Abstract 4549: SNP array-based molecular analysis predicts response to neoadjuvant chemotherapy in triple negative and HER2-positive breast cancers

2012 ◽  
Author(s):  
Mamoru Takada ◽  
Yasihiko Kaneko ◽  
Masayuki Haruta
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Molecular Analysis ◽  
Triple Negative ◽  
Snp Array ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Response To Neoadjuvant Chemotherapy

Association of pathological complete response rates and TILs in triple-negative breast cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12596-e12596
Author(s):  
Mahmoud Kassem ◽  
Daniel Goldstein ◽  
Patrick Schnell ◽  
Michael Grimm ◽  
Dionisia Marie Quiroga ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Working Group ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Comprehensive Cancer Center ◽  
Breast Cancers ◽  
Long Term Prognosis ◽  
Response To Neoadjuvant Chemotherapy

e12596 Background: Triple negative breast cancers (TNBC), characterized by the lack of expression of estrogen receptors and progesterone receptors as well as human epidermal growth factor receptor 2, are associated with high distant recurrence rate and death. As a result, the majority of patients with TNBC are treated with perioperative chemotherapy with the goal of eradicating micrometastases and preventing distrant relapse. The preoperative systemic therapy offers the advantages of permitting an assessment of chemo-sensitivity, increased rates of breast conserving surgery and the ability to adapt postoperative therapies depending on the response. Recently, neoadjuvant chemotherapy has been used at an increasing frequency. The response to neoadjuvant chemotherapy, as measured by the residual cancer burden index, for example, is correlated with the long-term prognosis of TNBC and HER2 expressing breast cancers. Previous studies suggest that tumor-infiltrating lymphocytes (TILs) may correlate with pathological complete response (pCR) rates in TNBC patients treated with neoadjuvant chemotherapy. The pathologic evaluation of TILs in TNBC has been recommended by the International TILs working group since 2014. In this study we sought to analyze the association of TILs with pCR in a cohort of TNBC patients treated with neoadjuvant chemotherapy. Methods: An IRB-approved single-institution retrospective analysis was performed on 127 patients diagnosed with TNBC who received neoadjuvant anthracycline and taxane based chemotherapy at the Ohio State University Comprehensive Cancer Center between January 1st, 2012 and November 31st, 2018. We analyzed TILs as a continuous variable as a part of a secondary analysis of this data. Whole tissue sections from archived H&E stained glass slides were scanned using Philips UltraFast Scanner at ×40 magnification with a single-focus layer. TIL scoring was performed according to guideline recommendations from the International TILs Working Group (2014). Results: A total of 127 female patients with TNBC were identified. The median age at diagnosis was 52.0 years (range 32.0, 74.0) and patients were predominately white (103, 81%), post-menopausal (68, 53.5%) and presented with invasive ductal cancer (113, 89%), stage II (88, 69%), and high grade (108, 85%). Of those patients, 56 had TILs measurement available. pCR was associated with statistically higher level of TILs in core biopsies taken prior to chemotherapy had (Wilcoxon rank-sum test, p = 0.04). Conclusions: The long-term prognosis of patients with TNBC is predicted by the response to neoadjuvant chemotherapy. Consistent with other studies, our study revealed that TILs are associated with a higher probability of pCR. Our future goals are to identify which TIL subsets correlate best with pCR and to identify the mechanism for the increased chemotherapy responsiveness of lymphocyte-infiltrated tumors.

scholarly journals PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 746
Author(s):  
Beatriz Grandal ◽  
Manon Mangiardi-Veltin ◽  
Enora Laas ◽  
Marick Laé ◽  
Didier Meseure ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Rapid Development ◽  
Complete Response ◽  
Tumor Burden ◽  
Small Subset ◽  
Breast Cancers ◽  
Residual Cancer Burden

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

scholarly journals Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 2966-2973 ◽  
Author(s):  
Marco Colleoni ◽  
Bernard F. Cole ◽  
Giuseppe Viale ◽  
Meredith M. Regan ◽  
Karen N. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Triple Negative ◽  
Alkylating Agents ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Node Negative ◽  
Tumor Subtypes ◽  
Node Negative Breast Cancer

Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

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