Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: A population‐based analysis

Abstract

Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-a and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-a, ER-b, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUA TM ). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women ( p-trend 5 0.01, both comparisons), whereas among postmenopausal women, PR levels were associated directly with BMI ( p-trend 5 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) 5 0.86 (95% CI 5 0.69-1.07) for low PR and HER2 expression vs. OR 5 1.78 (95% CI 5 1.25-2.55) for high expression (p-heterogeneity 5 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers. ' 2007 Wiley-Liss, Inc.Key words: breast; etiology; hormones; epidemiology Amassing data suggest that breast cancers are characterized by ''molecular portraits'' that are established at inception, remain stable over time and represent critical determinants of tumor biology.1 Hormone receptor status is a key parameter in molecular classifications of breast cancer, 2,3 which serves as a marker of hormone-dependent growth and predictor of responsiveness to hormonal treatments. Consequently, researchers have hypothesized that etiologic factors mediated by hormones might be more strongly associated with breast cancers that express hormone receptors when compared with those that are receptor-negative. 4,5 A recent literature review found evidence that nulliparity, late age at first birth and postmenopausal obesity are associated with greater risk for estrogen receptor-a (ER-a)-positive cancers when compared with ER-a-negative tumors, and that early menarche was more strongly linked to tumors coexpressing ER-a and progesterone receptor (PR). 4 Subsequently, a metaanalysis updating this review affirmed the heterogeneous associations for nulliparity and late age at first birth, but not for age at menarche. 5 However, results of studies have not been entirely consistent, especially when limited by small sample sizes,...

Triple-negative breast cancer in Hispanic patients

“…They hypothesized that low serum hormone levels in overweight or obese, premenopausal women cause up-regulation of ER and PR levels in normal breast epithelium, leading to an exaggerated hormone response after menopause. 47 In our study population, the median age at diagnosis of breast cancer was 11 years younger than that reported in US patients (50 years vs 61 years). 48 Our study supports the finding of Rodriguez-Cuevas et al, who reported that the average age at diagnosis of breast cancer was 51 years in Mexican patients.…”

“…20 Another study demonstrated that the association between ER/ PR and HER2 expression and BMI varies according to menopause status. 47 In premenopausal women, BMI was associated inversely with hormone receptor expression; but, in postmenopausal women, BMI had a positive association with hormone receptor and HER2 levels. They hypothesized that low serum hormone levels in overweight or obese, premenopausal women cause up-regulation of ER and PR levels in normal breast epithelium, leading to an exaggerated hormone response after menopause.…”

Human epidermal growth factor receptor-2 and estrogen receptor expression, a demonstration project using the residual tissue respository of the Surveillance, Epidemiology, and End Results (SEER) program

“…Standard immunohistochemistry with antigen retrieval prior to antibody incubation was performed according to established protocols for estrogen receptor (ER, clone 6F11, dilution 1:200, Novocastra), progesterone receptor (PR, clone PgR636, dilution 1:1,000, Dako), human epidermal growth factor receptor-2 (HER2+, polyclonal, dilution 1:1,000, Dako), epidermal growth factor receptor (EGFR, clone 31G7, dilution 1:500, Zymed), and cytokeratin 5 (CK5, clone XM26, dilution 1:500, Novocastra) [3,4]. A single pathologist (MES) assessed the stains by examining microscopic TMA slides and scanned images of the TMA slides, using the Aperio TMA Lab system (http://www.aperio.com/), as previously described [4].…”

“…A single pathologist (MES) assessed the stains by examining microscopic TMA slides and scanned images of the TMA slides, using the Aperio TMA Lab system (http://www.aperio.com/), as previously described [4]. Each TMA core was scored for adequacy (satisfactory, suboptimal or unsatisfactory), staining intensity (0 = negative, 1 = weak, 2 = intermediate, and 3 = strong), and percentage of cells stained (0-100%).…”

Menopausal Hormone Therapy and Risk of Clinical Breast Cancer Subtypes

“…Breast cancer is a heterogeneous disease, and research suggests that subtypes may vary in their etiologies (1). Menopausal hormone therapy, particularly combined estrogen-progestagen therapy, has been shown to increase breast cancer risk and has been implicated in the increased incidence of breast cancer observed over the past three decades (2)(3)(4).…”