scholarly journals The Survival of Locally Advanced Breast Cancer Patients with Luminal Subtype after Modified Radical Mastectomy

2021 ◽  
Vol 8 (11) ◽  
pp. 191-197
Author(s):  
Jefri Adi Kam Sitepu ◽  
Marjono Dwi Wibowo ◽  
Iskandar Ali

Background: Breast cancer is the leading cause of cancer death in women worldwide. Breast cancer has been classified into several molecular subgroups with different prognostic consequences based on immunohistochemistry and molecular pathology. The prognosis that commonly used is 5-years survival. In this study we aimed to examine the relationship between luminal subtype and 5-year survival rate in patients with early post-mastectomy breast cancer. Methods: We recruited early breast cancer patient who underwent modified radical mastectomy (MRM) in Dr. Soetomo General Hospital (Surabaya, Indonesia) between 2010 – 2014. Breast cancer tissues were collected during surgery for immunohistochemistry. The patients’ 5-years survival data was obtained from medical records and by phone call to the patients or to the close relatives of the patients. Breast cancer subtype was determined based on the result of immunohistochemistry Results: A total of 84 patients was included in this study. The majority of patients were aged >40 years (72/84; 85.7%). There were 39 patients (39/84; 46.4%) with luminal A subtype and 45 patients (45/84; 53.6%) with luminal B subtype. Seventy-four patients were diagnosed as invasive ductal carcinoma histologically. Almost all of the patients were able to survive within 5 years (81/84; 96.4%). We found that luminal B had a 1.071 times higher risk of dying within 5 years after therapy than luminal type A, although the analysis did not show significant results (P = 0.101). Conclusion: Luminal B was the most prevalent breast cancer subtype in Surabaya, Indonesia. The prevalence of breast cancer was higher in patients aged >40 years. There was no significant difference between the 5-years survival of luminal A and luminal B subtypes. Keywords: survival, locally advanced breast cancer, luminal subtype, mastectomy.

2021 ◽  
pp. 1-4
Author(s):  
Dony Ruswendro ◽  
Salman Ardi Syamsu ◽  
Rudy Thabry ◽  
Arifin Seweng ◽  
Andi Nilawati Usman

BACKGROUND: Neoplasm is an abnormal mass of tissue that grows excessively and not coordinated with normal tissue growth and continues to do so even though the stimulation that triggered the change has stopped. Breast cancer can be known by using tumor marker, which has been used is mucin-like glycoprotein Carcinoma Antigen (CA 15-3) which is a tumor marker that is specific to breast cancer. METHOD: This study is a cross-sectional study to determine the association between molecular subtypes of locally advanced breast cancer with CA 15-3 level at Abdul Wahab Sjahranie Samarinda Hospital. The population in this study were all breast cancer patients that were confirmed by histopathological examination. RESULTS: A total of 75 patients were included for this study, 29 patients (38.7%) known as Overexpression HER2, 18 patients (24.0%) were Luminal B with HER2 (+), 11 patients (14.7%) were Luminal B with HER2 (−), 11 patients (14.7%) were Basal-like/TNBC, and 6 patients (8,0%) were Luminal A. From the ANOVA test, the value of p = 0.045 (p < 0.05) means there was an association between Ca 15-3 level and molecular subtypes in patients with locally advanced breast cancer at the Abdul Wahab Sjahranie Hospital in Samarinda 2017. In this study Ca 15-3 levels were obtained on average for Luminal A 16.98 U/mL, Luminal B with HER2 (−) 42.41 U/mL, Luminal B with HER2 (+) 73.75 U/mL, Overexpression HER2 47.73 U/mL, and Basal Like /TNBC 63.50 U/mL. CONCLUSION: Statistically, it was found that there was an association between Ca 15-3 levels and molecular subtypes in patients with locally advanced breast cancer at the Abdul Wahab Sjahranie Hospital in Samarinda 2017.


2021 ◽  
Vol 5 (4) ◽  
pp. 877-881
Author(s):  
Eric Hartoyo Salim ◽  
Eddy Herman Tanggo ◽  
Dwi Hari Susilo

Background. Breast cancer is the highest prevalence of malignancy for women in Indonesia and important national health problem. Estimated 2 million women developed breast cancer in 2018 with a mortality rate of 14.1 in every 100,000 women. Regarding the relationship between subtypes and breast cancer recurrence Several studies on gene expression have shown several subtypes of breast cancer, including the two most important subtypes, estrogen receptor (ER) positive (Luminal A and Luminal B) and ER negative (Triple negative and Her2 positive). Based on the explanation above, currently there is no data in Soetomo Hospital that discusses the role of breast cancer subtypes as a prognostic factor in determining the recurrence rate in locally advanced breast cancer.Methods. The research design is an associative test using a retrospective cohort observational analytical study design, associating the relationship between tumor subtypes with recurrence in locally advanced breast cancer patients after mastectomy and has received additional therapy according to standard procedures at Dr. Soetomo Surabaya This study used secondary data from the medical records of the Oncology Polyclinic, RSUD Dr. Soetomo Surabaya from 2014 to 2019.Results. The research subjects who have been selected according to inclusion criteria are 214 people, with the proportion in the population of luminal A and luminal B subtypes of 107 people each. Based on this study, it was found that the subtype was positively correlated with recurrence in LABC patients who had undergonecmastectomy with a significance value of p = 0.000 (p <0.05; 99% CI).Conclusion. There is a relationship between the recurrence rate and the molecular subtype of breast cancer in locally advanced breast cancer (LABC) patients after mastectomy at Dr Soetomo Hospital.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13507-e13507
Author(s):  
Talal Ahmed ◽  
Mark Carty ◽  
Stephane Wenric ◽  
Raphael Pelossof

e13507 Background: Recent advances in transcriptomics have resulted in the emergence of several publicly available breast cancer RNA-Seq datasets, such as TCGA, SCAN-B, and METABRIC. However, molecular predictors cannot be applied across datasets without the correction of batch differences. In this study, we demonstrate a homogenization algorithm that allows the transfer of molecular subtype predictors from one RNA-Seq cohort to another. The algorithm only uses cohort-level RNA-Seq summary statistics, and therefore, does not require joint normalization of both datasets nor the transfer of patient information. Using this approach, we transferred a breast cancer subtype (Luminal A, Luminal B, HER2+, Basal) predictor trained on SCAN-B data to accurately predict subtypes from TCGA. Methods: First, we randomly split the TCGA cohort (n = 481 Luminal A, n = 189 Luminal B, n = 73 Her2+, n = 168 Basal) into two sets: TCGA-train and held-out TCGA-test (n = 455 and n = 456, respectively). Second, the SCAN-B cohort (n = 837) was homogenized with the TCGA-train set. Third, a molecular subtype predictor, based on a logistic regression model, was trained on homogenized SCAN-B RNA-Seq samples and used to predict the subtypes of TCGA-test RNA-Seq samples. For baseline comparison, a similar predictor trained on the non-homogenized SCAN-B cohort was tested on the TCGA-test set. The experimental framework was iterated 250 times. Reported P-values reflect a paired one-sided t-test. Results: To quantify model performance, we measured the average F1 score for each tumor subtype prediction from the held-out TCGA test set with and without cohort homogenization. The average F1 scores with vs. without homogenization were: Luminal A, 0.88 vs. 0.85 ( P< 1e-69); Luminal B, 0.74 vs. 0.51 ( P< 1e-183); Her2+, 0.73 vs. 0.53 ( P< 1e-99); Basal, 0.98 vs. 0.97 ( P< 1e-53). Overall, homogenization significantly outperformed no homogenization. Conclusions: We developed a novel homogenization algorithm that accurately transfers subtype predictors across diverse, independent breast cancer cohorts.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22119-e22119
Author(s):  
Maria Gonzalez Cao ◽  
Carlota Costa ◽  
Miguel Angel Molina-Vila ◽  
Maria Teresa Cusido ◽  
Santiago Viteri Ramirez ◽  
...  

e22119 Background: Although it is know that pCR following neoadjuvant chemotherapy is more frequent in some subtypes of breast cancer such as Triple Negative (TN) or erb2 tumors, the predictive role of gene expression and mutation status is not well defined in this setting. Methods: We analyzed samples from 41 patients (p) prospectively treated with neoadjuvant chemotherapy (sequential AC followed by weekly TXL, or inverse sequence, plus trastuzumab for erb2 positive p). Pathologic response (PR) was classified according to Miller-Payne and RCB criteria. Radiologic evaluation was performed by ultrasonography, dynamic MR and PET-TAC after each chemotherapy sequence. We performed expression analysis of AXL, BRCA1, RAP80, BIM, EZH2, ROR1, FGFR1, PTPN12, YAP, GAS6, beta-TRCP, HIF1 alpha and ZNF217 by RT-PCR, and mutational status of p53 and PI3K genes in pretreatment biopsies. Statistical analysis was performed using Mann-Whitney U and Pearson’s chi-squared tests. Results: pCR was detected in 5 p (3TN, 2 erb2) of 25 p (9 luminal A, 5 luminal B, 6 erb2 and 5 TN) evaluated for PR at time of submitting this abstract. TN tumors had lower levels of RAP80 (p=.0013), PTPN12 (p=.003), beta TRCP (p=.001), ZNF217 (p=.014) and YAP (p=.097). Luminal B tumors had low levels of YAP and the highest levels of FGFR1 (p=.09) and ZNF217 (p=.014). Luminal A tumors had high levels of beta-TRCP (p=.003). We found no differences in BRCA1, AXL, BIM, EZH2, ROR1, GAS6 and HIF1 levels by breast cancer subtype. P with low levels of FGFR1 (p=.087), HIF1alpha (p=.07) or EZH2 (p=.005) had higher probability of pCR. No pCR was observed in p with higher levels of AXL, EZH2, RAP80, GAS6, beta TRCP, HIF alpha. Four p had p53 mutations (1 luminal B, 1 erb2 and 2 TN) and 4 p had PI3K mutations (2 luminal A, 1 erb2, 1 luminal B). There was no correlation between p53 status and PR. P with PI3K mutations did not achieve pCR vs 46% of p with wild type PI3K (p=.23). Conclusions: Gene expression profile varies by breast cancer subtype. Chemosensitivity could be higher in tumors with lower levels of FGFR1, HIF1alpha or EZH2. Further results will be presented.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12638-e12638
Author(s):  
Zhaoyun Liu ◽  
Jinjin Wang ◽  
Chenxi Yuan ◽  
Zhiyong Yu ◽  
Wendy Wu ◽  
...  

e12638 Background: In the last decade, the treatment approach for locally advanced breast cancer (BC) patients has partly shifted from adjuvant treatment to neoadjuvant treatment. Systemic neoadjuvant treatment can downstage the tumor for less extensive surgery and improve cosmetic outcomes. Differential subtypes of BC responded unevenly to neoadjuvant chemotherapy. Luminal B type with the relatively higher prevalence (40% in all 4 subtypes) had better therapeutic effect to neoadjuvant treatment than luminal A type, but worse than HER2-positive patients. Methods: We enrolled 87 BC patients for genotyping with multiple cancer-related genes. Among them, 17 patients were luminal A, 21 were HER2-negative luminal B, 23 were HER2-positive luminal B, 17 were HER2-positive and 9 were triple-negative. According to the RECIST, the patients were divided into 1-4 and 5 grades. Fisher test was used to analyze the difference of SNV and CNV between the two primary tumors, as well as TMB difference between post-neoadjuvant chemotherapy and past-neoadjuvant chemotherapy. Results: Base mutations in all patients showed discrepant preference between 1-4 grades and 5 grade groups, G-to-A in 1-4 grades, while A-to-G, A-to-T and G-to-T in 5 grade. In luminal B group (combine liminal B-negative and luminal B-positive groups), FLT4 gene mutation occurred more frequent in 5 grade than 1-4 grades (4/16 vs 0/28, P = 0.01). CNV analysis in NFKBIA and ZNF217 distinguished the two therapeutic efficiency groups in luminal B-positive group. The amplification of NFKBIA and ZNF217 was higher in 1-4 grades than 5 grade (8/14 vs 1/9, P = 0.036; 9/14 vs 1/9, P = 0.017). TMB difference between post and past neoadjuvant chemotherapy in luminal B-positive group was also significant in 5 grade (4.36 vs 1.99, P = 0.002). Conclusions: NFKBIA and ZNF217 amplification notably differentiated the 1-4 grades and 5 grade groups in luminal B-positive patients, suggesting the potential prognostic biomarkers of neoadjuvant chemotherapy in this locally advanced breast cancer subtype, which would be improved by further large-scale cohort study. The differences of TMB and FLT4 gene mutation were also found between the two therapeutic efficiency groups.


2021 ◽  
Vol 2 (3) ◽  
pp. 6-12
Author(s):  
E. M. Frantsiyants ◽  
N. Yu. Samaneva ◽  
L. Yu. Vladimirova ◽  
A. E. Storozhakova ◽  
E. A. Kalabanova ◽  
...  

Purpose of the study. An analysis of blood levels of TGF-β, TGFR2, TNF-α, TNF-αR1, TNF-αR2, CD44 and MMP9 in patients with various biological subtypes of breast cancer receiving neoadjuvant chemotherapy.Materials and methods. This article presents an analysis of levels of growth and progression factors (TGF-β, TGFR2, TNF-α, TNF-αR1, TNF-αR2, CD44 and MMP9) in the blood of 162 patients with various biological subtypes of locally advanced breast cancer receiving 8 cycles of neoadjuvant chemotherapy.Results. Levels of TGF-β, TGFR2, TNF, TNF-α, TNFR1, TNFR2, CD44, MMP9 in patients with all BC subtypes were high before the treatment. After chemotherapy cycles, the values decreased statistically significantly in all BC subtypes: CD44 decreased by 25.2 %, 30 % and 54.7 % in luminal A, luminal B and TNBC, respectively; TNFα– by 26.2 %, 48.3 % and 50.8 %, respectively; TNFα-R1 – by 52.1 %, 39.2 % and 50.3 % respectively; TNFα-R2 – by 31.7 %, 32.8 % and 41.9 % respectively; MMP9 – 35.3 %, 32.6 % and 43.3 % respectively.Conclusions. We identified a combination of growth and progression factors which determines the chemotherapy sensitivity and resistance in all subtypes of breast cancer; so, a decline in the levels of TGF-β, TNFα, MMP9 and CD44 after neoadjuvant chemotherapy predicts further remission for at least 3 years. On the contrary, stabilization or an increase of these indicators leads to the early tumor progression.


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