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R T Chlebowski

Publications and source records attributed to R T Chlebowski.

At least 19 recordsLinked to original sources
PubMed2001

Factors influencing the role of bisphosphonates in breast cancer management.

Bone metastases represent a significant tumor-related complication affecting many breast cancer patients. The resulting bone destruction or osteolysis that frequently accompanies metastatic bone disease results in considerable morbidity for patients including a high rate of skeletal complications, severe pain, and a reduced quality of life. Traditionally, the treatment of metastatic bone disease has relied heavily on the use of multidisciplinary therapies, such as radiotherapy in combination with systemic treatment, supported by analgesia. Bisphosphonates are a class of pyrophosphate analogs that actively inhibit bone resorption. As a result, their clinical application has expanded greatly over the past 5 to 10 years and, in addition to being the treatment of choice for hypercalcemia of malignancy, they have been shown to be effective in reducing the skeletal morbidity associated with metastatic breast cancer. Furthermore, recent data from animal and in vitro studies suggest that bisphosphonates may actually have an antiapoptotic and antiproliferative effect not only on osteoclasts, but also on macrophages and tumor cells. Recent improvements in our understanding of the underlying molecular mechanisms in breast cancer, the diagnosis of the disease itself, and the development of new systemic therapies has led to improved survival benefit for many breast cancer patients. However, because survival duration has also been related to the risk of developing skeletal complications, bisphosphonates may play an ever greater role in the management and prevention of skeletal morbidity in the future.

Bone Neoplasms↗
PubMed2000

American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonates Expert Panel.

PURPOSE: To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of bone metastases in breast cancer and their role relative to other therapies for this condition. METHODS: An expert multidisciplinary panel reviewed pertinent information from the published literature and meeting abstracts through May 1999. Additional data collected as part of randomized trials and submitted to the United States Food and Drug Administration were also reviewed, and investigators were contacted for more recent information. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the panel. Expert consensus was used if there were insufficient published data. The panel addressed which patients to treat and when in their course of disease, specific drug delivery issues, duration of therapy, management of bony metastases with other therapies, and the public policy implications. The guideline underwent external review by selected physicians, members of the American Society of Clinical Oncology (ASCO) Health Services Research Committee, and the ASCO Board of Directors. RESULTS: Bisphosphonates have not had an impact on the most reliable cancer end point: overall survival. The benefits have been reductions in skeletal complications, ie, pathologic fractures, surgery for fracture or impending fracture, radiation, spinal cord compression, and hypercalcemia. Intravenous (IV) pamidronate 90 mg delivered over 1 to 2 hours every 3 to 4 weeks is recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. For women with only an abnormal bone scan but without bony destruction by imaging studies or localized pain, there is insufficient evidence to suggest starting bisphosphonates. Starting bisphosphonates in patients without evidence of bony metastasis, even in the presence of other extraskeletal metastases, is not recommended. Studies of bisphosphonates in the adjuvant setting have yielded inconsistent results. Starting bisphosphonates in patients at any stage of their nonosseous disease, outside of clinical trials, despite a high risk for future bone metastasis, is currently not recommended. Oral bisphosphonates are one of several options which can be used for preservation of bone density in premenopausal patients with treatment-induced menopause. The panel suggests that, once initiated, IV bisphosphonates be continued until evidence of substantial decline in a patient's general performance status. The panel stresses that clinical judgment must guide what is a substantial decline. There is no evidence addressing the consequences of stopping bisphosphonates after one or more adverse skeletal events. Symptoms in the spine, pelvis, or femur require careful evaluation for spinal cord compression and pathologic fracture before bisphosphonate use and if symptoms recur, persist, or worsen during therapy. The panel recommends that current standards of care for cancer pain, analgesics and local radiation therapy, not be displaced by bisphosphonates. IV pamidronate is recommended in women with pain caused by osteolytic metastasis to relieve pain when used concurrently with systemic chemotherapy and/or hormonal therapy, since it was associated with a modest pain control benefit in controlled trials. CONCLUSION: Bisphosphonates provide a meaningful supportive but not life-prolonging benefit to many patients with bone metastases from cancer. Further research is warranted to identify clinical predictors of when to start and stop therapy, to integrate their use with other treatments for bone metastases, to identify their role in the adjuvant setting in preventing bone metastases, and to better determine their cost-benefit consequences.

Bone Neoplasms↗
PubMed1999

Elements of informed consent for hormone replacement therapy in patients with diagnosed breast cancer.

PURPOSE: An approach to providing informed consent to breast cancer survivors considering hormone replacement therapy (HRT) is offered. METHODS: Current information on HRT, breast cancer, and chronic disease prevention is reviewed in the context of risks faced by women with resected breast cancer. RESULTS: Breast cancer patients, unwilling to trade symptom reduction for even a small increase in recurrence risk, are at substantially increased risk of death from breast cancer relative to other causes. Observational studies suggest that long-term HRT increases breast cancer development. The influence of HRT on the growth of established breast cancer has not been determined; however, estrogen reduction (oophorectomy) significantly reduces recurrence in premenopausal women, and current evidence cannot exclude a risk that HRT increases recurrence to the same degree. The following issues are of particular relevance to breast cancer survivors: HRT reduces mammographic sensitivity, increases thromboembolic events, and increases endometrial cancer risk. Although benefit for HRT is commonly inferred from observational studies, randomized trials of HRT on all-cause mortality have not been completed. For coronary heart disease prevention, an array of strategies independent of HRT are available, with some (tamoxifen, selective estrogen receptor modifiers [SERMs], diet, and exercise) likely to favorably influence breast cancer risk; for osteoporosis prevention, an array of strategies also are available, with some (bisphosphonates, tamoxifen, SERMs, and exercise) likely to favorably influence breast cancer risk. CONCLUSION: Current data preclude the generation of evidence-based guidelines for HRT use in breast cancer survivors, and clinical trials in this setting should be supported. However, given available therapeutic alternatives for menopausal symptom management and chronic disease prevention, breast cancer survivors should be offered HRT only with caution and with their full participation in the decision-making process.

Breast Neoplasms↗
PubMed1999

American Society of Clinical Oncology technology assessment on breast cancer risk reduction strategies: tamoxifen and raloxifene.

OBJECTIVE: To conduct an evidence-based technology assessment to determine whether tamoxifen and raloxifene as breast cancer risk-reduction strategies are appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTION: Tamoxifen and raloxifene. OUTCOME: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefits. EVIDENCE: A comprehensive, formal literature review was conducted for tamoxifen and raloxifene on the following topics: breast cancer risk reduction; tamoxifen side effects and toxicity, including endometrial cancer risk; tamoxifen influences on nonmalignant diseases, including coronary heart disease and osteoporosis; and decision making by women at risk for breast cancer. Testimony was collected from invited experts and interested parties. VALUES: More weight was given to publications that described randomized trials. BENEFITS/HARMS/COSTS: The American Society of Clinical Oncology (ASCO) Working Group acknowledges that a woman's decision regarding breast cancer risk-reduction strategies will depend on the importance and weight attributed to the information provided regarding both cancer and non-cancer-related risks. CONCLUSIONS: For women with a defined 5-year projected risk of breast cancer of >/= 1.66%, tamoxifen (at 20 mg/d for up to 5 years) may be offered to reduce their risk. It is premature to recommend raloxifene use to lower the risk of developing breast cancer outside of a clinical trial setting. On the basis of available information, use of raloxifene should currently be reserved for its approved indication to prevent bone loss in postmenopausal women. Conclusions are based on single-agent use of the drugs. At the present time, the effect of using tamoxifen or raloxifene with other medications (such as hormone replacement therapy), or using tamoxifen and raloxifene in combination or sequentially, has not been studied adequately. The continuing use of placebo-controlled trials in other risk-reduction trials highlights the current unanswered issues concerning the use of such interventions, especially when the influence on net health benefit remains to be determined. Breast cancer risk reduction is a rapidly evolving area. This technology assessment represents an ongoing process with existing plans to monitor and review data and to update recommendations in a timely matter. (See VALIDATION: The conclusions of the Working Group were evaluated by the ASCO Health Services Research Committee and by the ASCO Board of Directors. SPONSOR: American Society of Clinical Oncology.

Anticarcinogenic Agents↗
PubMed1996

Gender influence on weight-loss pattern and survival of nonsmall cell lung carcinoma patients.

BACKGROUND: Gender has recently emerged as a discriminating factor in nonsmall lung carcinoma (NSCLC) patient outcome. Since the potential for interaction among established prognostic factors and gender in this common disease has not been explored, the authors evaluated the role of gender and weight-loss pattern in predicting clinical outcome in a balanced population of men and women presenting with NSCLC. METHODS: From a tumor registry population of 368 NSCLC patients, a gender-balanced sample of 152 cases was randomly selected for review, using prospective inclusion criteria. Study parameters were age, race, tobacco and alcohol history, gender, weight-loss pattern, histology, TNM stage, Eastern Cooperative Oncology Group performance status, and therapy. Influences of study variables on Kaplan-Meier estimates of survival were subsequently determined using univariate and multivariate analyses. RESULTS: Overall median survival after diagnosis was significantly shorter for men with NSCLC than for women with the disease (40 vs. 78 weeks, P = 0.001). Men lost significantly more weight over their disease course than women (12.2 vs. 5.4 pounds, P = 0.006) and experienced an eightfold faster rate of initial weight loss (0.25 vs. 0.03 pounds per week, P = 0.001). In multivariate analysis, the strongest independent predictors of NSCLC patient survival were stage of disease, initial weight-loss rate, and gender (all P < 0.0001). CONCLUSIONS: These results suggest that weight loss may play a role in mediating gender-related differences in NSCLC patient survival and provide an impetus for further studies of gender influence on cancer outcome.

Analysis of Variance↗
PubMed1996

Recent implications of weight loss in lung cancer management.

Successful lung cancer management has been hindered by the limited efficacy of dietary and pharmacologic interventions to prevent or reverse cancer-associated weight loss. The addition of total parenteral nutrition to chemotherapy in early trials was associated with survival detriment. Dietary counseling and enteral supplement use are common strategies that, when evaluated in randomized trials, do not improve anthropometrics or clinical outcome in lung cancer. Pharmacologic agents including corticosteroids, cyproheptadine, growth hormone, hydrazine sulfate, dronabinol, and pentoxyphylline also have failed to improve even anthropometric parameters in this condition. Megestrol acetate use is associated with appetite stimulation and non-fluid weight gain but, when evaluated in small cell lung cancer patients receiving defined chemotherapy, failed to improve global quality of life, and survival and was associated with toxicity. New strategies for nutrition-based interventions in lung cancer cachexia must consider their potential influence on tumor growth as well as on nutritional status. Recent lung cancer prognostic analyses have identified gender differences in outcome and weight loss that suggest potential targets for combined hormonal and nutrition interventions. Emerging information regarding the influence of specific fatty acids on tumor growth and cachexia development have identified additional approaches for future evaluation.

Cachexia↗
PubMed1996

Monitoring dietary change in a low-fat diet intervention study: advantages of using 24-hour dietary recalls vs food records.

OBJECTIVE: The purpose of the study was to evaluate two methods of dietary assessment for monitoring change in fat intake in a low-fat diet intervention study. DESIGN: The two dietary assessment methods were a 4-day food record (4DFR) and an unannounced 24-hour dietary recall conducted by telephone interview (referred to as a telephone recall [TR]). Subjects were assigned randomly to either a low-fat diet intervention group or a control group that received no counseling about fat intake. Dietary data were collected at baseline, 6 months, and 12 months. SUBJECTS: Two hundred ninety postmenopausal women with localized breast cancer were recruited at seven clinical centers in the United States. STATISTICAL ANALYSIS: Analysis of variance was used to test for significant differences in mean fat and energy intakes. RESULTS: Three sources of error were identified: (a) an instrument effect, suggesting underreporting at baseline of approximately 8% in mean energy intake and 11% in mean fat intake in the TR group compared with the 4DFR group (P = .0001); (b) a repeated measures effect observed for the 4DFR, suggesting underreporting of approximately 7% for energy intake and 14% for fat intake in the control group at 6 and 12 months compared with baseline values (P < .001); and (c) an adherence effect (or compliance bias), suggesting greater compliance to the low-fat intervention diet when subjects were keeping food records than when estimates were based on the unannounced TR. Compared with the TR, the 4DFR overestimated the extent of fat reduction in the low-fat diet intervention group by 41% (P = .08) and 25% (P = .62) at 6 and 12 months, respectively. APPLICATION: Multiple days of unannounced 24-hour recalls may be preferable to multiple-day food records for monitoring dietary change in diet intervention studies.

Aged↗
PubMed1995

Dietary intake and counseling, weight maintenance, and the course of HIV infection.

OBJECTIVE: To define relationships among dietary intake and counseling, weight maintenance, and the clinical course of patients infected with the human immunodeficiency virus (HIV). DESIGN: A prospective cohort study in an HIV clinic in a county hospital. SUBJECTS: HIV-infected patients (68 with and 40 without acquired immunodeficiency syndrome [AIDS]) who had a good performance status and no chronic diarrhea were assessed at entry to the study and after 6 months. The following assessments were made: energy and nutrient intake based on 7-day food records, anthropometric measurements, immunologic function as lymphocyte T-cell subpopulations (ratio of CD4 to CD8), and serum cholesterol level. Patients were monitored to determine clinical outcome. INTERVENTION: All patients received standardized dietary counseling designed to address identified intake deficiencies and maintain body weight. MAIN OUTCOME MEASURES: Changes in energy and nutrient intake, body weight, and clinical outcome (ie, time to AIDS-defining illness and overall survival time). STATISTICAL ANALYSES PERFORMED: Group differences (HIV group vs AIDS group) were sought using chi 2 analyses and Student's t test. A multivariate regression model was used to determined the best predictors of clinical outcome. RESULTS: At baseline, total energy intake (based on 30 kcal/kg usual body weight) was adequate in both HIV and AIDS patients (101 +/- 4% and 103 +/- 5% [mean +/- standard deviation] of need, respectively). Despite dietary counseling and continued maintenance of energy intake, body weight, serum cholesterol level, and CD4 level progressively decreased. Consequently, saturated fat intake was found to be inversely related (P < .01) to serum cholesterol level. Clinical outcome (after 3.5 years) was associated with baseline ratio of CD4 to CD8 (P < .001), weight (P < .01), and serum cholesterol level (P < .001). Multivariate analysis related ratio of CD4 to CD8 (P < .001) and weight maintenance (P < .001) to favorable outcome in the final model. APPLICATIONS: Weight loss in patients with HIV infection is independently prognostic of clinical outcome, and development of hypocholesterolemia is not favorable for clinical outcome. Because weight loss progresses despite conventional dietary counseling to identify energy need, interventions earlier in the disease course should be considered along with increased target levels for energy intake.

Adult↗
PubMed1995

Altered metabolism and mortality in patients with colon cancer receiving chemotherapy.

To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate therapy, 22 patients with colon cancer were admitted prospectively to a Clinical Research Center for serial measurement of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation. Combined therapy was associated with a significant reduction in fasting glucose level (98 +/- 2 mg/dL to 94 +/- 2, P < 0.025) without a significant fall in fasting HGP (2.09 +/- 0.11 mg/kg/min versus 2.03 +/- 0.13; P > 0.05). The decreased fasting glucose value was associated with a mild but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (1.34 +/- 0.07 %/min vs 1.47 +/- 0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2 months of therapy (63.3 +/- 3.0 mumol/kg/hr vs 57.1 +/- 3.9 mumol/kg/hr; P < 0.025), but leucine oxidation (11.5 +/- 1.1 mumol/kg/hr vs 11.2 +/- 1.1 mumol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine concentrations significantly increased with therapy, it was not associated with plasma LA. Half of the patients with cancer died 14 +/- 4 months after the study, and the other half were alive 58 +/- 2 months later. Survival time can be estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and insulin concentration. Multiple regression analysis identified that plasma LA was related directly to length of survival time, and baseline HGP, carcino-embryonic antigen, and insulin concentration were related inversely to length of survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

The scope of nutrition intervention trials with cancer-related endpoints.

The National Cancer Institute currently is supporting three full-scale dietary modification trials with cancer-related endpoints. These studies are the dietary component of the Women's Health Initiative, designed to determine whether a low-fat diet will reduce the incidence of breast and colorectal cancer and/or coronary heart disease; the Women's Intervention Nutrition Study, designed to test whether a dietary fat reduction program will decrease breast cancer recurrence and increase patient survival; and the Polyp Prevention Trial, designed to determine whether a low-fat, high-fiber diet will reduce the recurrence of adenomatous polyps. Design issues associated with these full-scale dietary modification outcome trials have been addressed successfully in a series of feasibility studies. The ability to achieve a sustained reduction of 50% in dietary fat intake with maintenance of nutritional adequacy has been demonstrated in randomized trials of postmenopausal populations with resected breast cancer and in populations at increased risk for breast cancer. In these studies comparing dietary fat reduction programs with control lifestyles, a series of associated biologic changes, consistent with the self-reported dietary alterations, have been observed. These changes include body weight reduction, serum and/or plasma estradiol concentration reduction, fasting plasma cholesterol concentration reduction, and alteration in free fatty acid levels. Such results provide a substantial basis for reliably estimating the level of adherence that can be anticipated in trials of dietary change, a prerequisite for appropriate calculation of the sample size needed for multicenter, full-scale outcome studies. As a result, the efficacy of a series of dietary alterations (including fat reduction, fiber addition, and/or increased fruit and vegetable intake) on cancer-related endpoints with potential major public health significance (breast cancer recurrence, breast cancer development, and colonic polyp recurrence) now are being addressed definitively in prospective clinical trials.

Breast Neoplasms↗
PubMed1994

5-fluorouracil vs. epirubicin vs. 5-fluorouracil plus epirubicin in advanced gastric carcinoma.

From January, 1985, through January, 1987, 165 patients with advanced gastric cancer were randomized to receive epirubicin (E) alone (90 mg/m2 day 1), 5-Fluorouracil (5-FU) alone (500 mg/m2 days 1-5), or the combination of E (90 mg/m2 day 1) and 5-FU (400 mg/m2 days 1-5). Courses were repeated every four weeks. Patients were stratified by extent (locally advanced vs. metastatic), evaluability (measurable vs. nonmeasurable) and by history of prior radiotherapy (yes vs. no). Randomization to single arm epirubicin was stopped after 26 patients were enrolled. Objective responses occurred in only 1/16 (6%) of the patients treated with E alone, 1/40 (5%) with 5-FU alone and 4/33 (12%) with both 5-FU and E. There were no significant differences in all eligible patients with respect to time to progression or overall survival in the three treatment arms. Toxicity was primarily hematologic and more pronounced in the combination arm. Neither 5-FU alone, epirubicin alone, or the combination have a major impact in the treatment of gastric carcinoma.

Adenocarcinoma↗
PubMed1994

Late mortality and levamisole adjuvant therapy in colorectal cancer.

Beginning in 1975, 78 patients with resected stage B and C colorectal carcinoma were randomly assigned (2:1) to receive either levamisole 2.5 mg kg-1 day-1 given for 2 days every week for 18 months or placebo therapy in the same schedule. Pretreatment characteristics (age, gender, disease site, CEA and stage) and the pattern of follow-up were similar in both groups. For the first 5 years following randomisation, relapse-free survival and overall survival were similar in the two treatment groups. Subsequently, excess late mortality was associated with levamisole group assignment. Consequently, overall survival was somewhat greater in the placebo group than in the levamisole group, 68% vs 38% (P < 0.08). For patients surviving 5 years from randomisation, subsequent survival favoured placebo over levamisole (100% vs 57%; P < 0.03). The absolute numbers of deaths were 27 in the levamisole group (19 definitely cancer related) and seven in the group placebo (five definitely cancer related). This long-term result seen with a more intensive adjuvant levamisole dose and schedule suggests: (1) other levamisole adjuvant trials in patients with colorectal cancer should be examined for long-term outcome; (2) future trials utilising the even higher levamisole dosage required for clinical immunomodulation should proceed cautiously.

Aged↗
PubMed1994

A decade of breast cancer clinical investigation: results as reported in the Program/Proceedings of the American Society of Clinical Oncology.

PURPOSE: To test the hypothesis that clinical research results have driven changes in recent breast cancer management recommendations. METHODS: All breast cancer abstracts in the Program/Proceedings of the American Society of Clinical Oncology (ASCO) from 1984 to 1993 were prospectively reviewed in 31 areas and categorized by study type, study question, whether statistical significance was claimed, and whether the abstract was presented. RESULTS: Of 1,372 abstracts, 54% reported on prospective clinical trials (PCTs) and 17% on randomized clinical trials (RCTs). The total number of published abstracts progressively increased (from 87 in 1984 to 221 in 1993) and author citations nearly quadrupled (from 430 in 1984 to 1,642 in 1993, P < .01); however, RCTs have come to represent a smaller proportion of reports: 37% (33 of 89) in 1986 versus 10% (22 of 221) in 1993 (P < .001). The size of adjuvant-therapy RCTs has progressively increased (mean +/- SEM subjects/trial, 237 +/- 43 in 1984 to 874 +/- 374 in 1993), but has remained small in advanced-disease RCTs (mean +/- SEM subjects/trial, 145 +/- 25 in 1984 to 146 +/- 34 in 1993). For adjuvant therapy, 14 of 90 RCTs (with 51,207 patients) reported a significant (P < .05) survival benefit for investigational therapies (16%). For advanced-disease therapy, only three of 141 RCTs (with 26,281 patients) reported a significant (P < .05) survival benefit for investigational therapies (2%). Randomization was rarely used in trials of dose-intensity with blood-product support (zero of 86 trials) or locally advanced disease. CONCLUSION: For breast cancer ASCO abstracts in the past decade, we determined the following: (1) adjuvant trials have not infrequently supported study hypotheses; and (2) advanced-disease trials have consistently failed to identify new approaches with a significant impact on survival. These results suggest that a critical process evaluation of current policy and procedures involved in directing breast cancer research is warranted, especially for strategies in advanced disease.

Breast Neoplasms↗
PubMed1993

Breast cancer chemoprevention. Tamoxifen: current issues and future prospective.

Intervention clinical trials are under way to address whether tamoxifen can prevent breast cancer development. This effort is based on laboratory evidence that tamoxifen interferes with the initiation and promotion of mammary cancer, clinical evidence of decreased breast cancer incidence in the opposite breast of women participating in tamoxifen adjuvant breast cancer trials, and a favorable toxicity profile of tamoxifen providing reasonable assurance of drug safety when used in a population without cancer. The apparently favorable effects of tamoxifen on lipid metabolism and bone mineral density provide additional impetus to this evaluation. Potentially life threatening toxicity of thromboembolism and development of a second cancer remain concerns. With respect to implications of such clinical trials, even upon successful study completion, difficult issues will remain; these issues include the potential for interaction between tamoxifen and dietary fat reduction (also proposed as potential breast cancer prevention), the cost and cost-effectiveness of wide scale (or selective) implementation of positive results, and the generalizability of study results to socioeconomically disadvantaged and racial and ethnic minority populations that historically have been under-represented in medical clinical trials. These important issues should be addressed concurrently as large-scale prevention trials go forward to optimize the practical utility of efficacy data obtained.

Breast Neoplasms↗
PubMed1993

The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients.

The purpose of the study was to determine the effect of a low-fat dietary intervention, with or without concomitant tamoxifen adjuvant therapy, on serum estrogen and sex hormone-binding globulin (SHBG) levels in postmenopausal patients with resected breast cancer. Ninety-three patients were randomized to either reduce their fat intake to 15-20% of total calories, or to a dietary control group. Serum estradiol, estrone, estrone sulfate, and SHBG concentrations were assayed at baseline, and at 6, 12, and 18 months thereafter. In 19% of patients, the preintervention serum estradiol levels were below the sensitivity of the assay (5 pg/ml). Tamoxifen had no significant effect on serum estrogen levels, but produced an elevation in SHBG. Patients with reliably quantifiable preintervention estradiol concentrations (> or = 10 pg/ml) showed a significant reduction in serum estradiol after 6 months on the low-fat diet (average, 20%; p < 0.005); this was sustained over the 18 month study period. Serum SHBG levels were increased by tamoxifen therapy, but were reduced significantly (p = 0.01) after 12 months on the low-fat diet in patients not receiving tamoxifen. No changes in serum estrone or estrone sulfate resulted from the dietary intervention. While the low-fat diet produced significant weight loss, patients treated with tamoxifen without dietary intervention showed a gain in body weight. These weight changes produced disruptions in the normal positive correlation between body weight and serum estrone sulfate, and the negative correlation with SHBG concentration.

Aged↗