Refine Search

New Search

Results: 6

(searched for: doi:10.3816/cbc.2011.n.010)
Save to Scifeed
Page of 1
Articles per Page
by
Show export options
  Select all
, Kai Ding, William Horne, Jay K. Kolls, Tian Du, Peter C. Lucas, Jens-Uwe Blohmer, Carsten Denkert, Anna Machleidt, Barbara Ingold-Heppner, et al.
Breast Cancer Research, Volume 23, pp 1-14; doi:10.1186/s13058-020-01379-3

Abstract:
Background Endocrine therapy resistance is a hallmark of advanced estrogen receptor (ER)-positive breast cancer. In this study, we aimed to determine acquired genomic changes in endocrine-resistant disease. Methods We performed DNA/RNA hybrid-capture sequencing on 12 locoregional recurrences after long-term estrogen deprivation and identified acquired genomic changes versus each tumor’s matched primary. Results Despite being up to 7 years removed from the primary lesion, most recurrences harbored similar intrinsic transcriptional and copy number profiles. Only two genes, AKAP9 and KMT2C, were found to have single nucleotide variant (SNV) enrichments in more than one recurrence. Enriched mutations in single cases included SNVs within transcriptional regulators such as ARID1A, TP53, FOXO1, BRD1, NCOA1, and NCOR2 with one local recurrence gaining three PIK3CA mutations. In contrast to DNA-level changes, we discovered recurrent outlier mRNA expression alterations were common—including outlier gains in TP63 (n = 5 cases [42%]), NTRK3 (n = 5 [42%]), NTRK2 (n = 4 [33%]), PAX3 (n = 4 [33%]), FGFR4 (n = 3 [25%]), and TERT (n = 3 [25%]). Recurrent losses involved ESR1 (n = 5 [42%]), RELN (n = 5 [42%]), SFRP4 (n = 4 [33%]), and FOSB (n = 4 [33%]). ESR1-depleted recurrences harbored shared transcriptional remodeling events including upregulation of PROM1 and other basal cancer markers. Conclusions Taken together, this study defines acquired genomic changes in long-term, estrogen-deprived disease; highlights the importance of longitudinal RNA profiling; and identifies a common ESR1-depleted endocrine-resistant breast cancer subtype with basal-like transcriptional reprogramming.
Published: 9 June 2020
Abstract:
Endocrine therapy resistance is a hallmark of advanced estrogen receptor (ER) positive breast cancer. In this study, we performed DNA/RNA hybrid-capture sequencing on 12 locoregional recurrences after long-term estrogen-deprivation along with each tumor’s matched primary. Despite being up to 7 years removed from the primary lesion, most recurrences harbored similar intrinsic transcriptional and copy number profiles. Only two genes, AKAP9 and KMT2C, were found to have single nucleotide variant (SNV) enrichments in more than one recurrence. Enriched mutations in single cases included SNVs within transcriptional regulators such as ARID1A, TP53, FOXO1, BRD1, NCOA1 and NCOR2 with one local recurrence gaining three PIK3CA mutations. In contrast to DNA-level changes, we discovered recurrent outlier mRNA expression alterations were common—including outlier gains in TP63 (n=5 cases [42%]), NTRK3 [n=5 [42%]), NTRK2 (n=4 [33%]), PAX3 (n=4 [33%]), FGFR4 (n=3 [25%]) and TERT (n=3 [25%]). Recurrent losses involved ESR1 (n=5 [42%]), RELN (n=5 [42%]), SFRP4 (n=4 [33%]) and FOSB (n=4 [33%]). ESR1-depleted recurrences harbored shared transcriptional remodeling events including upregulation of PROM1 and other basal cancer markers. Taken together, this study defines acquired genomic changes in long-term, estrogen-deprived disease, highlights longitudinal RNA-profiling and identifies a common endocrine-resistant breast cancer subtype with basal-like transcriptional reprogramming.
, Yevgeniy Gindin, Charles Lu, , , Dong Shen, Jeremy Hoog, , , Mark Watson, et al.
Nature Communications, Volume 7; doi:10.1038/ncomms12498

Abstract:
Resistance to oestrogen-deprivation therapy is common in oestrogen-receptor-positive (ER+) breast cancer. To better understand the contributions of tumour heterogeneity and evolution to resistance, here we perform comprehensive genomic characterization of 22 primary tumours sampled before and after 4 months of neoadjuvant aromatase inhibitor (NAI) treatment. Comparing whole-genome sequencing of tumour/normal pairs from the two time points, with coincident tumour RNA sequencing, reveals widespread spatial and temporal heterogeneity, with marked remodelling of the clonal landscape in response to NAI. Two cases have genomic evidence of two independent tumours, most obviously an ER− ‘collision tumour’, which was only detected after NAI treatment of baseline ER+ disease. Many mutations are newly detected or enriched post treatment, including two ligand-binding domain mutations in ESR1. The observed clonal complexity of the ER+ breast cancer genome suggests that precision medicine approaches based on genomic analysis of a single specimen are likely insufficient to capture all clinically significant information.
Mikako Tamaoki, Yoshinori Nio, Kazuhiko Tsuboi, Marika Nio, Masashi Tamaoki, Riruke Maruyama
Published: 14 February 2014
Oncology Letters, Volume 7, pp 1001-1006; doi:10.3892/ol.2014.1885

Abstract:
The double presentation of breast cancer and follicular lymphoma is extremely rare, and only six cases have previously been reported in the literature. In the present study, a case of synchronous ductal carcinoma in situ (DCIS) of the breast and follicular lymphoma is reported. During an annual breast screening procedure, a 49-year-old female presented with a hard induration under the nipple of the right breast and swelling of a soft lymph node (LN) in the right axilla. Mammography and ultrasonography revealed two lesions in the right breast: One was a tumor with microcalcification, 1.0 cm in diameter, and the other was a large, crude calcification, 2.5 cm in diameter. In addition, computed tomography and positron emission tomography revealed swellings of the bilateral axillary (Ax) LN and intra-abdominal para-aortic LN. The patient underwent excisions of the large calcified mass, a micro-calcified tumor and the right AxLN. The pathological and immunohistochemical studies revealed fat necrosis and DCIS of the breast, which was positive for the estrogen receptor and the progesterone receptor, while human epidermal growth factor receptor II protein expression was evaluated as 2+ and stage was classified as pTis pN0 M0, stage 0. Furthermore, the Ax node was diagnosed as follicular lymphoma, which was positive for cluster of differentiation (CD)20, CD79a, CD10 and B-cell lymphoma (Bcl)-2 protein, but negative for Bcl-6 protein. The clinical stage was classified as stage III. The patient was administered chemotherapy followed by radiotherapy to the conserved breast. Two years have passed since the surgery, and the patient is disease-free.
Isabel T. Rubio, Sebastian Arana, Jorge Vasquez-Del-Aguila, ,
American Journal of Case Reports, Volume 14, pp 322-325; doi:10.12659/AJCR.884000

Abstract:
Background: Lymphatic mapping of axillary breast cancer metastases in the presence of concomitant lymphoproliferative disease is still a controversial topic. Previous reports have postulated that tumor collision in the lymph nodes could lead to false...
, Laura L. Jacimore
Case Reports in Oncological Medicine, Volume 2012, pp 1-4; doi:10.1155/2012/685919

Abstract:
The use of staging imaging modalities with increased sensitivity has led to an increase in the incidence of detection of simultaneous malignancies. These cases require careful evaluation and discussion in a multidisciplinary setting to establish a treatment plan that optimizes the outcome with respect to each malignancy, particularly when treatment modalities overlap. We report a case of a patient diagnosed with axillary nodal diffuse large B-cell lymphoma (DLBCL) in a community hospital where staging workup also revealed synchronous bilateral breast carcinomas. To our knowledge, this is only the second case report of a patient with three synchronous primary malignancies: bilateral breast carcinomas and axillary DLBCL. The only other similar case report had no role for radiation or chemotherapy in the management of the indolent follicular lymphoma.
Page of 1
Articles per Page
by
Show export options
  Select all
Back to Top Top