Dataset Information

The genetics of response to estrogen treatment.

ABSTRACT: It has been demonstrated that the response to estrogen treatment in postmenopausal women shows considerable variability. It has been speculated that this at least partly could be determined by heritable factors.The most obvious genes to investigate in this context are the estrogen receptor genes. It has been demonstrated that women with short alleles of the TA-repeat polymorphism in the estrogen receptor ? gene respond to hormone treatment with greater increases in bone mass at the lumbar spine. Also the two polymorphisms in the first intron of the same gene have been found to be associated with the response to estrogen. Several studies have found that women carrying the Pand the X-alleles respond to hormone therapy with greater increases in bone mass and sustain fewer fractures. Polymorphisms in the collagen type I?1 have been found to influence BMD. Conflicting results have been obtained with respect to the influence of these genetic variants on postmenopausal bone loss and response to hormone treatment. Furthermore, two polymorphisms in the promoter of the transforming growth factor ? gene and one polymorphism in the first exon of the osteoprotegerin gene have been demonstrated to interact with the response to hormone treatment in early postmenopausal women.The above mentioned results are obtained from relatively small studies and needs confirmation before the information can be used in the clinic.

SUBMITTER: Langdahl BL

PROVIDER: S-EPMC2781219 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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The genetics of response to estrogen treatment.

Langdahl Bente L BL

Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases 20090101 1

It has been demonstrated that the response to estrogen treatment in postmenopausal women shows considerable variability. It has been speculated that this at least partly could be determined by heritable factors.The most obvious genes to investigate in this context are the estrogen receptor genes. It has been demonstrated that women with short alleles of the TA-repeat polymorphism in the estrogen receptor α gene respond to hormone treatment with greater increases in bone mass at the lumbar spine. ...[more]

PMID: 22461097

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Project description:ImportanceThere is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor-positive breast cancer.ObjectiveTo investigate the associations of sperm-associated antigen 5 (SPAG5) transcript and SPAG5 protein expressions with treatment response in systemic therapy for estrogen receptor-positive breast cancer.Design, settings, and participantsThis retrospective cohort study included patients with estrogen receptor-positive breast cancer who received 5 years of adjuvant endocrine therapy with or without neoadjuvant anthracycline-based combination chemotherapy (NACT) derived from 11 cohorts from December 1, 1986, to November 28, 2019. The associations of SPAG5 transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association of SPAG5 mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse-free survival with SPAG5 transcript or SPAG5 protein expressions were analyzed. Data were analyzed from September 9, 2015, to November 28, 2019.Main outcomes and measuresThe primary outcomes were breast cancer-specific survival, distal relapse-free survival, pathological complete response, and clinical response. Outcomes were examined using Kaplan-Meier, multivariable logistic, and Cox regression models.ResultsThis study included 12 720 women aged 24 to 78 years (mean [SD] age, 58.46 [12.45] years) with estrogen receptor-positive breast cancer, including 1073 women with SPAG5 transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women with SPAG5 transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those without SPAG5 transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51]; P < .001; protein: odds ratio, 7.32 [95% CI, 3.33-16.22]; P < .001). Adding adjuvant anthracycline chemotherapy to adjuvant endocrine therapy for SPAG5 mRNA expression in estrogen receptor-positive breast cancer was associated with prolonged 5-year distal relapse-free survival in patients without lymph node involvement (hazard ratio, 0.34 [95% CI, 0.14-0.87]; P = .03) and patients with lymph node involvement (hazard ratio, 0.35 [95% CI, 0.18-0.68]; P = .002) compared with receiving 5-year endocrine therapy alone. Mean (SD) SPAG5 transcript was found to be downregulated after 2 weeks of neoadjuvant endocrine therapy compared with pretreatment levels in 68 of 92 patients (74%) (0.23 [0.18] vs 0.34 [0.24]; P < .001).Conclusions and relevanceThese findings suggest that SPAG5 transcript and SPAG5 protein expressions could be used to guide the optimal therapies for estrogen receptor-positive breast cancer. Retrospective and prospective clinical trials are warranted.

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The genetics of response to estrogen treatment.

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The genetics of response to estrogen treatment.

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