Neoadjuvant chemotherapy in triple-negative breast cancer: A multicentric retrospective observational study in real-life setting

2017 ◽  
Vol 233 (3) ◽  
pp. 2313-2323 ◽  
Author(s):  
Teresa Gamucci ◽  
Laura Pizzuti ◽  
Isabella Sperduti ◽  
Lucia Mentuccia ◽  
Angela Vaccaro ◽  
...  
Author(s):  
M. E. Cazzaniga ◽  
I. Vallini ◽  
E. Montagna ◽  
D. Amoroso ◽  
R. Berardi ◽  
...  

Abstract Purpose Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. Methods We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). Results Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines. Conclusion This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.


Oncotarget ◽  
2018 ◽  
Vol 9 (41) ◽  
pp. 26406-26416 ◽  
Author(s):  
Angela Santonja ◽  
Alfonso Sánchez-Muñoz ◽  
Ana Lluch ◽  
Maria Rosario Chica-Parrado ◽  
Joan Albanell ◽  
...  

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