Postmenopausal Cancer Research Articles

Evaluation of Risk Factors for Metabolic Syndrome in Postmenopausal Women Breast Cancer

OBJECTIVE: To assess the risk of metabolic syndrome (MetS) in postmenopausal women breast cancer survivors compared to postmenopausal women without breast cancer. METHODS: In this cross-sectional study, 104 women breast cancer survivors were compared with 208 postmenopausal women (control), seeking healthcare at a University Hospital. Eligibility criteria included women with amenorrhea> 12 months and age 45 years, treated for breast cancer and no recorrences for at least five years. The control group consisted of women with amenorrhea> 12 months and age 45 years without breast cancer matched by age, in proportion 1:2. Dates on clinical antecedents and anthropometric indicators were collected. The biochemical parameters, including total cholesterol, HDL, LDL, triglycerides, glucose and C-reactive protein (CRP), were measured. MetS was diagnosed as the presence of at least three components among: waist circumference (WC) 88cm, blood pressure 130/85mmHg, triglycerides 150mg/dl, HDL 88 cm) affecting 62.5% of women breast cancer survivors and 67.8% of control group. Women breast cancer survivors had a higher risk for metabolic syndrome (OR 1.66, 95% CI 1.04-2.68), dysglycemia (OR 1.05, 95% CI 1.09- 3.03) and hypertension (OR 1.71, 95% CI 1.02-2.89) compared to women without breast cancer. DISCUSSION: This study demonstrated an association between the metabolic syndrome, obesity and breast cancer patients treated in postmenopausal women. The risk of postmenopausal patients treated for breast cancer to develop metabolic syndrome, hypertension and dysglycemia was higher when compared to age-matched women without the disease. MetS was present in 50% of patients treated for breast cancer and 37.5% in the control group. Among the criteria used for diagnosis of MS, the most common among patients treated for breast cancer were central obesity (62.5%) and hipetrigliceridemia (45.2%). CONCLUSION: Postmenopausal women breast cancer survivors had higher risk of developing metabolic syndrome compared to women without breast cancer.

The crucial role of osteocyte-derived RANKL in bone homeostasis

Receptor activator of NF-κB ligand (RANKL; also known as TNFSF11), a TNF family molecule, and its receptor RANK (TNFRSF11A) are key regulators of osteoclast differentiation and function. Aberrant expression of RANKL explains why autoimmune diseases, cancers, leukemia and periodontal disease result in systemic and local bone loss. In particular, RANKL is the pathogenic factor that cause bone and cartilage destruction in arthritis. Inhibition of RANKL function by the natural decoy receptor osteoprotegerin (OPG; also known as TNFRSF11B) or anti-RANKL antibody prevents bone loss in postmenopausal osteoporosis, cancer metastases and arthritis. RANKL also regulates T cell/dendritic cell communications, dendritic cell survival and lymph node organogenesis. Intriguingly, RANKL and RANK play an essential role in the maturation of mammary glands in pregnancy and lactation. Bone homeostasis depends on the coordination of osteoclastic bone resorption and osteoblastic bone formation. We reported that RANKL induces osteoclast differentiation through activating a transcriptional programme mediated by the master transcription factor nuclear factor of activated T cells (NFAT) c1. Although it is well accepted that the RANKL-NFATc1 pathway is crucially important for osteoclast differentiation, little is known about the major cellular source of RANKL in the skeletal tissue. RANKL has been postulated to be mainly expressed by osteoblasts and bone marrow stromal cells. However, here we show that osteocytes embedded within the bone matrix are the critical source of RANKL in bone remodeling. Osteocytes, the most abundant cell type in bone, are thought to orchestrate bone homeostasis by regulating both osteoclastic bone resorption and osteoblastic bone formation, but in vivo evidence and the molecular basis for the regulation has not been sufficiently demonstrated. Using a newly established method for the isolation of high-purity dentin matrix protein 1-positive osteocytes from bone, we have found that osteocytes express a much higher amount of RANKL and have a much greater capacity to support osteoclast formation than osteoblasts and bone marrow stromal cells. The crucial role of RANKL expressed by osteocytes was validated by the severe osteopetrotic phenotype observed in mice lacking RANKL specifically in osteocytes. Thus, we provide in vivo evidence for the key role of osteocyte-derived RANKL in bone homeostasis, establishing a molecular basis for osteocyte regulation of bone resorption.

Physical activity and cancer prevention: a review of current evidence and biological mechanisms.

The main aim of this paper is to review the evidence available from the date of PubMed's inception to May 2011 for a link between cancer and physical activity (PA) in both animal models and humans. We decided to select studies that comply with the scheme proposed by the American College of Sports Medicine/American Heart Association (ACSM/AHA) that distinguish occupational physical activity (OPA) and leisure-time physical activity (LT-PA), further classified in three levels of intensity (low, moderate and heavy) based on the Metabolic Equivalent of Task (MET) index. Considering animal models, there was strong evidence for an inverse association between voluntary wheel exercise and the risk of colon and breast cancer. Regarding human studies, we identified the following main results: 1) colorectum: LT-PA provided an overall colon risk reduction of 13-14%; 2) breast: significant reduction in the frequency of post-menopausal (PMP) cancers in women that practiced heavy and moderate LT-PA; 3) prostate: heavy OPA and LT-PA seemed to reduce the risk of advanced prostate cancers; 4) endometrium: strong protective effect of heavy/moderate LT-PA among overweight/ obese women; 5) lung: inverse relationship between heavy LT-PA and lung cancer in former or current smokers across all histologies. Increased LT-PA is associated with cancer prevention in several organs, but strong biases, such as body mass index (BMI), gender and age, make it difficult to assess which aspects of PA contribute most strongly to the reduced risk. Furthermore, we found few studies that indicated a protective role for OPA in cancer prevention when compared with LT-PA.

Skeletal Remodeling Following Clinically Relevant Radiation-Induced Bone Damage Treated with Zoledronic Acid

Our aim was to determine if zoledronic acid (ZA) changes (45)Ca pharmacokinetics and bone microstructure in irradiated, ovary-intact (I) and irradiated, ovariectomized mice (OVX), two groups with different patterns of skeletal damage. The hind limbs of I and OVX BALB/c mice received a single 16-Gy radiation dose, simulating pre- and postmenopausal female cancer patients undergoing radiation treatment. All I and OVX mice were radiolabeled with 15μCi (45)Ca. Mice were treated with or without a 0.5mg/kg injection of ZA. The time course of bone mineral remodeling was evaluated using a fecal (45)Ca assay, measured by liquid scintillation. A group of nonirradiated, intact mice were used for the longitudinal evaluation of (45)Ca biodistribution. Distal femur bone histomorphometric parameters were measured using microCT at 50days post-ZA intervention. Most (45)Ca was incorporated into the skeleton and eliminated from the soft tissues within 3-5days postirradiation, attaining a steady state of excretion at 25-30days. ZA intervention in both groups resulted in a rapid decrease in fecal (45)Ca excretion. There was a significant difference in (45)Ca excretion in the OVX±ZA (P=0.005) group but not in the I±ZA (P=0.655) group. The rate of excretion of fecal (45)Ca was slower in the OVX+ZA compared to the I+ZA group (P=0.064). (45)Ca assay is useful to monitor the time course of bone mineral remodeling after an antiresorptive intervention in irradiated mice, providing a basis to investigate bone effects of cancer therapy protocols. For equivalent doses of ZA, recovery may depend on the nature and degree of skeletal damage.

Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise

The mechanism of chemotherapy-induced acceleration of ovarian aging is not fully understood. We used doxorubicin, a widely used cancer chemotherapeutic, in a variety of in vivo xenograft, and in vitro models to investigate the impact of chemotherapy-induced aging on the human ovary. Doxorubicin caused massive double-strand-DNA-breaks in primordial follicles, oocytes, and granulosa cells in a dose dependent fashion as revealed by accumulating γH2AX foci. This damage was associated with apoptotic oocyte death and resulted in the activation of ATM. It appeared that the repair response enabled a minor proportion of oocytes (34.7%) and granulosa cells (12.1%) to survive while the majority succumbed to apoptotic death. Paradoxically, inhibition of ATM by KU-55933 resulted in improved survival, probably via prevention of downstream activation of TAp63α. Furthermore, doxorubicin caused vascular and stromal damage in the human ovary, which might impair ovarian function both pre- and post-menopausally. Chemotherapy-induced premature ovarian aging appears to result from a complex process involving both the germ- and non-germ cell components of the ovary. These effects may have clinical implications in aging both for premenopausal and postmenopausal cancer survivors.

Postmenopausal hormone therapy and lung cancer

The latest recommendations on postmenopausal hormone therapy (HT) stress the need first to evaluate the individual benefits and risks and to prescribe the well-informed patient only when the balance is most favorable. As a result of recent studies on the association of lung cancer with HT, this common malignancy was added to the list of potential serious adverse effects of HT. However, data show that estrogen alone does not carry a risk, whereas a combined estrogen + progestin (E + P) regimen may be associated with higher mortality in lung cancer patients. Women usually take HT in the early postmenopausal period and for several years only. No increase in risk was found in E + P users aged 50–59 years, nor for those who used HT for less than 5 years. The absolute numbers involved are in the order of less than one additional case of lung cancer in 1000 woman/years of hormone use.

Preventable breast cancer is postmenopausal

Breast cancer incidence has markedly increased in Western countries for reasons that are not entirely understood. We characterized periodic and age-specific incidence trends of breast cancer in immigrants who migrated from low incidence areas to Sweden. The incidence in immigrants was compared to that in native Swedes and standardized incidence ratios (SIRs) were calculated, based on the Swedish Family-Cancer Database. Age-specific incidence data for low and high incidence populations were obtained from Cancer Incidence in Five Continents IX and NORDCAN. For immigrants from the seven lowest countries/regions 535 breast cancers were identified; the SIRs ranging from 0.45 for Turkish to 0.70 for Greek women. The SIR increased somewhat with the length of stay in Sweden, from 0.55 for stay between 0 and 10 years to 0.59 for a stay of 20+ years. The age-specific incidence curves for these immigrants were superimposable upon the earliest Swedish (year 1960) or Danish (1943) rates. These rates differed from the current Swedish rates by a much lower postmenopausal component. Large incidence differences were also observed between white Californians and immigrants from China and Korea. Our results show that the main difference between high and low incidence areas is in postmenopausal cancer which has increased preferentially during the past century. Immigrants from low risk areas to Sweden show age-specific incidence patterns of Swedes half a century ago. These differences offer opportunities for the identification of factors underlying breast cancer etiology and tools for prevention.

Abstract A19: Targeting follicle stimulating hormone receptor in postmenopausal epithelial ovarian cancer

Abstract Objectives: Recent studies have established expression of gonadotrphin receptor especially more important Follicle Stimulating hormone Receptor (FSHR) in ovarian surface epithelium (OSE), its benign and early malignant tumours. There is no explanation as yet for such unusual finding. Hence, an extensive search of concerned literatures is made to find out the probable cause of this aberrant expression. Materials and Methods: A systematic review of reports from MEDLINE/PUBMED was performed from May ′02 to June ′05 on mechanism of FSHR expression in OSE and ovarian cancer. Many reports were collected from journal and additional reports were perused from the reference lists of retrieved articles. Results: The neurotrophins (NT) including nerve growth factor (NGF) are a family of related growth factors that are of major importance in the regulation of neuronal survival and differentiation. In the ovary, they can help in follicular maturation and ovulation by inducing the FSH receptor (FSHR). NTs can be implicated as the cause of this aberrant expression of FSHR in OSE. This is because unlike other factors responsible for FSHR expression NT has central action and can lower serum FSH, as is found in such ovarian cancer. Conclusion: NGF deregulates expression of FSHR in OSE and secretion of FSH from the pituitary. This phenomenon may hold the key to the hitherto unexplained carcinogenic process of sporadic epithelial ovarian cancer. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A19

Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer

BackgroundAlterations of mitochondrial DNA (mtDNA) have been implicated in carcinogenesis. We developed an accurate multiplex quantitative real-time PCR for synchronized determination of mtDNA and nuclear DNA (nDNA). We sought to investigate whether mtDNA content in the peripheral blood of breast cancer patients is associated with clinical and pathological parameters.MethodsPeripheral blood samples were collected from 60 patients with breast cancer and 51 age-matched healthy individuals as control. DNA was extracted from peripheral blood for the quantification of mtDNA and nDNA, using a one-step multiplex real-time PCR. A FAM labeled MGB probe and primers were used to amplify the mtDNA sequence of the ATP 8 gene, and a VIC labeled MGB probe and primers were employed to amplify the glyceraldehyde-3-phosphate-dehydrogenase gene. mtDNA content was correlated with tumor stage, menstruation status, and age of patients as well as lymph node status and the expression of estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu protein.ResultsThe content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023). Reduced mtDNA was found often in post menopausal cancer group (P = 0.024). No difference in mtDNA content, in regards to age (p = 0.564), lymph node involvement (p = 0.673), ER (p = 0.877), PR (p = 0.763), and Her-2/neu expression (p = 0.335), was observed.ConclusionEarly detection of breast cancer has proved difficult and current detection methods are inadequate. In the present study, decreased mtDNA content in the peripheral blood of patients with breast cancer was strongly associated with stage I. The use of mtDNA may have diagnostic value and further studies are required to validate it as a potential biomarker for early detection of breast cancer.

Obesity and postmenopausal breast cancer: impact on risk, tumour stage and survival in an Irish population.

Abstract Abstract #6089 Background 
 The evidence that obesity adversely affects women's health is overwhelming and indisputable. The risk of postmenopausal breast cancer increases with obesity. Furthermore it is reported that obesity is associated with poorer prognosis of breast cancer.
 Objective
 To assess the relationship between obesity and postmenopausal breast cancer by examining the incidence, tumour size, pathological stage, axillary nodal involvement and survival in an Irish population.
 Design & Setting
 A retrospective case control study was undertaken in 200 patients presenting to a tertiary centre between 1998-2006. Data were compared to 519 healthy female controls. Multivariate logistic regression models were used to calculate the odds ratio (OR) of developing postmenopausal cancer according to body mass index (BMI), as well as the impact BMI has on tumour size, nodal involvement, pathological stage and survival. Actuarial survival was calculated from date of diagnosis by the Kaplein-Meier method and comparisons between the groups were made by the log rank test.
 Results
 Postmenopausal breast cancer patients were significantly heavier than age matched controls with 65% being overweight or obese versus 54% of controls (p=0.030). A dose dependent relationship existed between BMI and postmenopausal breast cancer incidence. The adjusted odds ratio was 2.2 (95%CI 1.3-3.7) for individuals in the highest BMI quartile compared to the lowest BMI quartile (P=0.002). Using common cut-offs for BMI, obese patients had double the risk of postmenopausal breast cancer compared to normal weight patients OR 2.04 (95%CI 1.3-3.3; p=0.004). There was no difference in symptomatic detection, assessment or treatment of breast cancer, however operative times were significantly longer for obese patients (P=0.05). Obesity was associated with larger tumours (P= 0.002) and a later stage of disease at presentation (P=0.026) but not with axillary nodal involvement (P=0.332). Median and overall survivals were equivalent (P=0.172) when comparing obese to non obese.
 Conclusion
 Obese women are twice as likely to get postmenopausal breast cancer compared to normal weight women. Understanding why obese women have a higher breast cancer incidence may lead to more effective breast cancer prevention and treatment interventions. Obesity is a preventable risk factor for breast cancer and given the high and increasing prevalence of obesity in Ireland, obesity needs to be addressed on a national level with targeted lifestyle treatment programs. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6089.

Transformation maligne postménopausique d’une endométriose extragénitale. À propos d’un cas

Malignant transformation of endometriosis is a rare event. The ovaries are the most common sites reported in the literature. Postmenopausal cancer arising in extragenital endometriosis is still more exceptional. Hormone replacement therapy and perhaps, to a lesser extent, Tamoxifen could be risk factors for the malignant transformation of endometriosis. We herein report the case of a patient who has developed, after 11 years of hormone replacement therapy, an extragenital endometrioid carcinoma in the vesico-uterine pouch.

Improving Libido in Postmenopausal Cancer Survivors

Sexual dysfunction is common among U.S. men and women, and it is especially prevalent among cancer survivors. In female cancer survivors, sexual

Prevention of osteoporosis by foods and dietary supplements. Soybean isoflavone and bone metabolism

Soybean isoflavones show structural similarity to estradiol and therefore are known as phytoestrogen. Recently, isoflavones have received a great deal of attention for their preventive roles against hormone dependent diseases including postmenopausal osteoporosis, hyperlipidemia and cancer. Particularly, a number of studies have reported that soybean isoflavones inhibited bone loss in both female and male osteoporotic animal models as well as in postmenopausal women. On the other hand, since a kind of tablet with concentrated isoflavones has been recently applied for foods for specified health use (FOSHU), which are functional foods permitted to label a health claim by the Ministry of Health, Labor and Welfare in Japan, Food Safety Commission submitted a report the upper limit of daily isoflavone aglycon intake from FOSHU as well as from soybean products. This report demonstrates the effects of isoflavones on bone metabolism and safety.

223-S: Use of Postmenopausal Hormones and Ovarian Cancer Risk

223-S: Use of Postmenopausal Hormones and Ovarian Cancer Risk

Estrogen receptor beta (ESR2 ) polymorphisms and endometrial cancer (United States).

We hypothesized that variations in the ESR2 gene may influence estrogen exposure in the uterus and thus influence endometrial cancer risk. We validated and screened for variants in the ESR2 gene and examined whether they are associated with endometrial cancer risk. We resequenced the promoter and coding regions of the ESR2 gene in 24 endometrial cancer cases, and genotyped the validated/discovered SNPs and intronic dinucleotide CA repeat in a nested case-control study of endometrial cancer (cases = 222, controls = 666) in the Nurses' Health Study (NHS). We also explored statistical interaction between ESR2 genotypes and body mass index (BMI) or hormone replacement therapy (HRT) use among postmenopausal women and cancer risk. Two SNPs were validated [rs1256049 in exon 5 (allelic frequencies = 98% G, 2% A) and rs1271572 in the promoter region (allelic frequencies = 60% G, 40% T)]. After adjusting for potential confounders, we observed no association between ESR2 gene polymorphisms and endometrial cancer risk [rs1256049 (OR = 1.2; 95%CI: 0.7-2.3), rs1271572 (OR = 0.8; 95%CI: 0.5-1.1) and CA repeat (22 repeat allele versus > or = 22 repeat allele, OR = 1.1; 95%CI: 0.7-1.7)]. We also did not observe any significant effect modification of the ESR2 polymorphisms by BMI or HRT use among postmenopausal women. Our results indicate that ESR2 polymorphisms may not be associated with endometrial cancer risk.

Postmenopausal cancer risk after self‐reported endometriosis diagnosis in the Iowa Women's Health Study

Endometriosis, the presence of endometrial tissue outside the uterus, has an estimated prevalence between 4% and 10%. A recent study reported that women with a hospital discharge diagnosis of endometriosis were at increased risk of cancer at any site, breast cancer, ovarian cancer, and hematopoietic malignancies, especially non-Hodgkin lymphoma (NHL). The authors examined whether self-reported diagnosis of endometriosis was associated with increased risk of various cancers in the Iowa Women's Health Study. Incident cancer cases were identified from 1986 through 1998. Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals for the particular cancers of interest. Of 37,434 participants in this analysis, 3.8% reported a history of endometriosis at baseline in 1986. After 13 years of follow-up, 1795 breast, 188 ovarian, and 243 NHL cases were detected in the cohort. Endometriosis was not associated with risk of all cancers combined (age-adjusted relative risk [RR], 0.9; 95% confidence interval [CI], 0.7-1.2), breast carcinoma (RR, 1.0; 95% CI, 0.8-1.3), or ovarian carcinoma (RR, 0.8; 95% CI, 0.2-2.4). However, endometriosis was significantly associated with risk of NHL (age-adjusted RR, 1.8; 95% CI, 1.0-3.0), especially diffuse NHL (RR, 3.2; 95% CI, 1.8-5.6). Multivariate adjustment had minimal effect on the point estimates of risk (NHL RR, 1.7; 95% CI, 0.97-2.7; diffuse NHL RR, 3.3; 95% CI, 1.9-5.9). Endometriosis was not associated with elevated risk of lung, urinary tract, endometrial, melanoma, or colorectal carcinomas (RRs, 1.2, 0.8, 1.2, 0.7, and 0.7, respectively). These results corroborate a previously reported association between endometriosis and increased risk of NHL but not cancer at other sites.

Aspirin, other NSAIDs, and ovarian cancer risk (United States).

We sought to evaluate the association between ovarian cancer risk and use of aspirin and nonsteroidal anti-inflammatories. We prospectively assessed use of aspirin, nonsteroidal anti-inflammatories (NSAIDs), and acetaminophen use in relation to ovarian cancer risk among 76,821 participants in the Nurses' Health Study who had no history of cancer other than non-melanoma skin cancer. Women reported known and suspected ovarian cancer risk factors in biennial mailed questionnaires from 1976 to 1996, along with new diagnoses of ovarian cancer. Aspirin use was assessed in 1980, 1982, 1984, and 1988-1994. We assessed NSAID use in 1980, and both NSAID and acetaminophen use in 1990, 1992, and 1994. During 16 years of follow-up and 1,222,412 person-years, 333 cases of invasive epithelial ovarian cancer were confirmed. We used pooled logistic regression to control for age, body mass index, oral contraceptive use, smoking history, parity, postmenopausal hormone use, tubal ligation, and other potential ovarian cancer risk factors. Aspirin use was not associated with ovarian cancer risk overall (RR for users compared with nonusers, 1.00, 95% confidence interval (CI 0.80-1.25). We found no association between aspirin dose (in number of weekly tablets) and ovarian cancer risk (RR for those taking 15 or more tablets weekly compared with nonusers, 0.98, 95% CI 0.63-1.52). Similarly, duration of aspirin use was not associated with risk (RR for aspirin use of 20 or more years, 0.99, 95% CI 0.69-1.43). In separate models assessing the relation between NSAID use and ovarian cancer risk we found a 40% reduction in risk among NSAID users versus nonusers (RR 0.60, 95% CI 0.38-0.95). However, when we examined this relationship in terms of days of NSAID use per month, we did not observe a dose-response with increasing NSAID use. We observed no association between aspirin use, dose, or duration and epithelial ovarian cancer risk. Although we found a modest reduction in risk associated with NSAID use, there was no dose-effect.

Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis

Abstract PURPOSE: Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States. Accumulating evidence indicates that postmenopausal hormone therapy may reduce the risk of colorectal cancer in women. METHODS: Through MEDLINE computer searches (January 1966 to September 1998) and a review of references, we identified English-language articles with quantitative data on the relation of postmenopausal hormone therapy to colorectal cancer. We reviewed the studies and made summary estimates of relative risks (RR) by weighting the results of each study in proportion to its precision, using a general variance-based, fixed-effects model. RESULTS: In our meta-analysis of 18 epidemiologic studies of postmenopausal hormone therapy and colorectal cancer, we found a 20% reduction [RR = 0.80, 95% confidence interval (CI), 0.74 to 0.86] in risk of colon cancer and a 19% decrease (RR = 0.81, 95% CI, 0.72 to 0.92) in the risk of rectal cancer for postmenopausal women who had ever taken hormone therapy compared with women who never used hormones. Much of the apparent reduction in colorectal cancer was limited to current hormone users (RR = 0.66, 95% CI, 0.59 to 0.74). CONCLUSION: Observational studies suggest a reduced risk of colorectal cancer among women taking postmenopausal hormones. There is biologic evidence to support this association.

Menstrual state should be considered in determining sero-positivity of soluble angiogenic factors in breast cancer.

We investigated whether blood angiogenic factor (vascular endothelial growth factor, VEGF; angiogenin; basic fibroblast growth factor, bFGF; platelet-derived growth factor-AB, PDGF-AB) levels change during menstrual cycle of healthy premenopausal females or after menopause. We also measured the serum angiogenic factor levels in 34 operable breast cancer patients and compared them to those of healthy volunteer controls. No differences in the four angiogenic factor levels were found between the follicular and luteal phases of normal menstruation. However, angiogenin and bFGF levels were higher in pre-menopausal females than post-menopausal female and young male healthy volunteers. In cancer patients, the sero-positivity rate of the bFGF was 8.8% with menstrual-state-unmatched cut-off points, which increased to 36.4% with menstrual-state-matched cut-off points. This discrepancy was especially high in post-menopausal cancer patients. In conclusion, physiological elevation of the bFGF during normal menstruation can influence the precise interpretation of the pathological elevation of the bFGF in pre-menopausal breast cancer patients.

Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer.

In human endometrium insulin-like growth factor binding protein (IGFBP)-1 inhibits the mitogenic action of insulin-like growth factor (IGF)-I by inhibiting the binding of IGF-I to its receptor. Our purpose was to compare circulating levels of IGF-I and IGFBP-1 in women with and without endometrial cancer. We assessed circulating levels of IGF-I and IGFBP-1 and IGFBP-3 in 23 patients with endometrial cancer, 11 patients with uterine cervical cancer and 27 healthy control women. The mean circulating level of IGF-I decreased significantly following menopause but was not correlated with age in the control group. The body mass index was significantly higher in the endometrial cancer group than in the control group. Analysis of covariance showed that even after the data were adjusted to eliminate the influence of the body mass index, the circulating IGF-I concentration was higher in postmenopausal endometrial cancer patients than in postmenopausal control subjects. The mean circulating level of IGFBP-1 was significantly lower in postmenopausal cancer patients than in postmenopausal control subjects. There were no significant differences in the serum levels of IGF-I and IGFBP-1 in the patients with cervical cancer and the control group. In conclusion, an increased circulating concentration of IGF-I and a decreased circulating concentration of IGFBP-1 are associated with endometrial cancer especially in postmenopausal women.