The CYP19 TTTA repeat polymorphism is related to the prognosis of premenopausal stage I-II and operable stage III breast cancers.
OBJECTIVE
Given the critical role of the CYP19 gene, encoding aromatase, in estrogen synthesis and the association of the estrogen level with its TTTA repeat polymorphism, the potential influence of this polymorphism on breast cancer survival, and hence management, deserves further study.


METHODS
Genotyping for the CYP19 TTTA repeat polymorphism was performed on 482 stage I-II and operable stage III Taiwanese breast cancer patients. Patients with more than seven TTTA repeats in either allele of CYP19 were defined as having the long allele. We correlated clinical variables and CYP19 genotypic polymorphism with outcome.


RESULTS
In hormone receptor (HR)-positive breast cancers, premenopausal patients with the long allele of the CYP19 polymorphism had a significantly higher overall survival (OS) rate (8-year, 89% versus 68%; p= .003) than those without it. This difference was further demonstrated by a multivariate analysis (OS hazard ratio, 1.53; p= .041). In postmenopausal women or patients with HR-negative breast cancer, there was no significant difference in OS between patients with or without the long allele. In premenopausal women with HR-positive cancers, adequate intensity adjuvant chemotherapy did not achieve a greater OS rate than suboptimal chemotherapy in patients with the long allele, but it resulted in a significantly higher OS rate (p= .011) than suboptimal chemotherapy in women without the long allele.


CONCLUSIONS
The CYP19 TTTA repeat polymorphism is associated with survival in premenopausal women, but not in postmenopausal women, with HR-positive breast cancers. Premenopausal women with the long allele have a greater survival rate and may not gain benefit from adjuvant chemotherapy.
Huang
Chiun-Sheng
CS
Department of Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan. huangcs@ntu.edu.tw
Kuo
Sung-Hsin
SH
Lien
Huang-Chun
HC
Yang
Shi-Yi
SY
You
San-Lin
SL
Shen
Chen-Yang
CY
Lin
Ching-Hung
CH
Lu
Yen-Sen
YS
Chang
King-Jeng
KJ
D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D053208:Kaplan-Meier Estimate; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D017698:Postmenopause; D017697:Premenopause
D001141:Aromatase