scholarly journals Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2657
Author(s):  
Luca Campedel ◽  
Paul Blanc-Durand ◽  
Asker Bin Asker ◽  
Jacqueline Lehmann-Che ◽  
Caroline Cuvier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Dose Dense ◽  
The Impact

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

A meta-analysis of platinum-based neoadjuvant chemotherapy versus standard neoadjuvant chemotherapy for triple-negative breast cancer

2019 ◽  
Vol 15 (23) ◽  
pp. 2779-2790 ◽  
Author(s):  
Dong Wang ◽  
Jiafu Feng ◽  
Bei Xu
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Randomized Clinical Trials ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Complete Response ◽  
Breast Cancers ◽  
Dna Damaging Agents ◽  
Platinum Agents

Aim: Platinum agents are DNA damaging agents with promising activity in breast cancers, especially in triple-negative subgroup. This meta-analysis was conducted to compare the treatments of platinum-based neoadjuvant chemotherapy (NAC) and standard NAC for triple-negative breast cancers (TNBCs). Materials & methods: Diverse electronic databases were searched to identify the randomized clinical trials that directly compared the treatments of platinum-based NAC versus NAC in TNBC patients. Toxicity of platinum-based regimens was further evaluated. Results: Addition of platinum agents significantly improved the pathological complete response rates in TNBC patients compared with the standard NAC. Unfortunately, platinum-based regimens were more likely to develop higher incidence of hematologic toxicities. Conclusion: Platinum-based NAC regimens could achieve significant pathological complete response improvement with well-tolerated toxicity in TNBC patients.

scholarly journals PD-L1 Expression in TNBC: A Predictive Biomarker of Response to Neoadjuvant Chemotherapy?

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Bruna Cerbelli ◽  
Angelina Pernazza ◽  
Andrea Botticelli ◽  
Lucio Fortunato ◽  
Massimo Monti ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Predictive Biomarker ◽  
Complete Response ◽  
Response To Therapy ◽  
Neoplastic Progression ◽  
Infiltrating Lymphocytes

Triple negative breast cancer (TNBC) has an aggressive clinical behaviour, with a poorer prognosis compared to other subtypes. Recently, tumor-infiltrating lymphocytes (TILs) have been proposed as a predictive biomarker for a better clinical outcome and pathological response (pR) after neoadjuvant chemotherapy (NACT) in TNBC. These data confirm the role of the immune system in the neoplastic progression and in the response to therapy. We performed a retrospective analysis of 54 pre-NACT biopsies of TNBC and compared both the percentage of stromal TILs and the degree of PD-L1 expression with the extent of pR to standard NACT. A pathological complete response (pCR) was achieved in 35% of cases. Univariate analysis showed (i) a significant association between PD-L1 expression in ≥25% of neoplastic cells and the achievement of a pCR (p=0.024); (ii) a significantly higher frequency of pCR in cases showing ≥50% stromal TILs (p<0.001). However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01–1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy. These data need to be confirmed by larger studies.

scholarly journals Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

2015 ◽  
Vol 33 (1) ◽  
pp. 13-21 ◽  
Author(s):  
William M. Sikov ◽  
Donald A. Berry ◽  
Charles M. Perou ◽  
Baljit Singh ◽  
Constance T. Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Stage Ii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Dense ◽  
The Impact

Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.

Are BRCA1 mutations a predictive factor for anthracycline-based neoadjuvant chemotherapy response in triple-negative breast cancers?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 580-580 ◽  
Author(s):  
T. Petit ◽  
M. Wilt ◽  
J. Rodier ◽  
D. Muller ◽  
J. Ghnassia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Platinum Compounds ◽  
Response To Chemotherapy ◽  
Chemotherapy Efficacy

580 Background: BRCA1 being involved in DNA repair and apoptosis, its mutations may influence response to chemotherapy. In vitro studies demonstrated that loss of BRCA1 function increased sensitivity to platinum compounds and induced resistance to anthracyclines. BRCA1-related breast cancers tend to be ductal carcinomas with high tumor grade, absence of hormonal receptors and no HER2 overexpression, so called triple-negative. We retrospectively analyzed anthracycline-based neoadjuvant chemotherapy efficacy in triple- negative tumors according to BRCA1 status. Methods: 393 breast cancer pts were treated with FEC100 neoadjuvant chemotherapy (FU 500 mg/m2, epirubicine 100 mg/m2, cyclophosphamide 500 mg/m2) between 1/2000 and 12/2006. Out of them, 14% had a triple-negative phenotype (55 pts). Patients with young age at diagnosis or family history of breast cancer were offered genetic testing for BRCA1 and BRCA2 mutations. Twelve of these patients had a BRCA1 deleterious mutation with a triple-negative tumor. Characteristics of these 12 pts at diagnosis were: median age = 38, tumor stage = 7 T2N0, 2 T2N1, 2 T3N0, 1 T3N1. Results: Pathological complete response was defined as absence of invasive tumor in breast and axillary nodes. After 6 cycles of FEC100, 42% of patients with triple-negative tumors (23/55) had a pathological complete response, compared to 17% (2/12) with a BRCA1 mutation. Only one of the 12 BRCA1 patients had an axillary node involvement. Conclusions: In our series, BRCA1 deleterious mutations decreased anthracycline-based chemotherapy efficacy in triple- negative breast cancers. Platinum compounds should be evaluated in these BRCA1-related tumors. No significant financial relationships to disclose.

Impact of sequence order of anthracyclines and taxanes in neoadjuvant chemotherapy for breast cancer: Results from a prospective institutional database.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12619-e12619
Author(s):  
Megan Tesch ◽  
Nathalie LeVasseur ◽  
Christine E. Simmons ◽  
Stephen K. L. Chia
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Breast Cancer Patients ◽  
Duration Of Treatment ◽  
Eligibility Criteria ◽  
The Impact

e12619 Background: There has been growing interest in the optimal sequencing of anthracyclines and taxanes in neoadjuvant chemotherapy (NACT) for breast cancer. However, data comparing efficacy of administering taxanes prior to anthracyclines as opposed to the opposite sequence remains limited and inconsistent. The objective of our study was to assess the impact of sequence order on pathologic and clinical outcomes in a real-world setting. Methods: A prospective institutional database was analyzed to identify all HER2-negative breast cancer patients treated with NACT from 2012 to 2019. Rates of pathologic complete response (pCR), down-staging, and breast-conserving surgery were compared between patients who received anthracyclines followed by taxanes (AC-T) to those who received taxanes followed by anthracyclines (T-AC). Chi-square and independent sample non-parametric tests were used to test for associations between variables and outcomes. Results: Of the 270 patients who met eligibility criteria, 175 (65%) received AC-T and 95 (35%) received T-AC. Median age was 55 (IQR 24-86). Overall, 83% of patients had stage IIB or greater tumors, 40% had grade 3 histology, and 36% had triple-negative disease. Characteristics were balanced between the AC-T and T-AC groups (all p < 0.05). Median duration of treatment with NACT was 102 days (IQR 29-203). Rates of pCR (19% vs 21%, p = 0.750), down-staging (68% vs 61%, p = 0.188), and conversion to breast-conserving surgery (26% vs 20%, p = 0.314) were similar for AC-T vs T-AC, respectively. pCR was higher in triple-negative compared to hormone-positive cases (33% vs 13%, p < 0.001). Conclusions: In this small population-based cohort, sequence order of anthracyclines and taxanes did not demonstrate statistically significant differences in evaluated outcomes from NACT for breast cancer. This supports the current variation in prescribing practice and highlights the need for further studies in this area.

scholarly journals Evaluation of PD-L1 and tumor infiltrating lymphocytes in paired pretreatment biopsies and post neoadjuvant chemotherapy surgical specimens of breast carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lucas Grecco Hoffmann ◽  
Luis Otavio Sarian ◽  
José Vassallo ◽  
Geisilene Russano de Paiva Silva ◽  
Susana Oliveira Botelho Ramalho ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Histological Grade ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Immunohistochemical Expression ◽  
Residual Cancer Burden ◽  
Grade 3 ◽  
The Impact

AbstractHerein it was evaluated the impact of PD-L1 immunohistochemical expression and stromal tumor-infiltrating lymphocyte (sTIL) counts in pretreatment needle core biopsy on response to neoadjuvant chemotherapy (NACT) for patients with breast carcinomas (BC). In 127 paired pre- and post-NACT BC specimens, immunohistochemical expression of PD-L1 was evaluated in stroma and in neoplastic cells. In the same samples sTILs were semi-quantified in tumor stroma. Post-NACT specimens were histologically rated as having residual cancer burden (RCB of any degree), or with complete pathological response (pCR). PD-L1 expression and higher sTIL counts were associated with histological grade 3 BC. PD-L1 expression was also associated with the non-luminal-HER2+ and triple negative immunohistochemical profiles of BC. Pathological complete response was associated with histological grade 3 tumors, and with the non-luminal-HER2+ and triple negative profiles. Additionally, our results support an association between PD-L1 expression and pCR to NACT. It was also observed that there is a trend to reduction of sTIL counts in the post-NACT specimens of patients with pCR. Of note, PD-L1 was expressed in half of the hormone receptor positive cases, a finding that might expand the potential use of immune checkpoint inhibitors for BC patients.

Survival of patients with locally advanced triple-negative breast cancer after neoadjuvant platinum-containing chemotherapy: Experience of a single institute.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 274-274
Author(s):  
E. A. Ibrahim
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Biological Entity ◽  
Breast Cancers

274 Background: Primary systemic chemotherapy is a standard approach to treating women with locally advanced breast cancers, with higher survival rates reported among patients who attain a pathologic complete response. Triple-negative breast cancer is a special biological entity that remains major challenge to oncologist. Around 12%-20% of breast cancers are triple negative. The current phase II study was conducted to evaluate the pathological complete response (pCR) using cis-platinum containing regimen as neoadjuvant chemotherapy in locally advanced triple negative breast cancer. Methods: Eighteen women with stage III triple negative breast cancer who were recruited between July 2007 and February 2010 at King Fahad Specialist Hospital, Dammam, Saudi Arabia. Neoadjuvant chemotherapy consisted of 4 cycles of AC or FEC 100, followed by 4 cycles consisted of docetaxel-cisplatin every 3 weeks. Primary end point was pathological complete response. Results: Median age: 49 y (24-70); premenopausal: 16; 25% were below 35 years of age; Median tumor size: 9 cm (3.5-19); Grade III: 15; Stage IIIA: 3, IIIB:14, IIIC:1; all but 2 had positive nodes at diagnosis (89%). Clinical evaluation of response by RECIST criteria pre surgery: OR: 17/18 (94%), CR: 9 (50%); PR: 8 (44%).The second sequence with D-Cis-T doubled the rate of clinical CR obtained with AC/FEC. One patient was not operated due to disease progression. Pathological assessment, revealed that 8 (47%) pts had no residual invasive carcinoma in the breast; 3 (18%) had residual occasional scattered tumor cells less than 5 mm (pT1a); 10 (59%) had negative nodes; 8 achieved CpR and 2 nCpR. Patients with residual invasive component and/or nodal involvement had high baseline Ki 67 level. After a median follow up of 24 months, cumulative overall survival at 24 months is 88.9% for whole group. Cumulative overall survival in relation to response was 100% for patients who achieved pCR while overall cumulative survival rate for patients without pCR was 83.3% without statistical significance. Conclusions: This cisplatin based neoadjuvant chemotherapy regimen was well tolerated and achieved a high rate of pCR/npCR.

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