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.

Singh B, Smith JA, Axelrod DM, Ameri P, Levitt H, Danoff A, Lesser M, de Angelis C, Illa-Bochaca I, Lubitz S, Huberman D, Darvishian F, Kleinberg DL

Breast cancer research : BCR11 Nov 2014Cited by 17 (Europe PMC)

PMID25385439PMCIDPMC4303192DOI10.1186/s13058-014-0463-1PepBankPUB-25385439

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Summary

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 registrationNCT01372644 Trial date: July 1, 2007.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study15

15 results from studies that gave the peptide. 15 results from people.

01HumanNon-randomized trialEfficacy outcome
In women with atypical hyperplasia, pasireotide reduced proliferation from 3.6 ± 2.6% to 1.3 ± 1.2%.
In plain wordsIn women with atypical hyperplasia, proliferation decreased after pasireotide compared with baseline.
Peptide
Pasireotide
Outcome
DecreaseAH proliferation
Study
n = 13
Comparator
Pre-treatment values
Analysis
Primary
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Measurements
Proliferation
3.6%
all atypical hyperplasia, before treatment (± 2.6%)
Proliferation
1.3%
all atypical hyperplasia, after pasireotide (± 1.2%)
Source sentences
Summary
Pasireotide 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).
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543901
02HumanNon-randomized trialEfficacy outcome
In women with atypical hyperplasia, pasireotide increased apoptosis from 0.3 ± 0.2% to 1.5 ± 1.6%.
In plain wordsIn women with atypical hyperplasia, apoptosis increased after pasireotide compared with baseline.
Peptide
Pasireotide
Outcome
IncreaseAH apoptosis
Study
n = 13
Comparator
Pre-treatment values
Analysis
Primary
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Measurements
Apoptosis
0.3%
all atypical hyperplasia, before treatment (± 0.2%)
Apoptosis
1.5%
all atypical hyperplasia, after pasireotide (± 1.6%)
Source sentences
Summary
Pasireotide 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).
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543902
03HumanNon-randomized trialEfficacy outcome
In women with proliferative breast lesions, pasireotide reduced proliferation from 3.8 ± 2.5% to 1.8 ± 1.8%.
In plain wordsIn women with proliferative breast lesions, proliferation decreased after pasireotide compared with baseline.
Peptide
Pasireotide
Outcome
DecreaseProliferative lesion proliferation
Study
n = 12
Comparator
Pre-treatment values
Analysis
Primary
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Measurements
Proliferation
3.8%
proliferative lesions, before treatment (± 2.5%)
Proliferation
1.8%
proliferative lesions, after pasireotide (± 1.8%)
Source sentences
Summary
Pasireotide 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).
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543903
04HumanNon-randomized trialEfficacy outcome
In women with proliferative breast lesions, pasireotide increased apoptosis from 0.3 ± 0.2% to 1.3 ± 0.6%.
In plain wordsIn women with proliferative breast lesions, apoptosis increased after pasireotide compared with baseline.
Peptide
Pasireotide
Outcome
IncreaseProliferative lesion apoptosis
Study
n = 12
Comparator
Pre-treatment values
Analysis
Primary
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Measurements
Apoptosis
0.3%
proliferative lesions, before treatment (± 0.2%)
Apoptosis
1.3%
proliferative lesions, after pasireotide (± 0.6%)
Source sentences
Summary
Pasireotide 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).
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543904
05HumanNon-randomized trialEfficacy outcome
In one woman with DCIS, proliferation decreased after pasireotide, similarly to the other breast lesions.
In plain wordsIn one woman with DCIS, proliferation decreased after pasireotide compared with baseline.
Peptide
Pasireotide
Outcome
DecreaseDCIS proliferation
Study
n = 1
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
The DCIS responded similarly.
3 context sentences(design, population, supporting numbers)
Summary · context
Pasireotide 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).
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543905
06HumanNon-randomized trialEfficacy outcome
In one woman with DCIS, apoptosis increased after pasireotide, similarly to the other breast lesions.
In plain wordsIn one woman with DCIS, apoptosis increased after pasireotide compared with baseline.
Peptide
Pasireotide
Outcome
IncreaseDCIS apoptosis
Study
n = 1
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
The DCIS responded similarly.
2 context sentences(design, population, supporting numbers)
Summary · context
Pasireotide 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).
Summary · context
In 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.
Show in the study text Report a problemFND-2538543915
07HumanNon-randomized trialMechanism
In breast lesions, pasireotide did not affect ER expression.
In plain wordsIn breast lesions, ER expression did not change after pasireotide.
Peptide
Pasireotide
Outcome
No significant changeER expression
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543906
08HumanNon-randomized trialMechanism
In breast lesions, pasireotide did not affect PR expression.
In plain wordsIn breast lesions, PR expression did not change after pasireotide.
Peptide
Pasireotide
Outcome
No significant changePR expression
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543907
09HumanNon-randomized trialMechanism
In breast lesions, pasireotide significantly reduced IGF-1R phosphorylation.
In plain wordsIn breast lesions, IGF-1R phosphorylation decreased after pasireotide.
Peptide
Pasireotide
Outcome
DecreaseIGF-1R phosphorylation
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543908
10HumanNon-randomized trialMechanism
In breast lesions, pasireotide significantly reduced ERK1/2 phosphorylation.
In plain wordsIn breast lesions, ERK1/2 phosphorylation decreased after pasireotide.
Peptide
Pasireotide
Outcome
DecreaseERK1/2 phosphorylation
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543909
11HumanNon-randomized trialMechanism
In breast lesions, pasireotide significantly reduced AKT phosphorylation.
In plain wordsIn breast lesions, AKT phosphorylation decreased after pasireotide.
Peptide
Pasireotide
Outcome
DecreaseAKT phosphorylation
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543910
12HumanNon-randomized trialSafety outcome
In women receiving pasireotide, mild to moderate hyperglycemia occurred.
In plain wordsWomen receiving pasireotide developed mild to moderate high blood sugar.
Peptide
Pasireotide
Outcome
IncreaseHyperglycemia
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
Mild to moderate hyperglycemia associated with reduced insulin levels was found.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543911
13HumanNon-randomized trialMechanism
In women receiving pasireotide, insulin levels decreased with hyperglycemia.
In plain wordsWomen receiving pasireotide had reduced insulin levels with high blood sugar.
Peptide
Pasireotide
Outcome
DecreaseInsulin levels
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
Mild to moderate hyperglycemia associated with reduced insulin levels was found.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543912
14HumanNon-randomized trialSafety outcome
In treated women, glucose returned to the normal range after pasireotide discontinuation.
In plain wordsIn treated women, blood sugar returned to normal after pasireotide stopped.
Peptide
Pasireotide
Outcome
DecreaseGlucose after discontinuation
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
Glucose fell into the normal range after discontinuing treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543913
15HumanNon-randomized trialSafety outcome
In treated women, pasireotide did not cause symptoms of estrogen deprivation.
In plain wordsWomen receiving pasireotide had no symptoms of estrogen deprivation.
Peptide
Pasireotide
Outcome
Not applicableEstrogen deprivation symptoms
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · 10 daysAs given in this study (human).
Source sentences
Summary
Pasireotide was well tolerated and did not cause symptoms of estrogen deprivation.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
Core and excision biopsies from 14 untreated patients served as non-blinded controls.
Show in the study text Report a problemFND-2538543914

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1NCT01372644

Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor: A Proof of Principle Trial

NYU Langone Healthn = 15Nov 2007 to Nov 2013

Atypical Ductal Breast Hyperplasia · Lobular Carcinoma in Situ (LCIS) · Atypical Lobular Hyperplasia (ALH) of Breast

Trial page ClinicalTrials.govUpdated 5 Dec 2016

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:34 UTC
First added · source update from Europe PMC

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