Dataset Information

Selected estrogen receptor 1 and androgen receptor gene polymorphisms in relation to risk of breast cancer and fibrocystic breast conditions among Chinese women.

ABSTRACT:

Background

Polymorphisms in sex hormone receptor-encoding genes may alter the activity of sex hormone receptors and thereby affect susceptibility to breast cancer and related outcomes.

Methods

In a case-control study of women from Shanghai, China, we examined the risk of breast cancer and fibrocystic breast conditions associated with the ESR1 PvuII (rs2234693) and XbaI (rs9340799) and AR CAG repeat ((CAG)(n)) and GGC repeat ((GGC)(n)) polymorphisms among 614 women with breast cancer, 467 women with fibrocystic conditions, and 879 women without breast disease. We also evaluated whether risk differed by the presence/absence of proliferative changes (in the extratumoral epithelium or fibrocystic lesion), menopausal status, or body mass index (BMI). Age-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using logistic regression.

Results

Only associations with AR (CAG)(n) and (GGC)(n) genotypes were detected. Allocating AR (CAG)(n) genotypes into six categories, with the (CAG)(22-24)/(CAG)(22-24) genotype category designated as the reference group, the (CAG)(>24)/(CAG)(>24) genotype category was associated with an increased risk of fibrocystic breast conditions (OR, 1.8; 95% CI, 1.1-3.0). Relative to the AR (GGC)(17)/(GGC)(17) genotype, the (GGC)(17)/(GGC)(14) genotype was associated with elevated risks of incident breast cancer (OR, 2.6; 95% CI, 1.3-5.4) and fibrocystic conditions (OR, 2.3; 95% CI, 1.1-4.5). Results did not differ according to proliferation status, menopausal status, or BMI.

Conclusion

Although these data lend support for a link between AR variation and breast disease development, given the low frequency of the putative risk-conferring genotypes and other constraints, further confirmation of our results is needed.

SUBMITTER: Sakoda LC

PROVIDER: S-EPMC3062069 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

Selected estrogen receptor 1 and androgen receptor gene polymorphisms in relation to risk of breast cancer and fibrocystic breast conditions among Chinese women.

Sakoda Lori C LC Blackston Christie R CR Doherty Jennifer A JA Ray Roberta M RM Lin Ming Gang MG Gao Dao Li DL Stalsberg Helge H Feng Ziding Z Thomas David B DB Chen Chu C

Cancer epidemiology 20100917 1

<h4>Background</h4>Polymorphisms in sex hormone receptor-encoding genes may alter the activity of sex hormone receptors and thereby affect susceptibility to breast cancer and related outcomes.<h4>Methods</h4>In a case-control study of women from Shanghai, China, we examined the risk of breast cancer and fibrocystic breast conditions associated with the ESR1 PvuII (rs2234693) and XbaI (rs9340799) and AR CAG repeat ((CAG)(n)) and GGC repeat ((GGC)(n)) polymorphisms among 614 women with breast canc ...[more]

PMID: 20846920

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Project description:LESSONS LEARNED:Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)-resistant breast cancer are limited. Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor-positive and AI-resistant disease in this phase II, single-arm study. The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage. BACKGROUND:Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR-positive triple-negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)-positive and AR-positive advanced breast cancer. METHODS:A Simon's two-stage, phase II, single-arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ?4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression-free survival (PFS), and tolerability. RESULTS:A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow-up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated. CONCLUSION:Bicalutamide in combination with another AI did not show synergistic activity in patients with ER-positive breast cancer and AI resistance. Results suggest that no more large-sample clinical trials should be conducted in this population for overcoming endocrine resistance.

Dataset Information

Selected estrogen receptor 1 and androgen receptor gene polymorphisms in relation to risk of breast cancer and fibrocystic breast conditions among Chinese women.

Background

Methods

Results

Conclusion

Publications

Selected estrogen receptor 1 and androgen receptor gene polymorphisms in relation to risk of breast cancer and fibrocystic breast conditions among Chinese women.

Similar Datasets

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