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.     

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.     

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)     

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.     

The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer

BACKGROUND: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. OBJECTIVE: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. DESIGN: Prospective cohort study. SETTING: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. PARTICIPANTS: Random sample of 41,837 female Iowa residents 55 to 69 years of age. MEASUREMENTS: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index. RESULTS: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10,000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10,000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10,000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10,000 person-years [CI, 69 to 92 deaths]). CONCLUSIONS: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.     

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.     

The role of reproductive factors and use of oral contraceptives in the aetiology of breast cancer in women aged 50 to 74 years

BACKGROUND: We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind, placebo-controlled, prospectively randomized 12-wk controlled trial at a university research center. OBJECTIVE: We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone. DESIGN: Eighty-three healthy subjects (46 men and 37 women aged 34-78 y) with hyperlipidemia [total cholesterol, 5.28-8.74 mmol/L (204-338 mg/dL); LDL cholesterol, 3.31-7.16 mmol/L (128-277 mg/dL); triacylglycerol, 0.62-2.78 mmol/L (55-246 mg/dL); and HDL cholesterol 0.78-2.46 mmol/L (30-95 mg/dL)] who were not being treated with lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat, and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9, 11, and 12. RESULTS: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [(x+/-SD) 6.57+/-0.93 mmol/L (254+/-36 mg/dL) to 5.38+/-0.80 mmol/L (208+/-31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. CONCLUSIONS: Red yeast rice significantly reduces total cholesterol, LDL cholesterol, and total triacylglycerol concentrations compared with placebo and provides a new, novel, food-based approach to lowering cholesterol in the general population.     

Physical fitness of Danish men and women aged 50 to 80 years

Maximal power in sustained work in originally randomly selected men and women, born in 1914, was studied five times between the ages of 50 and 80 years in a longitudinal design. Of the originally 514 men and 461 women in 1964 living in the Western suburbs of Copenhagen, 23 men and 18 women performed a bicycle test at age 50, 60, 70, 75 and 80. The mean annual decline in body mass adjusted maximal power in sustained work (W/kg) was 1.43% in the 18 men and 1.64% in the 23 women. Based on "cross-sectional" comparisons of all subjects tested at any age, the mean annual decline in men was 1.56%; in women the corresponding figure was 1.80%. When the results of the "longitudinal" and "cross-sectional" analyses were compared with each other, a rather similar picture of the age-related decline in maximal power was obtained, especially in women. In the longitudinal data only moderate (women) or zero (men) correlations were observed between the submaximal test results at the ages of 50 and 60 years and the maximal test results at higher ages. The physical work load at the age of 50 years had no significant correlation with maximal power at that age or thereafter. There were only minor changes in mean body height, body mass and BMI during the follow-up.     

Plasma prolactin levels in women at postmenopausal age with a family history of breast cancer or a prescription for antihypertensive Rauwolfia treatment

An investigation was made of daytime plasma prolactin levels in three groups of women aged 50 to 64 years: (1) 139 women with a family history of breast cancer; (2) 50 women on Rauwolfia treatment for hypertension, and (3) 90 women of a control group. A significant difference in prolactin levels was found between groups 2 and 3 but not between 1 and 3. These findings are considered in relation to the results of a breast cancer screening programme in which the women took part. Here, it was the women with a family history of breast cancer who showed an increased breast cancer risk, whereas the risk in women on Rauwolfia was not significantly higher than expected on the basis of the experience among controls. It is concluded that the role of prolactin in the etiology of breast cancer is still not clear.     

Vaginal cancer in a woman with a family history of ovarian cancer

The proband was referred to familial ovarian cancer surveillance because two of her sisters died of carcinoma of the ovary. Her third sister succumbed of cervical cancer and her brother had acute myeloblastic leukaemia. Her second brother is alive and healthy. None of her parents and their sibs suffered of malignant disease. The offspring of the proband's sibs are young and appear to be normal. During surveillance she developed a stage I vaginal cancer. Following preoperative brachytherapy she underwent a radical hysterectomy and bilateral salpingoophorectomy with pelvic lymphadenectomy, and she is free of disease during 2 years of follow-up. The authors are not aware of any similar case.     

Total hip arthroplasty performed without cement in patients with femoral head osteonecrosis who are less than 50 years old

Seventy-two cementless total hip arthroplasties were performed by a single surgeon in 58 patients with the diagnosis of femoral head osteonecrosis. All patients were less than 50 years old (mean, 37 years). The mean follow-up was 84 months with a minimum of 48 months. Good-to-excellent results were maintained at final follow-up in 94% of the hips. Revision rate was 1.5% each for the cups and the stems. Mechanical failure rate was 7.6% for the cups, and 6% for the stems. If the results were analyzed excluding the data from the group of patients who received the Mittelmeier prostheses, the mechanical failure rates for the cups was 0% and for the stems was 4.2%. The probability of survival for the entire series using revision as the endpoint was 96.9% at 11 years. Survival probability decreased to 88.5% if radiographic failures were included. Excluding the Mittelmeier prostheses, survival probability was estimated to be 100% for the cups using both revision and radiographic failures as endpoints; for the stems, the survival probability was 98.0% using revision as the endpoint and 95.8% including radiographic failures. Femoral osteolysis was observed in 1.5% of the hips. No hip had acetabular osteolysis. No measurements of polyethylene wear were attempted in this study. These results appeared superior to total hip arthroplasties done with early cementing techniques in this population of young patients with femoral head osteonecrosis.     

Surgical treatment of primary lung cancer in patients less than 40 years of age

PURPOSE AND METHODS: The major purpose of this study was to determine whether the survival rate in young lung cancer patients after surgical treatment differs from that in older patients. An analysis was performed for all patients with bronchogenic carcinoma who underwent surgery at Mie University Hospital from 1965 to 1990. RESULTS: Of 803 patients, 24 (2.99%) were 33 to 39 years old. At the time of surgery, the disease was diagnosed as stage I in seven patients (29%), stage II in four (17%), stage IIIa in seven (29%), stage IIIb in two (8%), and stage IV in four (17%), while 46.3% of the patients older than 40 years of age had either stage IIIa, IIIb, or IV disease. All of the 24 patients less than 40 years of age underwent thoracotomy: curative resection in 14 cases, palliative resection in sex, and probe-thoracotomy in four. The 5-year survival rate for all stages of disease was 31.4% in these 24 patients, and 41.9% in 603 patients greater than 40 years of age. The 5-year survival rate for stage I disease was 35.7% in the seven younger patients and 78.0% in the 207 older patients; for stage II, it was 25.5% in the four younger patients and 40.6% in the 98 older patients; for stage III, it was 33.3% in the nine younger patients and 15.6% in the 250 older patients; and for stage IV, it was 25% in the four younger patients and 6.6% in the 48 older patients. There were no significant differences in survival rate between the two age groups for all patients or for those with each stage of disease. CONCLUSION: Although younger patients tended to have more advanced disease, long-term survival in these patients did not differ from that of older patients.     

Characteristics of women with a family history of ovarian cancer. I. Galactose consumption and metabolism

BACKGROUND: Galactose metabolism may be a risk factor for ovarian cancer based upon evidence that galactose causes ovarian failure and that ovarian cancer arises from premature ovarian failure. This study examines galactose-1-phosphate uridyl transferase (GALT) activity in women with a family history of ovarian cancer (FOC) to determine if low GALT activity occurs in women who are at risk for but in whom ovarian cancer has not yet developed. METHODS: The authors studied 106 premenopausal women (FOC patients) with one primary or two second-degree relatives with ovarian cancer compared with 116 age matched control subjects without a family history of ovarian cancer (FOC controls). All women completed questionnaires and had blood drawn to measure GALT activity and genotype. RESULTS: Mean erythrocyte GALT activity, in micromoles of hexose conversion per hour per gram of hemoglobin was 21.5 in FOC patients, significantly lower than the mean of 23.1 observed in FOC control subjects, (P = 0.001). FOC patients more frequently displayed the Duarte variant of galactosemia as detected by electrophoresis. In a subset of 87 patients and 113 control subjects for whom DNA was available, the allelelic frequency of the Duarte variant based upon molecular genetic detection of the N314D mutation that is associated with the Duarte variant was 15.5% among FOC cases compared with 7.5% among control subjects (P < 0.02). Galactose consumption did not differ between FOC patients and control subjects. CONCLUSION: Galactose metabolism differs between women with and without a family history of ovarian cancer, suggesting that it may be a genetic risk factor for ovarian cancer, possibly mediated through oocyte toxicity from galactose.     

The evaluation of breast masses in women younger than forty years of age

BACKGROUND: Breast masses in young women are common, but carcinoma is rare. This study was undertaken to determine how often a complaint of mass was found to represent a dominant mass and to define the role of breast imaging and fine-needle aspiration cytology (FNA) in the evaluation of clinically nonworrisome masses. METHODS: A retrospective review was made of 605 patients younger than 40 years of age with a breast mass between February 1994 and February 1996. RESULTS: Dominant masses were confirmed by surgeon examination in 36% of 484 self-detected masses compared with 29% of physician-detected masses (difference not significant). With pathologic confirmation, 29% of self-detected masses had a dominant mass compared with 19% of physician-detected masses (P = .02). Carcinoma was present in 5% of both groups and not predicted by family history. Imaging studies were not useful in patients with normal examinations but were more likely to identify dominant masses in patients with an examination described as benign (P < .001). FNA did not identify any cancers in normal or benign examinations. CONCLUSIONS: Self-examination is as reliable as a general physician examination in detecting breast masses. When an examination by an experienced surgeon is normal, imaging studies and FNA are low yield. When the examination is equivocal, directed ultrasonography is a useful adjunct.     

The benefits of mammography are not limited to women of ages older than 50 years

BACKGROUND: Although the benefits of mammography are established in women age < or = 50 years, its use in women age < 50 years is controversial. It is the purpose of this study to determine whether the better outcome in mammographically detected breast carcinoma compared with clinically detected breast carcinoma observed in women age > or = 50 years also is observed in women age < 50 years. METHODS: The authors analyzed 869 cases of Stage I and II breast carcinoma in women treated with breast-conserving therapy between 1984-1994. The median follow-up was 43 months (range, 3-128 months). Three hundred and eighteen patients (37%) presented with mammographic abnormalities without clinical signs of disease and 551 patients (63%) presented with clinical signs of disease. The median age of the patients was 56 years (range, 22-88 years). Three hundred and four patients (35%) were age < 50 years. RESULTS: Mammographically detected tumors in women age < 50 years were of similar size to those in women age > or = 50 years (median 1.1 cm vs. 1.0 cm). Axillary lymph node involvement and tumor grade were not significantly different between these two groups. However, in women age < 50 years the clinically detected tumors were found to be significantly larger, more likely to be axillary lymph node positive, and of higher grade compared with tumors in older women. Consequently, in patients with mammographically detected tumors, there was no significant difference in recurrence free survival (RFS) between women age < 50 years compared with women age > or = 50 years (90% and 92%, respectively; P=0.4), whereas in patients with clinically detected tumors there was a significant difference in 5-year RFS (77% vs. 87%, respectively; P=0.02). CONCLUSIONS: Mammography results in the diagnosis of smaller and lower grade breast carcinoma. If mammographically detected, there appears to be no difference in RFS between women age < 50 years and those women age > or = 50 but there is a difference if the tumors are clinically detected. If left to grow to the size necessary for clinical detectability, the disease appears to be more aggressive in younger women.     

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.     

Reduced breast cancer mortality in women under age 50: updated results from the Malm? Mammographic Screening Program

This article provides additional follow-up data of two cohorts from the Malm? Mammographic Screening Trial (MMST). The first cohort, MMST I, contained 7,984 women under age 50 at entry into MMST who were born between 1927 and 1932. Half were assigned to a control group and were not invited for examination until four years after the code was broken in the MMST in 1988. The second cohort, MMST II, contained 17,786 women born between 1933 and 1945. Fifty four percent of these women were randomly invited to screening between 1978 and 1990. The remaining 46%--the control group--was invited to screening between 1991 and 1994. Nine screening rounds were completed in MMST I, and a mean of five rounds were completed in MMST II; the screening interval ranged from 18 to 24 months. The effect of screening on breast cancer mortality was assessed by pooling the two cohorts. At the end of follow-up--December 1993 for MMST I and December 1995 for MMST II--there was a statistically significant 36% reduction in breast cancer mortality in the intervention groups (relative risk = 0.64; 95% CI: 0.45-0.89; P = 0.009). A harm-benefit analysis showed, however, that for every two breast cancer deaths prevented, one clinically insignificant cancer was diagnosed; for each breast cancer death prevented, 63 cancer-free women had been called back for further examinations; and for every 20 lives saved, one radiation-induced breast cancer death may have occurred. Recommendations for screening must therefore weigh mortality benefits against these negative effects.     

Abnormal tryptophan metabolism in a family with a history of bladder cancer

Tryptophan metabolism was studied in a family in which a sister and brother had bladder cancer. Urinary tryptophan metabolites after administration of 2 g L-tryptophan were measured in 4 sisters and 1 brother, all free of disease when studied. One sister with and 2 without histories of bladder cancer had significantly elevated levels of kynurenine, acetylkynurenine, and 3-hydroxykynurenine. Administration of 100 mg pyridoxine hydrochloride returned the tryptophan metabolism to normal in these 3 individuals. One brother with a 1 sister without bladder cancer had normal metabolism. A repeat study 2 years later confirmed the abnormal metabolism in the 3 sisters. Two sisters with abnormal tryptophan metabolism were given 200 mg L-kynurenine sulfate orally to bypass the effects of tryptophan oxygenase activity. Both excreted elevated levels of kynurenine and 1 excreted elevated levels of 3-hydroxykynurenine.