Frequency distribution of SPARC in triple-negative breast cancer patients.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 37-37
Author(s):  
G. Basu ◽  
G. Van Vickle ◽  
A. Ghazalpour ◽  
R. Ashfaq ◽  
Z. Gatalica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Frequency Distribution ◽  
Triple Negative Breast Cancer ◽  
Polyclonal Antibody ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Large Patient

37 Background: SPARC (secreted protein acid rich in cysteine) belongs to a group of extracellular matrix proteins and promotes adhesion of cells from the matrix. It plays an important role in tumor development in breast cancer and has a significant bearing on patient prognosis and long term survival. It is also known to predict response to nab-paclitaxel in certain tumor types including breast cancer. In 2005, FDA approved a solvent free formulation of paclitaxel for the treatment of metastatic breast cancer that utilizes albumin bound (nab) technology (nab-paclitaxel). Clinical studies have shown that nab-paclitaxel is significantly more effective than paclitaxel. Our study evaluated the frequency distribution of SPARC among triple negative breast cancer patients in which identification of a novel therapeutic target is warranted. Methods: In a total of 951 breast cancer patients, we analyzed tumor SPARC expression by immunohistochemistry (IHC) using a monoclonal (R&D Systems) and a polyclonal antibody (Exalpha Biologicals). Immunoreactivity was assessed by scoring the percentage of cells stained in each field and by the intensity of staining. A cutoff point of 2+ and >30% stained tumor cells were considered as positive. Results: From our analysis of 951 breast cancer patients profiled, a total of 165 patients (17%) were triple negative for ER, PR and HER2. Within this pathologic subtype, 29% patients stained positive with SPARC monoclonal antibody and 21% stained positive with SPARC polyclonal antibody. The correlation of SPARC tumor staining with hormone receptor status will be presented in detail. Conclusions: We conclude that SPARC over-expression is a functionally important feature of a subset of triple negative breast cancer patients. The triple negative subset of tumors generally has a more aggressive clinical course and does not benefit from conventional targeted therapies. Our study suggests that nab-paclitaxel may serve as a therapeutic agent for the subset of triple negative patients that over-express SPARC. To the best of our knowledge, this is the first study involving a large patient pool in which SPARC has been investigated in a single clinical laboratory using standardized IHC with two different SPARC antibodies.

Functional hotness score based on three genes predicts long-term survival of triple-negative breast cancer independent from tumor mutational burden.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12583-e12583
Author(s):  
Eriko Katsuta ◽  
Li Yan ◽  
Mateusz Opyrchal ◽  
Pawel Kalinski ◽  
Kazuaki Takabe
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Expression Levels ◽  
Cancer Immunity ◽  
Anti Cancer

e12583 Background: Cytotoxic T-lymphocytes (CTLs) infiltration into tumor is a positive prognostic factor in breast cancer. Infiltration of CTLs are believed to be driven by mutation-induced neoantigens, thus, higher tumor mutation burden (TMB) is considered an important predictor of tumor immunogenicity and response to immunotherapy, but the association between intratumoral CTL counts and TMB in the overall cancer prognosis remains unclear. Methods: Utilizing publicly available breast cancer cohorts, we established Functional Hotness Score (FHS), based on CD8A, GZMB and CXCL10 gene expression levels of bulk tumors. The associations of FHS and breast cancer patient prognosis as well as distinct immunity markers were analyzed. Results: Breast cancer patients with high-FHS tumors demonstrated significantly better survival. FHS was lower in metastatic breast cancer. Among breast cancer subtypes, triple-negative breast cancer (TNBC) showed the highest FHS. FHS predicted patient survival not in hormone receptor (HR)-positive but in HR-negative, especially TNBCs. The high-FHS TNBCs enhanced not only CD8+ T cell infiltration, but also a broader type-1 anti-cancer immunity. The patients with the high-FHS patients showed better prognosis not only in high-TMB tumors but also in low-TMB TNBCs. The combination of high-TMB with high-FHS identified the unique subset of patients who did not recur over time. Conclusions: In conclusion, TNBCs with high-FHS based on the expression levels of CD8A, GZMB and CXCL10 showed improved prognosis with higher anti-cancer immunity regardless of TMB, and constituting an independent prognostic marker of survival, particularly robust when combined with TMB.

Efficacy and safety of metronomic capecitabine and gefitinib in heavily pretreated metastatic triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1071-1071
Author(s):  
Anantbhushan Ranade ◽  
Kanaka Govind Babu ◽  
Purvish M. Parikh ◽  
Jk Singh ◽  
Manisha Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Visceral Metastasis ◽  
Egfr Expression ◽  
Heavily Pretreated

1071 Background: Metronomic chemotherapy regimens have shown efficacy in patients with metastatic breast cancer by antiangiogenic mechanisms. When used metronomically the toxicity profile of capecitabine is low. Triple negative breast cancer is a common problem in India and developing countries. Approximately 30% of triple negative breast cancer express EGFR and its mutation. Methods: Since October 2003 to December 2011 we objectively tested response rates, clinical benefit, and safety of gefitinib and capecitabine administered with a metronomic schedule of 500 mg thrice daily in heavily pretreated metastatic breast cancer patients with gefitinib 250 mg once daily. 300 patients were screened for EGFR expression. Among 85 enrolled patients with EGFR positivity, 76 were evaluable. ECOG performance status (PS) was 0-2, median age 52 years (range 36-65), bone plus visceral metastasis in 40% of patients. Rest had only visceral metastasis. All the patients were pretreated with anthracyclines and taxanes. The combination was administered for a median duration of 32 weeks (range 12-166). Results: We observed 18 partial responses (PR: 24%), 42 (55%) stable disease (SD). Median time to progression was 53 weeks, (95% CI, range 12-166 weeks). Safety of metronomic capecitabine with gefitinib was excellent. Neither grade 2-4 haematological or clinical side effects were recorded. Only 12 patients experienced grade I (WHO) hand-foot syndrome. Conclusions: Treatment with metronomic capecitabine and gefitinib was effective and minimally toxic in heavily pretreated breast cancer patients.

scholarly journals PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Predictive Value ◽  
Untreated Patient ◽  
Triple Negative ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
The Impact

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

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