Prevalence Of Estrogen Receptor Research Articles

Association of Use of the Oral Contraceptive Pill (OCP) with the Expression Pattern of Different Molecular Subtypes of Breast Cancer

Background: Triple-negative breast carcinoma (TNBC) is a breast cancer subtype associated with high mortality and inadequate therapeutic options when compared to non-TNBC. Clinical data indirectly suggests where Oral Contraceptive Pill (OCP) usage is high, the prevalence of Estrogen Receptor+ (ER+) breast cancer is high, and the prevalence of TNBC is low. This has lead to our hypothesis that OCP use may increase the risk of ER+ breast cancer, and OCP use may reduce the risk of TNBC. We aimed to compare the prevalence and association of subtypes of breast cancer in OCP users with that of non-users among women 30 to 60 years of age. Methods: This hospital-based observational study of three-year duration included 155 subjects of primary invasive breast cancer who got admitted to our institution. The data was obtained for ER, PR, HER2 status, clinical classification, and data in relation to demographic factors, reproductive history, and history of OCP use. 155 subjects were divided into two groups. Group-1 included 48 patients with a history of OCP use, and group-2 included 107 patients who have not used OCP. Data was analysed using SPSS-20. Results: A significant increase in the prevalence of molecular subtypes ER+, Progesterone Receptor+ (PR+) and Luminal B breast cancer in OCP users was observed compared to non-users. There was a significant decrease in the age at the time of admission in ER+ cancer in OCP users (45.3 years) compared to non-users (52.2years). While age at the time of admission of Basal (TNBC) cancer patients in OCP users (53.1 years) was higher when compared to non-users (45.4years). Upon logistic regression, the likelihood of ER+, PR+ and Luminal B in OCP users was 11%,10% and 13% less, respectively, with 1 year of higher age and the likelihood of TNBC in OCP users was 18% more and 8% less in non-users. Conclusion: OCP use may be associated with increased prevalence of ER+, PR+ and Luminal B breast cancer. On the contrary, OCP use may be associated with a delay in the progression of the TNBC.

Epidemiology and prevalence of breast cancer: A retrospective study in a tertiary health care center in Kolkata over one decade

Background: Breast cancer is a major public health problem for women throughout the world. According to GLOBOCAN 2012, India along with the United States and China is responsible for almost one-third of global breast cancer burden. There has been 11.54% increase in incidence and 13.82% increase in mortality due to breast cancer in India from 2008 to 2012. According to GLOBOCAN 2018, for both sexes, breast cancer second most common cancer after lung cancer accounting for 11.6% of total cases. Most of the cases diagnosis at an advanced stage because of inadequate screening, lack of appropriate medical facilities thereby increasing breast cancer mortality. It is the second most common malignancy among Indian women accounting for 7% of global burden of breast cancer. Incidence of breast carcinoma varied in the different regions of the world with lowest incidence in Africa, Asia and highest incidence in North America and Europe. This geographic variability is not only to environmental factors but also to lifestyle. There is a paucity of epidemiological data regarding carcinoma of breast. Objectives: The aims of our study were to evaluate the prevalence and epidemiology of breast cancer in our institution, N.R.S. Medical College Kolkata. Materials and Methods: We have analyzed 4172 newly diagnosed breast carcinoma cases, registered at N.R.S. Medical College and Hospital, Kolkata, West Bengal, India, over one decade, in between January 2008 and December 2017 retrospectively. A total of 4172 cases confirmed by pathological examination were included for analysis. Demographic and clinicopathological profile and management offered to the breast cancer patients were recorded from the medical records file. The staging was performed using American Joint Committee on Cancer tumor, node, and metastasis classification staging system. Results: In our study, about 63% of the patients came from urban areas and 37% from rural areas. The mean age at diagnosis was 52 ± 9.5 years, with a range from 26 to 82 years. The age at menarche in this study ranged from 10 to 16 years, mean being 12 ± 1.5 years. Age at the time of first pregnancy ranged from 19 to 32 years, with the mean age being 22 ± 6.2 years. Family history of breast carcinoma in first and second degree relatives was found in 92 (2.2%) patients in this study. Approximately 5% (216) patients were nulliparous. About 63% of the patients were postmenopausal while 36% were premenopausal. Common presenting symptoms include breast lump (100%) and axillary swelling (33%). Histologically, 99.5% cases were infiltrating ductal carcinoma, and it was most common histology. Most patients were diagnosed with Grade II tumors (45%) followed by Grades I and III, and approximately 75% of the patients were in Stages II and III and 10% patients in Stage IV. The most common site of metastasis was lung (33%), bone (26%), liver (23%), and brain (14%). Conclusions: The majority of the breast carcinoma patients presented with Stages II and III disease, approximately 99% cases were infiltrating ductal carcinoma, not otherwise specified and were mainly Grade II followed by Grade III disease. The prevalence of estrogen receptor, progesterone receptor hormone receptor status and Her2/neu status in the population needs further investigation in the future. The government needs to urgently strengthen and augment the existing facilities including screening, which is inadequate at present to handle the current breast cancer load in India.

Abstract P6-12-14: Comparative analysis of breast cancer phenotypes in African American, White American, and African patients- Correlation between African ancestry and triple negative breast cancer

Abstract Introduction: Population-based incidence rates of triple negative breast cancer (TNBC) are higher for African American (AA) compared to White American (WA) women, but it is unclear whether TNBC risk is genetically associated with African ancestry because AA women represent an ancestrally admixed population. Higher frequencies of TNBC have also been observed in sub-Saharan African breast cancer (BC) patients, but comparative analyses of biomarker expression among datasets that include AA, WA, and African women are sparse. We report findings from an international registry that features specimens from a diverse patient population in Detroit, Michigan as well as a hospital in Kumasi, Ghana. Methods: The study dataset included formalin-fixed, paraffin-embedded invasive BC tumors diagnosed between 1998 and 2014 at the Komfo Anokye Teaching Hospital in Ghana and the prospectively-maintained/annotated Henry Ford Health System cohort in Michigan. All Ghanaian tumors underwent pathology confirmation and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR) and HER2/neu expression at the University of Michigan. Women were classified into five BC phenotypes and dichotomized into two age groups, <50 and ≥50 years. Polychotomous multivariate GLM models were developed to estimate the risk for each BC phenotype. Statistical analyses were performed in SAS v. 9.0 (Carey, NC). This research was approved by the Institutional Review Boards of the participating institutions. Results: A total of 234 Ghanaian cases with mean age 49 years (range 24-92); 271 AA with mean age 60 (range 27-87); and 321 WA with mean age 62 (range 31-91) (P=0.001) contributed to this study. Prevalence of histologic grade 3 was lowest in WA (n=107, 33.7%) which was statistically significant from the observed prevalence in AA (n=135, 50.4%) and Ghanaians (n=84, 53.8%) (P<0.0001). ER-negative and TNBC were more common among Ghanaian and AA compared to WA cases (frequency ER-negativity 67.5%, 37.1%, and 19.8%, respectively, p<0.0001; frequency TNBC 53.2%, 29.8%, and 15.5%, respectively, p<0.0001). In the age group <50 years, 82 women (42.5%) were diagnosed with ER+/PR+/HER2-, 65 (33.7%) with TNBC, 27 (14.0%) with ER+/PR+/HER2+, 14 (7.2%) with ER-/PR-/HER2+ and 5(2.6%) with ER-/PR+/HER2- phenotypes. In this young age group, prevalence of TNBC remained highest among Ghanaian women (50.8%), followed by AA (34.3%) and WA (15.9%); (P=.0006). In contrast, highest prevalence of ER+/PR+/HER2+ and ER+/PR+/HER2- phenotypes was observed in WA, followed by AA and Ghanaians. On multivariate analysis histologic grade 3 and racial heritage remained statistically significantly associated with the TNBC phenotype (OR for AA vs. WA with TNBC 1.87, 95% CI 1.15-3.04; OR for Ghanaian vs. WA with TNBC 10.63, 95% CI 5.32-21.25; OR for Grade 3 vs Grade 1 histology with TNBC 33.3, 95% CI 13.45-82.4). Conclusions: This study confirms an association between the TNBC phenotype and African ancestry; furthermore, extent of African ancestry appears to be associated with an increased likelihood of having a TNBC tumor, since frequency of TNBC among AA patients was intermediate between WA and Ghanaian patients. Citation Format: Newman LA, Jiagge E, Bensenhaver JM, Chitale D, Kleer C, Merajver S, Kyei I, Aitpillah F, Oppong J, Amankwaa-Frempong E, Adjei E, Wicha M, Awuah B, Stark A. Comparative analysis of breast cancer phenotypes in African American, White American, and African patients- Correlation between African ancestry and triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-12-14.

Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype.

The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide.

Immunohistochemical detection of P53in canine mammary tumors

Mammary gland tumors are the most common neoplasms in female dogs and represent the second most frequently recognized tumors in dogs. Incidence of mammary tumor is as high as 50 per cent of all neoplasms in female dogs as compared to breast cancer in women. The prevalence of Estrogen Receptor (ER) Progesterone Receptor (PR) has been reported to be < 50% in mammary tumors in dogs and 60–75% in breast cancer in human beings. Apart from hormonal receptors, proliferative markers like P53 and C-erb B2 can be measured by using IHC studies which are of prognostic relevance. In the present study IHC studies were carried out on 24 malignant CMTs consisting of adenocarcinoma (20), solid carcinoma (2), mixed mammary tumor (2) to know the rate of proliferation. P53 mutation was evident in 5 (20.83%) of 24 CMTs. P53 mutation was evident in 27.2% of the tumors that were declared positive for either or one of the hormone receptors. 20% of adenocarcinomas (4) and 50% of solid carcinoma (1) were found positive for P53 immunoreactivity. None of the mixed mammary tumors could express the P53 positivity.

Re: Racial Disparities in Cancer Survival Among Randomized Clinical Trials of the Southwest Oncology Group

Albain et al. (1) present provocative data from Southwest Oncology Group (SWOG) clinical trials indicating that African American patients with breast or other sex-specific cancers are less likely than white patients to survive their disease even when they receive equal treatment. The authors posit that this survival gap most likely reflects racial differences in tumor and host biology. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) program to explore racial survival disparity for breast cancer in the general population (2). Surprisingly, little disparity was explained by differences in tumor biology, such as higher prevalence of estrogen receptor–negative disease among African American women. Rather, the disparity was mostly explained by the consistently higher risk for breast cancer death among African American patients irrespective of estrogen receptor expression, especially during the first few years after diagnosis. Previously, reports from the National Surgical Adjuvant Breast and Bowel Project (NSABP) (3,4) showed that African American and white patients with breast cancer who had similar diagnosis and treatment experienced comparable benefits of treatment. Our results and those from the NSABP suggest that unequal access to quality cancer care is a major driver of disparity, not simply racial differences in tumor biology. How can one reconcile the SWOG, SEER, and NSABP studies? Media reports on the SWOG study stated that African American patients with “equal care” are more likely to “die of breast cancer” than white patients. In fact, the primary SWOG analysis demonstrates that African American patients who received the same investigational treatments were ultimately more likely to die of all causes than white patients. It is well known that African American patients with breast cancer have substantially higher competing mortality than white patients (5). Hence, use of all-cause mortality as the endpoint in the SWOG analysis, rather than breast cancer–specific survival as in the SEER and NSABP studies, may yield upwardly biased estimates of the relative rate of death from breast cancer. This potential bias is particularly relevant for tumors such as breast cancers with comparatively long times to recurrence and death. Albain et al. briefly describe a sensitivity analysis that attempts to substitute for standard analysis of breast cancer–specific survival, but it is hard to see how this can be done effectively, given that the SWOG did not have “detailed cause of death data.” It is also difficult to see how participants in breast cancer trials would receive equal health care after the trials were closed. Rather, all-cause mortality rates observed in the SWOG studies may reflect an initial period with equal cancer care provided by the trials, followed by a longer period of overall care received in the general medical community. If so, it is not clear how the SWOG study can illuminate racial differences in breast tumor biology free of the effects of racial differences in access to health care. Our working model is that biology and access to health care are both key determinants of racial disparity for breast and other cancers. Biology is certainly important (6), but consistent access to quality cancer care is a crucial issue for cancer-specific and all-cause mortality.

Impact of Recording of Pre-Analytical Specimen Handling Conditions for ER and PR Testing in Women with Breast Cancer.

Abstract Background: Hormone receptor testing is important in the management of women with breast cancer. We previously reported potential adverse effects of variable specimen and prolonged specimen handling conditions on ER (estrogen receptor) test results (2005 SABCS, abstract#5107).Objective: To compare prevalence of ER and PR (progesterone receptor) negative test results following standardization of pre-analytical specimen handling conditions at Intermountain facilities.Methods: Prospective, quasi-experimental study design of 6 Intermountain facilities. Facilities were separated into 2 categories: experimental (2 facilities) and control (4 facilities) groups. Pre-analytical specimen handling conditions (including recording of time to fixative and duration of fixation in neutral buffered formalin) were standardized at experimental facilities but not at control facilities. Standardization consisted of educating operating and grossing room staff about appropriate specimen handling and the value of recording time to fixation and fixative duration as a way to improve pre-analytic standardization. OR staff was called in any cases where times were not recorded. Study population includes women undergoing breast cancer surgery and who were tested for ER/PR status between January 2008 and January 2009. Specimen handling conditions and ER/PR test results were collected manually. Covariates were retrieved from cancer registry and included age, grade, positive lymph nodes, specimen type, and tumor stage. Multivariate logistic regression was used to compare prevalence of ER and PR negativity between experimental and control facilities after controlling for covariates.Results: 1054 women with breast cancer were tested for ER/PR status during the study period. The average age was 60.2 years (59.2 years for control cases and 61.1 years for the experimental group). The overall prevalence of ER and PR negative tests was respectively 18.5% and 27.3%. Average time to fixative at experimental facilities was 18.4 minutes (SE=3.1; 95% CI, 12.2-25.6) and average time in fixative was 18.0 hours (SE=0.4; 95% CI, 17.2-18.8). Compared to experimental facilities, both the prevalence of ER and PR negativity was higher (16.9% vs 19.7%) and (23.9% vs 30.0%) at control facilities. After controlling for covariates there was no difference in prevalence of ER negativity (p=0.13) between the two groups. However, the prevalence of PR negativity remains significantly higher (p&amp;lt;0.01) at control facilities compared to experimental facilities even after controlling for covariates.Conclusions: The prevalence of ER and PR negative results was lower following staff education and recording of pre-analytical specimen handling conditions. Our data suggest that staff education and recording of pre-analytical specimen handling conditions has the potential to optimize hormone receptor test results. It also shows the feasibility of fixing tissue routinely after less than an hour interval between time of breast cancer tissue removal and fixation and underscores the value of standardization of pre-analytic handling as a method to improve ER and PR testing on breast cancer specimens. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4154.

HER-2, Hormone Receptors, and clinicopathologic characteristics in Uruguayan breast cancer patients

e22202 Background: Few Latin-American studies and none Uruguayan study have evaluated HER-2, estrogen receptor (ER) and progesterone receptor (PR) in breast cancer (BC). The purpose of the study was to investigate the frequency of these markers and the relationship between them and with clinicopathologic features in Uruguayan BC patients (pts). Methods: We retrospectively reviewed clinical records from pts who underwent curative surgery for stage I-III invasive BC at the Oncology Units of 4 institutions in Montevideo between march 2006 and march 2008. We obtained the following data: age, TNM, ER/PR status by immunohistochemistry (IHC) and HER2 status by IHC and FISH in HER2 IHC 2+. Fisher's exact test was used to analyze the data. Results: 427 pts were included. Median age was 60 years-old (range: 24–93 y), postmenopausal 75%, stages: I 33%, II 42%, III 23%, unknown 2%. ER/PR status was known in 94,6% of cases: ER+/PR+ 66,1%, ER+/PR- 11,1%, ER-/PR+ 3,5%, ER-/PR- 19,3%. HER2 status was known in 47% (199/427) of cases, being positive (IHC 3+ or FISH+) in 13.6%. Triple negative tumors were found in 32 of 199 pts (16%). HER2 was positive in 8% of pts with ER+ and/or PR+ tumors, and in 18% of pts with ER-PR- disease (p=0.08). We did not find a significant association between axillary lymph node status and HER2 status. Besides, triple negative BC did not correlate with axillary lymph node status. When analized by menopausal status, the frequency of triple negative pts was 14% in the premenopausal group and 4% in the postmenopausal group (p=0.005). In addition, the rate of triple negative BC was 0% in pts with histologic grade 1 and 10% in pts with histologic grade 2–3 (p = 0.0005). Conclusions: Our data from Uruguayan pts show a lower prevalence of HER2 positive but a similar prevalence of ER+ and PR+ operable BC than the prevalence reported in most American and European studies. In accordance with previous reports, triple negative BC correlated with younger age and higher histologic grade. No significant financial relationships to disclose.

Mechanisms of estrogenic vascular protection

cardiovascular disease is a leading cause of death, the rate of which is greater in men compared with age-matched premenopausal women ([1][1]). However, the long-standing hypothesis that estrogen may contribute to this sex-based difference in disease presentation by providing “vascular protection

E4F1, a Novel Estrogen-Responsive Gene in Possible Atheroprotection, Revealed by Microarray Analysis

Estrogen has been postulated to be involved in inhibition of vascular smooth muscle cell (VSMC) proliferation mainly via estrogen receptor (ER), but the detailed mechanism has remained primarily unknown. Therefore, in this study, microarray analysis was used in two types of cultured human VSMCs: one positive for ER alpha, and the other for ER beta, which were treated by estrogens to detect the estrogen-responsive genes. We also used quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate mRNA levels of selective target gene (TG) in these cells. We further studied whether the TG product was involved in inhibition of proliferation using small interfering RNA (siRNA) of the TG transfection. We subsequently used quantitative RT-PCR and in situ hybridization analysis to evaluate the expression of these gene products in human aorta. E4F1, a possible inducer of cell growth arrest, was markedly increased only in ER alpha-positive VSMCs by estrogens in both microarray and RT-PCR analyses. Blocking of E4F1 using siRNA suppressed estrogenic inhibition of ER alpha-positive VSMC proliferation. E4F1 mRNA was abundant in premenopausal female aorta with mild atherosclerotic changes. E4F1 is therefore considered one of the estrogen-responsive genes involving ER alpha-mediated inhibition of VSMC proliferation and may play an important role in estrogen-related atheroprotection of human aorta.

Estrogen and colon cancer:current issues

Carcinoma of the colon is common and its incidence varies according to the geographical location and dietary habits. The aims of this paper are, first, to review the current epidemiological data on theincidence and mortality of colon cancer in postmenopausal women using hormone replacement therapy (HRT); second, to review the published data on the prevalence of estrogen receptors in healthy and malignantcolonic tissue; and third, to examine the available evidence of gene silencing as applicable to this and other neoplastic conditions. Estrogen use confers overall protection, with a reduction in the incidenceof colon adenoma and carcinoma of about 30%. Estrogen use reduces the colon cancer-related mortality. The risk of colon cancer is decreased among current and recent users of postmenopausal HRT but the molecularmechanisms involved remain unclear.Estrogen acts either on a single major transformation step in the oncogenetic process, or is involved in multiple events that avert the course of this transformation.Aberrant methylation of the CpG islands in the promoter regions of the estrogen receptor gene, as well as of other genes, is equivalent to the silencing of that gene, with the consequence of inactivation,or reduced expression, of a number of genes downstream, including tumor suppressor genes. This epigenetic mechanism, when reversed, suppresses the growth of cancer cells in vitro and in vivo.The ubiquitous distribution of the estrogen receptor genes and their isoforms, in a tissue-specific manner, opens new avenues for the understanding of cellular behavior in health and disease.

Chapter 2 Estrogen modulates oxytocin gene expression in regions of the rat supraoptic and paraventricular nuclei that contain estrogen receptor-β

Oxytocin is an important modulator of female reproductive functions including parturition, lactation and maternal behavior, while vasopressin regulates water balance and acts as a neurotransmitter. For decades, it has been suggested that estrogen regulates the production and/or release of oxytocin and vasopressin in the rodent brain. Although several studies demonstrated that estrogen can modulate vasopressin mRNA levels in regions known to contain estrogen receptor (ER), such as the bed nucleus of the stria terminalis and medial amygdala, data from the paraventricular and supraoptic nuclei were inconclusive. Since early immunohistochemical and in situ hybridization studies revealed few, if any, ER containing cells in these hypothalamic nuclei, it was thought that oxytocin and vasopressin were not directly regulated by estrogen. The discovery of a second ER (ER-beta) in the late 1990s suggested that estrogen could act in many brain regions heretofore not considered targets for estrogen action. Initial in situ hybridization studies revealed a wide distribution of ER-beta mRNA in the rat brain including neurons of the supraoptic nucleus and the parvocellular and magnocellular divisions of the paraventricular nucleus. Subsequent double-label in situ hybridization/immunocytochemistry studies showed that ER-beta mRNA was present in oxytocin and vasopressin neurons, with the degree of colocalization being both neuropeptide and region specific. In an attempt to demonstrate that ER-beta mRNA was translated into a biologically active protein, a series of in vivo binding studies were conducted in rats with 125I-estrogen. These data revealed the presence of nuclear estrogen binding sites in neurons of the magnocellular system indicating that ER-beta mRNA was translated into protein. Concurrent studies in mice found that the distribution of ER-beta mRNA and 125I-estrogen binding was similar to rats, although there were some notable differences. For example, ER-beta mRNA and binding were not detected in the mouse supraoptic nucleus and although ER-beta was the principle ER in the paraventricular nucleus, ER-alpha was also present. The prevalence of ERs in the mouse paraventricular nucleus was further investigated using ER-alpha and ER-beta knockout mice for in vivo binding studies with 125I-estrogen. The results of these studies showed that ER-beta was the predominant ER in the paraventricular nucleus and confirmed the presence of ER-beta in other brain regions. Moreover, our group recently generated and characterized several polyclonal antisera raised against the C-terminus of ER-beta. Through the use of these antisera, we have confirmed the presence of ER-beta in the rat paraventricular and supraoptic nuclei and shown that ER-beta is colocalized, in part, with oxytocin and vasopressin. To assess the ability of estrogen to modulate the expression of oxytocin mRNA, ovariectomized rats were treated with vehicle or estradiol and the brains processed for in situ hybridization. The results of these studies revealed that estradiol down-regulated oxytocin mRNA in the rat paraventricular nucleus within 6 h of treatment. Together these data and the observation that some of the oxytocin and vasopressin neurons contain ER-beta suggest that estrogen, acting through ER-beta, may directly regulate oxytocin gene expression. However, since the paraventricular nucleus has many subdivisions with different projections and the degree of colocalization of ER-beta with oxytocin/vasopressin varies among subdivisions, the effects of estrogen treatment on gene expression requires further study to ascertain the role of estrogen action in this neuronal systems.

Relevance of estrogen and progesterone receptors enzyme immunoassay in malignant, benign and surrounding normal thyroid tissue

Several authors have demonstrated the presence of estrogen receptors (ER) and progesterone receptors (PR) in thyroid tissue, generally using dextran coated charcoal method (DCCA). The aim of the study was to measure ER and PR in thyroid specimens using an immunoenzymatic method, and to evaluate the meaning of different prevalence of ER and PR in malignant and benign thyroid disease, as compared with normal thyroid tissue. We have measured ER and PR in thyroid tissue from 28 benign and 20 malignant thyroid lesions, and in 38 samples of surrounding normal thyroid tissues. The sensitivity of ER-EIA and PR-EIA was 1.0 and 1.5 fmol/mg protein, respectively. In thyroid carcinoma the frequency of ER positivity (ER+) was 7/20 (35%); it was significantly higher in the surrounding normal tissue (15/20; 71%) (p = 0.03). In benign thyroid disease, the prevalence of ER+ was 11/28 (39%) and in the surrounding normal tissue it was 11/18 (61%) (p = not significant). PR+ was detected in 7/20 (35%) thyroid cancers and in 15/28 (53%) benign lesions without significant difference with the frequency detected in the surrounding normal tissues. ER and PR concentrations (mean +/- SD) in thyroid cancer was 2.2 +/- 2.2 and 2.2 +/- 2.9 respectively, similarly to that detected in benign thyroid disease and in normal tissue. The simultaneous presence of ER and PR (ER+PR+) was also evaluated. We have found that the frequency of ER+ PR+ was significantly higher in benign lesions (8/28; 28.6%) as compared with malignant samples (1/20; 5%) (p < 0.05); the frequency of ER+PR+ was significantly higher in normal tissue surrounding the malignant lesions (9/20; 45) (p = 0.003). Our data indicate i) EIA method is appropriate to detect ER and PR in thyroid tissue. ii) The frequency of ER+ and ER+PR+ specimens is significantly higher in normal thyroid tissue than in pathologic tissues. This indicates that ER and PR immunoassays may be useful tools to evaluate the normal biological activity of thyroid cells.

Prevalence of aneuploidy, overexpressed ER, and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer

Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available. We initiated this study to determine 1) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer, and 2) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women. Eligible high risk women were those with a first degree relative with breast cancer, prior breast cancer, or precancerous mastopathy. Low risk women were those without these or other major identifiable risk factors. Ductal cells were obtained via random fine needle aspirations and cytologically classified. Biomarkers included DNA ploidy, estrogen receptor (ER), and epidermal growth factor receptor (EGFR). The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5%. The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls (p < 0.002), whose median 10 year Gail risk was 0.7%. The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant (p = 0.095). This may be due to the low prevalence of overexpressed ER and the small number of controls. A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women (p < 0.001). A large prospective trial is needed to determine if one or more of these biomarkers, is predictive of breast cancer development.