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Insulin-like growth factor-I inhibition with pasireotide decreases cell proliferation and increases apoptosis in pre-malignant lesions of the breast: a phase 1 proof of principle trial

Overview of attention for article published in Breast Cancer Research, November 2014
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (79th percentile)
  • Good Attention Score compared to outputs of the same age and source (78th percentile)

Mentioned by

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6 X users
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1 patent
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1 Facebook page

Citations

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18 Dimensions

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45 Mendeley
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Title
Insulin-like growth factor-I inhibition with pasireotide decreases cell proliferation and increases apoptosis in pre-malignant lesions of the breast: a phase 1 proof of principle trial
Published in
Breast Cancer Research, November 2014
DOI 10.1186/s13058-014-0463-1
Pubmed ID
Authors

Baljit Singh, Julia A Smith, Deborah M Axelrod, Pietro Ameri, Heather Levitt, Ann Danoff, Martin Lesser, Cristina de Angelis, Irineu Illa-Bochaca, Sara Lubitz, Daniel Huberman, Farbod Darvishian, David L Kleinberg

Abstract

IntroductionEstrogen inhibition is effective in preventing breast cancer in only up to 50% of women with precancerous lesions and many experience side effects that are poorly tolerated. As insulin-like growth factor I (IGF-I) underlies both estrogen and progesterone actions and has other direct effects on mammary development and carcinogenesis, we hypothesized that IGF-I inhibition might provide a novel approach for breast cancer chemoprevention.MethodsIn total, 13 women with core breast biopsies diagnostic of atypical hyperplasia (AH) were treated for 10 days with pasireotide, a somatostatin analog which uniquely inhibits IGF-I action in the mammary gland. They then had excision biopsies. 12 patients also had proliferative lesions and one a ductal carcinoma in situ (DCIS). Primary outcomes were changes in cell proliferation and apoptosis after treatment. Expression of estrogen receptor (ER), progesterone receptor (PR), and phosphorylated Insulin-like growth factor I receptor (IGF-1R), protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2) were also assessed. Core and excision biopsies from 14 untreated patients served as non-blinded controls. Hyperglycemia and other side effects were carefully monitored.ResultsPasireotide decreased proliferation and increased apoptosis in all AH (from 3.6¿±¿2.6% to 1.3¿±¿1.2% and from 0.3¿±¿0.2% to 1.5¿±¿1.6%, respectively) and proliferative lesions (from 3.8¿±¿2.5% to 1.8¿±¿1.8% and from 0.3¿±¿0.2% to 1.3¿±¿0.6%, respectively). The DCIS responded similarly. ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly. In contrast, tissue from untreated controls showed no change in cell proliferation or phosphorylation of IGF-1R, AKT or ERK 1/2. Mild to moderate hyperglycemia associated with reduced insulin levels was found. Glucose fell into the normal range after discontinuing treatment. Pasireotide was well tolerated and did not cause symptoms of estrogen deprivation.ConclusionsIGF-I inhibition by pasireotide, acting through the IGF-1R, was associated with decreased proliferation and increased apoptosis in pre-malignant breast lesions and one DCIS. Assuming hyperglycemia can be controlled, these data suggest that inhibiting the IGF-I pathway may prove an effective alternative for breast cancer chemoprevention.Trial registration NCT01372644 Trial date: July 1, 2007.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Russia 1 2%
Norway 1 2%
Unknown 43 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 20%
Student > Ph. D. Student 7 16%
Student > Doctoral Student 4 9%
Student > Bachelor 3 7%
Professor > Associate Professor 3 7%
Other 7 16%
Unknown 12 27%
Readers by discipline Count As %
Medicine and Dentistry 14 31%
Agricultural and Biological Sciences 6 13%
Biochemistry, Genetics and Molecular Biology 3 7%
Psychology 2 4%
Environmental Science 1 2%
Other 3 7%
Unknown 16 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 November 2023.
All research outputs
#5,211,074
of 25,374,647 outputs
Outputs from Breast Cancer Research
#611
of 2,053 outputs
Outputs of similar age
#56,221
of 271,257 outputs
Outputs of similar age from Breast Cancer Research
#11
of 50 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,053 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one has gotten more attention than average, scoring higher than 70% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 271,257 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 79% of its contemporaries.
We're also able to compare this research output to 50 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.