Abstract A092: DNA repair proficiency predicts disparities in triple negative breast cancer outcomes

Author(s):  
Chinnadurai Mani ◽  
Jonnalagadda Shirisha ◽  
Awasthi Sanjay ◽  
Manne Upender ◽  
Palle Komaraiah
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 523-523
Author(s):  
Malgorzata Nowakowska ◽  
Xiudong Lei ◽  
Mikayla R Thompson ◽  
Simona Flora Shaitelman ◽  
Mackenzie Wehner ◽  
...  

523 Background: Statins have been shown to target pathways related to breast cancer carcinogenesis, specifically in more aggressive breast cancer subtypes such as triple negative breast cancer (TNBC). Given the limited toxicity profile, low cost, and ease of use of statins, an association between statin therapy and improved breast cancer outcomes, particularly in aggressive breast cancers with more limited treatment options, could have important public health implications. Here we examine the association of statin therapy with breast cancer outcomes in women with stage I-III breast cancer, specifically TNBC. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry (TCR)-Medicare data. We included women age 66 years or older with histologically confirmed stage I-III breast cancer diagnosed from 2008-2015. We used multivariable Cox proportional hazards regression models to examine the association of statin use with overall survival (OS) and breast cancer specific survival (BCSS) adjusting for age, race, education, state buy-in, residence area, stage, subtype, endocrine therapy, radiation, chemotherapy, surgery, baseline statin use, comorbidity, and baseline hypertension. For BCSS, we accounted for the competing risk of death using the Fine and Grey method. We required all individuals to survive until 12 months post-diagnosis, which we defined as the start of the follow-up period, to account for immortal time bias. Results: We identified 45,063 patients with stage I-III breast cancer meeting inclusion criteria, out of which 22,518 (50.0%) received a statin within one year following diagnosis (statin-users). The 5-year cumulative estimates of breast cancer specific deaths were 5.9% and 6.9% for statin-users and non-users (P <.001), respectively. In the overall cohort, adjusted models showed a statistically significant association between statin use and improved BCSS (subdistribution hazard ratio [SHR], 0.82; 95% CI, 0.70 to 0.97; P =.021), but no association with OS (hazard ratio [HR], 0.96; 95% CI, 0.90 to 1.03; P =.23). The association was strongest in patients with TNBC for BCSS (SHR, 0.60; 95% CI, 0.42 to 0.86; P =.006) and OS (HR, 0.76; 95% CI, 0.61 to 0.95; P =.018). Stratification by stage showed that the effect of statin therapy in TNBC was limited to patients with localized disease. Our results were consistent using propensity score matched models and when limiting our analysis to statin therapy initiated following breast cancer diagnosis. Conclusions: Among women with non-metastatic breast cancer, we found that statin use was associated with an OS and BCSS benefit among women with TNBC. Our data suggest that statins may have a role as an adjuvant therapy in select patients with breast cancer and supports further investigation, particularly among patients with TNBC, for whom effective treatment options are more limited.


2017 ◽  
Vol 6 (3) ◽  
pp. 526-536 ◽  
Author(s):  
Elisabetta Rapiti ◽  
Kim Pinaud ◽  
Pierre O. Chappuis ◽  
Valeria Viassolo ◽  
Aurélie Ayme ◽  
...  

2015 ◽  
Vol 152 (1) ◽  
pp. 183-191 ◽  
Author(s):  
Yan Liu ◽  
Qiuyin Cai ◽  
Ping-Ping Bao ◽  
Yinghao Su ◽  
Hui Cai ◽  
...  

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Erica M. Stringer-Reasor ◽  
Jori E. May ◽  
Eva Olariu ◽  
Valerie Caterinicchia ◽  
Yufeng Li ◽  
...  

Abstract Background Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Methods A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded. Results Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0–2). Fifty percent of patients were Caucasian, 45% African–American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug–drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed. Trial registration ClinicalTrials.gov, NCT02158507. Registered on 12 September 2014


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