Risk Of Estrogen Receptor-negative Breast Cancer Research Articles

Abstract 5247: Aspirin use and estrogen receptor-negative breast cancer risk in African American women

Abstract Introduction: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of breast cancer; however, results of epidemiological studies have been mixed. Further, few previous studies investigated these associations among African American women and no studies that included African Americans evaluated whether associations differ by estrogen receptor (ER) status. Methods: To assess the relation of aspirin use to risk of ER+ and ER- breast cancer in African American women, we conducted a prospective analysis within the Black Women's Health Study, an ongoing nationwide cohort of 59,000 black women that began in 1995. On baseline and biennial follow-up questionnaires, women reported regular aspirin use (defined as use at least three days per week) and years of use. Acetaminophen use was queried similarly. Among women with available information on aspirin use, 1701 invasive breast cancers occurred during follow-up through 2015, including 962 ER+ and 492 ER- tumors. All cancers were confirmed through pathology reports or state cancer registry data. We used age-stratified Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of aspirin use with risk of ER+ and ER- breast cancer. All models adjusted for age at menarche, oral contraceptive use, parity, age at first birth, estrogen plus progestin use, body mass index, alcohol consumption, and use of other NSAIDs. Results: Compared to never use, current regular use of aspirin was associated with lower risk of breast cancer overall (HR 0.87; 95% CI 0.76, 1.00). The association was driven by a statistically significant inverse association for ER- breast cancer (HR 0.76; 95% CI 0.58, 0.99); for ER+ breast cancer, the corresponding HR was 0.92 (95% CI 0.77, 1.09). In contrast, we found no associations with acetaminophen use. Conclusions: Our observation of reduced risk of ER- breast cancer in relation to current regular use of aspirin is consistent with anti-inflammatory effects of aspirin, rather than hormone-dependent pathways. Aspirin may represent a potential opportunity for chemoprevention of ER- breast cancer; however, these findings require corroboration in additional studies. Citation Format: Kimberly A. Bertrand, Traci N. Bethea, Hanna Gerlovin, Patricia Coogan, Lucile L. Adams-Campbell, Lynn Rosenberg, Julie R. Palmer. Aspirin use and estrogen receptor-negative breast cancer risk in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5247.

Polymorphisms in the telomerase reverse transcriptase promoter are associated with risk of breast cancer: A meta-analysis.

Recently, the relationship between telomerase reverse transcriptase (TERT) polymorphisms and breast cancer risk has been investigated in several publications. However, the results were inconclusive. In this study, we examined the association between TERT polymorphisms and breast cancer risk by meta-analysis. The PubMed, Cochrane Library, and EMBASE databases were searched independently by two investigators to retrieve relevant studies published to March 21, 2015. The strength of the association was calculated with the odds ratio (OR) and 95% confidence interval (CI). All statistical tests were used by the RevMan 5.1 software (Nordic Cochrane Center, Copenhagen, Denmark). We observed a statistically significant association between rs2736109 polymorphism and breast cancer risk (OR = 1.13; 95% CI: 1.00-1.28; P = 0.04). In addition, rs2736109 polymorphism was associated with breast cancer risk in Caucasian population (OR = 1.18; 95% CI: 1.00-1.38; P = 0.04). We also found rs2853669 and rs2736098 polymorphisms were significantly associated with breast cancer risk (OR = 0.76; 95% CI: 0.63-0.90; P = 0.002 and OR = 0.79; 95% CI: 0.72-0.87; P < 0.00001), respectively. Furthermore, rs10069690 polymorphism was showed to be associated with breast cancer risk (OR = 1.16; 95% CI: 1.11-1.22; P < 0.00001). In the subgroup analysis, this polymorphism might be associated with estrogen receptor-negative breast cancer risk (OR = 1.16; 95% CI: 1.12-1.21; P < 0.00001) and breast cancer risk in Caucasian population (OR = 1.18; 95% CI: 1.14-1.23; P < 0.00001). One single nucleotide polymorphism, rs2735940, was not significantly associated with breast cancer risk (OR = 0.85; 95% CI: 0.66-1.11; P = 0.24). This meta-analysis suggested that TERT rs2736109, rs2853669, rs2736098, and rs10069690 polymorphisms were associated with increased risk of developing breast cancer.

Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women

BackgroundDiets high in carbohydrates may result in chronically elevated insulin concentrations and may affect breast cancer risk by stimulation of insulin receptors or through insulin-like growth factor I (IGF-I)–mediated mitogenesis. Insulin response to carbohydrate intake is increased in insulin-resistant states such as obesity. ObjectiveWe sought to evaluate carbohydrate intake, glycemic index (GI), and glycemic load (GL) and subsequent overall and hormone-receptor-defined breast cancer risk among postmenopausal women. DesignA prospective cohort analysis of dietary carbohydrate and fiber intakes was conducted among 62 739 postmenopausal women from the E3N French study who had completed a validated dietary history questionnaire in 1993. During a 9-y period, 1812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized into quartiles and energy-adjusted with the regression-residual method. Cox model–derived relative risks (RRs) were adjusted for known determinants in breast cancer. ResultsDietary carbohydrate and fiber intakes were not associated with overall breast cancer risk. Among overweight women, we observed an association between GI and breast cancer (RRQ1–Q4: 1.35; 95% CI: 1.00, 1.82; P for trend = 0.04). For women in the highest category of waist circumference, the RRQ1–Q4 was 1.28 (95% CI: 0.98, 1.67; P for trend = 0.10) for carbohydrates, 1.35 (95% CI: 1.04, 1.75; P for trend = 0.01) for GI, and 1.37 (95% CI: 1.05, 1.77; P for trend = 0.003) for GL. We also observed a direct association between carbohydrate intake, GL, and estrogen receptor–negative breast cancer risk. ConclusionsRapidly absorbed carbohydrates are associated with postmenopausal breast cancer risk among overweight women and women with large waist circumference. Carbohydrate intake may also be associated with estrogen receptor–negative breast cancer.

Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women

Since it is well established that inactivation of p53 is involved in pathogenesis of breast cancer, it seems to be reasonable to assume that p53 genetic polymorphism at codon 72 (p53 Arg72Pro) which affects the function of p53 might have an influence on breast cancer risk. Thus, in the present study, we have studied the association of p53 Arg72Pro polymorphism with breast cancer risk. A case–control study was conducted with 191 breast cancer patients and 218 healthy female controls. p53 Arg72Pro polymorphism was examined in their association with breast cancer risk after adjustment for the epidemiological risk factors. Relationship between p53 Arg72Pro polymorphism and clinicopathological characteristics of breast cancers was also studied. In addition, frequency of somatic p53 mutation was compared according to the genotype of p53 Arg72Pro polymorphism. p53 72Pro/Pro homozygotes showed a significant increase in the risk of estrogen receptor (ER) positive breast cancer (adjusted odds ratio (OR)=2.04, P=0.04) as compared with p53 72Arg/Arg homozygotes, whereas such an association was not found between p53 72Pro/Pro homozygotes and ER negative breast cancer risk. Subset analysis according to menopausal status showed that p53 72Pro/Pro homozygotes were significantly associated with ER positive breast cancer risk in postmenopausal women (adjusted OR=3.42, P=0.01) but not in premenopausal women. Frequency of ER positive tumors was significantly ( p<0.01) higher in breast cancer patients with p53 72Pro/Pro genotype (82.8%) than those with p53 72Arg/Arg genotype (54.5%). Mutational analysis of p53 in tumors showed that p53 72Pro/Pro homozygotes had a lower frequency of p53 mutation (3.5%) than p53 72Arg/Arg homozygotes (10.5%). It is suggested that p53 Arg72Pro polymorphism is associated with ER positive breast cancer risk, especially, in postmenopausal women. The higher frequency of p53 somatic mutation in p53 72Arg/Arg homozygotes than p53 72Pro/Pro homozygotes is consistent with the thesis that the function of p53 72Pro/Pro is impaired so that a further alteration of p53 gene is less required in p53 72Pro/Pro homozygotes than p53 72Arg/Arg homozygotes.