Breast Cancer Abstracts 12

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Trace elements and heavy metals in hair of stage III breast cancer patients.
            (Benderli Cihan et al., 2011)  Download
This prospective study was designed to compare the hair levels of 36 elements in 52 patients with stage III breast cancer to those of an equal number of healthy individuals. Principal component and cluster analysis were used for source of identification and apportionment of heavy metals and trace elements in these two groups. A higher average level of iron was found in samples from patients while controls had higher levels of calcium. Both patients and controls had elevated levels of tin, magnesium, zinc, and sodium. Almost all element values in cancer patients showed higher dispersion and asymmetry than in healthy controls. Between the two groups, there were statistically significant differences in the concentrations of silver, arsenic, gold, boron, barium, beryllium, calcium, cadmium, cerium, cobalt, cesium, gadolinium, manganese, nickel, lead, antimony, scandium, selenium, and zinc (p < 0.05). Strong positive correlations were found between lead and gold (r = 0.785) in the cancer group and between palladium and cobalt (r = 0.945) in the healthy individuals. Our results show that there are distinct patterns of heavy metals and trace elements in the hair of breast cancer patients in comparison to healthy controls. These results could be of significance in the diagnosis of breast cancer.

Metals and breast cancer.
            (Byrne et al., 2013)  Download
Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol. The metalloestrogens fall into two subclasses: metal/metalloid anions and bivalent cationic metals. The metal/metalloid anions include compounds such as arsenite, nitrite, selenite, and vanadate while the bivalent cations include metals such as cadmium, calcium, cobalt, copper, nickel, chromium, lead, mercury, and tin. The best studied metalloestrogen is cadmium. It is a heavy metal and a prevalent environmental contaminant with no known physiological function. This review addresses our current understanding of the mechanism by which cadmium and the bivalent cationic metals activate estrogen receptor-α. The review also summarizes the in vitro and in vivo evidence that cadmium functions as an estrogen and the potential role of cadmium in breast cancer.


 

Estrogen signaling and the DNA damage response in hormone dependent breast cancers.
            (Caldon, 2014) Download
Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR) and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1, and p53 and the feedback on estrogen receptor signaling from these proteins. We put forward the hypothesis that estrogen receptor signaling converges to suppress effective DNA repair and apoptosis in favor of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer, which will further change the processing of DNA damage. Finally, the action of estrogen signaling on DNA damage is also relevant to the therapeutic setting as the suppression of a DDR by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice.
            (Castillo-Pichardo et al., 2013)  Download
BACKGROUND:  Resveratrol, a polyphenol from grapes and red wine has many health beneficial effects, including protection against cardiovascular and neurodegenerative diseases and cancer. However, our group and others have provided evidence for a dual cancer promoting or inhibitory role for resveratrol in breast cancer, dependent on estrogenic or antiestrogenic activities. Moreover, much of the inhibitory effects of resveratrol have been reported from studies with high non-physiological concentrations. METHODS:  We investigated the effects of a range of concentrations (0.5, 5, 50 mg/kg body weight) of resveratrol on mammary tumor development post-initiation, using immunocompromised mice. RESULTS:  Our findings suggest promotion of mammary tumor growth and metastasis by resveratrol at all concentrations tested in tumors derived from the low metastatic estrogen receptor (ER)α(-), ERβ(+) MDA-MB-231 and the highly metastatic ER(-) MDA-MB-435 cancer cell lines. Additionally, the activity of the migration/invasion regulator Rac, which we have previously shown to be regulated by resveratrol in vitro, was measured in tumors from resveratrol treated mice. Our results show a significant induction of tumoral Rac activity and a trend in increased expression of the Rac downstream effector PAK1 and other tumor promoting molecules following resveratrol treatment. CONCLUSION:  Taken together, our findings implicate low concentrations of resveratrol in potential promotion of breast cancer. Therefore, this study illuminates the importance of further delineating resveratrol's concentration dependent effects, particularly in breast cancer, before it can be tested in the clinic or used as a dietary supplement for breast cancer patients.

Is green tea drinking associated with a later onset of breast cancer
            (Dai et al., 2010)  Download
BACKGROUND:  Studies have found that tea polyphenols inhibit aromatase. Because of the substantial difference in levels of estrogens between premenopausal and postmenopausal women, the relationship between tea consumption and breast cancer risk may depend on menopausal status. METHODS:  We examined this hypothesis in the Shanghai Women's Health Study, a population-based cohort study of 74,942 Chinese women. RESULTS:  We found a time-dependent interaction between green tea consumption and age of breast cancer onset (p for interaction, 0.03). In comparison with non-tea drinkers, women who started tea-drinking at 25 years of age or younger had a hazard ratio (HR) of 0.69 (95% confidence interval [CI]: 0.41-1.17) to develop premenopausal breast cancer. On the other hand, compared with non-tea drinkers, women who started tea drinking at 25 years of age or younger had an increased risk of postmenopausal breast cancer with an HR of 1.61 (95% CI: 1.18-2.20). Additional analyses suggest regularly drinking green tea may delay the onset of breast cancer. CONCLUSIONS:  Further studies are needed to confirm our findings.

Metformin may protect nondiabetic breast cancer women from metastasis.
            (El-Haggar et al., 2016)  Download
Metformin, a widely prescribed oral hypoglycemic agent, has recently received a big interest because of its potential antitumorigenic effects in different cancer types. The present study investigated the impact of adding metformin to breast cancer adjuvant therapy in nondiabetic women on, insulin like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), insulin, fasting blood glucose (FBG), the molar ratio of IGF-1 to IGFBP-3, homeostatic model assessment of insulin resistance (HOMA-IR) and metastasis. 102 women with newly diagnosed breast cancer were divided into 2 main groups, a control group and a metformin group. All women were treated with adjuvant therapy, according to the protocols of Ministry of Health and Population and National Cancer Institute, Egypt. Moreover, the women in the metformin group received 850 mg of metformin twice daily. Blood samples were collected at baseline, after chemotherapy (CT), after 6 months of hormonal therapy (6-HT) and 12 months of hormonal therapy (12-HT) for analysis of serum IGF-1, IGFBP-3, insulin, FBG and cancer antigen 15-3 (CA15-3). Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR. On the other hand, metformin caused a significant increase of IGFBP-3. Moreover, metformin significantly decreased the numbers of metastatic cases after 6-HT. Metformin may have potential antitumor and antimetastatic effects that need further clinical investigations. This may be attributed to either the significant increase of the apoptotic inducer IGFBP-3 or/and the significant reduction of mitogenic insulin, IGF-1, free bioactive IGF-1, FBG and HOMA-IR.

Metals and breast cancer: risk factors or healing agents
            (Florea and Büsselberg, 2011)  Download
Metals and metal compounds are part of our environment. Several metals are essential for physiological functions (e.g., zinc or magnesium); while the beneficial effects of others are uncertain (e.g., manganese), some metals are proven to be toxic (e.g., mercury, lead). Additionally there are organic metal compounds; some of them are extremely toxic (e.g., trimethyltin, methylmercury), but there is very little knowledge available how they are handled by organisms. Scientific evidence indicates that long-term exposure to (some) metallic compounds induces different forms of cancer, including breast cancer. On the other side, several metal compounds have clinical use in treating life-threatening diseases such as cancer. In this paper we discuss the recent literature that shows a correlation between metal exposure and breast cancer.

Early pregnancy sex steroids and maternal breast cancer: a nested case-control study.
            (Fortner et al., 2014) Download
Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n = 1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. ORs were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 [4th vs. 1st quartile OR 1.60 (1.07-2.39); Ptrend = 0.01], and inversely associated with breast cancer diagnosed at age ≥40 [4th vs. 1st quartile OR 0.71 (0.51-1.00); Ptrend = 0.02]. Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER(+)/PR(+) disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER(-)/PR(-) breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor-negative cancers is needed to further characterize this association.

Targeting breast stem cells with the cancer preventive compounds curcumin and piperine
            (Kakarala et al., 2010) Download
The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 microM and completely at 10 microM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 microM and completely at 10 microM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.

Arsenic and breast cancer: a systematic review of epidemiologic studies.
            (Khanjani et al., 2017)  Download
INTRODUCTION:  Arsenic is one of the heavy metals known to be a cause of cancer and many other serious human health problems. The International Agency for Research on Cancer (IARC), has classified arsenic as a Group 1 carcinogen. Studies were performed in different populations to investigate the association between arsenic and breast cancer and the present paper attempts to review these studies. METHODS AND MATERIALS:  Accessible electronic resources including, PubMed, Web of Knowledge, Science Direct and Scopus and Google Scholar were searched, with relevant phrases up to October 30, 2016. All articles were reviewed by two people separately and among them, original epidemiologic studies that investigated the association between breast cancer and exposure to arsenic were included. RESULTS:  Eventually seven articles were selected from 126 retrieved articles. Although three studies (one case-control and two ecological) were not able to show a significant affect, others provide some evidence of a relation between arsenic and breast cancer in specific subgroups. CONCLUSION:  Exposure to arsenic may increase the risk of breast cancer. The strength of this relation can vary due to regional and individual differences.

 

Why pesticides could be a common cause of prostate and breast cancers in the French Caribbean Island, Martinique. An overview on key mechanisms of pesticide-induced cancer.
            (Landau-Ossondo et al., 2009)  Download
Prostate and breast cancers have become very frequent in Martinique. We previously conducted a multifactorial analysis in the French Caribbean Island, Martinique, in order to elucidate the aetiology of prostate cancer. Using a linear regression analysis, we found that the growth curves of incidence rates for Martinique and metropolitan France have been significantly diverging since 1983. Although a Caribbean genetic susceptibility factor may be involved in prostate carcinogenesis: this factor, because it could not have changed during the observation period, cannot per se account for the growing incidence of this cancer in the island. We therefore suggested that among possible environmental factors, the intensive and prolonged exposure to Carcinogenic, Mutagenic and/or Reprotoxic (CMR) or presumed CMR pesticides may account for the observed growing incidence of prostate cancer and thus may be involved in prostate carcinogenesis. In this study, we further attempt to show that due to their carcinogenic properties, pesticides and especially organochlorine pesticides may in fact be causally implicated in the growing incidence of prostate cancer in Martinique. Also, we suggest that CMR or presumed CMR pesticides may be causally involved in the growing incidence of breast cancer through a common endocrine disruption mechanism. We therefore propose that protective medical recommendations should be immediately set up and carried out by general practitioners, paediatricians, obstetricians, gynaecologists and urologists; and that public health measures of primary precaution and prevention should be urgently taken in close collaboration with health professionals in order to protect population, more especially pregnant women and children, with the final objective perhaps that these medical recommendations and public health measures will stop Martinique's cancer epidemic.

Do viruses cause breast cancer?
            (Lawson, 2009)  Download
Because mouse mammary tumor virus (MMTV; the Bittner virus) is the proven cause of breast cancer in both field and experimental mice, similar viruses have long been suspects as a potential cause of human breast cancer. MMTV-like viral genetic material has been identified in human breast tumors, but there is no definitive evidence whether MMTV is causal and not merely an innocuous infection in humans. High-risk human papilloma viruses (HPVs), Epstein-Barr (EBV), and other viruses also have been identified in human breast tumors, but again there is no definitive evidence for a causal role. Any viral hypothesis as a cause of breast cancer must take into account the most striking epidemiologic feature of human breast cancer, the three- to sixfold differences in mortality and up to eightfold differences in incidence between some Asian and Western populations. These differences dramatically lessen to a two- to threefold difference within one or two generations of migration of females from low to high risk of breast cancer countries. In this chapter, a plausible explanation for these phenomena is offered; that is, the hypothesis that oncogenic viruses such as MMTV and high-risk HPVs may initiate some breast cancers in most populations. Furthermore, dietary patterns are suggested to determine circulating sex hormone levels, which in turn promote the replication of the hormone-dependent viruses MMTV and HPV. In addition, diet and hormones promote growth of both normal and malignant cells. Finally, the hypothesis that migrants from low to high risk of breast cancer countries change their food consumption patterns is suggested, which leads to higher circulating hormone levels, which in turn promotes viral replication, which initiates breast oncogenesis, which is enhanced by sex and growth hormones.

Cruciferous vegetables intake is inversely associated with risk of breast cancer: a meta-analysis.
            (Liu and Lv, 2013)  Download
PURPOSE:  The objective of the study was to examine the associations of cruciferous vegetables intake with risk of breast cancer. METHODS:  Studies were identified by searching PubMed databases and screening the references of retrieved articles and reviews. Summary odds ratios (ORs) for the highest versus lowest cruciferous vegetables consumption levels were calculated using fixed or random effects models depending on heterogeneity between studies. Heterogeneity among studies was examined using Q and I(2) statistics. Publication bias was assessed using the Egger's and Begg's tests. RESULTS:  Thirteen epidemiologic studies (11 case-control and 2 cohort studies) were included in the meta-analysis. The combined results from all studies indicated that high cruciferous vegetables intake was significantly associated with reduced breast cancer risk (RR = 0.85, 95% CI = 0.77-0.94). CONCLUSION:  Findings from this meta-analysis suggest that cruciferous vegetables consumption may reduce the risk of breast cancer. Because of the limited number of studies, further prospective studies are needed to explore the protective effect of cruciferous vegetables on breast cancer.

The expression of prostate-specific antigen in invasive breast carcinoma and its relationship with routine clinicopathologic parameters
            (Mohammadizadeh et al., 2012)  Download
BACKGROUND: Invasive breast carcinoma is one of the most common cancers of women. Parameters such as lymph node status, tumor grade, and the status of hormone receptors are among the main prognostic determinants of this cancer. Immunohistochemical detection of prostate-specific antigen (PSA) is widely used to identify metastatic prostatic adenocarcinoma. However, its immunoreactivity has been found in some non-prostatic tissues. This study was conducted to assess PSA expression in invasive breast carcinoma and its relationship with routine clinicopathologic parameters. MATERIALS AND METHODS: 100 formalin-fixed and paraffin-embedded invasive breast carcinoma tissue specimens from the pathology archive of Alzahra hospital (Isfahan, Iran) were studied for the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and PSA by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing PSA staining. The relationship between PSA expression and other markers, age, lymph node status, tumor subtype, and tumor grade was then studied. RESULTS: No association was found between PSA expression on one hand and PR, Her2/neu, age, lymph node status, tumor grade, and tumor subtype on the other. PSA score was reversely correlated with ER expression (P = 0.015). CONCLUSION: Despite the reverse relationship between PSA expression and the immunoreactivity of ER, PSA expression was not correlated with other prognostic factors. Therefore, the detection of PSA by immunohistochemistry does not seem to be a significant prognostic parameter in patients with invasive breast carcinoma.

Fragrance compounds: The wolves in sheep's clothings.
            (Patel, 2017)  Download
In the past few decades, synthetic fragrance compounds have become ubiquitous components of personal care and household cleaning products. Overwhelming consumerism trends have led to the excess usage of these chemicals. It has been observed that this fragrance-laden unhealthy lifestyle runs parallel with the unprecedented rates of diabetes, cancer, neural ailments, teratogenicity, and transgender instances. The link between fragrances as and the multiplicity of pathogens remained latent for decades. However, now this health hazard and its role in homeostasis breakdown is getting attention. The adverse effects of the fragrance constituents as phthalates, paraben, glutaraldehyde, hydroperoxides, oil of turpentine, metals, nitro musks, and essential oils, among others, are being identified. The endocrine-immune-neural axis perturbation pathways of these chemicals are being proven. Despite the revelations of cause-effect nexus, a majority of the vulnerable populations are unaware and unmotivated to avoid these 'slow poisons'. Hence, the researchers need to further validate the toxicity of fragrance compounds, and raise awareness towards the health risks. In this regard, a number of pathologies triggered by fragrance exposure, yet proven only scantily have been hypothesized. Analysis of the health issues from multiple facets, including the pivotal 'stressors - extracellular acidosis - aromatase upregulation - estrogen hyperproduction - inflammation' link has been proposed. Fragrance compounds share configurational similarity with carcinogenic environmental hydrocarbons and they provoke the expression of cytochrome group monooxygenase enzyme aromatase. This enzyme aromatizes androgens to form estrogen, the powerful signaling hormone, which underlies the majority of morbidities. This holistic review with a repertoire of preliminary evidences and robust hypotheses is expected to usher in deserving extent of research on this pervasive health risk.

Changes in Dietary Iodine Explains Increasing Incidence of Breast Cancer with Distant Involvement in Young Women.
            (Rappaport, 2017)  Download
The incidence of breast cancer with distant involvement at diagnosis is increasing in young women. The hypothesis that iodine deficiency in the United States, plays a role in the increased incidence of breast cancer with distant involvement, is discussed. Increased iodine demand in women is likely due to the increased uptake of iodine in breast tissue, in addition to the thyroid gland, where iodine plays a role in the development and maintenance of healthy breast tissue (expanding after puberty) and in breast remodeling during lactation, and pregnancy. According to the CDC’s 2012 Second National Report of Biochemical Indicators of Diet and Nutrition in the U.S. Population, women of childbearing age exhibited the lowest urinary iodine levels of any age group.

Pathogenetic mechanisms of heavy metals effect on proapoptotic and proliferative potential of breast cancer.
            (Romaniuk et al., 2015)  Download
MATERIALS AND METHODS:  Chemical composition was studied with the help of the scanning electron microscope with energy-dispersion spectrometer. Immunohistochemical reaction showed the p53 and Ki-67 receptors expression. The study of DNA fragmentation was performed in agarose gel. RESULTS:  There was an interrelation between the accumulations of the trace elements with the degree of cancer malignancy. There were 85% of cases with positive reaction to Ki-67 and 40% cases with positive reaction to p53. We found a moderate correlation between the accumulation of microelements in the breast cancer tissue and the level of proliferative activity. We noted the combination of the increase of DNA fragmentation with the expression of p53 and Ki-67 receptors. CONCLUSIONS:  The trace elements can cause the initiation and the progression of the tumorous growth, which is expressed in the increased proliferation of tumor cells. This leads to the destabilization of the genetic material which can be expressed in the synthesis of mutant p53 protein. Finally, it leads to the block of apoptosis and regulatory effects of cells. This can cause the tumor progression and the destabilization of the genome, which is reflected in the increased DNA fragmentation.

Diurnal cortisol rhythm as a predictor of breast cancer survival.
            (Sephton et al., 2000)  Download
BACKGROUND:  : Abnormal circadian rhythms have been observed in patients with cancer, but the prognostic value of such alterations has not been confirmed. We examined the association between diurnal variation of salivary cortisol in patients with metastatic breast cancer and subsequent survival. We explored relationships between cortisol rhythms, circulating natural killer (NK) cell counts and activity, prognostic indicators, medical treatment, and psychosocial variables. METHODS:  Salivary cortisol levels of 104 patients with metastatic breast cancer were assessed at study entry at 0800, 1200, 1700, and 2100 hours on each of 3 consecutive days, and the slope of diurnal cortisol variation was calculated using a regression of log-transformed cortisol concentrations on sample collection time. NK cell numbers were measured by flow cytometry, and NK cell activity was measured by the chromium release assay. The survival analysis was conducted by the Cox proportional hazards regression model with two-sided statistical testing. RESULTS:  Cortisol slope predicted subsequent survival up to 7 years later. Earlier mortality occurred among patients with relatively "flat" rhythms, indicating a lack of normal diurnal variation (Cox proportional hazards, P =. 0036). Patients with chest metastases, as opposed to those with visceral or bone metastases, had more rhythmic cortisol profiles. Flattened profiles were linked with low counts and suppressed activity of NK cells. After adjustment for each of these and other factors, the cortisol slope remained a statistically significant, independent predictor of survival time. NK cell count emerged as a secondary predictor of survival. CONCLUSIONS:  Patients with metastatic breast cancer whose diurnal cortisol rhythms were flattened or abnormal had earlier mortality. Suppression of NK cell count and NK function may be a mediator or a marker of more rapid disease progression.

Relationships between critical period of estrogen exposure and circulating levels of insulin-like growth factor-I (IGF-I) in breast cancer: evidence from a case-control study
            (Wu et al., 2009) Download
Epidemiological observations suggest that insulin-like growth factor-I (IGF-I), a potent mitogenic and anti-apoptotic peptide, plays a role in the etiology of breast cancer. Estrogen, which is crucial in breast carcinogenesis, both regulates and is influenced by IGF-I family. A case-control study was conducted to assess the role of IGF-I as a biomarker for breast cancer and to evaluate the potential joint effect of circulating IGF-I and critical period of estrogen exposure, as estimated by the interval between age at menarche and age at first full-term pregnancy on the risk of breast cancer. Questionnaire information and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2006. Plasma levels of IGF-I and IGFBP-3 were measured by immunoradiometric assay. Conditional logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our case-control data indicate that breast cancer risk related to IGF-I differs according to menopausal status. High circulating levels of IGF-I increased risk of pre- but not postmenopausal breast cancer (top vs. bottom tertile, adjusted OR, 1.86; 95% CI, 1.01-3.44). Furthermore, elevated IGF-I concentrations in conjunction with prolonged interval of critical period of estrogen exposure were associated with significantly increased risk of breast cancer, particularly among estrogen-positive cases (adjusted OR, 2.42, 95% CI, 1.33-4.38). These results suggest that the joint effect of IGF-I and estrogens may provide novel methods of breast cancer risk reduction among women.

Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up
            (Zhang et al., 2013) Download
Plasma estrogen and androgen levels are positively associated with postmenopausal breast cancer risk, but how long a single blood measurement can predict risk and whether the associations vary by tumor hormone receptor status remain unclear. We conducted nested case-control analyses within the Nurses' Health Study. Blood samples were collected in 1989-1990 and again in 2000-2002. Among postmenopausal women not using postmenopausal hormones at blood collection, 707 cases were diagnosed through June 2010, with two matched controls per case. We used unconditional logistic regression analyses to estimate the relative risks controlling for other breast cancer risk factors. The intra-class correlation coefficients for two blood measurements collected 10 years apart ranged from 0.54 (dehydroepiandrosterone sulfate, DHEAS) to 0.74 (sex hormone-binding globulin, SHBG). Overall, women in the top (vs. bottom) 25 % of levels of estradiol, free estradiol, testosterone, free testosterone, and DHEAS were at a 50-110 % higher risk of breast cancer (p (trend) < 0.001). SHBG was inversely associated with risk (p (trend) = 0.004). RRs were similar when comparing cases diagnosed 1-10 versus 11-20 years (or 16-20 years) after blood collection (p (interaction) > 0.2). Except for DHEAS, the associations varied significantly by hormone receptor status (p (heterogeneity) </= 0.02). For example, the RRs (95 % CIs) comparing the highest versus lowest quartile were 2.8 (2.0-4.0; p (trend) < 0.001) for ER +/PR + tumors versus 1.1 (0.6-2.1; p (trend) = 0.98) for ER-/PR- tumors for estradiol, and 1.8 (1.3-2.5; p (trend) < 0.001) versus 0.6 (0.3-1.2; p (trend) = 0.35) for testosterone. One measure of circulating sex hormones in postmenopausal women can predict risk of hormone receptor positive breast cancer for up to 16-20 years.

 


References

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