scholarly journals High-dose chemotherapy for triple negative breast cancer

2007 ◽  
Vol 18 (1) ◽  
pp. 202-203 ◽  
Author(s):  
U. De Giorgi ◽  
G. Rosti ◽  
L. Frassineti ◽  
B. Kopf ◽  
N. Giovannini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
High Dose Chemotherapy ◽  
High Dose

scholarly journals CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 898
Author(s):  
Ghazal Nabil ◽  
Rami Alzhrani ◽  
Hashem Alsaab ◽  
Mohammed Atef ◽  
Samaresh Sau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
In Vivo Studies ◽  
High Dose ◽  
Luminal A ◽  
Combination Strategy ◽  
Ongoing Research

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15–20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution.

Inhibiting fatty acid synthase in operable triple negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 584-584
Author(s):  
Sagar D. Sardesai ◽  
Alexandra Thomas ◽  
Christopher Gallagher ◽  
Filipa Lynce ◽  
Yvonne Lynn Ottaviano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Triple Negative Breast Cancer ◽  
Fatty Acid Synthase ◽  
Triple Negative ◽  
Population Change ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Breast Cancer Cell Lines ◽  
High Dose

584 Background: Fatty acid synthase (FASN) is overexpressed in 70% of newly diagnosed triple negative breast cancer (TNBC) and is associated with poor prognosis. In vitro, FASN overexpression induces drug resistance to DNA damaging agents. Proton pump inhibitors (PPI) selectively inhibit FASN activity and induce apoptosis in breast cancer cell lines with minimal effect on non-malignant cells. We report the results of a single arm phase II study of high dose omeprazole (OMP) in combination with anthracycline- taxane (AC-T) based neoadjuvant chemotherapy. Methods: Patients (pts) with operable TNBC independent of baseline FASN expression; and no prior PPI use within 12 months were enrolled. Pts began OMP 80 mg PO BID for 4-7 days prior to AC-T; carboplatin was allowed per physician discretion. OMP was continued until surgery. Paired biopsy samples were obtained before and after OMP monotherapy. The primary endpoint was pathologic complete response (pCR), defined as no residual invasive disease in breast or axilla, in pts with baseline FASN expression (FASN+) assessed using immunohistochemistry. Relevant secondary endpoints included pCR in the intent to treat population, change in FASN expression, enzyme activity and downstream target gene expression after OMP monotherapy; safety and limited OMP pharmacokinetics. We targeted a pCR rate of 60% in FASN+ pts (null pCR ~ 40%) with 80% power and alpha of 0.10. Results: A total of 42 pts were recruited from 5 US sites. Median age was 51y (28-72). Most pts had >cT2 (33, 79%) and ≥N1 (22, 52%) disease. 14 (33%) were African American. FASN expression prior to AC-T was identified in 28 (85%) samples available for analysis. The pCR rate was 71.4% (95% CI 51.3 to 86.8) in FASN+ pts and 71.8 %( 95% CI 55.1 to 85.0) in all enrolled pts. Fifteen pts (36%) received carboplatin with AC-T; pCR in this subset was 73%. Peak OMP concentration was significantly higher than IC50 observed during preclinical testing; FASN positivity significantly decreased with OMP monotherapy from 0.53(SD 0.25) at baseline to 0.38(SD 0.30; p = 0.02). OMP was well tolerated with no known grade (G) 3 or 4 toxicities. Chemotherapy toxicity was similar to prior studies using AC-T with G3 or 4 neutropenia (19%), febrile neutropenia (7%) and peripheral neuropathy (7%) being the most common. Conclusions: Consistent with previous studies, FASN is frequently expressed in early stage TNBC. OMP can be safely administered in doses that inhibit FASN. The addition of high dose OMP to neoadjuvant AC-T yields a promising pCR rate without adding toxicity. Funded by the Breast Cancer Research Foundation. Clinical trial information: NCT02595372 .

Atezolizumab-induced hemolytic anemia – A case report

2020 ◽  
pp. 107815522095772
Author(s):  
Christina M Younce ◽  
Jessica M Lawton ◽  
Dhimant R Patel
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Hemolytic Anemia ◽  
Triple Negative Breast Cancer ◽  
Side Effect ◽  
Triple Negative ◽  
Complete Blood Count ◽  
Locally Advanced ◽  
Macrocytic Anemia ◽  
High Dose

Introduction Atezolizumab is currently the only immunotherapy used in conjunction with nab-paclitaxel for locally advanced or triple negative breast cancer. Limited data is available regarding hemolytic anemia as a side effect of atezolizumab. Case report We describe a 59-year-old female with a history of triple negative breast cancer with bone metastases presenting for follow up on Cycle 1, Day 15 of atezolizumab and nab-paclitaxel (100 mg/m2). Patient’s complete blood count (CBC) showed macrocytic anemia, with further workup significant for autoimmune hemolytic anemia (AIHA) attributed to atezolizumab. Management and outcome: Patient was started on a high dose prednisone taper starting at 80 mg daily for 16 days, folic acid 1 mg three times daily, iron sucrose, and darbepoetin alfa. Patient’s counts recovered, and she was able to start Cycle 2 and continued through Cycle 10 without any additional pre-medications. Discussion Hemolytic anemia induced by atezolizumab is a rare side effect that was successfully treated in this patient with a prednisone taper.

scholarly journals Gene Expression Profiles Induced by High-dose Ionizing Radiation in MDA-MB-231 Triple-negative Breast Cancer Cell Line

2019 ◽  
Vol 16 (4) ◽  
pp. 257-266 ◽  
Author(s):  
VALENTINA BRAVATÀ ◽  
FRANCESCO PAOLO CAMMARATA ◽  
LUIGI MINAFRA ◽  
ROSA MUSSO ◽  
GAIA PUCCI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Ionizing Radiation ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cell Line ◽  
Triple Negative ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cancer Cell Line ◽  
High Dose
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