scholarly journals Assessment of Pathological Features and Molecular Profiling of Triple-Negative Breast Cancer: A Retrospective Study at King Abdulaziz University Hospital, Jeddah, Saudi Arabia

Author(s):  
Fatma Khinaifis Al-thoubaity

Background: Triple-negative breast cancer (TNBC) is a hostile sub-type consisting of nearly 10-20 % of breast cancer patients. TNBC has been known to have a poor prognosis and overall survival (OS) compared to many other breast cancer tumors categories. These tumors are highly aggressive and have a higher risk of early recurrence. Nevertheless, no evidence exists to date and this is also the situation in Saudi Arabia. Recently, it was found to be a heterogeneous disease. Objective: To subtype breast cancer (BC) following the recent advance molecular classification, and to ascertain the correlation of those sub-types with pathological parameters and to study triple-negative breast cancer and its correlation with other subtypes and its association with recurrence and poor prognosis. Methods: The study was performed on 740 breast cancer patients at the Department of Pathology, King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia diagnosed between 2005 to 2018. The parameters like Estrogen receptor (ER), Progesterone receptor (PR), and human epidermal growth factor receptor immunostaining were analyzed semi-quantitatively to establish the HER-2, triple-negative, molecular subtypes of luminal A and B in paraffin-embedded sections of BC. We review the histopathology report, tumor invasion, grade, margin, type of surgery, recurrence, metastases, and survival rate. Results: The most common sub-types were luminal B (19.7%), followed by triple-negative breast cancer (10.9%) and HER2-positive (9.5%), whereas luminal A was the least common subtype (8.1 %). In luminal A majority of their age less than or equal to 50 years, most of these subtypes have tumor invasion, 59.2% of triple-negative breast cancer had positive axillary lymph node involvement. 63.4 % of triple-negative breast cancer had grade 3 tumors most of the recurrence in luminal B. Conclusion: The biological behaviors of each molecular subtype is likely to be with characteristic pathological features. In addition to molecular sub-typing and further prognostic indicators, might be useful in investigating the prognosis and management of BC patients. The early diagnosis and screening of BC are recommended in our population.

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11573-e11573
Author(s):  
Sandro Barni ◽  
Ilaria Vallini ◽  
Marta Bonotto ◽  
Antonella Brunello ◽  
Monica Indelli ◽  
...  

e11573 Background: Several studies suggest that newer therapies can improve survival in MBC, but a different impact on overall survival (OS) is observed according to histology, extension of disease and prognostic factors. This survey was performed for evaluate Italian experience in cancer treatment in the last ten years. Methods: We collected data from 13 Italian Medical Oncology Unit; we registered all consecutive patients (pts) with breast cancer who have developed metastasis between 2000 and 2008. Demographic data, pathological characteristics and treatment were reported. OS was calculated from time of recurrence and stratified according to biological characteristics and to recurrence date. Results: 1542 pts was suitable for analysis; median age 61,7 (range 22-94); MBC at diagnosis 21,8%. Site of disease recurrence: bone 26,2%, visceral 25,4%, bone and visceral 20,7%, soft tissue 11,5%, soft tissue and visceral 8,4%, bone and soft tissue 7,8%. Molecolar classification: luminal A 66,3%, luminal B 14,5%, triple negative 11,5%, HER2+ like 7,7%. Pts received a median of 2 lines of chemotherapy (range 0-10) and 1 line of hormonal therapy (range 0-7); 22,5% received biological drugs. 15,5% of metastatic pts were enrolled in clinical trials. After a median follow up of 7.1 years 84,1% pts died (1297/1542 pts) and median OS was 2,7 years (range 2,6-2,9). We did not observe difference in OS for pts divided into 3 groups according to recurrence date (2000-2002, 2003-2005, 2006-2008). A longer median OS was observed in luminal B (3,8 years) versus luminal A and HER2+ like (2,8 years) and triple negative disease (1,2 years). Conclusions: Our survey describe a large number of MBC pts treated in 13 Italian Oncology Unit. OS analysis did not show significant differences according to recurrence date, but for different prognostic factors. OS data are superimposable to literature ones, showing a good transfer from clinical trials to clinical practice.


2020 ◽  
pp. 111-118
Author(s):  
Hugo Castro-Salguero ◽  
Luis García Aceituno ◽  
Alba Kihn ◽  
Raúl Jiménez ◽  
Allan Ramos-Esquivel

Background: Breast cancer (BC) is a leading cause of cancer related death worldwide. Unfortunately, data concerning clinicopathologic features of this malignancy in non-developed countries is scarce. This study aims to characterize a cohort of Guatemalan female patients with non-metastatic BC and to determine risk factors for overall survival (OS).Methods: We retrieved data on consecutive patients from the Instituto Guatemalteco de Seguridad Social that were treated from 2008 to 2014. Clinical features and long-term outcomes were retrieved from medical records. Univariate and multivariate Cox regression analyses were conducted to identify variables associated with OS. Results: 954 BC patients were identified during the time frame. A total of 436 women (46%) were younger than 50 years old. BC molecular subtypes categorized 537 patients (56.3%) with luminal A disease, 186 (19.5%) patients with triple negative tumors, 153 cases (16.1%) with HER-2 enriched tumors, and 78 patients (8.2%) with luminal B tumors. Clinical stage at presentation was stage I: 4.7% (n=45); stage II: 48.1% (n=459), and stage III: 47.2% (n=450). The overall 5-year survival rate was 75.2% (95% Confidence Interval: 72.0–78.3). In the multivariate analysis clinical stage, triple negative tumors and HER2 enriched tumors were independently associated with poor survival.Conclusion: The majority of patients with non-metastatic BC are diagnosed with advanced disease and many of them are younger than 50 years old. OS in this cohort of Guatemalan patients is lower than that reported in developed countries.


Author(s):  
Norikazu Masuda ◽  
Hiroko Bando ◽  
Takashi Yamanaka ◽  
Takayuki Kadoya ◽  
Masato Takahashi ◽  
...  

Abstract Purpose To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Methods Patients in group A (aged < 65 years with homologous recombination deficiency, HRD, score ≥ 42, or those at any age with germline BRCA mutation, gBRCAm) were randomized to 4 cycles of paclitaxel plus carboplatin (group A1) or eribulin plus carboplatin (group A2), followed by 4 cycles of anthracycline. Patients in group B (aged < 65 years with HRD score < 42, or aged ≥ 65 years without gBRCAm) were randomized to 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2); non-responders to the first 4 cycles of the eribulin-based therapy received anthracycline. Primary endpoint was pCR rate (ypT0-is, ypN0; centrally confirmed). Main secondary endpoint was safety. Results The full analysis set comprised 99 patients. The pCR rate was 65% (90% CI, 46%–81%) and 45% (27%–65%) in groups A1 and A2, respectively, and 19% (8%–35%) in both groups B1 and B2. No major difference was seen in secondary endpoints, but peripheral neuropathy incidence was 74% in group A1, whereas it was 32%, 22%, and 26% in groups A2, B1, and B2, respectively. Conclusions In patients aged < 65 years with high HRD score or gBRCAm, weekly paclitaxel plus carboplatin and eribulin plus carboplatin followed by anthracycline resulted in a pCR rate of > 60% and > 40%, respectively, suggesting potential usefulness of patient stratification using HRD; pCR tended to be low in patients with HRD-negative tumors. Neurotoxicity was less frequent with the eribulin-based regimen. Trial registration:The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (http://www.umin.ac.jp/ctr/index-j.htm) with unique trial number UMIN000023162. The Japan Breast Cancer Research Group trial number is JBCRG-22.


2021 ◽  
Vol 15 ◽  
pp. 117822342110169
Author(s):  
Maria A Arafah ◽  
Abderrahman Ouban ◽  
Omar Z Ameer ◽  
Ko Jin Quek

Purpose: Triple-negative breast cancer (TNBC) is a subset of breast cancer which is known to carry a poor prognosis because of lack of targets for hormonal therapy. Research efforts have focused in recent years on discovering biomarkers of management in TNBCs. KI-67 Labelling Index (LI) is a nuclear protein which has proven to play diagnostic and prognostic roles in many cancers. Materials and methods: We analysed the expression of KI-67 LI by immunohistochemistry in TNBC cases from the University hospital. This expression was cross-checked against clinical-pathological criteria of TNBC patients and against Vimentin expression in TNBC patients with significant KI-67 expression. Results: KI-67 LI was significantly expressed in the majority of TNBC cases. This expression was significantly correlated with lymph node metastases, tumour invasion, high tumour nuclear grade, clinical stage, adverse survival outcome, and failure to achieve pathological complete response. TNBCs’ KI-67 LI expression was also correlated with Vimentin expression, the mesenchymal chief marker of the EMT phenomenon. Conclusion: Collectively, our study presents a strong argument for the use of KI-67 LI as a biomarker of aggressive, metastatic TNBC disease with poor outcome. This study, along with mounting evidence in the scientific literature, presents a case for the use of this nuclear protein in diagnosis, prognosis, and follow-up of patients with this difficult diagnosis.


Breast Care ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. 248-252 ◽  
Author(s):  
Muhammet A. Kaplan ◽  
Ulku Y. Arslan ◽  
Abdurrahman Işıkdogan ◽  
Faysal Dane ◽  
Berna Oksuzoglu ◽  
...  

Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. Methods: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. Results: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.


2020 ◽  
Author(s):  
Bo-yue Han ◽  
Xiao-guang Li ◽  
Hai-yun Zhao ◽  
Xin Hu ◽  
Hong Ling

Abstract Purpose: Pregnancy-associated breast cancer (PABC) is an aggressive disease, and sinceChinese authoritybegan to encourage childbearing in 2015, the incidence of PABC has increased. This study investigated the characteristics and survival of PABC patients. Methods: Patients with PABC who underwent surgery at Fudan University, Shanghai Cancer Center between 2005 and 2018 were enrolled.Data concerning the tumor characteristics, maternal state (whether first or non-first pregnancy ) and survival outcome were recorded. Pearson Chi-square tests were used to compare the characteristics of the tumors, and Kaplan-Meier methods were used to perform the survival analysis. Results: Overall, 203 PABC patients were recruited. Since 2015, 65.5% of non-first pregnant women were diagnosed with breast cancer, it’s 5.7 fold of the incidence of PABC in non-first pregnant women. No significant differences in tumor characteristics were observed between the patients who were in their first pregnancy and those in non-first pregnancy. Among the entire PABC population, luminal B breast cancer accounted for the largest proportion (38.4%), followed by triple-negative breast cancer (TNBC, 30.0%). The distribution of the molecular subtypes of PABC and non-PABC differed (P<0.001) as follows: in the PABC patients, Luminal B 38.4%, Triple negative breast cancer (TNBC) 30.1%, Human Epidermal Growth Factor Receptor 2 (HER-2) overexpression 15.8%, and Luminal A 10.8%; in the non-PABC patients, Luminal A 50.9%, Luminal B 20.1%, TNBC 17.4%, and HER-2 overexpression 8.0%. The 3-year disease free survival (DFS) of all PABC patients was 80.3%. The 3-year DFS of the patients in the first-pregnancy group was 78.4%, and that of the patients in the non-first-pregnancy group was 83.7% (P=0.325). Conclusions: Our study proved that the proportion of women who developed PABC during the second or third pregnancy was extremely high relative to the newborn populations. The patients in the PABC population tended to present more luminal B and TNBC breast cancer than the non-PABC patients.


2020 ◽  
Vol 42 (1) ◽  
pp. 75
Author(s):  
Suzita Hirachan ◽  
Yogendra P Singh

Introduction Breast cancer is the second most common malignancy in Nepalese women. It represents a group of heterogenous disease with diverse biologic, clinical and molecular characteristics requiring personalized treatment. Based on Immunohistochemical markers, breast cancer is classified into distinct molecular subtypes. The aim of the study was to analyze the incidence of molecular subtypes of all breast cancer patients treated at University Hospital of Nepal in the period over 3 years. MethodsA retrospective observational study was carried out in Breast Unit of Tribhuvan University Teaching Hospital, Kathmandu. Electronic medical records of all breast cancer patients treated between January 2017 to December 2019 were retrieved from the hospital database. Patient’s characteristic, histological features and molecular subtypes were collected and analyzed. ResultsA total of 156 surgically treated breast carcinoma patients were studied. The median age of study population was 55 years (range 28–82years). Among these, 69 (44%) were of ≤45 years and 87 (56%) were over 45 years. The mean tumor size was 29 mm (range 50-140 mm). The most common histology was invasive ductal carcinoma (93.5%). Luminal type A was positive in 68 (43%) patients while luminal type B was present in 12 (7.6%) patients. Triple negative subtype was observed in 50 (32%) patients while HER2 rich subtype was seen in 25(16%). Incidence of Triple negative subtype was highest in patients less than 45 years (42%). Luminal A subtype was correlated with low tumor grade and less positive lymph nodes metastasis. ConclusionThe most common molecular subtype of breast cancer in Nepal is Luminal A having favorable features. The incidence of triple negative breast cancer is higher in Nepal, having an aggressive and clinically distinct subtype and is important for personalized treatment plan.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 565-565
Author(s):  
Naoki Niikura ◽  
Shinobu Masuda ◽  
Mizuho Terada ◽  
Mayako Terao ◽  
Nobue Kumaki ◽  
...  

565 Background: Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67 labeling index is chiefly important for distinguishing between “Luminal A” and “Luminal B (HER2 negative)” subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate, and high Ki67 levels in each subgroup. Methods: We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000, and December 31, 2010. Ki67 was defined as low if <10% Ki67 was detected, as Intermediate if 10–20% Ki67 was detected, and as high if >20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: We identified 1331 primary breast cancer patients without metastasis, of whom 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (p = 0.009) and low Ki67 (p < 0.001). Patients with intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001). In ER-positive cases (n = 1059), patients with high and intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001 and p = 0.002, respectively). In HER2-positive and ER-negative cases (n = 103), patients with high Ki67 had poorer RFS than patients with low Ki67 (p = 0.002). In triple-negative cases (n = 164), patients with high Ki67 tended to have poorer RFS than patients with low Ki67 (p = 0.064). Conclusions: Our data demonstrated that low, intermediate, and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11515-e11515
Author(s):  
Aydan Akdeniz ◽  
Selim Yalcin ◽  
Samed Rahatli ◽  
Nadire Kucukoztas ◽  
Mahmut Can Yagmurdur ◽  
...  

e11515 Background: Triple negative breast cancer in which estrogen, progesterone receptors and c-erbB2 overexpression are negative, seems to have different clinical course and recurrence pattern. Methods: We evaluated retrospectively clinical demographic and pathological characteristics of triple negative breast cancers and investigated the association of these characteristics with OS and PFS. Results: 59 early stage patients with triple negative breast cancer patients followed in Baskent University Hospital between 1997-2009 were enrolled into the study. The median age of patients was 49. Median follow-up duration was 27 months (0.27-132 months). Two patients died during the follow-up. Invasive ductal carcinoma pathology was reported in 38 patients, invasive lobular in 3 patients, medullary in 5 patients.Almost half of the patients had LVI. 79% of patients had a T2 disease. 30% of patients’ tumor histological grade was III. Cancer history in the family was present in 95% of patients. Almost half of the patients had stage II disease. Adjuvant chemotherapy was given to 43 patients. Relapses were observed in 15 patients.The most common metastatic site was lung. Patients having high grade tumor, >3 (+) lymph nodes, younger age have higher chance of relapse during follow-up. Conclusions: In accordance with the literature, our triple negative breast cancer patients showed more aggressive characteristics. Although median follow-up is short, one-fourth of the patients having recurrence support natue of the triple negative breast cancer patients. In our study, triple negative patients had younger age at diagnosis, high grade tumors and more tendency to metastasize to visceral organs.


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