Kathy Allen

The Specific Role of Isoflavones on Estrogen Metabolism in Premenopausal Women

There is increasing evidence that dietary factors may play a role in the production, metabolism, and bioavailability of sex hormones and their impact on target tissues. The specific objective of this study was to evaluate the effectiveness of supplementing a group of premenopausal women who were free of breast carcinoma with a dietary supplement of isoflavones (40 mg per day) in producing a change in steroid hormones and menstrual cycle length.

Timing of weight gain and breast cancer risk

Background. Obesity and body‐fat distribution have been associated with the incidence of breast and endometrial cancers. It may be critical to determine if the timing of weight gain during periods of hormonal change, such as menarche, pregnancy, or menopause, has different biologic effects, especially secondary to differences in the localization of body fat during these periods. The objective of the current study was to determine if excess weight in any particular decade of life or the timing of weight gain was more significant relative to breast cancer risk.

A Phase II Randomized, Placebo-Controlled Clinical Trial of Purified Isoflavones in Modulating Steroid Hormones in Men Diagnosed With Localized Prostate Cancer

Abstract Our purpose was to evaluate the safety and effectiveness of purified isoflavones in producing an increase in plasma isoflavones and a corresponding change in serum sex hormone binding globulin (SHBG) and steroid hormone levels in men diagnosed with early stage prostate cancer. In this Phase II randomized, double-blinded, placebo-controlled trial, 53 prostate cancer patients with a Gleason score of 6 or below were supplemented with 80 mg purified isoflavones or placebo for 12 weeks. Changes in plasma isoflavones, serum steroid hormones, and safety markers were analyzed from baseline to 12 wk. A total of 50 subjects completed the study. Although significant increases in plasma isoflavones (P < 0.001) was observed with no clinical toxicity, the corresponding modulation of serum SHBG, total estradiol, and testosterone in the isoflavone-treated group compared to men receiving placebo was nonsignificant. Increasing plasma isoflavones failed to produce a corresponding modulation of serum steroid hormone levels in men with localized prostate cancer. The study establishes the need to explore other potential mechanisms by which prolonged and consistent purified isoflavone consumption may modulate prostate cancer risk.

Weight gain associated with adjuvant tamoxifen therapy in stage I and II breast cancer: fact or artifact?

There is a perception that tamoxifen causes weightgain in breast cancer patients. The purpose ofthis research study was to determine if weightgain is associated with tamoxifen therapy and toobserve the impact of weight gain on recurrenceand survival. Prognostic indicators, changes in weight, anddisease status from diagnosis to the end oftreatment were studied in 200 consecutive Stage Iand II breast cancer patients, not receiving systemicchemotherapy, admitted from 1986 to the present, withobservation periods ranging from 3–5 years. A meanweight gain of 1.2 Kgs was seen inall patients; however, weight gain was not significantlydifferent for those receiving tamoxifen vs. those notreceiving tamoxifen, (P=0.66, CI 95% forthe difference –1.8 Kgs to +1.2 Kgs). Weightgain during treatment with tamoxifen was not correlatedwith treatment duration or with recurrence or survival.Age at diagnosis was positively correlated to weightgain in all groups. Our data failed toshow that tamoxifen is associated with weight gain.The moderate weight gain observed in this patientpopulation is comparable to the general aging disease-freepopulation and may not be treatment-related. These findingsmay help to alleviate some concerns of bothphysicians and patients when tamoxifen is the drugof choice for adjuvant therapy.

Perioperative herbal supplement use in cancer patients: potential implications and recommendations for presurgical screening.

BACKGROUND Products made from botanicals that are used to maintain or improve health are known as herbal supplements, botanicals, or phytomedicines. Many herbs have a long history of use and claimed health benefits. However, many herbal supplements and botanicals have potent pharmacologic activity that can contribute to adverse effects and drug interactions. The use of herbal supplements by cancer patients in the perioperative period is common and consistent with the substantial increase in the use of alternative medical therapies. METHODS We reviewed the literature to examine the constituents, safety, pharmacokinetics, and pharmacodynamics of those herbal supplements that are predominantly used by cancer patients. RESULTS Different supplements possess antiplatelet activity, adversely interact with corticosteroids and central nervous system depressant drugs, have gastrointestinal manifestations, produce hepatotoxicity and nephrotoxicity, and produce additive effects when used with opioid analgesics. CONCLUSIONS With the increasing use of herbal supplements by cancer patients, surgical staff need to screen patients pre-surgically for use of these supplements. Clinical practice guidelines are needed for screening and prevention of herbal supplement usage to prevent potential adverse events that may arise from herbal medications taken alone or combined with conventional therapies during the perioperative period.

Use of complementary/integrative nutritional therapies during cancer treatment: implications in clinical practice.

BACKGROUND The objectives of this study were to determine the prevalence and characterize the use of complementary/integrative nutritional therapies (CINTs) by patients during cancer treatment. METHODS This retrospective review used data collected as a part of standard clinical care provided by the registered clinical dietitians and included nutritional history, demographic variables, anthropometrics, prevalence of use, and the specific integrative nutritional therapies used by these patients during cancer treatment. RESULTS Twenty-nine percent of 820 patients reported use of CINTs not prescribed by their physician. Caucasians and patients over age 60 were the principal users of CINTs during treatment. Modular vitamins were the most frequently reported additive (86.9%), followed by botanicals/biologics (43.8%) and mineral supplements (28.6%). CONCLUSIONS A considerable proportion of cancer patients use unproven CINTs during cancer treatment. The health professional should become more aware of the complementary/integrative therapies that their patients are using during cancer treatment.

Results of a Randomized Clinical Trial of the Action of Several Doses of Lycopene in Localized Prostate Cancer: Administration Prior to Radical Prostatectomy

Purpose The purpose of this Phase II randomized-controlled trial was to evaluate the safety and effect of administering several doses of lycopene to men with clinically localized prostate cancer, on intermediate endpoint biomarkers implicated in prostate carcinogenesis. Methods Forty-five eligible men with clinically localized prostate cancer were supplemented with 15, 30 or 45 mg of lycopene or no supplement from biopsy to prostatectomy. Compliance to study agent, toxicity, changes in plasma lycopene, serum steroid hormones, PSA and tissue Ki-67 were analyzed from baseline to completion of intervention. Results Forty-two of forty-five five subjects completed the intervention for approximately 30 days from the time of biopsy until prostatectomy. Plasma lycopene increased from baseline to post treatment in all treatment groups with greatest increase observed in the 45 mg lycopene-supplemented arm compared to the control arm without producing any toxicity. Overall, subjects with prostate cancer had lower baseline levels of plasma lycopene similar to those observed in previous studies in men with prostate cancer. Serum free testosterone decreased with 30 mg lycopene supplementation and total estradiol increased significantly with 30 mg and 45 mg supplementation from baseline to end of treatment, with no significant increases in serum PSA or tissue Ki-67. These changes were not significant compared to the control arm for this sample size and duration of intervention. Conclusions Although antioxidant properties of lycopene have been hypothesized to be primarily responsible for its beneficial effects, our study suggests that other mechanisms mediated by steroid hormones may also be involved.

Safety of Purified Isoflavones in Men With Clinically Localized Prostate Cancer

Abstract Our purpose was to evaluate the safety of 80 mg of purified isoflavones administered to men with early stage prostate cancer. A total of 53 men with clinically localized prostate cancer, Gleason score of 6 or below, were supplemented with 80 mg purified isoflavones or placebo for 12 wk administered in 2 divided doses of 40 mg to provide a continuous dose of isoflavones. Compliance, changes in plasma isoflavones, and clinical toxicity were analyzed at baseline, 4, and 12 wk. A total of 50 subjects completed the 12-wk intervention. A continuous, divided-dose administration of 80 mg/day of purified isoflavones at amounts that exceeded normal American dietary intakes significantly increased (P < 0.001) plasma isoflavones in the isoflavone-treated group compared to placebo and produced no clinical toxicity. With the current evidence on the cancer preventive properties of isoflavones, these results are significant and offer promise for these phytochemicals to be developed as potent agents to prevent cancer progression.

A Case‐Control Study Evaluating the Association of Purposeful Physical Activity, Body Fat Distribution, and Steroid Hormones on Premenopausal Breast Cancer Risk

Abstract:  The objective of this case‐control study was to investigate the relationship between purposeful physical activity, body fat distribution, body mass index, and steroid hormones. These factors are known to be implicated in modulating breast cancer risk in premenopausal women. A total of 112 newly diagnosed, premenopausal breast cancer patients and 106 age‐matched premenopausal disease‐free controls were admitted to the study. Information regarding personal, medical, hormonal, and reproductive history, smoking and alcohol use, physical activity history, and anthropometric measurements was obtained. Serum samples for steroid hormone assays were collected and analyzed. Disease‐free premenopausal controls had a significantly higher physical activity index (PAI) (p ≤ 0.05), however, significantly higher weight (p ≤ 0.05), body mass index (BMI) (p = 0.01), waist (p ≤ 0.005) and hip (p ≤ 0.05) circumferences, waist:hip ratios (p ≤ 0.05), and serum total estradiol levels (p < 0.0005) were observed in cancer cases. The final model using stepwise logistic regression analysis indicates that the variables that significantly predicted breast cancer risk were waist:hip ratio (odds ratio [OR] = 1.11, p ≤ 0.005) and serum total estradiol levels (OR = 1.03, p ≤ 0.0001). Our study provides some evidence that purposeful physical activity may reduce upper body fat distribution associated with adult weight gain. This may be a result of alterations in the steroid hormone pathway, such as reduced estradiol levels. This demonstrates the potential mechanism through which increased physical activity can reduce the risk for breast cancer in premenopausal women.