization of tissue microarray technique for breast cancer patients: a short communication.

Tissue microarray (TMA) is a novel technique for studying different types of cancer tissues in one block. TMA is not yet established in Syria, so we aimed in this project to apply and set the most optimal conditions of TMA creation of breast cancer tissues at the Pathology Department of our institute. Eighty-eight blocks of breast cancer tissues were selected, considering the inclusion criteria. The tissue specimens of breast cancer patients were manually placed in the block by punching a core from a paraffin block, which was then released into a recipient block using a small trocar. Three different conditions were tested on the constructed TMA block. We determined the most effective parameters that proved high quality: incubating the newly constructed block at a temperature of 43°C for 24h in the oven and then cutting it the next day after cooling it to room temperature; also, cutting with a 5μm thickness created the preferable stained slides later. CD3 staining showed high expression of tumor-infiltrating lymphocytes among triple-negative breast cancer patients and high expression of CD3 in triple-negative cancer patients. The optimization of parameters presented in our study resulted in perfect TMA generation and successful immunohistochemistry staining for cancer research at our institution.

Intramedullary rod failure in metastatic breast cancer: Do triple negative cancer patients have more revision surgery?

BackgroundBreast cancer is the most common cancer and second cause of death in women worldwide. Patients with breast cancer are classified into subgroups based on the presence or absence of hormone receptors and the human epidermal growth factor 2-neu (HER-2) marker, the different molecular profiles come with an associated prognosis and variety of possible treatment options. Patients with triple negative cancer have a worse prognosis, a more aggressive behavior, higher likelihood of spreading, a higher risk of recurrence and a poorer outcome overall. Intramedullary rod fixation has proven to provide a good outcome and function in patients with metastatic breast cancer, but no study has addressed the receptor-status potential outcome differences that may affect disease progression at an orthopaedic surgery site. Questions/Purposes(1) Do patients with triple negative breast cancer have a higher revision rate of intramedullary rod fixation of bone metastases? (2) Do patients with metastatic triple negative breast cancer have a higher revision rate of intramedullary rod fixation due to local disease progression? MethodsThis was a single-center, observational, retrospective cohort study. Fifty-seven patients with a diagnosis of breast cancer metastatic to long bones who underwent surgical fixation with an intramedullary rod for a pathological fracture or an impending fracture due to a bone metastasis with a Mirels’ score equal or above 8 between January 2004 and December 2016 at our institution were included. All implants used were from the same manufacturer (Stryker Corp., Mahwah, NJ, USA). Patients were divided into two groups based on the receptor status of the tumor and were classified either as triple negative, when the tumor lacked progesterone, estrogen and HER-2 receptors, or as receptor-positive when the presence of one or a combination of either three was proven. In the triple-negative tumor group the mean follow up time was 26 months (SD 29) and median follow up time was 16 months. In the receptor-positive tumor group mean follow up was 27 months (SD 24) with a median follow up of 19 months. To assess possible associations between different factors and the outcomes of interest, we used either the chi-square test or Fisher’s exact test for categorical variables and the ANOVA test for continuous variables. For the survival assessment, a Kaplan-Meier analysis was performed and for the cumulative incidence a competing risk analysis was utilized. ResultsThe intramedullary rod revision rate for patients in the triple-negative tumor group was 17%, while for the receptor-positive group it was 12%, this was not statistically different for our sample size. The mean time for revision of the intramedullary rod in the whole sample was 19 months (SD 11, range 6–40). The causes of revision were disease progression (43%), nonunion (29%) and surgeon error (29%). The cumulative incidence of revision surgery was 6% (CI 95%, 2–14%) at 12 months and 20% (CI 95%, 8–36%) at 60 months. ConclusionsIntramedullary rodding can be considered for the treatment of long bones metastases in breast cancer patients for an impending or actual pathological fracture. There is no difference in the intramedullary rod revision rate among patients with different receptor-status when comparing triple-negative tumor patients and receptor-positive ones. Level of EvidenceLevel III, therapeutic study.

Abstract B082: Role of CD44v6 in acquired resistance to anti-angiogenic therapy of triple-negative breast cancer

Abstract Triple-negative breast tumors do not offer many therapeutic opportunities beyond chemotherapy. Lately, new hope for the treatment of this type of cancer has been brought by anti-angiogenic agents. However, clinical trials showed that, although angiogenesis inhibitors increase progression-free survival of triple negative cancer patients, they do not improve overall survival, suggesting the occurrence of acquired resistance. Understanding the molecular mechanisms underlying resistance to angiogenesis inhibitors is an important step towards the development of therapies that prevent this process. Using a vital library of human primary breast cancers, we developed an orthotopic mouse model of triple negative carcinoma that allows studying acquired resistance to angiogenesis inhibitors in a controlled setting. This model unveiled that anti-angiogenic drugs reduce tumor growth on one hand but enhance metastasis on the other. FACS analysis of tumor cells revealed that angiogenesis inhibitors enrich for cells expressing CD44v6, a splice variant of the trans-membrane glycoprotein CD44. Expression of CD44v6 has been associated with tumor invasion and metastasis in a variety of human cancers, including breast. Furthermore, CD44v6 has been shown to be a co-receptor for Hepatocyte Growth Factor (HGF) and to be essential for the activation of c-Met, a master regulator of invasive growth. Interestingly, treatment with HGF/Met inhibitors reduced tumor growth, prevented selection of CD44v6+ cells and suppressed angiogenesis inhibitor-induced metastasis. These results point at a causative role of CD44v6 in acquired resistance to anti-angiogenic therapy and suggest the opportunity of combining HGF/Met inhibitors with anti-angiogenic drugs. Note:This abstract was not presented at the conference. Citation Format: Virginia Morello, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Paolo Michieli. Role of CD44v6 in acquired resistance to anti-angiogenic therapy of triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B082.

O3-028 - Prognostic Factor KI67 for Breast Cancer Patients in Each Subgroup

ABSTRACT Background Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67-labeling index is chiefly important for distinguishing between Luminal A and Luminal B (HER2 negative) subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate and high Ki67 levels. Methods We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between 1 January 2000, and 31 December 2010. Ki67 was defined as low if 20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results We identified 1331 primary breast cancer patients without metastasis; of whom, 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (P = 0.009) and low Ki67 (P Conclusion Our data demonstrated that low, intermediate and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.

381 - Study of Triple Negative Breast Cancer and Lymph Node Involvement Among Eastern Indian Patients- An Institutional Experience

ABSTRACT Background Breast Cancer is the most commonly diagnosed cancer among Indian women. Recent reports from India suggest a significant increase in the incidence of Estrogen and Progesterone receptor negative (ER-/PR-) breast cancer. Recently the targeted therapies improving the prognosis, so, know about receptor status becoming important. Yet very little is known about the specific histological subtypes or receptor status of breast cancer in women of eastern India. So a hospital based study was undertaken. Objectives This study was conducted to understand the frequency of occurrence of specific breast cancer subtypes and risk factors associated with the age, histologic subtypes among the patients and find the clinical features in relation to receptor status. Methods 224 breast cancer patients, who are operated during the period of Mar 2009 to Nov 2011 from our cancer hospital, were selected for the study. Personal history (i.e. Age, age of Menarche and menopause status etc), case report and histopathology report were analyzed. Statistical analysis was performed using Software SPSS version 16.0 Results Average age of the Patients 46.9 ± 1.32 Invasive- Ductal 66.51% Invasive- Lobular 10.71% Others (Fibrodenoma, infiltrating duct carcinoma etc.) 22.76% Tumor Grade Grade I 13.83% Grade II 54.46 % Grade III 31.69% Average Lymph Node Size 1.85 c.m ± 0.09 ER-/PR- Breast Cancer 45.53% ER-/PR-/Her2neu- (Triple Negative) 23.21% Average lymph node number of Triple negative cancer patients 12 ±0.54 Among the triple negative patients average age 44.9 ± 3.24 Average lymph node number of without Triple negative cancer patients 5.71 ±0.44 Her2neu+ 56.25% Conclusions Invasive Ductal carcinoma is very common among the eastern Indian patients. Maximum patients contains Garde II tumor. Among ER, PR negative breast cancer patient 50% does not possess Her2Neu receptor (triple negative). The Triple negative cancer patients contain a significantly high number of Lymph node (p Disclosure All authors have declared no conflicts of interest.

Prognostic factor Ki67 for breast cancer patients in each subgroup.

565 Background: Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67 labeling index is chiefly important for distinguishing between “Luminal A” and “Luminal B (HER2 negative)” subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate, and high Ki67 levels in each subgroup. Methods: We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000, and December 31, 2010. Ki67 was defined as low if <10% Ki67 was detected, as Intermediate if 10–20% Ki67 was detected, and as high if >20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: We identified 1331 primary breast cancer patients without metastasis, of whom 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (p = 0.009) and low Ki67 (p < 0.001). Patients with intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001). In ER-positive cases (n = 1059), patients with high and intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001 and p = 0.002, respectively). In HER2-positive and ER-negative cases (n = 103), patients with high Ki67 had poorer RFS than patients with low Ki67 (p = 0.002). In triple-negative cases (n = 164), patients with high Ki67 tended to have poorer RFS than patients with low Ki67 (p = 0.064). Conclusions: Our data demonstrated that low, intermediate, and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.