Using breast cancer risk associated polymorphisms to identify women for breast cancer chemoprevention

Elad Ziv, Jeffrey A. Tice, Brian Sprague, Celine M Vachon, Steven R. Cummings, Karla Kerlikowske

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention. Methods: We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention. Results: We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (∼21% of all women), ∼75% of the benefit of testing all women (shifting women above or below 3% 5-year risk) would be derived. If women with a 5-year risk of >1.5% are tested (∼36% of all women), ∼90% of the benefit of testing all women would be derived. Conclusion: SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.

Original languageEnglish (US)
Article numbere0168601
JournalPLoS One
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

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chemoprevention
Chemoprevention
Polymorphism
breast neoplasms
genetic polymorphism
Breast Neoplasms
Nucleotides
single nucleotide polymorphism
Single Nucleotide Polymorphism
Testing
testing
monitoring
Aromatase Inhibitors
Estrogen Receptors
modifiers (genes)
Advisory Committees
taxonomic revisions
Population

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Using breast cancer risk associated polymorphisms to identify women for breast cancer chemoprevention. / Ziv, Elad; Tice, Jeffrey A.; Sprague, Brian; Vachon, Celine M; Cummings, Steven R.; Kerlikowske, Karla.

In: PLoS One, Vol. 12, No. 1, e0168601, 01.01.2017.

Research output: Contribution to journalArticle

Ziv, Elad ; Tice, Jeffrey A. ; Sprague, Brian ; Vachon, Celine M ; Cummings, Steven R. ; Kerlikowske, Karla. / Using breast cancer risk associated polymorphisms to identify women for breast cancer chemoprevention. In: PLoS One. 2017 ; Vol. 12, No. 1.
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abstract = "Background: Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3{\%} consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention. Methods: We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention. Results: We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0{\%} are tested (∼21{\%} of all women), ∼75{\%} of the benefit of testing all women (shifting women above or below 3{\%} 5-year risk) would be derived. If women with a 5-year risk of >1.5{\%} are tested (∼36{\%} of all women), ∼90{\%} of the benefit of testing all women would be derived. Conclusion: SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5{\%} 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.",
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N2 - Background: Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention. Methods: We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention. Results: We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (∼21% of all women), ∼75% of the benefit of testing all women (shifting women above or below 3% 5-year risk) would be derived. If women with a 5-year risk of >1.5% are tested (∼36% of all women), ∼90% of the benefit of testing all women would be derived. Conclusion: SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.

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