scholarly journals Associations of MDM2 and MDM4 Polymorphisms with Early-Stage Breast Cancer

2021 ◽  
Vol 10 (4) ◽  
pp. 866
Author(s):  
Agnė Bartnykaitė ◽  
Aistė Savukaitytė ◽  
Rasa Ugenskienė ◽  
Monika Daukšaitė ◽  
Erika Korobeinikova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Estrogen Receptor Status ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Disease Assessment ◽  
Her2 Status ◽  
Nucleotide Polymorphisms ◽  
Pcr Rflp ◽  
Epidermal Growth

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I–II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment.

scholarly journals Biomarkers Changes after Neoadjuvant Chemotherapy in Breast Cancer: A Seven-Year Single Institution Experience

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2249
Author(s):  
Saverio Coiro ◽  
Elisa Gasparini ◽  
Giuseppe Falco ◽  
Giacomo Santandrea ◽  
Moira Foroni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptors ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Residual Tumor ◽  
Intrinsic Subtype ◽  
Her2 Status ◽  
Epidermal Growth ◽  
Prognostic Implications

The adoption of neoadjuvant chemotherapy (NACT) for breast cancer (BC) is increasing. The need to repeat the biomarkers on a residual tumor after NACT is still a matter of debate. We verified estrogen receptors (ER), progesterone receptors (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) status changes impact in a retrospective monocentric series of 265 BCs undergoing NACT. All biomarkers changed with an overall tendency toward a reduced expression. Changes in PR and Ki67 were statistically significant (p = 0.001). Ki67 changed in 114/265 (43.0%) cases, PR in 44/265 (16.6%), ER in 31/265 (11.7%) and HER2 in 26/265 (9.8%). Overall, intrinsic subtype changed in 72/265 (27.2%) cases after NACT, and 10/265 (3.8%) cases switched to a different adjuvant therapy accordingly. Luminal subtypes changed most frequently (66/175; 31.7%) but with less impact on therapy (5/175; 2.8%). Only 3 of 58 triple-negative BCs (5.2%) changed their intrinsic subtype, but all of them switched treatment. No correlation was found between intrinsic subtype changes and clinicopathological features. To conclude, biomarkers changes with prognostic implications occurred in all BC intrinsic subtypes, albeit they impacted therapy mostly in HER2 negative and/or hormone receptors negative BCs. Biomarkers retesting after NACT is important to improve both tailored adjuvant therapies and prognostication of patients.

scholarly journals Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1417
Author(s):  
Binafsha M. Syed ◽  
Andrew R. Green ◽  
Emad A. Rakha ◽  
David A.L. Morgan ◽  
Ian O. Ellis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Histological Grade ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Biological Characteristics ◽  
Cancer Specific Survival ◽  
Age Related ◽  
Significant Difference

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.

scholarly journals Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3427
Author(s):  
Reyhaneh Farghadani ◽  
Rakesh Naidu
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Mapk Pathway ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Drug Candidate ◽  
Molecular Signaling ◽  
Her2 Positive ◽  
Therapeutic Implications ◽  
Epidermal Growth

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-ĸB pathway, p53 pathway, and Wnt/β-catenin, as well as apoptotic and cell cycle pathways. Besides, its therapeutic implications in clinical trials are here presented.

Automated NLP Extraction of Clinical Rationale for Treatment Discontinuation in Breast Cancer

2021 ◽  
pp. 550-560
Author(s):  
Matthew S. Alkaitis ◽  
Monica N. Agrawal ◽  
Gregory J. Riely ◽  
Pedram Razavi ◽  
David Sontag
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Logistic Regression ◽  
Standard Deviation ◽  
Early Stage ◽  
Area Under The Curve ◽  
Growth Factor Receptor ◽  
Treatment Discontinuation ◽  
High Dimensional ◽  
Epidermal Growth

PURPOSE Key oncology end points are not routinely encoded into electronic medical records (EMRs). We assessed whether natural language processing (NLP) can abstract treatment discontinuation rationale from unstructured EMR notes to estimate toxicity incidence and progression-free survival (PFS). METHODS We constructed a retrospective cohort of 6,115 patients with early-stage and 701 patients with metastatic breast cancer initiating care at Memorial Sloan Kettering Cancer Center from 2008 to 2019. Each cohort was divided into training (70%), validation (15%), and test (15%) subsets. Human abstractors identified the clinical rationale associated with treatment discontinuation events. Concatenated EMR notes were used to train high-dimensional logistic regression and convolutional neural network models. Kaplan-Meier analyses were used to compare toxicity incidence and PFS estimated by our NLP models to estimates generated by manual labeling and time-to-treatment discontinuation (TTD). RESULTS Our best high-dimensional logistic regression models identified toxicity events in early-stage patients with an area under the curve of the receiver-operator characteristic of 0.857 ± 0.014 (standard deviation) and progression events in metastatic patients with an area under the curve of 0.752 ± 0.027 (standard deviation). NLP-extracted toxicity incidence and PFS curves were not significantly different from manually extracted curves ( P = .95 and P = .67, respectively). By contrast, TTD overestimated toxicity in early-stage patients ( P < .001) and underestimated PFS in metastatic patients ( P < .001). Additionally, we tested an extrapolation approach in which 20% of the metastatic cohort were labeled manually, and NLP algorithms were used to abstract the remaining 80%. This extrapolated outcomes approach resolved PFS differences between receptor subtypes ( P < .001 for hormone receptor+/human epidermal growth factor receptor 2− v human epidermal growth factor receptor 2+ v triple-negative) that could not be resolved with TTD. CONCLUSION NLP models are capable of abstracting treatment discontinuation rationale with minimal manual labeling.

scholarly journals Practical Approach to Triple-Negative Breast Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Management Strategies ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Proven Method

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.

scholarly journals Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 737 ◽  
Author(s):  
Denis M. Collins ◽  
Neil T. Conlon ◽  
Srinivasaraghavan Kannan ◽  
Chandra S. Verma ◽  
Lisa D. Eli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Epidermal Growth

An estimated 15–20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2/ERBB2/neu). Two small-molecule tyrosine kinase inhibitors (TKIs), lapatinib and neratinib, have been approved for the treatment of HER2-positive (HER2+) breast cancer. Lapatinib, a reversible epidermal growth factor receptor (EGFR/ERBB1/HER1) and HER2 TKI, is used for the treatment of advanced HER2+ breast cancer in combination with capecitabine, in combination with trastuzumab in patients with hormone receptor-negative metastatic breast cancer, and in combination with an aromatase inhibitor for the first-line treatment of HER2+ breast cancer. Neratinib, a next-generation, irreversible pan-HER TKI, is used in the US for extended adjuvant treatment of adult patients with early-stage HER2+ breast cancer following 1 year of trastuzumab. In Europe, neratinib is used in the extended adjuvant treatment of adult patients with early-stage hormone receptor-positive HER2+ breast cancer who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy. Preclinical studies have shown that these agents have distinct properties that may impact their clinical activity. This review describes the preclinical characterization of lapatinib and neratinib, with a focus on the differences between these two agents that may have implications for patient management.

Expression of Estrogen, Progesterone Receptors, and Human Epidermal Growth Factor Receptor 2 in Women With Breast Cancer

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S89-S89
Author(s):  
Angela Mlole
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
The Mean

Abstract Introduction Globally, breast cancer is a leading cause of female cancer-related mortality and most predominant in the premenopausal stage. Expression of hormone receptors and human epidermal growth factor receptor 2, HER2/neu, appears to be different in the premenopausal group. However, there are limited data on hormone receptor expressions among women in Uganda. Therefore, the objective of this study was to determine the expression of estrogen, progesterone receptors, and human epidermal growth factor receptor 2 in women with breast cancer. Methods This was a retrospective descriptive cross-sectional laboratory-based study conducted in the Department of Pathology, Makerere University. Paraffin-embedded tissue blocks were retrieved from the archive and stained with H&E for histological confirmation and establishment of histological grade and type. Immunohistochemistry staining using a mouse-derived monoclonal antibody for hormonal receptors and HER2/neu expression was also done. Data were analyzed using STATA version 13. Results A total of 103 patients’ tissue blocks were analyzed. The mean ± SD age of the cases was 49 ± 15 years. The majority, 55/103 (53.4%), had intermediate cancer grade and 39/103 (37.9%) had triple-negative breast cancer. The majority, 55/103 (53.4%), were positive for ER hormone expression, 48/103 (46.6%) showed positive PR hormone expression, and only 19/103 (18.5%) were HER2/neu positive. Age of the cases showed statistical significance with hormonal receptor expressions and triple-negative breast cancer (P < .05), with high-grade cancers being more common among premenopausal women. Conclusion The study found that the mean age of breast cancer was 49 years, invasive carcinoma of no special type (NST) was the commonest histological type, and the majority were of intermediate cancer grade. In total, 53.4% of patients were ER positive, 46.6% were PR positive, 18.5% were HER2/neu positive, and 37.9% were triple negative. Age was the only factor significantly associated with hormonal receptors and triple-negative breast cancers.

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