scholarly journals The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

2021 ◽  
Vol 23 (1) ◽  
pp. 424
Author(s):  
Chiara Chiodo ◽  
Catia Morelli ◽  
Fabiola Cavaliere ◽  
Diego Sisci ◽  
Marilena Lanzino

Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 585-585
Author(s):  
W. Y. Chen ◽  
G. A. Colditz ◽  
B. Rosner

585 Background: Although breast cancers categorized by estrogen receptor (ER) and progesterone receptor (PR) status are recognized to differ in their associations with standard breast cancer risk factors, little data exist on differences by HER2/neu status. Methods: The Nurses’ Health Study is a prospective cohort study of 121,700 registered nurses aged 30–55 in 1976 who answered biennial questionnaires to update medical and lifestyle factors and disease occurrence. Medical record review was used to confirm invasive breast cancer and abstract ER, PR, and HER2/neu status. Statistical analyses included both proportional hazards models to estimate relative risks and control for potential confounders and polytomous logistic regression to compare the effects. Only cases diagnosed from return of the 1998 questionnaire until June 2002 were included in the analysis since HER2/neu was only routinely assessed beginning with the 1998 follow-up cycle. Results: 211 HER2/neu positive and 770 HER2/neu negative cases were included in the analysis. In this predominantly postmenopausal group aged 52–77 in 1998, HER2neu negative cancers were more likely to be ER+/PR+ (72%) and less likely to be ER-/PR- (11%) than HER2/neu positive ones (58% ER+/PR+ and 24% ER-/PR-), but the majority of cancers were still ER+/PR+. In multivariate models, risk factor associations by HER2/neu status were similar with positive associations seen for family history, benign breast disease, body mass index, current postmenopausal hormone use, and cumulative alcohol consumption. However, when the subgroup of ER-/PR-/HER2/neu negative cancers were evaluated separately (N=83), most of these risk factor associations disappeared with the only significant risk factor being a prior history of benign breast disease. Conclusions: This is the first prospective data study to report on risk factor association by HER2/neu status. For the standard epidemiologic breast cancer risk factors, ER and PR status appear to better represent separate etiologic pathways, rather than HER2/neu status. However, the subgroup of ER/PR/HER2neu negative breast cancers appears to be distinct, although power was limited and HER2/neu status was not confirmed by central review. Additional analyses stratified by ER/PR status will also be presented. No significant financial relationships to disclose.


Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 1029-1031 ◽  
Author(s):  
Yussanne P. Ma ◽  
Flora E. van Leeuwen ◽  
Rosie Cooke ◽  
Annegien Broeks ◽  
Victor Enciso-Mora ◽  
...  

Abstract Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.


2017 ◽  
Vol 21 (8) ◽  
pp. 464-470 ◽  
Author(s):  
Abdolreza Daraei ◽  
Pantea Izadi ◽  
Ghasemali Khorasani ◽  
Nahid Nafissi ◽  
Mohammad Mehdi Naghizadeh ◽  
...  

2007 ◽  
Vol 5 (8) ◽  
pp. 774
Author(s):  
_ _

Breast cancer is the most commonly diagnosed cancer in American women, with an estimated 214,640 cases and 41,430 deaths occurring in 2006. Estimating breast cancer risk for individual women is difficult, and most breast cancers are not attributable to risk factors other than female gender and increased age. Developing effective strategies for reducing breast cancer incidence is also difficult because few existing risk factors are modifiable and some potentially modifiable risk factors have social implications. Nevertheless, effective breast cancer risk reduction agents and strategies, such as tamoxifen, raloxifene, and risk reduction surgery, have been identified. These guidelines were developed to help women at increased risk for breast cancer and their physicians apply individualized strategies to reduce breast cancer risk. For the most recent version of the guidelines, please visit NCCN.org


2002 ◽  
Vol 20 (8) ◽  
pp. 2085-2091 ◽  
Author(s):  
Lisa Diller ◽  
Cheryl Medeiros Nancarrow ◽  
Kitt Shaffer ◽  
Ursula Matulonis ◽  
Peter Mauch ◽  
...  

PURPOSE: Young women who are exposed to chest irradiation for Hodgkin’s disease (HD) are at increased risk of breast cancer; this study investigated patient awareness of breast cancer risk and patient screening behavior and assessed the utility of mammographic screening in HD survivors. PATIENTS AND METHODS: This is a prospective cohort study of 90 female long-term survivors of HD who had been treated ≥ 8 years previously with mantle irradiation (current age, 24 to 51 years). Participants completed surveys of their perceptions of breast cancer risk and screening behaviors and received written recommendations for breast examinations and mammography. Annual follow-up was conducted through medical records, telephone, and/or mailed questionnaires. RESULTS: At baseline, women were often unaware of their increased risk of breast cancer; 40% (35 of 87) reported themselves to be at equal or lower risk than women of the same age. Only 47% (41 of 87) reported having had a mammogram in the previous 24 months. Women who had received information from an oncologist were more likely to assess correctly their risk than women who received information from other sources (P < .001). Ten women developed 12 breast cancers (ductal carcinoma-in-situ [n = 2], invasive ductal carcinoma [n = 10]) during the study; two were diagnosed at study entry, and 10 during follow-up (median, 3.1 years). All cancers were evident on mammogram, and eight of 10 invasive cancers were node negative. CONCLUSION: Practitioners who care for women after HD therapy need to educate patients regarding their risks and begin early screening. Screening by mammography can detect small, node-negative breast cancers in these patients.


2017 ◽  
Author(s):  
Kevin C. Johnson ◽  
E. Andres Houseman ◽  
Jessica E. King ◽  
Brock C. Christensen

AbstractBackgroundThe underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies.ResultsHere we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors: age, body mass index, parity, and family history of disease with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 CpG sites that demonstrated significant associations (Q-value < 0.01) with subject age. Notably, DNA methylation was not strongly associated with the other evaluated breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations of normal breast tissue (n = 18) and normal-adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in cancer in both pre-invasive (n = 40, P=3.0E-03) and invasive breast tumors (n = 731, P=1.1E-13).ConclusionsDNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.


2020 ◽  
Vol 11 (SPL3) ◽  
pp. 1439-1445
Author(s):  
Indumathi M ◽  
Kavitha S ◽  
Vishnupriya V ◽  
Gayathri R

Globally the major cause of cancer associated death among women is breast cancer. Reports showed that all over world approximately 1.15 million women are affected by breast cancer. Lack of awareness and late diagnosis are the prime reasons behind the raising mortality associated with breast cancer. Breast cancer is becoming the principal cause of mortality worldwide and has greater impact in developing countries. The aim of the present study is to access the knowledge and awareness on risk factors of breast cancers among homemakers. About 150 participants were involved in the study. Self-administered questionnaire of close ended questions was prepared related to risk factors, symptoms, diagnostic modalities, prevention and treatment of breast cancer and distributed among homemakers through online survey forms. In the present study about 62.7% were aware of risk factors of breast cancer and 37.3% were not aware. Regarding the information source of breast cancer risk factors, most of the participants (43.3%) responded to from school or college education. The majority of the participants (60.7%) were aware that breast cancer is among the most prevailing cancers among women. Regarding the risk factors of breast cancer, 36% responded to obesity,10% responded to advanced age and 54% responded to family history of breast cancer. The majority of the participants (56.7%) responded age as a major risk factor. In the present study, knowledge and awareness on the breast cancer, risk factors among homemakers is moderate.


Author(s):  
Leena Hilakivi-Clarke ◽  
Sonia de Assis ◽  
Anni Warri ◽  
Riitta Luoto

AbstractPregnancy can both reduce and increase lifetime breast cancer risk, and it also induces a short-term, transient increase in risk. Several biological mechanisms have been proposed to explain the protective effect, including pregnancy-induced increase in circulating estrogen levels leading to reduced estrogen receptor (ER) expression and activity. Persistent changes in ER-regulated gene expression may then alter the response of the breast to postpregnancy hormonal exposures originating, for example, from food. Understanding how pregnancy increases breast cancer risk has received less attention. Human studies indicate that those women who were exposed to an elevated pregnancy estrogenic environment, such as women who took the synthetic estrogen diethylstilbestrol or who had the highest circulating estrogen levels at the beginning or end of pregnancy, are at increased risk of developing breast cancer. There is also evidence that elevated leptin levels, for example, in pregnant women who gained excessive amount of weight, increase later breast cancer risk. This may reflect a close interaction between estradiol (E2), ER, and leptin. Our preclinical study suggests that an exposure to excess pregnancy E2 and leptin levels reverses the protective changes in genomic signaling pathways seen in the breast/mammary gland of parous women and rodents. Recent findings indicate that involution – the period after lactation when the breast regresses back to prepregnancy stage – may be related to some pregnancy-associated breast cancers. Importantly, in a preclinical model, the increase can be reversed by anti-inflammatory treatment, offering hope that the increase in lifelong breast cancer risk induced by late first pregnancy or by an exposure of pregnant women to an excessive hormonal environment may be reversible.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Alicia Heath ◽  
David Muller ◽  
Piet van den Brandt ◽  
Nikos Papadimitriou ◽  
Elena Critselis ◽  
...  

AbstractSeveral dietary factors have been extensively investigated for associations with risk of breast cancer, but to date unequivocal evidence only exists for alcohol consumption. We sought to systematically evaluate the association between 92 dietary factors and breast cancer risk using a nutrient-wide association study approach. Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression with age as the time scale and adjustment for potential confounders, was used to quantify the association between each food or nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to evaluate in the independent replication cohort, the Netherlands Cohort Study (NLCS). During a median follow-up time of 15 years, 10,979 incident invasive breast cancers were identified in the women from the EPIC study. Six foods and nutrients were associated with risk of breast cancer when controlling the FDR at 0.05. Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% confidence interval (CI) 1.03–1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03–1.06 and 1.04, 95% CI 1.02–1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94–0.98; 0.96, 95% CI 0.94–0.99; and 0.96, 95% CI 0.95–0.98, respectively). When evaluated in the NLCS (2368 invasive breast cancer cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk of breast cancer in the NLCS. Our findings confirm the well-established increased risk of breast cancer associated with alcohol consumption, and suggest that higher intake of dietary fibre, and possibly fruit and carbohydrates, might be associated with reduced breast cancer risk.


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