ESR1 promoter hypermethylation does not predict atypia in RPFNA nor persistent atypia after 12 months tamoxifen chemoprevention.
OBJECTIVE
Currently, we lack biomarkers to predict whether high-risk women with mammary atypia will respond to tamoxifen chemoprevention.


METHODS
Thirty-four women with cytologic mammary atypia from the Duke University High-Risk clinic were offered tamoxifen chemoprevention. We tested whether ESR1 promoter hypermethylation and/or estrogen receptor (ER) protein expression by immunohistochemistry predicted persistent atypia in 18 women who were treated with tamoxifen for 12 months and in 16 untreated controls.


RESULTS
We observed a statistically significant decrease in the Masood score of women on tamoxifen chemoprevention for 12 months compared with control women. This was a significant interaction effect of time (0, 6, and 12 months) and treatment group (tamoxifen versus control) P = 0.0007. However, neither ESR1 promoter hypermethylation nor low ER expression predicted persistent atypia in Random Periareolar Fine Needle Aspiration after 12 months tamoxifen prevention.


CONCLUSIONS
Results from this single institution pilot study provide evidence that, unlike for invasive breast cancer, ESR1 promoter hypermethylation and/or low ER expression is not a reliable marker of tamoxifen-resistant atypia.
Baker
Joseph C
JC
Duke University Medical Center, Durham, NC 27710, USA.
Ostrander
Julie H
JH
Lem
Siya
S
Broadwater
Gloria
G
Bean
Gregory R
GR
D'Amato
Nicholas C
NC
Goldenberg
Vanessa K
VK
Rowell
Craig
C
Ibarra-Drendall
Catherine
C
Grant
Tracey
T
Pilie
Patrick G
PG
Vasilatos
Shauna N
SN
Troch
Michelle M
MM
Scott
Victoria
V
Wilke
Lee G
LG
Paisie
Carolyn
C
Rabiner
Sarah M
SM
Torres-Hernandez
Alejandro
A
Zalles
Carola M
CM
Seewaldt
Victoria L
VL
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D044963:Biopsy, Fine-Needle / Q000379:methods*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D018890:Chemoprevention; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D018931:Antineoplastic Agents, Hormonal; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D013629:Tamoxifen