Risk factors for breast cancer in women with a breast cancer family history

For the study of the relationship of the pelviureteric system of one kidney to that of the contralateral one, bilateral cutaneous ureterostomy was performed in 14 dogs. The renal pelvis (RP) and ureter (U) of one side were distended separately with a balloon filled with saline in increments of 1 and 0.25 ml, respectively, and the pressure response of the contralateral RP and U was recorded. The test was repeated after anesthetization of the RP and U. RP distension with 1 ml of saline effected a pressure rise (P < 0.05) in the ipsilateral RP but no pressure response in the ipsilateral U or the contralateral RP or U (P > 0.05). RP distension with 2, 3, and 4 ml of saline induced a significant pressure rise in the ipsi- and contralateral RP but not in the ureters. Ureteric distension produced a pressure elevation (P < 0.05) on the ipsilateral U but had no effect on the contralateral U (P > 0.05) or on either of the renal pelves (P > 0.05). Distension of the anesthetized RP or U effected no pressure response in any of the ipsi- or contralateral RPs or Us. In conclusion, distension of the RP with large volumes led to an increase in pressure in the contralateral RP but not in the U. A reflex relationship is postulated to exist between the two renal pelves and to be mediated through a reflex we call the reno-renal pelvic reflex. It seems that this reflex acts to allow either of the kidneys to share an extra load of the other one by increasing the contractile activity of the RP, thus assumedly assisting the regulation of urine flow.     

Low biologic aggressiveness in breast cancer in women using hormone replacement therapy

In a multicenter study the metabolic effects of 5 yr of GH therapy in children with idiopathic short stature were evaluated. Patients received 0.3 mg/kg.week recombinant human GH. Of the 121 patients who entered the study, data for 62 were analyzed at the final 5 yr point. Routine laboratory determinations were available for all 62 subjects at the 5 yr point. Special laboratory determinations, such as postprandial glucose and insulin, were available for only a subset of patients. Mean insulin-like growth factor I levels rose to 283 +/- 101 micrograms/L, within the normal range using age-appropriate reference standards. T4, cholesterol, triglycerides, blood chemistries, and blood pressure showed no significant changes during the 5-yr period. Mean baseline and 2-h postprandial glucose levels remained unchanged. Both fasting and postprandial insulin levels rose substantively from low normal levels to the normal range (median, 4.9-43 mU/L). Mean hemoglobin A1c levels remained within the normal range throughout the study. In summary, careful monitoring has not revealed any currently discernible metabolic side-effects of clinical significance after GH therapy in this 5-yr study of children with idiopathic short stature.     

Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer

BACKGROUND: Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete. METHODS: We conducted a retrospective study of all women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. The women were divided into two groups - high risk and moderate risk - on the basis of family history. A control study of the sisters of the high-risk probands and the Gail model were used to predict the number of breast cancers expected in these two groups in the absence of prophylactic mastectomy. RESULTS: We identified 639 women with a family history of breast cancer who had undergone bilateral prophylactic mastectomy: 214 at high risk and 425 at moderate risk. The median length of follow-up was 14 years. The median age at prophylactic mastectomy was 42 years. According to the Gall model, 37.4 breast cancers were expected in the moderate-risk group; 4 breast cancers occurred (reduction in risk, 89.5 percent; P<0.001). We compared the numbers of breast cancers among the 214 high-risk probands with the numbers among their 403 sisters who had not undergone prophylactic mastectomy. Of these sisters, 38.7 percent (156) had been given a diagnosis of breast cancer (115 cases were diagnosed before the respective proband's prophylactic mastectomy, 38 were diagnosed afterward, and the time of the diagnosis was unknown in 3 cases). By contrast, breast cancer was diagnosed in 1.4 percent (3 of 214) of the probands. Thus, prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90 percent. CONCLUSIONS: In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer.     

Hormonal replacement therapy in menopause and the risk of breast cancer

We report three patients with severe pontocerebellar atrophy (PCA) associated with a variable degree of cerebral atrophy. The clinical features consisted of progressive microcephaly, central hypotonia, visual impairment, abnormal eye movements and delayed psychomotor development. These are similar but not identical to the features of pontocerebellar hypoplasia type 2 described by Barth. The picture also differs from the classical form of autosomal dominant olivopontocerebellar atrophy. While in two patients the disease seemed to be genetic with highly suspicious autosomal recessive inheritance, the etiology in the third patient was probably nongenetic. We suggest that PCA is a morphologic entity with distinct radiologic features but variable clinical, pathophysiologic and etiologic backgrounds.     

Screening women aged less than 50 years with a family history of breast cancer

Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.     

Breast cancer and family history: a multivariate analysis of levels of tumor HER2 protein and family history of cancer in women who have breast cancer

BACKGROUND: The HER2 gene, located on the long arm of chromosome 17, codes for a protein with the characteristics of a growth factor receptor. In a preliminary study, we reported that high levels of tumor HER2 (erbB-2/neu) protein are associated with a family history of breast cancer (that is, one or more female blood relatives with breast cancer). METHODS: We have now collected a larger number of subjects (94) and performed a multivariate analysis of the independent variables family history of breast cancer, tumor estrogen receptor, age, and tumor DNA index. Family history of breast cancer was assessed by questioning the patient, in many cases by telephone. RESULTS: HER2 levels were significantly higher in women with a family history of breast cancer (p = 0.015, two-tailed t-test). The 27 women with family history were predominantly postmenopausal, mean age 61 +/- 2.3 (mean +/- SEM), versus a mean age of 56 +/- 1.7 for the 67 women with no family history. Of the 27 women with a family history of breast cancer, 13 had a first-degree relative (mother or sister) with the disease. The remaining 14 women had other relatives (grandmothers, aunts, cousins, or a niece) with breast cancer. The results of multiple linear regression analysis, with HER2 as the dependent variable, showed that family history of breast cancer was significantly associated with elevated HER2 levels in the tumors (p = 0.0038), after controlling for the effects of age, tumor estrogen receptor, and DNA index. CONCLUSIONS: The association of family history of breast cancer and elevated tumor HER2 protein suggests that postmenopausal familial breast cancer may be associated with altered HER2 expression.     

Development of endometrial cancer in women on estrogen and progestin hormone replacement therapy

The presenting symptoms, hormonal regimens, treatment modalities, tumor pathology, and follow-up of 25 women developing endometrial cancer while receiving postmenopausal estrogen and progestin therapy were investigated retrospectively. Patients were interviewed and hormone therapies were confirmed through medical records. Pathology specimens were reviewed. Patients received conjugated estrogens (n = 20) or another estrogen (n = 5). For those on conjugated estrogens, the mean daily dose was 0.68 mg, monthly duration was 24.9 days, and monthly dose was 17.0 mg. Women also received medroxyprogesterone acetate (n = 23) or norethindrone acetate (n = 2). The most common regimen was sequential medroxyprogesterone acetate, at a mean daily dose of 7.5 mg, monthly duration of 9.3 days, and monthly dose of 68 mg (mean duration = 5.7 years). Most tumors were low stage and grade, with few demonstrating grade 3 disease (n = 2) or greater than 50% myometrial invasion (n = 2). Twenty-three (92%) had disease limited to the uterus, while two had stage IIIA disease. All are alive and disease-free after a median follow-up of 26 months. Estrogen and progestin therapy does not prevent endometrial cancer in all patients. Women who developed this tumor on sequential therapy in general received less than the recommended guidelines for daily dosage and monthly duration of progestin. Most patients had early-stage and low-grade disease. Continued vigilance in the care of women on hormone replacement therapy is necessary even when combination therapy is prescribed.     

Re-framing the representation of women in advertisements for hormone replacement therapy

This review focuses on new developments in the pathophysiology and treatment of von Willebrand disease (vWd). New aspects of the cell biology, gene control, and structure-function correlates of von Willebrand factor (vWf) are reviewed. vWd is more prevalent than previously recognized, affecting up to 1% of the population; this is particularly evident in women's health. Blood group is an important determinant of von Willebrand factor levels; individuals of blood group O tend to have lower plasma levels of vWf than those in other blood groups. Currently available blood tests of vWf quantity and function are discussed, in addition to newer tests undergoing validation. Treatment of classical vWd with desmopressin acetate and plasma derivatives is discussed, as is the potential for intravenous immunoglobulin and corticosteroids in acquired vWd. Special situations, such as the management of vWd in pregnancy, are also discussed.     

Estrogen replacement in women treated for breast cancer

Oestrogen replacement therapy in women with a history of breast cancer has long been considered contraindicated. However, the literature does not indicate an increased risk of recurrent breast cancer in postmenopausal women receiving oestrogen replacement therapy. We advocate that women with a history of breast cancer without nodal involvement could be offered oestrogen replacement therapy and thereby benefit from prevention of cardiovascular disease and osteoporosis. But the patients must accept a potentially increased risk of recurrence. We emphasize the need for randomized prospective studies.     

Distress, personality, and mammography utilization among women with a family history of breast cancer.

The authors examined the impact of psychological distress and the personality construct of conscientiousness (as measured by the Neuroticism, Extraversion, and Openness—Five Factor Inventory) on mammography utilization among women who were at increased risk for breast cancer. Participants were 200 women who had at least 1 first degree relative with breast cancer. Overall, 80% of the participants had obtained a mammogram in the previous year. Analyses controlling for potential confounders (perceived risk, decisional balance, and physician recommendation for mammography), revealed that distress was negatively associated with mammography utilization among participants who were low in conscientiousness. Distress was not significantly related to mammography utilization among highly conscientious women. The results are discussed in terms of their implications regarding interventions designed to increase mammography utilization in this population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of family history on the risk of breast cancer among the Japanese

OBJECTIVE: The serum concentration of the high-affinity growth hormone-binding protein (GHBP) is increased in obesity but the mechanisms are poorly understood. This study assessed the physiological mechanisms involved in the regulation of GHBP in adiposity. SUBJECTS AND MEASUREMENTS: We tested a number of obesity specific parameters for their association with GHBP. In this study, 199 normal or overweight children and adolescents (101 boys, 98 girls, aged (mean +/- s.d.): 13.7 +/- 2.3 y) underwent an anthropometric evaluation (circumference measurements and bioimpedance analysis) combined with blood withdrawal for the measurement of insulin-like growth factor-I (IGF-I), insulin, leptin and GHBP (by specific RIA), uric acid, triglycerides and cholesterol. RESULTS: By linear regression analysis GHBP correlated significantly (P < 0.001) with percent body fat mass (r = 0.71), waist (r = 0.73) and hip (r = 0.69) circumference, weight (r = 0.61) waist hip ratio (WHR) (r = 0.54), as well as with the serum concentrations of leptin (r = 0.64), uric acid (r = 0.54), insulin (r = 0.45), LDL-cholesterol (r = 0.43), cholesterol (r =0.33), LDL/HDL ratio (r = 0.47), triglycerides (r = 0.30) and with height standard deviations scores (SDS) (r = 0.23). Age, gender and pubertal stage had no impact on GHBP. In a multiple regression analysis containing age and gender, as well as the anthropometric variables, percent fat mass and waist circumference, as independent variables, associations between GHBP and leptin (P < 0.001), cholesterol (P < 0.01), LDL-cholesterol (P = 0.01), LDL/HDL ratio (P = 0.02), triglycerides (P = 0.01) remained significant. In a final model using the stepwise analysis involving age, gender and all the independent predictors of GHBP, waist circumference (P < 0.001), accounted for 49.5% of the 60.0% total variability in GHBP, while the implication of leptin (P < 0.001), age (P < 0.01) and cholesterol (P < 0.05) increased the predicted variability for 7.5%, 1.9%, and 1.0%, respectively. Serum GHBP was significantly reduced in a subgroup of 104 overweight or obese patients during a diet-induced weight loss programme, the coefficient of correlation between GHBP and leptin after (r = 0.45, P < 0.001) and before weight reduction (r = 0.41, P < 0.001) were comparable. CONCLUSION: Waist circumference, an indicator of abdominal body fat mass, is a major determinant of GHBP levels during childhood, while leptin may be one candidate for a signal linking adipocytes to the growth hormone receptor related GHBP release. Additionally, elevated serum levels of GHBP may reflect metabolic disturbances of adiposity.     

A review on family history of breast cancer: screening and counseling proposals for women with familial (non-hereditary) breast cancer

In a neural model of olfactory bulb processing, we demonstrate the putative role of the modulation of two types of inhibition, inspired by electrophysiological data on the effect of acetylcholine and noradrenaline on olfactory bulb synaptic transmission. Feedback regulation of modulation based on bulbar activity serves to 'normalize' the activity of output neurons in response to different levels of input activities. This mechanism also decreases the overlap between pairs of output patterns (Mitral cell activities), enhancing the discrimination between overlapping olfactory input patterns. The effect of the modulation at the two levels of interneurons is complementary: while an increase in periglomerular inhibition decreases the number of responding output neurons, a decrease in granule cell inhibition increases the firing frequencies of these neurons.     

Physiologic effects of steroid hormones and postmenopausal hormone replacement on the female breast and breast cancer risk

Most data demonstrate that breast cancer is hormonally influenced. For the woman with no history of breast cancer, the benefits of HRT may outweigh the risks. Although it remains the standard of care to discourage hormone use in patients who have had breast cancer, future studies may result in a change of this standard. There needs to be more research into these complex hormonal interactions so that we will have a better understanding of the true risks and benefits when we attempt to advise our patients regarding the best treatment regimens for them.     

Is there an association between hormone replacement therapy and breast cancer?

The fear of breast cancer has been suggested as a potential reason why only a relatively small percentage of postmenopausal women who would benefit from hormone replacement therapy (HRT) are current users. The equivocal results from a large number of epidemiologic studies make it difficult to evaluate whether an association does indeed exist between the use of HRT and the incidence of breast cancer. The inability to provide conclusive evidence for or against this relationship may be attributed to methodologic problems in these studies, including small sample sizes, lack of information on specific hormonal preparations (e.g., dose and type), failure to control for the type of menopause, and surveillance bias. In an attempt to generalize results from different studies in a systematic manner, several meta-analyses have been conducted of the effects of estrogen replacement therapy (ERT) or HRT on the risk of breast cancer. This article summarizes the data from these meta-analyses and incorporates data from studies published after these meta-analyses that have addressed this question. Data from ongoing studies that use a randomized, controlled, longitudinal design on large numbers of women are necessary before a possible association between the use of HRT and breast cancer can be ascertained.     

Hormone replacement therapy in women with breast cancer. Do the risks outweigh the benefits?

PURPOSE: To review critically the literature regarding effects of estrogen replacement therapy (ERT)/combined estrogen and progesterone replacement therapy (HRT) on the risk of breast cancer and on other health risks and benefits in postmenopausal women, with a focus on risks and benefits in women with a previous diagnosis of breast cancer. METHOD: A literature search was conducted using Medline, Cancerline, and the bibliographies of reports published as of March 1995. All five published meta-analyses that examined the risk of breast cancer in relation to ERT/HRT in otherwise healthy women were critically reviewed. All known reports of women with a history of breast cancer given ERT/HRT subsequent to diagnosis and additional reports regarding the benefits of ERT/HRT were also reviewed. RESULTS: None of the five meta-analyses demonstrated a significantly increased risk of developing breast cancer in ever users compared with never users of ERT/HRT. Current use may be associated with a small increased risk. This increased risk should be balanced by the expected benefits of ERT/HRT on quality of life, bone metabolism, and cardiovascular function. Preliminary information does not suggest a major detrimental effect of ERT/HRT in women with a previous diagnosis of breast cancer, but these reports include few women with limited follow-up data. There are no randomized trials in women with a previous diagnosis of breast cancer. CONCLUSION: In healthy postmenopausal women, the benefits associated with ERT/HRT outweigh the risks. In women with a previous diagnosis of breast cancer, the balance of risks and benefits should be explored in randomized controlled trials.     

Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women

BACKGROUND: A positive relationship has generally been observed between plasma estrogen levels and breast cancer risk in postmenopausal women, but most of these studies have been small and few have evaluated specific estrogen fractions (such as percent bioavailable estradiol). In addition, few studies have evaluated plasma androgen levels in relation to breast cancer risk, and their results have been inconsistent. We prospectively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses' Health Study. METHODS: Blood samples were collected during the period from 1989 through 1990. Among postmenopausal women not using hormone replacement therapy at blood collection (n = 11,169 women), 156 women were diagnosed with breast cancer after blood collection but before June 1, 1994. Two control subjects were selected per case subject and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at the time of blood collection. RESULTS: From comparisons of highest and lowest (reference) quartiles, we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol (multivariate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06-3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05-3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23-4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11-4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy. CONCLUSION: Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer.