scholarly journals NEOADJUVANT APPROACH AS A PLATFORM FOR TREATMENT PERSONALIZATION: FOCUS ON HER2-POSITIVE AND TRIPLE-NEGATIVE BREAST CANCER

2021 ◽  
pp. 102222
Author(s):  
Federica Miglietta ◽  
Maria Vittoria Dieci ◽  
Gaia Griguolo ◽  
Valentina Guarneri
Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.


2019 ◽  
Vol 20 (12) ◽  
pp. 3080 ◽  
Author(s):  
Fan Wu ◽  
Robert D. McCuaig ◽  
Christopher R. Sutton ◽  
Abel H. Y. Tan ◽  
Yoshni Jeelall ◽  
...  

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.


2013 ◽  
Author(s):  
Sibylle Loibl ◽  
Carsten Denkert ◽  
Sherene Loi ◽  
Fabrice Andre ◽  
Annika Lehmann ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18624-e18624
Author(s):  
Maithreyi Sarma ◽  
Ashwini Ronghe ◽  
Samar Nasir ◽  
Ankita Kapoor ◽  
Kristopher Attwood ◽  
...  

e18624 Background: Triple negative breast cancer (TNBC) & HER2 positive breast cancer (Her2BC), are aggressive breast cancer subtypes. Both are associated with higher mortality in Non-Hispanic Black (NHB) compared to Non-Hispanic White women (NHW). Factors attributed to this racial disparity include socioeconomic status, insurance status, diagnosis(dx)/ treatment delays & comorbidities. We examined the association between race & clinical outcomes (pathological complete response, pCR; recurrence free survival, RFS & overall survival, OS) in patients (pts) dxed with TNBC/Her2BC treated with neoadjuvant chemotherapy (NAC) at Roswell Park Comprehensive Cancer Center. Methods: Pts dxed with Stage I-III TNBC/Her2BC who received NAC from 2000-2018 were included. pCR was defined as absence of residual invasive cancer in the breast & lymph nodes after NAC. Association of race with pCR & survival outcomes was evaluated using logistic & Cox regression models, respectively. Multivariate (MV) models were used to evaluate the association between race & pCR or survival while controlling for relevant confounders including age, BMI, insurance, comorbidities, clinical stage, grade & time from dx to chemotherapy(chemo)/surgery. Analysis was conducted using SAS v9.4 at a significance level of 0.05. Results: 174 TNBC (49 NHB, 125 NHW) & 80 Her2BC (13 NHB, 67 NHW) pts were analyzed. Among TNBC pts, NHB pts had higher baseline BMI(34.3 vs 28.6 kg/m2; p<0.001), higher incidence of hypertension (HTN) (45% vs. 24%; p<0.01), diabetes mellitus (20% vs 8%; p<0.05) & higher Medicare/Medicaid use (M/M) (55% vs. 28%; p<0.01). Among Her2BC pts, NHB pts had higher incidence of HTN (54% vs 25%; p<0.05). There was no statistically significant difference in mean chemo relative dose intensity by race. Among TNBC pts, those with pCR were younger (47 vs 53 yrs; p=0.002) & had more grade 3 tumors (96% vs 80.5%; p<0.05) at dx compared to pts without pCR. Similarly, among Her2BC pts, those with pCR had more grade 3 tumors (64% vs 36%; p<0.05) at dx compared to pts without pCR. Among TNBC pts, advanced age, higher clinical stage & longer time from dx to surgery were associated with worse RFS & OS (p<0.05). Among Her2BC pts, M/M use & advanced clinical stage were associated with worse RFS & OS (p<0.05). There were no significant associations between race & pCR/RFS/OS on MV analysis (table below). Conclusions: Similar outcomes were noted between races for TNBC/Her2BC pts treated at a single academic center in Buffalo, NY. Given the known genetic diversity of African American ancestry in the US, further studies investigating the interplay between race, geography & clinical outcomes are warranted.[Table: see text]


2018 ◽  
Vol 69 (2) ◽  
pp. 157-168 ◽  
Author(s):  
Betul Bolat Kucukzeybek ◽  
Ibrahım V. Bayoglu ◽  
Yuksel Kucukzeybek ◽  
Yasar Yıldız ◽  
Utku Oflazoglu ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document