Molecular classification of breast cancer: An overview with emphasis on ethnic variations and future perspectives

Shawarby, Mohamed A.; Al-Tamimi, Dalal M.; Ahmed, Ayesha

doi:10.4103/1658-631x.112908

Cited by 13 publications

(12 citation statements)

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“…The 12 clinical samples in this study were randomly collected from Saudi women diagnosed with hormonal luminal-A breast cancer to investigate the most important targetable kinase pathways, and to compare the effect of HAA 2020 and dinaciclib to tamoxifen on those targets in MCF7 cells. The characteristics of the 12 samples were similar to previously reported Saudi luminal-A characteristics [ 4 , 5 ]. Notably, most of the samples in this study showed over 60% ER, and for this type of cancer, tamoxifen can be used as the first-line drug.…”

Section: Discussionsupporting

confidence: 81%

“…The characteristics of the samples included in this study are shown in Table 1 . Most of the clinical sample characteristics under study were similar to the characteristics of previous Saudi studies [ 4 , 5 ], as 50% of the samples were from pre-menopausal patients, and 66% and 34% were grade II and III, respectively. Additionally, 83% were ductal vs. 17% lobular samples.…”

Section: Resultssupporting

confidence: 56%

“…Additionally, the GO processes showed the importance of kinase phosphorylation to the tumorigenesis process of the luminal-A samples. Previously, some studies highlighted the importance of CDKs and cyclin D1 to Saudi BC patients [ 5 , 18 ]. Additionally, in another study that included 100 Saudi women with BC, cyclin D1 was found in 68% of the cases, which was significantly co-related with ER and PR status [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…As an example, an average of 34.7% was reported in Oman, 69% in Poland, and 47.4% and 54% for African and non-African Americans, respectively, during the period of 1993–2010 [ 4 ]. In a Saudi BC molecular profiling study, luminal CK8/18 (normal luminal epithelial like differentiation 8/18) and some genes, mainly cyclin D1 and LIV1 (Zin transporter LIV1), were reported to be associated with the luminal-A sub-type [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer

et al. 2020

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The hormonal luminal-A is the most pre-dominant sub type of breast cancer (BC), and it is associated with a high level of cyclin D1 in Saudi patients. Tamoxifen is the golden therapy for hormonal BC, but resistance of cancer cells to tamoxifen contributes to the recurrence of BC due to many reasons, including high levels of AIB1 and cyclin D1. Overcoming drug resistance could be achieved by exploring alternative targetable therapeutic pathways and new drugs or combinations. The objective of this study was to determine the differentially enriched pathways in 12 samples of Saudi women diagnosed with luminal-A using the PamChip peptide microarray-based kinase activity profiling, and to compare the activity of HAA2020 and dinaciclib with tamoxifen in singles and combinations in the MCF7 luminal-A cell line. Our results of network and pathway analysis of the 12 samples highlighted the importance of VEGFR and CDKs in promoting luminal-A breast cancer. The activation of VEGF signaling via VEGFR-2 leads to activation of PI3K/AKT kinases and an increase of cell survival, and leads to activation of Hsp90, which induces the phosphorylation of FAK1, resulting in cytoskeleton remodeling. PLC-gamma 1 is also activated, leading to FAK-2 and PKC activation. Notably, the G1/S cell cycle phases and phosphorylation processes contribute to the top seven tumorigenesis processes in the 12 samples. Further, the MTT combination of HAA2020 and dinaciclib showed the best combination index (CI), was more clonogenic against MCF7 cells compared to the other combinations, and it also showed the best selectivity index (SI) in normal MRC5 cells. Interestingly, HAA2020 and dinaciclib showed a synergistic apoptotic and G1 cell cycle effect in MCF7 cells, which was supported by their synergistic CDK2, cyclin D1, and PCNA inhibition activities. Additionally, the combination showed VEGFR-2 and Hsp90 inhibition activities in MCF7 cells. The results show the significance of targeting VEGFR-2 and cyclin D1 in Saudi luminal-A breast cancer patients, and the effect of combining HAA2020 and dinaciclib on those targets in the MCF7 model. It also warrants further preclinical and in vivo investigations for the combination of HAA2020 and dinaciclib as a possible future second-line treatment for luminal-A breast cancers.

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Section: Discussionsupporting

confidence: 81%

Section: Resultssupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer

et al. 2020

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“…Breast lesions are not a single entity, rather they represent a heterogeneous group of diseases with marked clinical and morphological diversity. 1 Breast tumors with similar histopathological appearance can exhibit divergent clinical presentations, disease aggressiveness and response to treatment. Benign breast diseases continue to dominate in early age group whereas malignancy is more prominent in older ages.…”

Section: Introductionmentioning

confidence: 99%

Role of p63 expression in non-proliferative and proliferative lesions of breast

et al. 2018

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Background: Breast lump among females, is a fairly common complaint. Breast lump have a variety of etiologies ranging from inflammatory to benign to malignant lesions. Myoepithelial markers are useful in helping to distinguish invasive carcinoma from benign proliferations with a similar morphological appearance, benign proliferative lesions and most pre-invasive lesions with an intact myoepithelium. Invasive carcinomas lack the myoepithelial cell layer that normally surrounds benign breast glands. p63 antibody is a myoepithelial cell marker that selectively stains nuclei. Also, it is negative in stromal, myofibroblastic and adipocytic cells. This makes p63 more specific and superior to other myoepithelial markers.Methods: The present study was done on a total of 151 cases of breast diseases, received in the form of core biopsy, tru cut biopsy, lumpectomy, and mastectomy specimens. Clinical history and examination findings of the patients were collected in all the cases. All specimens were routinely processed and stained with haematoxylin and Eosin (H and E) stain and only 50 cases were subjected to immunohistochemical staining for p63.Results: Out of total 151 cases, 09 were inadequate for evaluation, 96 cases benign and 46 malignant. In benign category, fibroadenoma was most common and infiltrating ductal carcinoma (NOS) was the most common in malignant category. Mean size of benign tumors was found to be less than that of malignant tumors. All malignant cases were negative for p63 expression. In the benign category, 88.6% cases showed positive expression for p63 while 11.4% were negative. Among the benign category, non-proliferative lesions were continuous positive, proliferative showed discontinuous positivity for p63.Conclusions: Myoepithelial markers are useful in helping to distinguish invasive carcinoma from benign proliferations with a similar morphological appearance, benign proliferative lesions and most pre-invasive lesions with an intact myoepithelium. Invasive carcinomas lack the myoepithelial cell layer while in the benign category, non-proliferative lesions are continuous positive, proliferative lesions show discontinuous positivity for p63.

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Molecular Subtypes and Ki-67 index in Breast Carcinoma with Special Emphasis on Triple Negative Breast Cancer. A 3-year Study in a Tertiary Care Center

Pai

Doreswamy

2023

Indian J Surg Oncol

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Molecular classification of breast cancer: An overview with emphasis on ethnic variations and future perspectives

Cited by 13 publications

References 1 publication

Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer

Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer

Role of p63 expression in non-proliferative and proliferative lesions of breast

Molecular Subtypes and Ki-67 index in Breast Carcinoma with Special Emphasis on Triple Negative Breast Cancer. A 3-year Study in a Tertiary Care Center

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