Is There a Difference in the Association between Percent Mammographic Density and Subtypes of Breast Cancer? Luminal A and Triple-Negative Breast Cancer

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15–20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution.

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Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

Medicina ◽

10.3390/medicina57080837 ◽

2021 ◽

Vol 57 (8) ◽

pp. 837

Author(s):

So-Woon Kim ◽

Jinah Chu ◽

Sung-Im Do ◽

Kiyong Na

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Poor Prognosis ◽

Triple Negative ◽

Histological Grade ◽

Growth Factor Receptor ◽

Hippo Signaling ◽

Luminal A ◽

Luminal B ◽

Epidermal Growth

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.

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Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple‐negative breast cancer: Caspase, ΔΨm, and pro‐apoptotic gene involvement

Fundamental and Clinical Pharmacology ◽

10.1111/fcp.12559 ◽

2020 ◽

Vol 34 (6) ◽

pp. 671-686 ◽

Cited By ~ 1

Author(s):

Vida Celeste Rosas‐González ◽

Martha Cecilia Téllez‐Bañuelos ◽

Georgina Hernández‐Flores ◽

Alejandro Bravo‐Cuellar ◽

Adriana Aguilar-Lemarroy ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Luminal A ◽

Differential Effects ◽

Apoptotic Gene

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An allomaltol derivative triggers distinct death pathways in luminal a and triple-negative breast cancer subtypes

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104403 ◽

2020 ◽

Vol 105 ◽

pp. 104403

Author(s):

A. Ercan ◽

S. Oncul ◽

G. Karakaya ◽

M. Aytemir

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Luminal A ◽

Cancer Subtypes

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High Expression of Trophoblast Cell Surface Antigen 2 in Triple-negative Breast Cancer Identifies a Novel Therapeutic Target

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz113.001 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S37-S37

Author(s):

Elias Makhoul ◽

Farnaz Dadmanesh

Keyword(s):

Breast Cancer ◽

Cell Surface ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Pairwise Comparison ◽

Control Group ◽

Bonferroni Correction ◽

Luminal A ◽

Membranous Staining

Abstract Objectives Patients with triple-negative breast cancer (TNBC) respond poorly to current therapeutic modalities. The newly FDA-approved drug conjugate, Sacituzumab Govitecan, targeting antitrophoblastic cell surface antigen 2 (Trop-2), offers a new modality to treat these subtypes of breast carcinoma (BC). Our study examines expression of Trop-2 by immunohistochemistry (IHC) in TNBC. Methods Forty cases of TNBC were selected from our files (34 ductal, 4 pleomorphic lobular, 1 metaplastic, and 1 mixed ductal and lobular carcinoma). A control group included 11 luminal A-like, 11 luminal B-like, and 8 HER2-like BC. Immunostaining for Trop-2 was performed on 4-micron-thick tissue sections using goat polyclonal antibody (R&D Systems). Three pathologists individually scored the % and intensity of membranous staining. The % of staining was defined as <10%, 10%-50%, and >50%. The intensity of staining was scored as 3+ (crisp circumferential membranous staining), 2+ (medium membranous staining), 1+ (patchy weak membranous staining), and 0 (no staining). A Kruskal-Wallis H-test and pairwise comparison with Bonferroni correction was performed to compare % and intensity of staining in TNBC to control group. Results TNBC exhibited stronger Trop-2 staining in both intensity and extent when compared to the control. The result was significantly different, χ2 (4) = 17.427, P = .001. A pairwise comparison with Bonferroni correction found significant difference between TNBC (42.55) and luminal A (16.65) (P < .001). There was significant agreement (P < .001) among 3 independent pathologists for assessing % and intensity of staining. Conclusion The extent and intensity of staining for Trop-2 is higher in TNBC than in other molecular subtypes of BC. These findings suggest that patients with TNBC may potentially benefit from this targeted therapy. Furthermore, identification of Trop-2 in other molecular subtypes may expand the therapeutic potential of this new drug. Further studies are needed to determine the efficacy of this marker.

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CD24 Overexpression Is Associated with Poor Prognosis in Luminal A and Triple-Negative Breast Cancer

PLoS ONE ◽

10.1371/journal.pone.0139112 ◽

2015 ◽

Vol 10 (10) ◽

pp. e0139112 ◽

Cited By ~ 29

Author(s):

Mi Jeong Kwon ◽

Jinil Han ◽

Ji Hyun Seo ◽

Kyoung Song ◽

Hae Min Jeong ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Poor Prognosis ◽

Triple Negative ◽

Luminal A

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Impact of Chemotherapy Relative dose Intensity on Breast Cancer-Specific and Overall Survival for Stage I-III Luminal A vs Triple Negative Breast Cancer

Annals of Epidemiology ◽

10.1016/j.annepidem.2017.07.132 ◽

2017 ◽

Vol 27 (8) ◽

pp. 508

Author(s):

Lu Zhang ◽

Qingzhao Yu ◽

Xiao-Cheng Wu ◽

Mei-Chin Hsieh ◽

Michelle Loch ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Dose Intensity ◽

Stage I ◽

Relative Dose Intensity ◽

Luminal A

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

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2020/v32i1430561 ◽

2020 ◽

pp. 22-38

Author(s):

Fatma Khinaifis Al-thoubaity

Keyword(s):

Breast Cancer ◽

Saudi Arabia ◽

Triple Negative Breast Cancer ◽

Tumor Invasion ◽

Triple Negative ◽

University Hospital ◽

Breast Cancer Patients ◽

Luminal A ◽

Luminal B ◽

King Abdulaziz University

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.

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Hubungan Ekspresi Tumor Infiltrating Lymphocytes dengan Klinikopatologi pada Subtipe Luminal A dan Triple Negative Kanker Payudara di Bali

JBN (Jurnal Bedah Nasional) ◽

10.24843/jbn.2020.v04.i02.p02 ◽

2020 ◽

Vol 4 (2) ◽

pp. 43

Author(s):

I Gede Tuban Eling Tulus Widiana ◽

Ida Bagus Made Suryawisesa ◽

I Ketut Widiana

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Tumor Infiltrating Lymphocytes ◽

Luminal A ◽

Stadium I ◽

Infiltrating Lymphocytes

Tujuan: Untuk membuktikan adanya hubungan ekspresi TIL dengan klinikopatologi pada subtipe luminal A dan subtipe TNBC beserta ada tidaknya perbedaan antara kedua subjek tersebut. Metode: Penelitian ini merupakan penelitian observasional, dirancang secara potong-lintang di RSUP Sanglah Denpasar. Kriteria inklusi adalah penderita kanker payudara subtipe luminal A dan subtipe TNBC (triple negative breast cancer) sebagai subjek penelitian. Hasil: Pada penelitian ini terdapat 31 subjek dengan Luminal A dan 40 subyek dengan TNBC. Penelitian ini didapatkan hubungan signifikan antara stadium dengan kadar TIL pada kanker payudara subtipe TNBC (p=0,01). Pada kanker payudara subtipe TNBC stadium tinggi, kemungkinan TIL tinggi 3 kali dibandingkan dengan subjek dengan stadium I-II. Adanya hubungan yang bermakna pada penderita dengan TIL tinggi dengan stadium lanjut pada subtype TNBC dan luminal A (p=0,028; PR 1,8; 95%CI 0,54-5,9). Simpulan: Tidak terdapat hubungan signifikan yang diperoleh antara TIL dengan ukuran tumor, stadium klinis, grade histopatologi pada kanker payudara subtipe luminal A maupun TNBC. Tidak terdapat pula hubungan ukuran tumor dan grading tumor antara kanker payudara dengan subtipe TNBC dan luminal A yang memiliki TIL yang tinggi, tetapi terdapat perbedaan pada stadium tumor.

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