Background: Breast cancer is the most common cancer in Indian women. Triple negative breast cancer (TNBC) is associated with poor prognosis at any stage of diagnosis. It is an aggressive disease with a 5-year survival rate of 77% compared to 93% for other subtypes. Prevalence of TNBC in India is higher compared to western populations, making it an important target for early detection and treatment. Potential superiority of dose-dense chemotherapy in comparison with conventional regimen has been recently demonstrated in a meta-analysis in 2017 across various subsets of breast cancer. Aim of this study was to analyse survival outcomes in TNBC treated with dose dense chemotherapy at a tertiary care centre in India. Methods: Retrospective analysis of patients diagnosed with TNBC stage I-III in last 8 years treated with 2 weekly dose dense AC regimen (adriamycin at 60mg/m 2 and cyclophosphamide at 600mg/m 2 for 4 cycles followed by 2 weekly Paclitaxel at175 mg/m 2 for 4 cycles or weekly Paclitaxel at 80 mg/m 2 for 12 cycles) with growth factor support in adjuvant or neoadjuvant (NACT) setting. Locally advanced breast cancer (LABC) was defined as T > 5cm and N2 disease. Kaplan-Meier method and log rank test were used to estimate survival functions. Results: 97 patients with ER, PR and Her2neu receptor negative status were evaluated. Median age at diagnosis was 44 years (range 26 -68 years). 56.7% had stage II disease, 36% stage III and rest stage I (7.2%). Disease free survival (DFS) rate 6 SE at 2 years and 5 years was 90% 6 3% and 75% 6 5% respectively. Overall survival (OS) rate 6 SE at 5 years was 82% 6 6%. 24 patients received NACT out of which 12 (50%) patients had pathCR. The DFS rate did not differ significantly between adjuvant and neoadjuvant subgroups. Early breast cancer and LABC subgroups had a statistically significant difference in DFS rates (p ¼ 0.0002). Conclusions: To our knowledge, this is the first study in India to evaluate survival outcomes of dose dense therapy in TNBC. The improved DFS (75%) and OS (82%) in this high risk subgroup are very promising, especially in patients with early disease. We advocate use of dose dense regimen in all patients of TNBC in curative setting.
Background: The presence of high levels of tumor infiltrating lymphocytes (TIL’s) has been associated with better prognosis in early triple-negative breast cancer (TNBC). The Immunoscore is a prognostic tool, which categorizes the densities of CD3 and CD8 cells in both invasive margins (IM) and the center of the tumor (CT) yielding a five-tiered classification (0-4). High immunoscores have been reported to predict improved outcomes in patients (pts) with colorectal cancer. Methods: The final retrospective report to be presented at the meeting will evaluate the immunoscore in 106 breast cancer (BC) patients undergoing neo-adjuvant chemotherapy. The current analysis include the results of the first 63 pts (TNBC=35, Luminal=20, Her2+=8) who received treatment with anthracycline and/or taxane and/or trastuzumab-based neo-adjuvant chemotherapy. Results: Pre-treatment tumor samples were immune-stained for T-cell (CD3, CD8) markers and quantitative analysis of the immune cells was carried out using a computer-assisted image analysis in different tumor locations. Results: A pathological complete response (pCR) was documented in 57%, 63% and 10% of TNBC, Her2-positive and luminal pts respectively. T-cell densities were significantly higher for TNBC pts compared to non-TNBC pts. A high density (more than 800mm2) of CD3 and CD8 positive T-cells in the CT was associated with higher pCR (CD8 CT: 69% vs. 16%, p = 0.00002) (CD3 CT: 57% vs. 14%, p=0.00015). Analysis of CD3 and CD8 in the IM (more than 500mm2) was also significant for an association with pCR (CD8 IM: 68% vs. 23%, p = 0.002) (CD3 IM: 68% vs. 16%, p=0.0005). In subgroup analyses, TNBC high density (more than 500mm2) of CD3 CT: 72% vs. 20%, p = 0.004 and CD8 CT: 78% vs. 35%, p = 0.001 was also significant for pCR. The immunoscore was also positively correlated with pCR (P=0.0002), and with clinical response (CR, PR, PD) (P=0.002). High immunoscore pts were at low risk of relapse, with 5-year TTR rates of 87.5 % (CI, 67-100 %) as compared to 54.9 % (CI, 29.6-100 %) in low immunoscore pts (HR=4.8 (CI 1.7-13.5), P<0.03). Conclusion: The results of this ongoing study show a significant prognostic and potentially predictive role for the immunoscore in BC pts, particularly in the TNBC subset. Citation Format: Bernardo Leon Rapoport, Simon Nayler, Jerome Galon, B Mlecnik, Teresa Smit, Jacqui Barnard-Tidy, Aurelie Fugon, Marine Martel, Ronwyn I Van Eeden, Ronald Anderson, Carol Benn. Focus on tumor infiltrating lymphocytes (TIL’s): High levels of spatially positioned CD3 and CD8 cells and high immunoscores are significantly associated with pathological complete responses in triple-negative breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-14.
Aim of study: The aim of this retrospective project is to evaluate the treatment outcomes including pathological complete response (pCR), time to progression and overall survival in patients (pts) treated with taxane, and/or anthracycline/alkylating agents based neoadjuvant chemotherapy (NAC). Background: Ki-67 immunohistochemical determination is a widely used biomarker of cell proliferation in pts undergoing endocrine treatment for breast cancer. The role of Ki-67 in triple negative breast cancer (TNBC) pts undergoing NAC for early disease remains controversial. Pathological Complete Response following NAC has been proposed as a prognostic indicator of long-term outcome. Methods: We analyzed retrospectively data on 86 pts with TNBC. Pathological complete response (pCR) was defined as the complete disappearance of the invasive cancer in the breast and absence of tumor in the axillary lymph nodes examined by axillary clearance. The purpose of this analysis was to investigate factors associated with combined pCR. Results: There were 35 pCR’s (40.7%). At 2 years 82% of pts who attained a pCR were disease free compared to 67% of pts who did not attain a pCR (log rank test p < 0.0117). On univariate analysis factors associated with higher combined pCR included primary tumor size (T1=84% vs T2 and T3 =50% of pts, chi2= 6.81, p<0.03317), Ki67 (>30=68% vs. eq or < 30%= 18% of pts, p<0.00020), age (< than 50 =71% vs. equal or >50 =44% of pts), tumor grade (1=88% vs. 2=60% vs. 3=44% of pts, chi2 = 6.2560 p<0.04381) and stage (I= 89% vs. IIA=60% vs. IIB=46% vs. III=40% of pts, p<0.01350). Factors not associated with a higher pCR included menopausal status, extranodal spread and lympho-vascular invasion. In a logistic regression model Ki-67 as a continuous variable (p<0.012577) and age < than 50 (p<0.03318) retained its significance; while tumor size, stage of disease, tumor grade loss significance. Conclusion: Ki67 and age are independent prognostic factors of pCR in pts with early TNBC undergoing NAC. Citation Format: Bernardo Leon Rapoport, Jacqui Barnard-Tidy, Ronwyn van Eeden, Teresa Smit, Simon Nayler, Carol Benn. Treatment outcomes in triple negative breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-20.
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