scholarly journals Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Francesco Schettini ◽  
Silvia Paola Corona ◽  
Fabiola Giudici ◽  
Carla Strina ◽  
Marianna Sirico ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Tumor Infiltrating Lymphocytes ◽  
Early Response ◽  
Window Of Opportunity ◽  
Immune Biomarkers

IntroductionOlaparib is effective in metastatic triple negative breast cancer (TNBC) carrying germline mutations in DNA damage repair (DDR) genes BRCA1/2 (gBRCA-mut). The OLTRE window-of-opportunity trial preliminarily investigated potential pathologic, radiometabolic and immune biomarkers of early-response to olaparib in gBRCA-wild-type (wt) TNBC and, as proof-of-concept in gBRCA-mut HER2-negative BC.MethodsPatients received olaparib for 3 weeks (3w) before standard neoadjuvant chemotherapy and underwent multiple FDG18-PET/CT scan (basal, after olaparib), clinical assessments (basal, every 3w), tumor biopsies and blood samplings (baseline, after olaparib). Clinical and radiometabolic responses were evaluated according to RECIST1.1 and PERCIST criteria.Results27 patients with gBRCA-wt TNBC and 8 with gBRCA-mut BC (6 TNBC, 2 HR+/HER2-negative) were enrolled. Three (11.1%) patients showed mutations in non-BRCA1/2 DDR genes and 4 (14.8%) in other genes. 3w olaparib induced 16/35 and 15/27 partial clinical and radiometabolic responses, including in 40.7% and 50.0% gBRCA-wt patients. gBRCA-mut tumors presented numerically higher tumor-infiltrating lymphocytes (TILs) levels and PD-L1 positive tumors. Clinical responders experienced a reduction in T-regs/T-eff ratio (p=0.05), B and NK lymphocytes (p=0.003 both), with an average increase in T-helpers rate (p<0.001) and CD4/CD8 ratio (p=0.02). Ki67% and TILs did not vary significantly (p=0.67 and p=0.77). A numerical increase in PD-L1 positive cases after olaparib was observed, though non-significant (p=0.134). No differences were observed according to gBRCA status and type of response.ConclusionsEarly-stage TNBC might be a target population for olaparib, irrespective of gBRCA mutations. Future trials should combine TILs, PD-L1 and gBRCA status to better identify candidates for escalated/de-escalated treatment strategies including olaparib.

scholarly journals Neoadjuvant Therapy in Operable Breast Cancer: Application to Triple Negative Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Foluso O. Ademuyiwa ◽  
Matthew J. Ellis ◽  
Cynthia X. Ma
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Surrogate Endpoint ◽  
Complete Response

Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification) has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today’s standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed.

scholarly journals Basal-Like Subgroup is Associated with Younger Age, Increased Expression of Androgen Receptor, and Worse Prognosis, while Non-basal-like Subtype is Associated with Higher BMI in Triple-Negative Breast Cancer Patients

2020 ◽  
Vol 12 (4) ◽  
pp. 349-354
Author(s):  
Ibnu Purwanto ◽  
Didik Setyo Heiyanto ◽  
Ahmad Ghozali ◽  
Irianiwati Widodo ◽  
Iwan Dwiprahasto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Locally Advanced ◽  
Clinicopathologic Feature ◽  
Younger Age ◽  
Depth Analysis ◽  
Worse Prognosis

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogenous disease which differ in characteristic, treatment response and prognosis. We aim to perform in-depth analysis on the clinicopathologic feature and the prognostic value of basal-like and non-basal-like TNBC patients in an Indonesian tertiary hospital.METHODS: We retrospectively included patients diagnosed with TNBC between 2014-2017. Clinical variables were collected from medical record. Expression of epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), p53 mutant and androgen receptor (AR) were examined by using immunohistochemistry (IHC).RESULTS: We included 67 subjects, 67.1% were basal-like and the remaining 32.9% were non-basal-like, with mean age of 51 years old, 59.7% subjects had BMI <25 and 40.3% subjects had BMI ≥25; 16.4%, 65.7%, and 17.9% subjects presented with early stage, locally advanced stage, and distant metastasis respectively; T<5 cm was found in 29.9% subjects, while 70.1% subjects had T≥5; 67.2% subjects presented with N-, while 32.8% subjects were N+. The most common histological type was infiltrating ductal (82% of subjects). P53 mutant and AR expressions were positive in 44.8% and 15% subjects, respectively. Basal-like subtype presented with younger age at and had higher expression of AR, while non-basal-like subtype is associated with BMI ≥25 (p<0.05). Basal-like subjects had shorter overall survival (23.9 months (95% CI: 21.9-25.9) vs. 26.1 months (95% CI: 23-29.2).CONCLUSION: Basal-like subtype is associated with worse prognosis, younger age at diagnosis and increased expression of AR, while non-basal-like subtype is associated with higher BMI in Indonesian TNBC.KEYWORDS: TNBC, subtype; basal-like, young age, Indonesia

scholarly journals Epidemiology, Pattern of Recurrence and Survival in Triple-negative Breast Cancer

2020 ◽  
Vol 5 (2) ◽  
pp. 87-94
Author(s):  
Dharmendra Singh ◽  
Niladri Roy ◽  
Sumana Maiti Das
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Health Care Access ◽  
Triple Negative ◽  
Early Stage ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Duration Of Symptoms ◽  
Epidemiological Characteristics

Background: Breast cancer is the most common cancer in the world. Triple-negative breast cancer (TNBC) characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and Her2neu receptor. This study investigated the epidemiological characteristics and survival in non-metastatic TNBC. Materials and methods: Data from medical records of patients with breast cancer between 20014 and 2018 were retrieved, and patients with TNBC were identified and analyzed for demographic and clinicopathological features. Survival analyses were performed using the Kaplan–Meier method for disease-free survival (DFS) and overall survival (OS). Results: A total of 457 nonmetastatic breast cancer patients were registered at our institute from January 2014 to August 2018, of which 137 were triple-negative breast cancer (TNBC). This accounted for 29.9% of nonmetastatic breast cancer during this period. With the median age of 45 years at diagnosis, the most common presenting complaint was breast lump. The median duration of symptoms was 30 months. The most commonly affected age group was 41-50 years. The majority of the patients were in a locally advanced stage (69.3%) while 30.7% were in the early stage. 29.2% recurrence at 38 months of median follow up. Recurrence was statistically significantly correlating with age ≤ 35 (p= < 0.001), pathological stage (p= < 0.001), nodal status at diagnosis (p= < 0.001), perineural invasion (PNI) (p= < 0.001), number of positive lymph nodes (p= < 0.001). The mean DFS and OS were 43.6 and 46 months respectively. 3-year DFS and OS were 65.5% and 66.2 % respectively. Conclusion: TNBCs are high-grade tumors mostly presented in locally advanced stages and most of the patients are young. TNBCs are clinically aggressive with high risk of metastasis to visceral organs. The survival of TNBCs in the Indian scenario is poor in comparison to Western populations, probably due to racial factors, socioeconomic factors and health care access facility.  

ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS597-TPS597
Author(s):  
Shigehira Saji ◽  
Heather L. McArthur ◽  
Michail Ignatiadis ◽  
Andrew Bailey ◽  
Sarra El-Abed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Phase 3 ◽  
Meaningful Improvement

TPS597 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting, it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. Atezolizumab (an anti–PD-L1 antibody), in combination with nab-paclitaxel has been approved in >70 countries for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. The phase 3 IMpassion031 study, evaluating atezolizumab in combination with chemotherapy (nab-paclitaxel followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy as neoadjuvant treatment demonstrated a statistically significant and clinically meaningful improvement in pCR in both PD-L1 positive and PD-L1 negative tumors. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial currently investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard anthracycline/taxane adjuvant chemotherapy versus chemotherapy alone in early stage TNBC. Methods: ALEXANDRA/IMpassion030 will randomize 2300 patients with operable stage II-III TNBC, confirmed by central pathology review. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant chemotherapy consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary endpoint is invasive disease-free survival (iDFS) and secondary endpoints include, iDFS in the PD-L1 selected tumour status (IC1/2/3) and node-positive subpopulations, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first site was activated on May 4 2018, and approximately 373 sites in 30 countries are currently participating in this trial. This trial is sponsored by F. Hoffmann-La Roche Ltd and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Clinical trial information: NCT03498716.

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