Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival

BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk and survival in breast cancer. This base pair transition (-9 T > C) leads to a valine to alanine amino acid change in the mitochondrial targeting sequence. A polymorphism has also been identified in the proximal region of the promoter (-102 C>T) that alters the recognition sequence of the AP-2 transcription factor, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the -102 C>T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study. MATERIALS AND METHODS: The relationship between the MnSOD -102 C>T polymorphism and survival was examined in a cohort of 291 women who received chemotherapy and/or radiotherapy for incident breast cancer. The MnSOD -102 C>T genotype was determined using a TaqMan allele discrimination assay. Patient survival was evaluated according to the MnSOD genotype using Kaplan–Meier survival functions. Hazard ratios were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. RESULTS: In an evaluation of all women, there was a borderline significant reduction in recurrence-free survival with either one or both variant alleles (CT + TT) when compared with patients with wild-type alleles (CC) (odds ratio, 0.65; 95% confidence interval, 0.42–1.01). When the analysis was restricted to patients receiving radiation therapy, there was a significant reduction in relapse-free survival in women who were heterozygous for the MnSOD -102 genotype (relative risk, 0.40; 95% confidence interval, 0.18–0.86). Similarly, when the homozygous and heterozygous variant genotypes were combined, there remained a significant reduction in relapse-free survival in this group (hazard ratio, 0.42; 95% confidence interval, 0.20–0.87). CONCLUSION: The MnSOD -102 variant allele appears to be associated with an improved recurrence-free survival in all patients, and more dramatically in subjects who received adjuvant radiation therapy

A survey of breast cancer physicians regarding patient involvement in breast cancer treatment decisions

Purpose: Shared breast cancer treatment decision-making between patients and physicians increases patient treatment satisfaction and compliance and is influenced by physician-related factors. Attitudes and behaviors about patient involvement in breast cancer treatment decisions and treatment-related communication were assessed by specialty among breast cancer physicians of women enrolled in the Breast Cancer Quality of Care Study (BQUAL). Results: Of 275 BQUAL physicians identified, 50.0% responded to the survey. Most physicians spend 46-60 min with the patient during the initial consult visit and 51.5% report that the treatment decision is made in one visit. Oncologists spend more time with new breast cancer patients during the initial consult (p = 0.021), and find it more difficult to handle their own feelings than breast surgeons (p = less than 0.001). Conclusion: Breast surgeons and oncologists share similar attitudes and behaviors related to patient involvement in treatment decision-making, yet oncologists report more difficulty managing their own feelings during the decision-making process

A case–control analysis of smoking and breast cancer in African American women: findings from the AMBER Consortium

Recent population studies suggest a role of smoking in the etiology of breast cancer, but few have been conducted among African American women. In a collaborative project of four large studies, we examined associations between smoking measures and breast cancer risk by menopause and hormone receptor status [estrogen receptor-positive (ER+), ER-negative (ER−) and triple-negative (ER−, PR−, HER2−)]. The study included 5791 African American women with breast cancer and 17376 African American controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multivariable logistic regression analysis with adjustment for study and risk factors. Results differed by menopausal status. Among postmenopausal women, positive associations were observed for long duration and greater pack-years of smoking: relative to never smoking, fully adjusted ORs were 1.14 (95% CI: 1.03–1.26) for duration ≥20 years and 1.16 (95% CI: 1.01–1.33) for ≥20 pack-years. By contrast, inverse associations were observed among premenopausal women, with ORs of 0.80 (95% CI: 0.68–95) for current smoking and 0.81 (95% CI: 0.69–0.96) for former smoking, without trends by duration. Associations among postmenopausal women were somewhat stronger for ER+ breast cancer. The findings suggest that the relation of cigarette smoking to breast cancer risk in African American women may vary by menopausal status and breast cancer subtype

Postmenopausal Female Hormone Use and Estrogen Receptor–Positive and –Negative Breast Cancer in African American Women

Use of estrogen with progestin (combination therapy) is associated with increased incidence of estrogen receptor–positive (ER+) breast cancer in observational studies and randomized trials among postmenopausal white women. Whether this is also the case among African American women is not established

Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium

We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes

Vigorous physical activity and risk of breast cancer in the African American breast cancer epidemiology and risk consortium

The relationship between physical activity and breast cancer risk has been extensively studied among women of European descent, with most studies reporting inverse associations. However, data on American women of African ancestry (AA) and by tumor subtypes are sparse. Thus, we examined associations of vigorous exercise and breast cancer risk overall, and by estrogen receptor (ER) status, in the African American Breast Cancer Epidemiology and Risk Consortium. We pooled data from four large studies on 2482 ER+ cases, 1374 ER− cases, and 16,959 controls. Multivariable logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for the risk of breast cancer overall, and polytomous logistic regression was used to model the risk of ER+ and ER− cancer. Recent vigorous exercise was associated with a statistically significant, modestly decreased risk for breast cancer overall (OR 0.88, 95 % CI 0.81–0.96) and for ER+ cancer (OR 0.88, 95 % CI 0.80–0.98), but not for ER− cancer (OR 0.93, 95 % CI 0.82–1.06). Overall, there was no strong evidence of effect modification by age, menopausal status, body mass index, and parity. However, our data were suggestive of modification by family history, such that an inverse association was present among women without a family history but not among those with a relative affected by breast cancer. Results from this large pooled analysis provide evidence that vigorous physical activity is associated with a modestly reduced risk of breast cancer in AA women, specifically ER+ cancer

Intratumoral heterogeneity as a source of discordance in breast cancer biomarker classification

Abstract Background Spatial heterogeneity in biomarker expression may impact breast cancer classification. The aims of this study were to estimate the frequency of spatial heterogeneity in biomarker expression within tumors, to identify technical and biological factors contributing to spatial heterogeneity, and to examine the impact of discordant biomarker status within tumors on clinical record agreement. Methods Tissue microarrays (TMAs) were constructed using two to four cores (1.0 mm) for each of 1085 invasive breast cancers from the Carolina Breast Cancer Study, which is part of the AMBER Consortium. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was quantified using automated digital imaging analysis. The biomarker status for each core and for each case was assigned using clinical thresholds. Cases with core-to-core biomarker discordance were manually reviewed to distinguish intratumoral biomarker heterogeneity from misclassification of biomarker status by the automated algorithm. The impact of core-to-core biomarker discordance on case-level agreement between TMAs and the clinical record was evaluated. Results On the basis of automated analysis, discordant biomarker status between TMA cores occurred in 9 %, 16 %, and 18 % of cases for ER, PR, and HER2, respectively. Misclassification of benign epithelium and/or ductal carcinoma in situ as invasive carcinoma by the automated algorithm was implicated in discordance among cores. However, manual review of discordant cases confirmed spatial heterogeneity as a source of discordant biomarker status between cores in 2 %, 7 %, and 8 % of cases for ER, PR, and HER2, respectively. Overall, agreement between TMA and clinical record was high for ER (94 %), PR (89 %), and HER2 (88 %), but it was reduced in cases with core-to-core discordance (agreement 70 % for ER, 61 % for PR, and 57 % for HER2). Conclusions Intratumoral biomarker heterogeneity may impact breast cancer classification accuracy, with implications for clinical management. Both manually confirmed biomarker heterogeneity and misclassification of biomarker status by automated image analysis contribute to discordant biomarker status between TMA cores. Given that manually confirmed heterogeneity is uncommon (<10 % of cases), large studies are needed to study the impact of heterogeneous biomarker expression on breast cancer classification and outcomes

Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women

Evidence on the relation of family history of cancers other than breast cancer to breast cancer risk is conflicting and most studies have not assessed specific breast cancer subtypes

Associations of Hair Dye and Relaxer Use with Breast Tumor Clinicopathologic Features: Findings from the Women’s Circle of Health Study

Background Building upon our earlier findings of significant associations between hair dye and relaxer use with increased breast cancer risk, we evaluated associations of select characteristics of use with breast tumor clinicopathology. Methods Using multivariable-adjusted models we examined the associations of interest in a case-only study of 2998 women with breast cancer, overall and stratified by race and estrogen receptor (ER) status, addressing multiple comparisons using Bonferroni correction. Results Compared to salon application of permanent hair dye, home kit and combination application (both salon and home kit application) were associated with increased odds of poorly differentiated tumors in the overall sample. This association was consistent among Black (home kit: OR 2.22, 95 % CI: 1.21–5.00; combination: OR 2.46, 95 % CI: 1.21–5.00), but not White women, and among ER+ (home kit: OR 1.47, 95 % CI: 0.82–2.63; combination: OR 2.98, 95 % CI: 1.62–5.49) but not ER-cases. Combination application of relaxers was associated with increased odds of tumors \u3e2.0 cm vs. \u3c1.0 cm (OR = 1.82, 95 % CI: 1.23–2.69). Longer duration and earlier use of relaxers and combination application of permanent hair dyes and relaxers were associated with breast tumor features including higher tumor grade and larger tumor size, which often denote more aggressive phenotypes, although the findings did not maintain significance with Bonferroni correction. Conclusions These novel data support reported associations between hair dye and relaxer use with breast cancer, showing for the first time, associations with breast tumor clinicopathologic features. Improved hair product exposure measurement is essential for fully understanding the impact of these environmental exposure with breast cancer and to guide risk reduction strategies in the future