Breast In Postmenopausal Women Research Articles

An ecological study of obesity-related cancer incidence trends in Australia from 1983 to 2017

SummaryBackgroundOverweight and obesity is a growing public health issue as it contributes to the future burden of obesity-related diseases, including cancer, especially in high-income countries. In Australia, 4.3% of all cancers diagnosed in 2013 were attributable to overweight and obesity. Our aim was to examine Australian age-specific incidence trends over the last 35 years for obesity-related cancers based on expert review (colorectal, liver, gallbladder, pancreas, breast in postmenopausal women, uterine, ovary, kidney, thyroid, and multiple myeloma) individually and pooled.MethodsAustralian incidence data for 10 obesity-related cancers among people aged 25–84 years, diagnosed from 1983 to 2017, were obtained from the Australian Cancer Database. We used age–period–cohort modelling and joinpoint analysis to assess trends, estimating incidence rate ratios (IRR) by birth-cohort for each individual cancer and pooled, and the annual percentage change. The analyses were also conducted for non-obesity-related cancers over the same period.FindingsThe total number of cancers where some proportion is obesity-related, diagnosed from 1983-2017, was 1,005,933. This grouping was 34.7% of cancers diagnosed. The IRR of obesity-related cancers increased from 0.77 (95% CI 0.73, 0.81) for the 1903 birth-cohort to 2.95 (95% CI 2.58, 3.38) for the recent 1988 cohort relative to the 1943 cohort. The IRRs of non-obesity related cancers were stable with non-significant decreases in younger cohorts. These trends were broadly similar across sex and age groups.InterpretationThe incidence of obesity-related cancers in Australia has increased by birth-cohort across all age-groups, which should be monitored. Obesity, a public health epidemic, needs to be addressed through increased awareness, policy support and evidence-based interventions.FundingThis research received no specific funding.

Effects of drospirenone and norethisterone acetate combined with estradiol on mammographic density and proliferation of breast epithelial cells—A prospective randomized trial

ObjectiveThere are no previous data on the influence of drospirenone (DRSP) in combination with estradiol (E2) on the breast in postmenopausal women. The objective of this study was to evaluate the effect of DRSP or norethisterone acetate (NETA) in continuous combination with E2 on two surrogate markers for breast cancer - mammographic breast density and proliferation of breast epithelial cells - in healthy postmenopausal women. Study design120 healthy, naturally postmenopausal women were randomized to either 2 mg of DRSP or 0.5 mg of NETA in continuous combination with 1 mg of oral E2. The women underwent mammography and fine-needle aspiration biopsy of the breast at baseline and after six months of treatment. Main outcome measuresDigitized mammographic breast density and breast cell proliferation. ResultsThere was a significant increase in mammographic breast density after treatment in both groups (median increase 5.5% for E2/DRSP and 2.3% for E2/NETA, respectively, p < 0.001), but with no significant difference between groups. The proliferation of breast epithelial cells also increased in both groups (p < 0.001, respectively), with a significantly larger increase in the E2/DRSP group than in the E2/NETA group (2.5% versus 0.7%, respectively, p < 0.05). Systolic blood pressure had decreased significantly after 6 months of treatment in the E2/DRSP group (p < 0.05) but not in the E2/NETA group. ConclusionsBreast density increased to a similar degree with E2/DRSP and E2/NETA. Proliferation of breast epithelial cells also increased significantly in both groups but was slightly more pronounced in the E2/DRSP group.

Genomic signature of parity in the breast of premenopausal women

BackgroundFull-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women.MethodsGene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues.ResultsDiscovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues.ConclusionsGenes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.

Breast Hormone Concentrations in Random Fine-Needle Aspirates of Healthy Women Associate with Cytological Atypia and Gene Methylation.

Sex steroid hormones contribute to breast cancer development, but data on concentrations of these within breast tissue are limited. We performed simultaneous multiparameter measurement of breast sex steroids, breast epithelial cytology, and DNA methylation in 119 healthy women (54 pre- and 65 postmenopausal) without a history of breast cancer. Random fine-needle aspiration (rFNA) of the breast was performed simultaneously with blood collection. Breast samples were analyzed by LC/MS-MS for estrone, estradiol, progesterone, androstenedione, and testosterone. Blood samples were assayed for estradiol and progesterone by immunoassay. Cytomorphology was classified using the Masood Score, and DNA methylation of eight genes was analyzed using quantitative multiplexed methylation-specific PCR, and expressed as the cumulative methylation index (CMI). Serum and breast concentrations of estradiol and progesterone showed significant correlation (Spearman r = 0.34, Padj = 0.001 and r = 0.69, Padj < 0.0006, respectively). Progesterone concentration was significantly higher in the premenopausal breast (Padj < 0.0008), and showed a luteal surge. Breast estrone and estradiol concentrations did not differ significantly by menopause, but androstenedione concentration was higher in the breasts of postmenopausal women (P = 0.026 and Padj = 0.208). Breast androgens were significantly correlated with breast density (Spearman r = 0.27, Padj = 0.02 for testosterone) and CMI (Spearman r = 0.3, Padj = 0.038 for androstenedione). Our data indicate that future larger studies of breast steroid hormones along with other parameters are feasible. Significant associations of breast androgen concentrations with breast density and gene methylation warrant future study. Cancer Prev Res; 11(9); 557-68. ©2018 AACR.

Comments on paper: “Quantitative determination of estrone by liquid chromatography–tandem mass spectrometry in subcutaneous adipose tissue from the breast in postmenopausal women” by Vihma et al.

Comments on paper: “Quantitative determination of estrone by liquid chromatography–tandem mass spectrometry in subcutaneous adipose tissue from the breast in postmenopausal women” by Vihma et al.

Quantitative determination of estrone by liquid chromatography–tandem mass spectrometry in subcutaneous adipose tissue from the breast in postmenopausal women

Estrone is the most abundant estrogen after the menopause. We developed a liquid chromatography-tandem mass spectrometric method (LC–MS/MS) for determination of estrone in adipose tissue. Subcutaneous adipose tissue from the breast was collected during elective surgery in postmenopausal women undergoing mastectomy for treatment of breast cancer (n=13) or reduction mammoplasty (controls, n=11). Homogenized adipose tissue was extracted with organic solvents and the estrone fraction was purified by LH-20 column chromatography from the excess of lipids. The concentration of estrone was analyzed by LC–MS/MS. The method was accurate with an intra-assay variation of 8% and an interassay variation of 10%. The median concentration of estrone in subcutaneous adipose tissue from the breast did not differ between breast cancer and control women, 920pmol/kg and 890pmol/kg, respectively. In breast cancer patients but not in the controls, breast adipose tissue estrone levels correlated positively with the serum estrone concentration. In conclusion, the new method provides a reliable means to measure estrone concentrations in adipose tissue in postmenopausal women.

The Role of Diabetes in Molecular Pathogenesis of Cancer

The incidence of cancer is increased in patients with diabetes mellitus. Numerous epidemiological studies confirm this phenomenon, specifically with malignancies of the pancreas, liver, bile ducts, uterus, kidney, breast in postmenopausal women, colon, bladder and aggressive forms of prostate cancer. Disruption of homeostatic glucose metabolism may play a significant role in malignant cellular transformation and disease progression. Additionally, recent advances in molecular and biochemical technology allow for deeper understanding of the pathophysiology of disrupted glucose-insulin axis pathways in diabetics at the subcellular level. These technological advances may provide answers as to how malignant cellular transformation occurs and identify potential treatment targets. Keywords: Carcinogenesis, diabetes, hyperglycemia, inflammation, insulin resistance, obesity.

Abstract P5-02-06: Digital quantification of estrogen receptor expression in normal breast in post-menopausal women with breast cancer and association with tumor subtypes

Abstract Background: ER expression in normal breast epithelium (NBR) is higher in women with a history of breast cancer (BC) compared to controls. In adjuvant setting, metanalysis showed effective Tamoxifen treatment was restricted to ER positive cancers. However, it is also known prophylactic oophorectomy (a form of estrogen suppression) significantly reduces the incidence of BC in BRCA1 carriers. This is in contrast with the 80% rate of ER negative tumors in BRCA1 patients. The aim of this study is to quantify ER expression in NBR away from tumor in women with BC and to correlate it with BC subtypes. Methods: 204 consecutive patients were identified for whom NBR away from tumor was available. 27 reduction mammoplasty (RM) tissues from women with no history of BC were used as controls. Tissue microarrays were constructed and slides were stained with ER and scanned using Aperio XT Scan Scope. Normal terminal duct lobular epithelium was manually circled on scanned images and annotations were recorded in separate digital layers. ER staining was quantitated in marked areas of the electronic image using an optimized scoring nuclear IHC algorithm (Aperio technologies, Inc., Vista, CA). Clinical information and tumor characteristics (menopausal status, ER, HER2 expression, grade, size, number of positive nodes, stage) were recorded based on pathology reports and tumor registry data. Results: The mean ER positivity in NBR was 16 ± 12.4 % (range: 0-5-5.7%) for all patients with BC, 20.8±13.9% for postmenopausal (n=74) and 13.7 ±10.9% for peri+ premenopausal (n=170) subgroups. ER positivity was higher in patients with BC compared to those undergoing RM with no history of BC. ER positivity in NBR did not vary by tumor size, positive lymph nodes status, tumor grade, or stage in post-menopausal, and pre + perimenopausal women. Older age at diagnosis was significantly associated (p&amp;lt;0.0001) with ER in NBR. In post- menopausal women ER expression in NBR was significantly higher in patients with ER negative or triple negative tumors. Estrogen receptor expression in normal terminal duct lobular units of post-menopausal women with breast cancer in relation to tumor subtypes. Postmenopausal (N=74) NMean % (SD)P ValueTumor ER Status 0.05 Negative1427.4 (13.9) Positive6019.3 (13.6) Tumor HER2 Status 0.34 Negative5721.8 (14.9) Positive817.7 (5.7) Tumor Triple Negative 0.05 No5319.7 (13.6) Yes1228.5 (14.7) HER2 status was not known in some cases and was excluded from statistical calculations. Conclusion: This computer assisted image analysis study confirms ER expression in NBR increases with age and menopausal status in women with BC. We report, for the first time, a significant association between ER expression in normal breast epithelium with ER negative and triple negative cancers in post-menopausal women. Our study suggests that ER expression in normal epithelium may play a role in development of hormone receptor negative breast cancers. Citation Format: H Evin Gulbahce, Cindy Blair, Carol Sweeney, Rachel Factor, Mohamed Salama. Digital quantification of estrogen receptor expression in normal breast in post-menopausal women with breast cancer and association with tumor subtypes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-06.

Abstract 2294: Pregnancy changes the DNA methylation profile of the breast in postmenopausal women

Abstract Recently, we have described that the breast of parous postmenopausal women exhibits a specific gene expression profile induced by full term pregnancy (FTP) [Belitskaya-Levy, I. et al. 2011 and Peri, S. et al. 2012], which is centered on chromatin remodeling [Russo, J. 2012]. In order to better understand the molecular mechanism of gene regulation induced by FTP, we have investigated the DNA methylation profile in breast core needle biopsies of five nulliparous (NP) and five parous (P) postmenopausal women between the ages of 50 and 69. DNA was extracted from core needle biopsies and highly methylated fragments of the DNA were separated from the un-methylated DNA using MBD-Capture. The hypermethylated DNA was then sequenced using the Illumina system. Image analysis and base calling were performed with the standard Illumina pipeline, and the reads were aligned to human reference genome (hg18). Differentially methylated regions (DMR) were identified by comparing the differences of averaged methylation values between P and NP samples using Student's t-test (P&amp;lt;0.01). 583 genes were differently methylated between P and NP, of which, 455 genes were hypermethylated in the P breast and 128 genes were hypermethylated in the NP. Additional visual analyses of the sequencing results were performed in these 583 genes using Integrative Genomics Viewer (IGV), of which, 53 genes with DMRs were identified. Analysis and research into the functions of these genes identified seven genes (DACT1, PPP2CA, GSK3B, ROBO1, INPP4B, IL6ST, FZD1) that have been described to interact with each other in either the Wnt signaling pathway or its controlling PI3K/AKT/mTOR pathways. The evaluation of these interactions suggests that beta-catenin, a downstream gene of the Wnt signaling pathway, is being inhibited in the P women. Wnt signaling plays different roles during the stages of the mammary gland development, and it is suggested that lowered beta-catenin expression is essential for proper mammary involution. This observed molecular machinery, leading to a decrease in beta-catenin production and accumulation, may be a leftover effect from mammary involution, last process that the parous mammary gland undergone and it may be, at least partially, responsible for their decreased risk of cancer. The pathways identified in this specific population are of the great importance and could represent a safeguard mechanism mediating the protection of the breast conferred by full term pregnancy. (The sample collection was supported by Avon Foundation for Women Breast Cancer Research Program grant 02-2010-117 and the methylation studies by NIH core grant CA06927 to Fox Chase Cancer Center). Citation Format: Julia Santucci-Pereira, Colleen O'Malley, Ricardo López de Cicco, Nameer B. Kirma, Tim H. Huang, Joseph Liu, Eric A. Ross, Michael Slifker, Suraj Peri, Irma H. Russo, Pal Bordas, Per Lenner, Göran Hallmans, Paolo Toniolo, Jose Russo. Pregnancy changes the DNA methylation profile of the breast in postmenopausal women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2294. doi:10.1158/1538-7445.AM2014-2294

Genesis and Outcome of a Breast Cancer Trial to Develop the Aromatase Inhibitor Anastrozole

Featured Article: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, ATAC Trialists' Group. Lancet 2005;365:60–2.2 Aromatase inhibitors block the enzyme aromatase, which is responsible for conversion of the adrenal derived precursor, androstenedione, to estrogen in tissues such as fat, muscle, and in the breast in postmenopausal women. Estrogens drive the proliferation and metastasis of estrogen receptor positive breast cancer (about 70% of the total). In the mid 20th century bilateral adrenalectomy was used to reduce postmenopausal estrogens but this major operation was replaced by use of the adrenal steroid hormone synthesis inhibitor, aminoglutethimide, although corticosteroid replacement had to be used. Aromatase inhibitors were the real advance, and the introduction of a simple once per day pill in the 1990s (1) lead the way to evaluation of their value, first in advanced breast cancer against standard therapy of tamoxifen …

Tumor de células granulares de mama. Un diagnóstico que se debe considerar

El tumor de células granulares es un tumor poco frecuente y generalmente benigno que se origina en las células de Schwann. Su localización habitual es en la cabeza y el cuello y su aparición en la mama es infrecuente. Aun siendo un tumor infrecuente, el tumor de células granulares de la mama tiene una prevalencia mayor de lo que anteriormente se ha reconocido. Este tumor habitualmente imita al carcinoma de mama por la clínica y datos de imagen y su diagnóstico es anatomopatológico. El tratamiento es escisión local amplia y su pronóstico es bueno con escasa tasa de recidivas. Presentamos dos casos de tumores de células granulares de mama en mujeres posmenopáusicas que simulaban un carcinoma de mama en ecografía y mamografía. La primera se detectó en el programa de cribado de cáncer de mama y la segunda durante el seguimiento después de un carcinoma ductal infiltrante. The granular cell tumour is a very rare tumour which originates in the Schwann cells, and is generally benign. It is usually located in the head and neck, and its appearance in the breast is uncommon. Although it is rare tumour, granular cell tumours of the breast have a higher prevalence than previously recognised. This tumour usually imitates breast cancer due to its clinical and imaging data, with its diagnosis being by histopathology. The treatment is a wide local excision, and its prognosis is good with a low recurrence rate. We present two cases of granular tumours of the breast in post-menopausal women that simulated a breast carcinoma in the ultrasound and mammography. The first was detected in the breast cancer screening program, and the second during follow up of an invasive ductal carcinoma.

Pregnancy‐induced chromatin remodeling in the breast of postmenopausal women

Early pregnancy and multiparity are known to reduce the risk of women to develop breast cancer at menopause. Based on the knowledge that the differentiation of the breast induced by the hormones of pregnancy plays a major role in this protection, this work was performed with the purpose of identifying what differentiation-associated molecular changes persist in the breast until menopause. Core needle biopsies (CNB) obtained from the breast of 42 nulliparous (NP) and 71 parous (P) postmenopausal women were analyzed in morphology, immunocytochemistry and gene expression. Whereas in the NP breast, nuclei of epithelial cells were large and euchromatic, in the P breast they were small and hyperchromatic, showing strong methylation of histone 3 at lysine 9 and 27. Transcriptomic analysis performed using Affymetrix HG_U133 oligonucleotide arrays revealed that in CNB of the P breast, there were 267 upregulated probesets that comprised genes controlling chromatin organization, transcription regulation, splicing machinery, mRNA processing and noncoding elements including XIST. We concluded that the differentiation process induced by pregnancy is centered in chromatin remodeling and in the mRNA processing reactome, both of which emerge as important regulatory pathways. These are indicative of a safeguard step that maintains the fidelity of the transcription process, becoming the ultimate mechanism mediating the protection of the breast conferred by full-term pregnancy.

Long-term endometrial and breast safety of a specific, standardized soy extract

Objective To assess the effects of an oral soy isoflavone extract (Phytosoya®) on endometrium and breast in postmenopausal women treated for 3 years.Methods A total of 395 postmenopausal women were included in this international prospective, open-label study. The number of patients who completed the 3-year study was 197. The women were treated for 3 years with a specific, standardized soy isoflavone extract (total 70 mg/day). Endometrial biopsy, transvaginal ultrasonography and mammography were performed before and after 3 years of treatment.Results No case of hyperplasia/cancer was diagnosed among the 192 interpretable biopsies at 3 years. Only one case of simple hyperplasia was diagnosed among 197 post-baseline interpretable biopsies. The endometrial safety of this extract has been demonstrated (point estimate 0.5%). There was no statistically significant change in endometrial thickness after 3 years (98.4% inactive or atrophic and 0.3% proliferative endometrium at 1 year). Mammography results showed no notable change from baseline. No patient in any set developed an ACR classification of 4 or 5 after 3 years of treatment. The global safety was rated as either ‘excellent’ or ‘good’ by 99.1% of investigators and 99.0% of patients after 3 years of treatment. The adverse events were as follows: eight patients had metrorrhagia and seven patients had at least one breast adverse event: three patients had ‘breast pain’, two patients reported ‘breast tenderness’ and two patients had ‘hypertrophic breast’ (most of them were possibly treatment-related).Conclusions As no case of hyperplasia was diagnosed among the 301 interpretable biopsies at 1 year and there was only one case of simple hyperplasia in the 197 post-baseline biopsies at 3 years, the endometrial safety of this extract has been demonstrated. Furthermore, as demonstrated by the lack of change in endometrial thickness associated with the histologic results, we suggest that this extract does not exert a mitogenic effect on the endometrium. These results suggest that daily administration of 70 mg of a specific, standardized isoflavone extract for 3 years could be a safe treatment for both endometrium and breast.

Aggressiveness of ‘true’ interval invasive ductal carcinomas of the breast in postmenopausal women

There is debate whether interval carcinomas differ from screen-detected tumours biologically. In this study, clinico-pathological parameters and the expression of well-validated biological markers were compared between ‘true’ interval carcinomas and screen-detected/missed carcinomas hypothesising that ‘true’ interval carcinomas show a more aggressive biological behaviour. The study group consisted of 92 consecutive postmenopausal women attending the breast screening programme and presenting with an invasive ductal carcinoma. All screening mammograms were re-reviewed. Sixteen patients had a ‘true’ interval carcinoma. Seven carcinomas were missed at screening, but detected on re-reviewing of the screening mammogram. Radiological characteristics were assessed from diagnostic mammograms. Data on patient- and tumour characteristics and follow-up data were recorded from hospital records. Median follow-up was 61 months. Immunohistochemistry for ER, PR, Her2/neu and p53 was performed on TMA sections. Univariate and multivariate logistic regression analyses were performed. In univariate analysis, ‘true’ interval carcinomas were significantly larger (odd ratios (OR) 7.2, 95% CI 1.8–28.1) and less frequently ER (OR 0.3, 95% CI 0.1–0.9) and PR (OR 0.3, 95% CI 0.1–1.0) positive. In multivariate analysis, ‘true’ interval carcinoma was independently associated with larger tumours (OR 7.0, 95% CI 1.4–36.2). A trend toward ER negativity was found (OR 0.3, 95% CI 0.1–1.1). ‘True’ interval carcinomas showed a trend toward a decreased relapse-free survival (HR 1.7 95% CI 0.9–3.1). Although ‘true’ interval carcinomas were significantly larger than screen-detected/missed interval carcinomas, it remains challenging to observe parameters that determine this difference between ‘true’ interval carcinomas and screen-detected lesions.

Cell turnover in apocrine metaplasia and apocrine adenosis of the breast

Apocrine metaplasia (APM) is a common finding in the breast of postmenopausal women and is seen in a broad spectrum of lesions ranging from microscopic cysts to invasive apocrine carcinoma. Apocrine metaplasia within sclerosing adenosis is known as apocrine adenosis (AA) and is considered a benign lesion of the breast. Apocrine metaplasia and AA have been the subject of many studies; however, little is known about the dynamics of cell turnover in these lesions. Recent studies have shown that some forms of AA may show altered degree of proliferation along with altered expression of bcl-2 and bax proteins. In the current study, we investigate further aspects of apoptosis to help understand the mechanisms of cell turnover in AA and APM. To investigate cell turnover in APM and AA, immunohistochemistry was used to study the expression of the apoptotic markers Bak, Mcl-1, Bcl-x, and Bcl-x(L) in 45 cases of APM (13 cases of nonpapillary APM, 21 cases of simple papillary APM, and 11 cases of complex papillary APM). Also, 34 cases of AA (23 cases of non-atypical AA [NAA] and 11 cases of atypical AA [AAA]) were included in the study. The expression of hTERT and the proliferation marker Ki-67 were also determined. The TdT-mediated dUTP nick-end labeling (TUNEL) technique was used to study the apoptotic status in 28 cases of APM (12 cases nonpapillary APM and 16 cases of papillary APM including simple and complex forms) and 22 cases of AA (15 cases of NAA and 7 cases of AAA). The results showed that all cases studied by immunohistochemistry were positive for the expression of Bak, Mcl-1, Bcl-x, and Bcl-x(L) showing a pattern of staining similar to that seen in the normal breast epithelium. There was no relation between hTERT positivity and the degree of proliferation in any of the lesions studied. The TUNEL results revealed an apoptotic index (AI) of 0.4% and 0.2% in the papillary and nonpapillary groups of APM, respectively. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The average Ki-67 index in the nonpapillary group was 0.7%, whereas in the papillary group, a value of 4% was recorded. In the cases of AA, an AI of 0.4% and 0.3% in NAA and AAA, respectively, was seen. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The Ki-67 index was 5.2% and 6.6% in the NAA and AAA, respectively. The current results show that apoptosis is not a common event in APM and AA even in the presence of increased proliferation, which may render some of these lesions more susceptible to oncogenic changes. Further studies are needed to study other apoptotic pathways that may be involved in cell turnover in these lesions.

Study showing the efficacy of aromasin in metastatic CA breast in postmenopausal women

12023 Background: Aromatase inhibitors have been shown to be better choice for Hormone therapy in Post menopausal receptor positive woman when compared to Tamoxifen. Methods: 22 patients with stage...

Effects of Tibolone on the Breast of Postmenopausal Women

For decades, hormone therapy (HT) has been the mainstay for managing menopausal symptoms. However, the prolonged use of either single estrogen therapy (ET) or a combination therapy of estrogen and progestogen (EPT) might be associated with a slightly increased risk of breast cancer. Alternative therapies that are effective in the prevention and/or treatment of menopause, having associated morbidities but no unwanted effects, are of primary interest in clinical practice. Tibolone (Livial; NV Organon, Oss, The Netherlands) is structurally related to 19-nortestosterone derivatives and is a new postmenopausal regimen with a unique pharmacological profile, licensed for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women. Tibolone exhibits weak estrogenic, progestogenic, and androgenic activities, which in theory might influence the breast. The effect of tibolone on breast tissue, however, is obscure. The purpose of this study was to assess the effects of tibolone on breast safety, and the collected data include preclinical models, clinical observation, and epidemiologic study. Although in vitro studies showed conflicting results (with the majority being favorable effects) regarding the effects of tibolone on breast cells, in vivo studies showed favorable effects of tibolone on the breast in animal models. Similarly, an epidemiologic study indicated an increased risk of breast cancer when tibolone was used to manage climacteric symptoms of postmenopausal women, but accumulated data obtained from radiologic studies (mammography) showed a possible protective effect of tibolone on the breast. Taken together, we conclude that tibolone, if not superior to conventional HT, may be more acceptable to clinicians as a therapeutic drug option for use with symptomatic menopausal women. Only time will tell whether tibolone will be the preferred option.

Tamoxifen therapy for breast cancer and endometrial pathology

Background: Tamoxifen, used as adjuvant therapy for carcinoma breast in postmenopausal women to prevent relapse has estrogenic effect on the endometrium. Methods: 104 patients on tamoxifen for more than six months were subjected to a clinical examination and transvaginal sonography. Patients with endometrial thickness > 8 mm were further evaluated by hysteroscopy and endometrial biopsy. Results: 35(34%) patients were symptomatic. The average endometrial thickness was 11.2 mm which correlated with duration of tamoxifen use. 27(48%) patients had abnormal hysteroscopic findings. 35 (63%) of endometrial biopsies revealed abnormal endometrium. One case of endometrial carcinoma was diagnosed. The results were statistically analysed. There is a significant association between symptomatic status and endometrial thickness and duration of tamoxifen use. Conclusion: All patients on long term tamoxifen should be annually screened for endometrial pathology.

Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women.

Experimental evidence suggests that insulin and insulin-related growth factors may play a role in breast pathology through their mitogenic and anti-apoptotic effects on breast cells. Our objective was to assess the relationship between serum concentrations of insulin-like growth factor-I (IGF-I), its major binding protein (IGFBP-3), the ratio IGF-I:IGFBP-3, c-peptide (a marker of insulin secretion) and the ratio c-peptide:fructosamine (a marker of insulin resistance) and the risk of epithelial hyperplasia (an established breast cancer risk factor) and localized breast cancer among postmenopausal women. Study subjects were patients who provided serum before breast biopsy or mastectomy in 3 hospitals in Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with epithelial hyperplasia of the breast and 185 subjects with localized breast cancer, were compared to 159 subjects with nonproliferative breast changes that have not been associated with increased breast cancer risk. Serum concentrations of IGF-I, IGFBP-3 and the ratio IGF-I:IGFBP-3 were not related to risk of either hyperplasia or breast cancer. For women in the highest quartile of c-peptide or of c-peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4-6.5) and 3.3 (95% CI 1.5-7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast cancer were 1.5 (95% CI 0.7-3.0) and 1.6 (95% CI 0.8-3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest that insulin and insulin resistance may play a role in breast pathology in postmenopausal women.

Overweight as an avoidable cause of cancer in Europe.

There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post-menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta-analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex-specific estimates of the prevalence of overweight [body mass index (BMI) 25-29 kg/m(2)] and obesity (BMI > or = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.