Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Sources of elevated serum androgens in postmenopausal women who develop breast cancer.

Postmenopausal women with elevated serum androgens are at an increased risk of breast cancer. High dehydroepiandrosterone sulfate concentrations in these women suggest increased adrenal secretion. Both the adrenals and ovaries could contribute to elevated concentrations of androstenedione (Delta4A). 11beta-Hydroxyandrostenedione (11betaOHA) is elevated, and the Delta4A:11betaOHA ratio is depressed when the adrenals are the primary source of elevated Delta4A in women. Conversely, Delta4A:11betaOHA is elevated when the ovaries are the primary source. We prospectively evaluated associations of serum 11betaOHA and Delta4A:11betaOHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of elevated Delta4A related to risk. Fifty-three postmenopausal women who were not taking estrogens when they donated blood and were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served as cases. Two controls, who were also postmenopausal and not taking estrogens, were matched to each case on age, date, and time of blood collection. Serum Delta4A concentration was significantly (trend P = 0.02) positively associated with breast cancer risk. Adjusted risk ratios for women in the lowest to highest tertiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9-6.5]. However, neither 11betaOHA concentration nor Delta4A:11betaOHA was related to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5-3.6) for 11betaOHA and 1.0, 1.2, and 1.2 (95% CI, 0.4-3.5) for Delta4A:11betaOHA. Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum Delta4A in postmenopausal women who develop breast cancer, but rather both may contribute.

Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA).

OBJECTIVE: To prospectively evaluate relationships of organochlorine pesticides and polychlorinated biphenyls (PCBs) with breast cancer, we conducted a case-control study nested in a cohort using the Columbia, Missouri Breast Cancer Serum Bank. METHODS: Women donated blood in 1977-87, and during up to 9.5 years follow-up, 105 donors who met the inclusion criteria for the current study were diagnosed with breast cancer. For each case, two controls matched on age and date of blood collection were selected. Five DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] analogs, 13 other organochlorine pesticides, and 27 PCBs were measured in serum. RESULTS: Women in the upper three quartiles of hexachlorobenzene were at twice the risk of breast cancer compared to those in the lowest quartile. However, there was no evidence for a dose-response relationship, and the association was limited to women whose blood was collected close to the time of diagnosis. Women with higher serum levels of other organochlorine pesticides and PCBs showed no increased risk of breast cancer overall, although positive associations were suggested for PCB-118 and PCB-138 when blood was collected close to the time of diagnosis. CONCLUSIONS: Results of this study do not support a role for organochlorine pesticides and PCBs in breast cancer etiology.

Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)

To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.

Future directions for resuscitation research. V. Ultra-advanced life support.

Standard external cardiopulmonary resuscitation (SECPR) frequently produces very low perfusion pressures, which are inadequate to achieve restoration of spontaneous circulation (ROSC) and intact survival, particularly when the heart is diseased. Ultra-advanced life support (UALS) techniques may allow support of vital organ systems until either the heart recovers or cardiac repair or replacement is performed. Closed-chest emergency cardiopulmonary bypass (CPB) provides control of blood flow, pressure, composition and temperature, but has so far been applied relatively late. This additional low-flow time may preclude conscious survival. An easy, quick method for vessel access and a small preprimed system that could be taken into the field are needed. Open-chest CPR (OCCPR) is physiologically superior to SECPR, but has also been initiated too late in prior studies. Its application in the field has recently proven feasible. Variations of OCCPR, which deserve clinical trials inside and outside hospitals, include 'minimally invasive direct cardiac massage' (MIDCM), using a pocket-size plunger-like device inserted via a small incision and 'direct mechanical ventricular actuation' (DMVA), using a machine that pneumatically drives a cup placed around the heart. Other novel UALS approaches for further research include the use of an aortic balloon catheter to improve coronary and cerebral blood flow during SECPR, aortic flush techniques and a double-balloon aortic catheter that could allow separate perfusion (and cooling) of the heart, brain and viscera for optimal resuscitation of each. Decision-making, initiation of UALS methods and diagnostic evaluations must be rapid to maximize the potential for ROSC and facilitate decision-making regarding long-term circulatory support versus withdrawal of life support for hopeless cases. Research and development of UALS techniques needs to be coordinated with cerebral resuscitation research.

Serum sex hormone levels are related to breast cancer risk in postmenopausal women.

We conducted a nested case-control study to prospectively evaluate the relationship of serum estrogens and androgens to risk of breast cancer in postmenopausal women. From 1977 to 1987, 3375 postmenopausal women free of cancer and not taking replacement estrogens donated blood to the Breast Cancer Serum Bank in Columbia, Missouri. Of these, 72 were subsequently diagnosed with breast cancer. For each case, two controls matched on age and date and time of day of blood collection were selected using incidence density matching. The median age of subjects at blood collection was 62 years; the time from blood collection to diagnosis ranged from less than 1 to 9.5 years with a median of 2.9 years. Risk of breast cancer was positively and significantly associated with serum levels of estrogens and androgens. Compared to women in the lowest quartile, those in the highest quartile for non-sex hormone-binding globulin (non-SHBG) bound (bioavailable) estradiol had a relative risk of 5.2 (95% confidence interval [CI] = 1.5-18.5) and those in the highest quartile for testosterone had a relative risk of 6.2 (95% CI = 2.0-19.0). Our results lend considerable support to the hypothesis that serum concentrations of estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women.

Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5-androstene-3 beta, 17 beta-diol to risk of breast cancer in postmenopausal women.

Laboratory evidence suggests a role for dehydroepiandrosterone (DHEA) and its metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) in mammary tumor growth. Serum DHEA also has been related to breast cancer in postmenopausal women, but the relationship of ADIOL to risk has not been evaluated previously. To assess the relationship of serum DHEA, its sulfate (DHEAS), and ADIOL with breast cancer risk in postmenopausal women, we conducted a prospective nested case-control study using serum from the Columbia, MO Breast Cancer Serum Bank. Cases included 71 healthy postmenopausal volunteers not taking replacement estrogens when they donated blood and who were diagnosed with breast cancer up to 10 years later (median, 2.9 years). Two randomly selected controls, who also were postmenopausal and not taking estrogens, were matched to each case on exact age, date (+/-1 year), and time (+/-2 h) of blood collection. Significant (trend P = 0.02) gradients of increasing risk of breast cancer were observed for increasing concentrations of DHEA and ADIOL, and women whose serum levels of these hormones were in the highest quartiles were at a significantly elevated risk compared to those in the lowest; their risk ratios were 4.0 [95% confidence interval (CI), 1.3-11.8) and 3.0 (95% CI, 1.0-8.6), respectively. The relationship of DHEAS to breast cancer was less consistent, but women whose serum DHEAS concentration was in the highest quartile also exhibited a significantly elevated risk ratio of 2.8 (95% CI, 1.1-7.4). Results of this prospective study support a role for the adrenal androgens, DHEA, DHEAS, and ADIOL, in the etiology of breast cancer.

Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk.

To evaluate the relation of serum sex hormones to breast cancer risk, we conducted a prospective nested case-control study using the Breast Cancer Serum Bank (Columbia, MO). This bank included serum from 3375 postmenopausal women free of cancer and not taking replacement estrogens when they donated blood between 1977 and 1987. Of these, 71 were diagnosed subsequently with breast cancer. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched to the case on age and on date and time of day of blood collection were selected as controls. The median age of subjects at blood collection was 62 years, and the time from blood collection to diagnosis ranged from less than 1 to 9.5 years, with a median of 2.9 years. Postmenopausal women with elevated serum levels of total and non-sex hormone-binding globulin-bound E2 were at an increased risk of developing breast cancer. For non-sex hormone-binding globulin-bound E2, risks were elevated 4-5 fold for women in the upper three quartiles relative to those in the lowest quartile. Although breast cancer was not related to estrone or estrone sulfate concentration, the ratio of estrone sulfate to estrone was significantly inversely associated with risk, suggesting that women who develop breast cancer may be less able to metabolize estrone to its less active form. Serum testosterone was significantly positively associated with postmenopausal breast cancer; the relative risk for women in the highest versus the lowest quartile was 6.2 (95% confidence interval, 2.0-19.0). Our results support the hypothesis that prediagnostic serum estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women.

Time to first pulse after automatic implantable cardioverter defibrillator implantation.

Should automatic implantable cardioverter defibrillator (AICD) power sources be explanted and discontinued if they have not pulsed during the first generator life? We have followed 59 patients an average of 23 months (range, 3 days to 8.4 years) after AICD implantation. The indication for AICD implantation was based on clinical dysrhythmia, history of sudden death, and findings at electrophysiologic study. Thirty-eight of 59 patients (64%) had experienced sudden death and 52/58 (90%) were inducible at electrophysiologic study. Excluding 5 inappropriate pulsing episodes, 31 of 59 patients (53%) had 235 pulses (range, 1 to 36; median, 2 pulses). The time to first pulse after implantation ranged from 1 day to 3.5 years with a median time of 2 months. In 6 patients, the first pulsing occurred later than 1 year after AICD implantation. Fifteen generators demonstrating impending power source failure have been replaced in 11 patients. Power source depletion occurred at an average of 24.1 months (range, 8 to 40 months). In 3 patients, the first pulsing occurred after generator depletion and replacement. By univariate analysis, none of 13 variables (sex, age, cardiac disease process, functional class, previous myocardial infarction, sudden death history, ejection fraction, type of dysrhythmia, inducibility with electrophysiologic testing, number of extra stimuli required for induction, left ventricular aneurysm resection, endocardial resection, or concomitant operation) was found to be a predictor of pulsing (p greater than 0.05). We conclude that the majority of patients with pulses after AICD implantation will have them during the first 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse effects of permanent cardiac internal defibrillator patches on external defibrillation.

At the time of left ventricular aneurysm resection, antiarrhythmic operations or other open-heart operative procedures in patients with ventricular dysrhythmia, permanent internal defibrillator patches may be inserted. Insertion of the energy source may be delayed due to its unavailability or to a desire for postoperative electrophysiologic study before its insertion. To assess the effects of permanent internal defibrillator patches on external defibrillation, 7 anesthetized calves were studied. Fibrillation-defibrillation studies were performed before and after insertion of permanent internal defibrillator patches (model L67, 27 cm2, Intec Systems), one on each ventricle. The values of percent successful defibrillation obtained before insertion of the patches, although much lower than values that would be expected in humans, are consistent with the results of an extensive earlier study involving this calf model. Similar values obtained after insertion of the patches are appreciably lower than the values obtained before implantation of the patches, and appreciably lower than the results predicted by the earlier study. A significant decrease in the percent of successful defibrillations (p less than 0.001) was observed for a shock intensity of approximately 400 J. Permanent internal cardiac defibrillator patches on the right and left ventricles reduce the probability of achieving successful defibrillation externally with unidirectional shocks. The wisdom of implanting permanent large internal cardiac defibrillator patches without the energy source is questioned.

Posttraumatic lobular squamous metaplasia of breast. An unusual pseudocarcinomatous metaplasia resembling squamous (necrotizing) sialometaplasia of the salivary gland.

Squamous metaplasia arising in nonneoplastic breast parenchyma is reportedly rare. We present a unique case which occurred following severe blunt trauma to the right breast of a 59-yr-old woman. The lesion contained sheets of squamous cells with a lobular growth pattern, bland cytology with few mitoses, and keratin and keratohyalin granules. It bore a striking resemblance to squamous (necrotizing) sialometaplasia of the salivary gland in that it exhibited lobular, pseudocarcinomatous growth. The patient has remained free of disease 49 mo after segmental resection of the lesion. Four previous cases of squamous metaplasia of the female breast have been reported, though none presented with a history of trauma or previous surgical manipulation. It is important to differentiate this entity from pure squamous cell carcinoma, and metaplastic change in ductal breast carcinoma, fibroadenoma, and other lesions. Breast aspiration biopsies revealing squamous cells cannot exclude carcinoma; thus, caution must be exercised.

A twenty-four year retrospective study of dependent catheter paracentesis.

Dependent catheter paracentesis has been used on 590 patients over the last 24 years. The complication rate is zero. It is faster, as accurate, cheaper and less hypersensitive than diagnostic peritoneal lavage. Open, semi-open and closed diagnostic peritoneal lavage when used with trocars is unjustified because of a significant complication rate.