Differences in clinicopathologic features and subtype distribution of invasive breast cancer between women older and younger than 40 years

OBJECTIVES: We investigated and compared clinicopathologic features and subtype distribution of invasive breast cancer among women <40 and ≥40 years of age. METHODS: We retrospectively compared clinicopathologic characteristics and subtype distribution of invasive breast cancer in women <40 and ≥40 years of age, in a cohort of 1,130 patients. Subtypes included luminal A (positive for hormone receptors [HR]—estrogen receptor [ER] and/or progesterone receptor [PR]—and negative for human epidermal growth factor receptor 2 [HER2] with low Ki67), luminal B (HER2(–)) (HR(+)/HER2(–)/Ki67(High)), luminal B (HER2(+)) (HR(+)/HER2(+)), HER2-overexpressing (HR(–)/HER2(+)), and triple negative (ER(–)/PR(–)/HER2(–)). RESULTS: Breast cancers in younger women had unfavorable clinicopathologic characteristics, including larger tumors and more frequent node involvement. Subtypes among the 1,130 tumors were luminal A: 36.4%, luminal B (HER2(–)): 35.0%, luminal B (HER2(+)): 7.5%, HER2-overexpressing: 7.1%, and triple negative: 14.0%. The age groups significantly differed in subtype distribution (P<0.001). Luminal A subtype was more common in the older group (38.5%) than the younger group (16.2%), and luminal B (HER2(–)) was more common in the younger group (52.2%) than in the older group (33.2%; P<0.001). CONCLUSIONS: Breast cancers in women younger than 40 years have unfavorable clinicopathologic characteristics and are more likely to be luminal B (HER2(–)) and less likely to be luminal A than breast cancers in older women

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Oncogenic Product HMGA1a Might Function as an Aberrant Splicing Inducer of Estrogen Receptor [alpha] in Breast Cancer

Estrogen receptor (ER)-[alpha]46 is known as an important isoform for ER[alpha]. It inhibits the function of full length ER[alpha] in MCF-7 mammary carcinoma cells and associated with cell cycle arrest. On the other hand, the oncogene _HMGA1_ (formally _HMG I/Y_) is known to have increased expression in mammary carcinoma correlating with the degree of malignancy. We present here that HMGA1a (HMG I) induces the exon skipped product, ER[alpha]46 mRNA, by tethering U1 snRNP to an upstream pseudo 5&#x27; splice site, which is quite analogous to the PSI-mediated splicing regulation of _Drosophila_ P-element.&#xd;&#xa

HMGA1a induces aberrant splicing of estrogen receptor &#x3b1; in MCF-7 breast cancer cells

The well known transcription factor, HMGA1a, also known as an oncogene, causes aberrant splicing of Presenilin-2 found in sporadic Alzheimer&#x27;s disease, through sequence specific RNA binding. Since HMGA1 protein levels correlate with tumorigenic malignancy, we are interested in the potential of HMGA1a as an aberrant splicing factor in cancer. The N-terminal truncated isoform of Estrogen Receptor alpha, ER&#x3b1;46, is known to increase expression when breast cancer cells (MCF-7) become hyperconfluent. Transiently expressed HMGA1a induced ER&#x3b1;46 mRNA expression. Plasmid driven micro RNA containing the presenilin-2 HMGA1a RNA binding site and a micro RNA nuclear localization signal (miR_HMGBS_NLS), inhibited ER&#x3b1;46 mRNA expression, acting as a decoy. Re-expressing HMGA1a restored ER&#x3b1;46 mRNA expression. An HMGA1a binding site was found in the skipped exon 1A, 33 bp upstream the authentic 5&#x2019; splice site, adjacent a pseudo 5&#x2019; splice site. RNA gel shift assay showed binding of HMGA1a to this site. Exon skipping by HMGA1a and exon inclusion by the HMGA1a binding site decoy could be reproduced in vitro in a heterologous context. Psoralen UV crosslinking showed HMGA1a anchored U1 snRNP to the upstream pseudo 5&#x2019; splice site. Psoralen UV crosslinking combined with antisense DNA oligo / RNaseH protection comfirmed U1 snRNP anchored to the upstream pseudo 5&#x2019; splice site by HMGA1a. This is the second example of the PSI model found in Drosophila, but the first in human. Finally, the stable transfectant of the decoy, miR_HMGBS_NLS (MCF-7 cells), which shows decreased ER&#x3b1;46 protein level, was prone to apoptosis by high dose estrogen. We hope this decoy, miR_HMGBS_NLS, in combination with high dose estrogen, will lead to development of a novel breast cancer therapy, an alternative of conventional estrogen deprivation

Differences in clinicopathologic features and subtype distribution of invasive breast cancer between elderly and non-elderly women

OBJECTIVES: This study aimed to investigate the clinicopathologic features and subtype distribution of invasive breast cancer in elderly women (≥70 years of age). METHODS: This retrospective study of 1,130 women compared the clinicopathologic characteristics and subtype distribution of invasive breast cancer in elderly (≥70 years) versus non-elderly (<70 years) women. Tumors were classified into five distinct subtypes based on the immunohistochemistry status of estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2). RESULTS: The two patient groups did not differ significantly regarding ER and HER2 status. Breast cancers in elderly women were more likely to have negative PR status (40.4% vs. 32.6%, P=0.033) and low Ki67 expression (62.0% vs. 54.4%, P=0.047) than those in non-elderly women. Elderly women were less likely to undergo axillary lymph node dissection and axillary surgery (P<0.001). Consequently, unknown node status was more common in elderly women than non-elderly women (11.1% vs. 1.4%, respectively, P<0.001), while node involvement was less common in elderly women than non-elderly women (26.9% vs. 37.7%, respectively, P<0.001). There was no significant difference in the distribution of subtypes between the two groups. CONCLUSIONS: Breast cancers in elderly women were less frequently node positive and more frequently PR negative and with low Ki67 expression than those in non-elderly women. Moreover, there was no difference in subtype distribution between the two age groups