scholarly journals Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Mutation Frequency ◽  
Triple Negative ◽  
Genetic Difference ◽  
Her2 Positive ◽  
Ki 67 ◽  
Hormone Receptor Positive ◽  
Somatic Alteration

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.

Response-Guided Neoadjuvant Chemotherapy for Breast Cancer

2013 ◽  
Vol 31 (29) ◽  
pp. 3623-3630 ◽  
Author(s):  
Gunter von Minckwitz ◽  
Jens Uwe Blohmer ◽  
Serban Dan Costa ◽  
Carsten Denkert ◽  
Holger Eidtmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Exploratory Analysis ◽  
Her2 Positive ◽  
Luminal B ◽  
Hormone Receptor Positive

Purpose We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer. Patients and Methods We treated 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) and randomly assigned early responders to four (n = 704) or six (n = 686) additional TAC cycles, and early nonresponders to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery. Results DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor–positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor–negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87). Pathologic complete response did not predict these survival effects. pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74). Conclusion This exploratory analysis suggests that response-guided neoadjuvant chemotherapy might improve survival and is most effective in hormone receptor–positive tumors. If confirmed, the response-guided approach could provide a clinically meaningful advantage for the neoadjuvant over the adjuvant approach in early breast cancer.

scholarly journals Leisure-Time Physical Activity is Associated with reduced Risk of Breast Cancer and Triple Negative Breast Cancer in Nigerian Women: a matched case-control study

2019 ◽  
Author(s):  
Galya Bigman ◽  
Sally N. Adebamowo ◽  
King-David Terna Yawe ◽  
Monday Yilkudi ◽  
Oluwole Olaomi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Leisure Time Physical Activity ◽  
Sub Saharan Africa ◽  
African Women ◽  
Hormone Receptor Positive ◽  
Sub Saharan

Abstract Background Physical activity is associated with reduced risk of breast cancer and its various subtypes but this association is less known in African women, particularly with triple-negative breast cancer that occurs more frequently in Sub-Saharan Africa compared to developed countries. In this study, we examined the association between leisure-time physical activity (LTPA) and breast cancer in total and by its subtypes in Nigerian women. Methods Overall, 630 newly diagnosed patients with primary invasive breast cancer were age-matched (±5years) with 630 controls from the Nigerian Integrative Epidemiology of Breast Cancer (NIBBLE) Study from 01/2014-07/2016. We derived the average amount of time spent on LTPA per week over the past year using a modified Nurses’ Health Study-II physical activity questionnaire. We calculated the total metabolic equivalents (METs) for each reported LTPA per hour/week (i.e. walking, cycling, and dancing) and compared odds of breast cancer among participants who attained the World Health Organization (WHO) physical activity(PA) recommendations of at least 150 minutes of moderate-intensity or/and 75 minutes of vigorous-intensity aerobic activity/week with those who did not. In addition, we evaluated this by categories of LTPA in quartiles of METs. We used conditional and unconditional logistic regression models to estimate the adjusted Odds Ratio(OR) of LTPA with overall breast cancer and by hormone receptor-positive and triple-negative breast cancer. Results The mean ages of cases and controls were similar after matching, 42.5±10.1 and 41.5±9.2 years (mean±SD), respectively. Women who attained the WHO PA recommendations had a 42% reduction in the odds of having breast cancer(OR=0.58 95% CI:0.43-0.78) compared with those who did not. LTPA was associated with reduced odds of having hormone receptor-positive by 41% and significantly associated with reduced odds of having triple-negative breast cancer by 45%. In addition, a significant dose-response relationship was observed, women with higher levels of LTPA had lower odds of having overall breast cancer as well as having triple-negative and hormone receptor-positive breast cancer. Conclusions Increasing LTPA in African women can play a significant role in reducing the incidence of breast cancer, particularly of the more aggressive subtype as triple-negative, which is more prevalent in Sub-Saharan Africa.

Frequency of TLE3 overexpression in breast carcinoma subtypes including a large cohort of triple-negative patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1040-1040
Author(s):  
Gargi D. Basu ◽  
Anatole Ghazalpour ◽  
David Arguello ◽  
Raheela Ashfaq ◽  
Zoran Gatalica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Large Cohort ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Triple Negative Subtype

1040 Background: The taxanes are an important class of agents for the treatment of a broad range of malignancies including breast cancer. They improve survival in patients with early stage and metastatic breast cancer. Transducin-like enhancer of split 3 (TLE3) is a transcriptional repressor which influences growth and microtubule stability and its expression has been implicated in response to taxane therapy in breast cancer. We investigated the tumor expression of TLE3 in breast cancer patients, including a large cohort of the triple negative subtype. Methods: We analyzed TLE3 (M-201), ER(1D5), PR(PgR636) and HER2/neu(Polyclonal) expression by immunohistochemistry in 978 breast cancer patients. Immunoreactivity was assessed by scoring the percentage of cells stained in each field and by the intensity of staining. Results: To sub-classify the 978 breast cancer patients, we utilized hormone receptors (ER and PR) and HER2 expression/amplification. Overall, 36% of the total breast cancer patients were hormone receptor positive, 15% were HER2 positive and 49% were triple negative. The percentage of triple negative patients was higher in our cohort, given the fact that molecular profiling services are used more frequently for this subtype. A total of 477 patients were triple negative of which 61% stained positive for TLE3 expression. Of the 150 HER2 positive patients, 73% stained positive for TLE3 expression as compared with 82% TLE3 positivity in the 351 hormone receptor positive patients. By pairwise comparison, the hormone receptor positive vs triple-negative subtype showed the highest statistical significance in ratios of TLE3 positives (p =2.5e-10). Conclusions: Our results show that TLE3 is over-expressed in the majority of HER2 positive and hormone receptor positive breast cancer patients. Interestingly, the frequency of over-expression of TLE3 was lowest in the triple negative subtype thereby making it more important to identify those patients in this group who are most likely to respond to taxanes prior to therapy. To our knowledge, this is the first study providing a comprehensive review of TLE expression in breast cancer subtypes.

Triple negative breast cancer compared to hormone receptor negative/HER2 positive breast cancer

2008 ◽  
Vol 26 (3) ◽  
pp. 335-343
Author(s):  
Irfan Cicin ◽  
Hakan Karagol ◽  
Ufuk Usta ◽  
Atakan Sezer ◽  
Sernaz Uzunoglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer
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