Abstract PD3-3: Next generation sequencing shows clonal selection after treatment with anastrozole or fulvestrant in a randomized trial of postmenopausal patients with large operable or locally-advanced hormone-receptor-positive breast cancer

2013 ◽  
Author(s):  
RD Iggo ◽  
HM Wood ◽  
P Rabbitts ◽  
N Quenel-Tueux ◽  
L Mauriac ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Next Generation Sequencing ◽  
Randomized Trial ◽  
Hormone Receptor ◽  
Clonal Selection ◽  
Locally Advanced ◽  
Next Generation ◽  
Hormone Receptor Positive ◽  
Generation Sequencing ◽  
Positive Breast Cancer

scholarly journals Next-Generation Sequencing of Patients With Breast Cancer in Community Oncology Clinics

2021 ◽  
pp. 1297-1311
Author(s):  
Emma G. Sturgill ◽  
Amanda Misch ◽  
Rebecca Lachs ◽  
Carissa C. Jones ◽  
Dan Schlauch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Next Generation Sequencing ◽  
Real World ◽  
Hormone Receptor ◽  
Next Generation ◽  
Data Set ◽  
Landscape Studies ◽  
Community Oncology ◽  
Genomic Landscape ◽  
Generation Sequencing

PURPOSE Molecular biomarkers informing disease diagnosis, prognosis, and treatment decisions in patients with breast cancer are being uncovered by next-generation sequencing (NGS) technologies. In this study, we survey how NGS is used for patients with breast cancer in real-world settings with a focus on physician behaviors and sequencing results. METHODS We conducted a retrospective analysis of patients with breast cancer who received NGS testing from commercial vendors as part of standard of care from 2014 to 2019. A total of 2,635 NGS reports from 2,316 unique breast cancer patients were assessed. Hormone receptor and human epidermal growth factor receptor 2 statuses were abstracted from patient medical records. Comparative gene amplification and mutation frequencies were analyzed using Pearson's correlation and Lin's concordance statistics. RESULTS The number of physicians ordering NGS tests for patients with breast cancer increased more than six-fold from 2014 to 2019. Tissue- and plasma-based tests were ordered roughly equally by 2019, with plasma-based testing ordered most frequently in hormone receptor–positive subtypes. Patients with triple-negative breast cancer were most likely to receive NGS testing. Gene amplifications including ERBB2 were detected less frequently in our real-world data set as compared to previous genomic landscape studies, whereas the opposite was true for gene mutations including ESR1. Pathogenic mutations in the PI3K pathway (38.6%) and DNA damage repair pathway (11.0%) were frequently reported. Alterations were also reported across other cellular pathways. CONCLUSION Overall, we found that an increasing number of physicians in community settings are adopting NGS in the care of patients with breast cancer. Discrepancies between our real-world NGS data and previous genomic landscape studies are likely owed to the prevalence of plasma-based testing in community oncology clinics, as the reference data were from tissue-based NGS alone.

ERBB2 amplifications and mutations in 109 advanced breast cancer patients by next-generation sequencing.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3565-3565
Author(s):  
Ami N. Shah ◽  
Brian Finkelman ◽  
Lorenzo Gerratana ◽  
Andrew A. Davis ◽  
Neelima Katam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Next Generation Sequencing ◽  
Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Her2 Status ◽  
Next Generation ◽  
Synonymous Mutations ◽  
Ctdna Analysis ◽  
Generation Sequencing

3565 Background: In advanced breast cancer (ABC) HER2 status is based on ASCO/CAP immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) criteria. Next generation sequencing (NGS) of tissue and blood can detect aberrations in ERBB2 such as copy number gain/amplifications (cng/amp) and mutations. Methods: We retrospectively identified patients (pts) seen at Northwestern University between 2015 and 2019 with ABC and an alteration in ERBB2 identified by tissue and/or circulating tumor DNA (ctDNA) NGS. We included pts with testing by Guardant360, TempusX, and/or FoundationOne platforms. NGS reports were evaluated for non-synonymous mutations and cng/amp. HR and HER2 status were determined based on the most recent pathologic assessment. Mutations were categorized as pathologic if they were consider oncogenic (level 1-2 evidence with direct functional data), likely oncogenic, or predicted oncogenic, based on OncoKB (Chakravarty et al., JCO PO 2017). Results: 109 cases of ABC (6 locally advanced, 103 metastatic) with ERBB2 alterations were identified. Tissue NGS was available from 43%, ctDNA from 72%, and both from 19%. The positive predictive value (PPV) of ERBB2 amp/cng by tissue NGS to predict HER2+ using the gold standard as IHC/FISH was 94% (33/35). The PPV of ERBB2 amp by ctDNA was 93% (40/43). ERBB2 mutations were detected in 52 pts. Of these, 23 pts were considered to harbor pathologic ERBB2 mutations, (19 oncogenic, 2 likely oncogenic, 1 predicted oncogenic) detected by ctDNA and tissue in 4, ctDNA in 16, and tissue in 3 pts. The most frequently detected mutations were V777L and S310. Four pts had co-mutations of ERBB2 V777L and S310F. Disease subtype among those with ERBB2 pathologic mutations was HR+ HER2- in 57%, HER2+ in 26%, and triple negative in 17%. In all patients with serial ctDNA analysis and pathologic ERBB2 mutations, the mutation was detected on the first analysis. Pathologic ERBB2 mutation represented the mutant with the highest mutant allele frequency (MAF) in 30% and top 3 highest MAF in an additional 35%. PIK3CA was co-mutated in 48%. Conclusions: The PPV of ERBB2 amp/cng by tissue and ctDNA NGS was high, and has potential utility for cancers where HER2 IHC/FISH is not standardly assessed or cases where biopsy is challenging. ERBB2 pathologic mutations were found in all breast cancer subtypes. When present, they were identified on the initial ctDNA analysis and often represented a significant clone, supporting its role as a ‘driver mutation’.

Therapeutic Place of Fulvestrant in the Management of Hormone-receptor Positive Breast Cancer

2016 ◽  
Vol 12 (01) ◽  
pp. 44 ◽  
Author(s):  
Yogesh R Belagali ◽  
Hanmant V Barkate ◽  
Jaykumar J Sejpal ◽  
Bhavesh B Parekh ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Oestrogen Receptor ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
First Line Therapy ◽  
Hormone Receptor Positive ◽  
Significant Difference ◽  
Turnover Markers ◽  
Positive Breast Cancer

Fulvestrant is an oestrogen-receptor antagonist that exerts selective oestrogen receptor downregulation, antiproliferative activity and induction of apoptosis. It is indicated for the treatment of postmenopausal women with locally advanced or metastatic breast cancer for disease relapse or progression on or after adjuvant anti-oestrogen therapy. Fulvestrant was initially approved at a dose of 250 mg, however, the results of the CONFIRM trial led to approval of 500 mg dose (i.e. 500 mg on days 0, 14 and 28, then 500 mg every 28 days). Fulvestrant has also shown superiority over anastrozole as first-line therapy in the phase II trial. There are contrasting data for its efficacy when used in combination with anastrozole. It is well tolerated, with no significant difference with respect to the toxicity profile of other hormonal therapies. Treatment with fulvestrant is not associated with any clinically significant effects on sex hormone levels, bone-specific turnover markers or endometrial thickening. Fulvestrant has been recommended by the National Comprehensive Cancer Network and the European School of Oncology guidelines as a treatment option in first- and second-line management of hormone-receptor positive breast cancer.

Use of platinum-based neoadjuvant chemotherapy (NACT) in patients (pts) with hormone receptor-positive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11038-e11038
Author(s):  
Christos Kyriakopoulos ◽  
Tadeu Frantz Ambros ◽  
Alberto J. Montero ◽  
Judith Hurley
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Menopausal Status ◽  
Locally Advanced ◽  
Comprehensive Cancer Center ◽  
Surgical Specimen ◽  
Hormone Receptor Positive ◽  
Her 2 ◽  
Positive Breast Cancer

e11038 Background: NACT is used for the treatment of locally advanced breast cancer. Evaluation of breast cancer subtypes and their responses to specific chemotherapy regimens is important. Methods: Retrospective review of medical records from University of Miami/Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital from 1998-2011. Complete pathologic response (pCR) was classified as absence of malignant tissue both in the breast and the lymph nodes in the surgical specimen. Results: One hundred ninety-one women with ER-positive breast cancer received platinum based NACT. Mean age was 52 years (range 31-83). One hundred eleven (58.1%) women were premenopausal and 80 (41.9%) postmenopausal. The clinical stage at presentation: IIA (6.3%), IIB (26.7%), IIIA (31.9%), IIIB (30.9%), IIIC (4.2%). Sixty one (31.9%) pts had her-2/neu positive tumors. pCR occurred in 17 patients (8.9%), premenopausal vs. postmenopausal (9.9% vs. 7.5%, p=0.56), white race vs. black (9.9% vs. 4.9%, p=0.32), Hispanic vs. non-Hispanic (9.4% vs. 6.8%, p=0.6), tumor size <=4 cm vs. >4 cm (14.7% vs. 7.6%, p=0.19), her-2/neu positive vs. her-2/neu negative (13.1% vs. 6.9%, p=0.16), T4 vs. T1-T3 (4.8% vs. 10.9%, p=0.19). Conclusions: pCR rates with platinum based NACT in pts with hormone receptor-positive tumors were low. The pCR rate did not appear to be influenced by her2/neu, tumor size, race, ethnicity or menopausal status.

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