Use of mutational profiling of metastatic ER+/HER2- breast cancers and the coexistence of KRAS, MET, BRAF, and FGFR3 with PIK3CA mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11003-11003
Author(s):  
Debora Fumagalli ◽  
Roberto Salgado ◽  
Carmen Criscitiello ◽  
Lina Pugliano ◽  
Ioanna Laios ◽  
...  
Keyword(s):  
Hormonal Treatment ◽  
Primary Diagnosis ◽  
Outcome Data ◽  
Her2 Status ◽  
Breast Cancers ◽  
Genetic Changes ◽  
Pik3ca Mutations ◽  
Paired Samples ◽  
Adjuvant Hormonal Treatment ◽  
High Concordance

11003 Background: ER+/HER2- breast cancers (BCs) constitute the most frequent BC subtype. Their response to endocrine therapy and degree of estrogen dependence are heterogeneous. There is little data available about the genetic changes associated with disease progression in this subtype. This information could facilitate drug development. Methods: A series of 132 ER+/HER2- BC patients diagnosed between 1982 and 2008, with known local-regional (n=10) or distant (n=98) relapse or both (n=24), and available FFPE blocks from their primary (P; n=132) and paired relapse (R; n=49) were identified at a single institution. ER and HER2 status were centrally confirmed. 120 mutations from 11 actionable genes and PTEN protein expression were determined using Fluidigm-based real-time PCR and IHC, respectively. Results: At primary diagnosis, median age was 57 years (27-90); median tumor size 2.5 cm (0.5-11); 75% had positive nodes, 26.5% were pre-menopausal; 80% received adjuvant hormonal treatment. Mutation frequency in P and R samples is presented in the Table. PIK3CA mutations were identified in 44% (58/132) P samples. HRAS, AKT1 and PIK3CA mutations were mutually exclusive. 62.5% (5/8) of KRAS-mutated, 75% (6/8) of MET-mutated, 100% (2/2) of BRAF-mutated and 33.3% (1/3) of FGFR3-mutated P had coexistent PIK3CA mutations. For the 49 evaluated pairs, high concordance for the mutations status was found between P and R. Conclusions: KRAS, BRAF, MET and FGFR3 mutations, found at relatively high frequency in this population of relapsed ER+/HER2- BCs, could represent clinically relevant targets and contribute to mechanisms of recurrence, particularly in PIK3CA-mutated BCs. Mutation profiling of additional paired samples is ongoing and clinical outcome data will be presented. [Table: see text]

scholarly journals Prognostic significance of receptor expression discordance between primary and recurrent breast cancers: a meta-analysis

2021 ◽  
Author(s):  
Sho Shiino ◽  
Graham Ball ◽  
Binafsha M. Syed ◽  
Sasagu Kurozumi ◽  
Andrew R. Green ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Outcome Data ◽  
Receptor Expression ◽  
Her2 Status ◽  
Breast Cancers ◽  
Recurrent Tumors ◽  
Recurrent Breast

Abstract Purpose This meta-analysis aimed to investigate whether receptor (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) discordances between primary and recurrent breast cancers affect patients’ survival. Methods Search terms contained ER, PR, and HER2 status details in both primary and recurrent tumors (local recurrence or distant metastasis) in addition to survival outcome data (overall survival [OS] or post-recurrence survival [PRS]). Results Loss of ER or PR in recurrent tumors was significantly associated with shorter OS as compared with receptor-positive concordance (hazard ratio [HR], 1.67; 95% confidence interval [% CI] 1.37–2.04; p < 0.00001 and HR, 1.45; 95% CI 1.21–1.75; p < 0.0001, respectively). Similar trends were observed in groups with only distant metastasis. Gain of ER was a significant predictor of longer PRS as compared with receptor-negative concordance (HR, 0.76; 95% CI 0.59–0.97; p = 0.03). Gain of PR was not a significant predictor of longer survival compared with receptor-negative concordance, but it could be related to better OS at distant metastasis. Both HER2 of loss and gain could be related to poor outcomes. Conclusion This meta-analysis showed that receptor conversion in recurrent tumors may affect patient survival as compared with receptor concordance.

scholarly journals High EGFR protein expression and exon 9 PIK3CA mutations are independent prognostic factors in triple negative breast cancers

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
William Jacot ◽  
Caroline Mollevi ◽  
Frédéric Fina ◽  
Evelyne Lopez-Crapez ◽  
Pierre-Marie Martin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Protein Expression ◽  
Triple Negative ◽  
Breast Cancers ◽  
Pik3ca Mutations ◽  
Exon 9

Survival outcome and treatment tolerability for postmenopausal females with early stage hormone receptor positive breast cancer treated with different adjuvant hormonal lines (TAM vs. AI vs. switching strategy) for 5 years

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Atef Youssef Riyad ◽  
Dalia Abdelghany Elkhodary ◽  
Wesam Reda Farag Elghamry ◽  
Islam Abdelrahman Kamel Mohamed Zaki
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Disease Free Survival ◽  
Hormonal Treatment ◽  
Hormone Receptor Positive ◽  
Adjuvant Hormonal Treatment ◽  
Her 2

Abstract Background The standard adjuvant endocrine treatment for postmenopausal female patients with hormone receptor positive early breast cancer was 5 years of tamoxifen, but recurrence and side effects restrict its usefulness. The aromatase inhibitor (anastrozole or exemestane or letrozole) was compared with tamoxifen for 5 years or started after completing 2-3 years of tamoxifen in postmenopausal female patients diagnosed with early breast cancer at "Ain Shams University Hospitals" Objective The aim of the study was to measure survival outcome and treatment tolerability for postmenopausal females with Hormone Receptor Positive early breast cancer who received adjuvant hormonal treatment with tamoxifen [TAM] only for 5 years versus those who received adjuvant hormonal treatment with tamoxifen [TAM] for 2 years switching to aromatase inhibitors [AI] in the sequential 3 years versus those who received adjuvant hormonal treatment with aromatase inhibitors [AI] solely for 5 years. Patients and methods This study included 100 postmenopausal women with early breast cancer who presented at the Clinical Oncology Department, Ain Shams University, in the interval from January 2010 until December 2015. Conclusion Similar disease free survival and overall survival were observed among the three studied groups. Switching tamoxifen to aromatase inhibitors provides better tolerability in terms of endometrial thickness when compared to 5 years of tamoxifen monotherapy. Patients who administer aromatase inhibitor included in the switching strategy experience less osteoporosis and less generalized bone pain compared to upfront aromatase inhibitor to 5 years. There was a significant improvement of disease free survival (DFS) in human epidermal growth factor receptor 2 (HER 2) negative patients receiving any adjuvant hormonal treatment line for five years in comparison to HER 2 positive patients receiving the same adjuvant hormonal treatment for five years.

scholarly journals Re-evaluation of HER2 status in 606 breast cancers—gene protein assay on tissue microarrays versus routine pathological assessment

2020 ◽  
Vol 477 (2) ◽  
pp. 317-320 ◽  
Author(s):  
Emma Sandén ◽  
Somayeh Khazaei ◽  
Helga Tryggvadottir ◽  
Signe Borgquist ◽  
Karolin Isaksson ◽  
...  
Keyword(s):  
Tissue Microarrays ◽  
Her2 Status ◽  
Breast Cancers ◽  
Protein Assay ◽  
Pathological Assessment

scholarly journals Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors

Science ◽  
2019 ◽  
Vol 366 (6466) ◽  
pp. 714-723 ◽  
Author(s):  
Neil Vasan ◽  
Pedram Razavi ◽  
Jared L. Johnson ◽  
Hong Shao ◽  
Hardik Shah ◽  
...  
Keyword(s):  
Membrane Lipid ◽  
Lipid Binding ◽  
Breast Cancers ◽  
Pik3ca Mutations ◽  
Downstream Signaling ◽  
Activating Mutations ◽  
Increased Sensitivity ◽  
Phosphoinositide 3 Kinase ◽  
Tumor Types ◽  
In Cis

Activating mutations in PIK3CA are frequent in human breast cancer, and phosphoinositide 3-kinase alpha (PI3Kα) inhibitors have been approved for therapy. To characterize determinants of sensitivity to these agents, we analyzed PIK3CA-mutant cancer genomes and observed the presence of multiple PIK3CA mutations in 12 to 15% of breast cancers and other tumor types, most of which (95%) are double mutations. Double PIK3CA mutations are in cis on the same allele and result in increased PI3K activity, enhanced downstream signaling, increased cell proliferation, and tumor growth. The biochemical mechanisms of dual mutations include increased disruption of p110α binding to the inhibitory subunit p85α, which relieves its catalytic inhibition, and increased p110α membrane lipid binding. Double PIK3CA mutations predict increased sensitivity to PI3Kα inhibitors compared with single-hotspot mutations.

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