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Fibrocystic Breast Disease



Use of vitamin E in chronic cystic mastitis.

Abrams, A.

N. Engl. J. Med. 1965; 272: 2388.

No Abstract Available

The effect of decreased caffeine consumption on benign proliferative breast disease: a randomized clinical trial.

Allen, S.S., Froberg, D.C.

Surgery 1985; 91: 263.

No abstract available.

The effect of decreased caffeine consumption on benign proliferative breast disease: a randomized clinical trial.

Allen SS, Froberg DG.

Surgery 1987 Jun;101(6):720-30

A single-blind, randomized clinical trial of 56 female subjects was conducted to determine whether decreased consumption of caffeine decreases breast pain/tenderness or nodularity in patients with suspected benign proliferative breast disease. The subjects were randomly assigned to one of three groups--a control group (no dietary restrictions), a placebo group (cholesterol-free diet), and an experimental group (caffeine-free diet). At the initial examination, the subjects reported on the presence of breast pain, the degree to which pain affects daily activities, the frequency of pain, the degree of pain associated with breast examinations, and the degree of pain associated with close-fitting clothing. Subjects were then examined and the four quadrants of each breast were rated on a scale of 0 to 3 (0 = normal, fatty tissue, 1 = little seedy bumps or fine nodularity, 2 = discrete nodules or ropy tissue, 3 = confluent areas, hard or soft masses). Subjects in all three groups returned for 2- and 4-month follow-up examinations. Total nodularity scores, degree of pain/tenderness, and compliance with dietary restrictions were analyzed. The data showed that decreased caffeine consumption did not result in a significant reduction of palpable breast nodules or in a lessening of breast pain/tenderness.

Benign Breast Conditions 1991, 1997.

Atlanta, GA: American Cancer Society.

American Cancer Society.

Caffeine labeling, a report on the safety of dietary caffeine.

AMA. American Medical Association's Council on Scientific Affairs.

JAMA 1984; 252: 803-6.

The American Medical Association Encyclopedia of Medicine 1989.


New York: Random House.

Dietary fiber content of selected foods.

Anderson JW, Bridges SR. VA Medical Center, Lexington, KY 40511.

Am J Clin Nutr 1988 Mar;47(3):440-7

Dietary fiber measurements are essential to assessment of the potential therapeutic and preventive effects of fiber intake. Ideally, dietary fiber analyses should measure all components--soluble polysaccharides, noncellulosic polysaccharides, cellulose, and lignin--and the constituent sugars of the soluble and noncellulosic polysaccharides. We modified existing techniques to measure reproducibly the total dietary fiber, polysaccharide, and lignin components and the sugar constituents of selected foods. Soluble-fiber content as percentage of total dietary fiber for groups of foods averaged 32% for cereal products, 32% for vegetables, 25% for dried beans, and 38% for fruits. Lignin content, estimated gravimetrically, was approximately 1.4 g/100 g dry wt for 24 foods. Detailed fiber measurements are critical for evaluating the potential health benefits of dietary fiber intake.

Benign breast conditions.


Reinsurance Notes 1998; 1: 12.

Professional Guide to Signs & Symptoms, Third Edition 2000.


Springhouse, PA: Springhouse.

Indole-3-carbinol as a scavenger of free radicals.

Arnao MB, Sanchez-Bravo J, Acosta M. Department of Plant Biology (Plant Physiology), University of Murcia, Spain.

Biochem Mol Biol Int 1996 Aug;39(6):1125-34

The ability of indole-3-carbinol (indole-3-methanol) to trap a metastable synthetic-free radical is presented. Indole-3-carbinol is capable of acting as a scavenger of free radicals in an in vitro system. The presence of indole-3-carbinol determines the disappearance of the free radicals, the reaction being time- and concentration-dependent. The scavenging activity of different indoles is compared. Indole-3-carbinol and indole-3-acetic acid are both able to scavenge free radicals, but indole-3-carbinol is more effective. Other indoles such as indole-3-aldehyde and indole-3-carboxylic acid do not show the ability to trap free radicals. Indole-3-aldehyde appears as a product of indole-3-carbinol reaction with free radicals. The formation of an adduct between the free radical generated in vitro and indole-3-carbinol has also been detected. Stability of indole-3-carbinol in buffered media at different pH values and formation of 3,3'-diindolylmethane from indole-3-carbinol is also studied. The scavenging activity of indole-3-carbinol and its implications on the anti-carcinogenesis process is discussed.

Dietary glycemic index and glycemic load, and breast cancer risk: a case-control study.

Augustin LS, Dal Maso L, La Vecchia C, Parpinel M, Negri E, Vaccarella S, Kendall CW, Jenkins DJ, Francesch S. Servizio di Epidemiologia, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, Aviano, Italy.

Ann Oncol 2001 Nov;12(11):1533-8

BACKGROUND: Certain types of carbohydrates increase glucose and insulin levels to a greater extent than others. In turn, insulin may raise levels of insulin-like growth factors, which may influence breast cancer risk. We analyzed the effect of type and amount of carbohydrates on breast cancer risk, using the glycemic index and the glycemic load measures in a large case-control study conducted in Italy. PATIENTS AND METHODS: Cases were 2,569 women with incident, histologically-confirmed breast cancer interviewed between 1991 and 1994. Controls were 2588 women admitted to the same hospital network for a variety of acute, non-neoplastic conditions. Average daily glycemic index and glycemic load were calculated from a validated 78-item food frequency questionnaire. RESULTS: Direct associations with breast cancer risk emerged for glycemic index (odds ratio, OR for highest vs. lowest quintile = 1.4; P for trend < 0.01) and glycemic load (OR = 1.3; < 0.01). High glycemic index foods, such as white bread, increased the risk of breast cancer (OR = 1.3) while the intake of pasta, a medium glycemic index food, seemed to have no influence (OR = 1.0). Findings were consistent across different strata of menopausal status, alcohol intake, and physical activity level. CONCLUSIONS: This study supports the hypothesis of moderate, direct associations between glycemic index or glycemic load and breast cancer risk and, consequently, a possible role of hyperinsulinemia/insulin resistance in breast cancer development.

The "luteal breast": hormonal and sonographic investigation of benign breast disease in patients with cyclic mastalgia.

Ayers JW, Gidwani GP.

Fertil Steril 1983 Dec;40(6):779-84

The pathophysiology, malignant potential, and hormonal therapy for benign breast disease remain controversial. This report investigates the anatomic and endocrinologic correlates of luteal phase mastodynia patients, compared with asymptomatic control subjects. Objective sonographic evidence of fibrocystic disease (FCD) was found in one-half of both mastodynia and control groups. Endocrine abnormalities observed in the mastodynia group included (1) significantly lower luteal phase progesterone and (2) prolactin hyperresponsiveness to thyroid-releasing factor. The presence or absence of anatomic FCD was not correlated with endocrine abnormalities. These data suggest that (1) cyclic mastalgia may be the end result of a dyshormonal milieu resembling the inadequate luteal phase; (2) FCD may be hormonally independent; and (3) cyclic mastalgia and FCD are different, if often coexistent, factors in benign breast disease syndromes.

Treatment of benign breast disease with vitamin A.

Band PR, Deschamps M, Falardeau M, Ladouceur J, Cote J.

Prev Med 1984 Sep;13(5):549-54

Twelve patients with benign breast disease (BBD) were treated with 150,000 IU of vitamin A daily taken orally. All patients were symptomatic and had measurable or evaluable breast masses. At 3 months of treatment, complete or partial responses were observed in five patients, and marked pain reduction in nine was observed. Side effects were generally mild in nature, consisting mostly of skin and mucosal changes, and were rapidly reversible upon discontinuation of the drug. Treatment was interrupted or discontinued in only two patients, and the dosage of vitamin A was reduced in one on account of toxicity. No hepatotoxicity was observed. Investigation of the chemopreventive role of either vitamin A or retinoids in patients with BBD who are at high risk of developing breast cancer is suggested.

Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid.

Banni S, Angioni E, Casu V, Melis MP, Carta G, Corongiu FP, Thompson H, Ip C. Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Universita degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.

Carcinogenesis 1999 Jun;20(6):1019-24

Previous research suggested that conjugated linoleic acid (CLA) feeding during the period of pubescent mammary gland development in the rat resulted in diminished mammary epithelial branching which might account for the reduction in mammary cancer risk. Terminal end buds (TEB) are the primary sites for the chemical induction of mammary carcinomas in rodents. One of the objectives of the present study was to investigate the modulation of TEB density by increasing levels of dietary CLA and to determine how this might affect the risk of methylnitrosourea-induced mammary carcinogenesis. The data show a graded and parallel reduction in TEB density and mammary tumor yield produced by 0.5 and 1% CLA. No further decrease in either parameter was observed when CLA in the diet was raised to 1.5 or 2%. Thus, optimal CLA nutrition during pubescence could conceivably control the population of cancer-sensitive target sites in the mammary gland. Since both CLA and linoleic acid are likely to share the same enzyme system for chain desaturation and elongation, it is possible that increased CLA intake may interfere with the further metabolism of linoleic acid. Fatty acid analysis of total lipid showed that CLA and CLA metabolites continued to accumulate in mammary tissue in a dose-dependent manner over the range 0.5-2% CLA. There was no perturbation in tissue linoleic acid, however, linoleic acid metabolites (including 18:3, 20:3 and 20:4) were consistently depressed by up to 1% CLA. Of particular interest was the significant drop in 20:4 (arachidonic acid), which is the substrate for the cyclooxygenase and lipoxygenase pathways of eicosanoid biosynthesis. Thus the CLA dose-response effect on arachidonic acid suppression corresponded closely with the CLA dose-response effect on cancer protection in the mammary gland. This information is critical in providing new insights regarding the biochemical action of CLA.

The epidemiology of DHEAS and cardiovascular disease.

Barrett-Connor E, Goodman-Gruen D. Department of Family and Preventive Medicine, University of California, San Diego, La Jolla 92093-0607, USA.

Ann N Y Acad Sci 1995 Dec 29;774:259-70

In 1986 we reported that high levels of plasma dehydroepiandrosterone sulfate (DHEAS) reduced the risk of fatal cardiovascular disease (CVD) in 242 men and increased the risk in 289 women from the Rancho Bernardo cohort who were followed up for 12 years. We report here an update on the epidemiology of DHEAS and CVD based on a 19-year follow-up of 1,029 men and 942 women aged 30-88 years from the same cohort. In cross-sectional analyses, DHEAS levels decreased with age in both sexes and were lower in women than men. Men who were overweight were more likely to have low DHEAS levels; women who had hypercholesterolemia or hypertension or were nonusers of estrogen therapy had higher DHEAS levels. Alcohol intake and cigarette smoking were associated with higher DHEAS levels in both sexes. All differences were no longer statistically significant after adjusting for alcohol intake. All participants were followed for vital status. After 19 years there were 254 CVD deaths in men and 199 CVD deaths in women. DHEAS was not associated with CVD or ischemic heart disease (IHD) deaths in age-adjusted analyses where the comparison group was individuals without CVD or IHD death. In contrast, when the comparison group was survivors, multiply adjusted models showed a statistically significant, modestly reduced risk of fatal CVD (RR = 0.85) in men and a nonsignificant increased risk of fatal CVD (RR = 1.11) in women.

Breast sonography.

Bassett, L.W., Kimme-Smith, C.

Am. J. Roentgenol. 1991; 156: 449-55.

No abstract available.

Effects of obesity on sex steroid metabolism.

Bates GW, Whitworth NS.

J Chronic Dis 1982;35(12):893-6

In a study designed to compare plasma androgens in obese, anovulatory women with non-obese, ovulatory women, we found a statistically significant increase in plasma androstenedione and testosterone in obese, anovulatory women. Plasma androstenedione was 252 18 ng/dl (mean SEM) in the obese women compared with 173 9 ng/dl in the non-obese ovulatory women (p less than 0.001). Plasma testosterone was 66 5.7 ng/dl (mean SEM) in the obese women compared with 41 3.0 ng/dl in the non-obese ovulatory women (p less than 0.001). Androstenedione and testosterone are the substrates for estrone and estradiol-17 beta production. Menstrual disorders associated with obesity are largely due to estrogen excess. From the findings of this study we suggest that androgen excess in obesity results in subsequent tonic estrogen production and estrogen excess.

Fruits and Vegetables and the Risk of Breast Cancer 1998 Dec.

BCERF. Program on Breast Cancer and Environmental Risk Factors in New York State. Ithaca, NY: Cornell University.

No abstract available.

Evening primrose oil and borage oil in rheumatologic conditions.

Belch, J.J., Hill, A. Department of Medicine, Ninewells Hospital and Medical School, Dundee, United Kingdom. j.j.f.belch@dundee.ac.uk

Am. J. Clin. Nutr. 2000 Jan; 71(1, Suppl.): 352S-356S.

Diets rich in arachidonic acid (20:4n-6) lead to the formation of 2-series prostaglandins (PGs) and 4-series leukotrienes (LTs), with proinflammatory effects. Nonsteroidal antiinflammatory drugs are used in rheumatoid arthritis to inhibit cyclooxygenase (prostaglandin-endoperoxide synthase), thereby decreasing production of 2-series PGs. Lipoxygenase activity remains intact, however, allowing LT production (eg, synthesis of LTB(4), a potent inflammatory mediator) to continue. Altering the essential fatty acid (EFA) content of the diet can modify some of these effects. Ingestion of a diet rich in evening primrose oil elevates concentrations of dihomo-gamma-linolenic acid (DGLA; 20:3n-6), which results in the production of 1-series PGs, eg, PGE(1). DGLA itself cannot be converted to LTs but can form a 15-hydroxyl derivative that blocks the transformation of arachidonic acid to LTs. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and thus suppress inflammation. The results of in vitro and animal work evaluating EFAs in inflammatory situations are encouraging, which has stimulated clinical workers to evaluate these compounds in rheumatoid arthritis. Several well-controlled, randomized clinical studies have now been completed in which various EFAs were evaluated as treatments. The results of most of these studies suggest some clinical benefit to these treatments; these data are reviewed here.


BeLieu RM. Department of Obstetrics and Gynecology, University of Missouri-Kansas City School of Medicine.

Obstet Gynecol Clin North Am. 1994 Sep;21(3):461-77.

The most important factors in the evaluation and treatment of breast pain consist of a thorough history, physical, and radiologic evaluation. These can be used to reassure the patient that she does not have breast cancer. In the 15% of mastalgia patients who have life-altering pain and still request treatment, therapy may consist of a well-fitting bra, a decrease in dietary fat intake, and discontinuance of oral contraceptives or hormone replacement therapy. Those women still resistant to therapy may experience relief from evening primrose oil supplements, bromocriptine, tamoxifen, or GnRH analogues. Predicting which treatment will be most useful for any particular woman may be challenging. No differences in success rates were found to be associated with factors such as reproductive history, presenting complaint, personal or family history of breast disease, or subsequent need for breast surgery. The peak (but not basal) serum prolactin levels in response to thyrotropin releasing hormone stimulus has been predictive of success for hormonal treatment but is relatively invasive. A survey of treatments actually used was obtained from 276 consultant surgeons in Britain in 1990. Of those, 75% prescribed danazol. Others used analgesia (21%), diuretics (18%), local excision (18%), bromocriptine (15%), evening primrose oil (13%), tamoxifen (9%), a well-fitting bra (3%), and no treatment (10%). Breast specialists were more likely to begin treatment with primrose oil, tamoxifen, vitamin B6, and analgesia, reserving other hormonal therapies for more difficult cases. To further evaluate the women who have severe mastalgia but do not complete treatment regimens, a questionnaire was sent to 79 patients who failed to return to the Longmore Breast Unit of Western General Hospital, Edinburgh. Seventy-one women responded. Of these, 36 said they felt better, 19 said they felt no more could be done, 18 learned to live with it, 14 were not worried even if the pain recurred, 2 were pregnant, 10 were postmenopausal, and 5 were still taking the medications previously prescribed. The prognosis for women with breast pain is not always predictable. Women with cyclic breast pain often are relieved by events that alter their hormonal milieu, whereas noncyclic breast pain may last only 1 to 2 years. Sitruk-Ware and colleagues conducted a study of French women with fibroadenomas. They found an association between fibroadenomas and cyclic mastalgia occurring more than 1 year prior to the first full-term pregnancy. A retrospective, case-control study to determine if cyclic mastalgia was a risk factor for breast cancer was conducted on 210 newly diagnosed women with breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Severe sexual impairment produced by morbid obesity. Report of a case.

Blum I, Marilus R, Barasch E, Sztern M, Bruhis S, Kaufman H. Department of Medicine C, Rokach (Hadassah) Hospital, Tel-Aviv, Israel.

Int J Obes 1988;12(3):185-9

A 45-year-old man, was admitted for investigation of severe sexual impairment. During 20 years of marriage, he had had no normal sexual intercourse and the couple was childless. Physical examination disclosed a severely obese man (weight 300 kg, height 1.75 m), with a relatively small and invaginated penis and small (5 ml) soft testes. Laboratory examinations disclosed the following: low serum testosterone (1 ng/ml), with a reduced response to HCG (3.8 ng/ml). Sex hormone binding globulin was at the lower limit of normal (0.38 microgram/dl), serum free testosterone was low (0.98% of total testosterone) as well as non-SHBG bound testosterone (22% of total testosterone). Daily total urinary estrogen excretion was increased (107 micrograms), the plasma estrone (78 pg/ml) and estradiol (74 pg/ml) were elevated. The gonadotropins were normal and responded adequately to LRH. Plasma growth hormone was decreased, prolactin, T4 and adrenal steroids were normal and responded normally to stimuli and inhibitors. Chromosomal constitution was 46XY. Thus, in this man the marked obesity produced a significant increase in estrogens which subsequently induced a severe decrease in testosterone and its free counterpart in excessive impairment of sexual function.

Benign breast diseases, carcinoma in situ, and breast cancer risk.

Bodian, C.A.

Epidemiol. Rev. 1993a; 15: 177-87.

No abstract available.

Prognostic significance of benign proliferative breast disease.

Bodian CA, Perzin KH, Lattes R, Hoffmann P, Abernathy TG.Department of Biomethematical Sciences, Mount Sinai Medical Center, New York, New York 10029.

Cancer 1993b Jun 15; 71(12): 3896-3907.

BACKGROUND. Recent studies concerning an association between benign breast diseases and risk of subsequent breast cancer have focused on benign proliferative lesions recognized in biopsy specimens. Some have implicated atypical hyperplasia as being associated with the greatest risk. METHODS. The histologic sections of specified benign breast lesions from 1799 women were reviewed and reclassified, using published criteria for proliferative disease. Prognostic significance was assessed by relating the pathologic findings to the development of breast cancer observed during an average 21 years of follow-up, in which time 157 women developed the disease. RESULTS. Benign proliferative changes were recognized in 85% of the patients, with a corresponding relative risk of subsequent carcinoma equal to 2.2 times population rates (95% confidence limits, 1.9 and 2.6). Increasing levels of hyperplasia and atypia in lobules or ducts were associated with modest increases in risk, ranging from 2.1 to 2.3 to 3.0 for proliferative changes with no atypia, mild atypia, and moderate to severe atypia, respectively. This trend was not statistically significant. The most significant risk indicators in this study were the presence of adenosis (relative risk, 3.7), and moderate or severe atypia in ducts (relative risk, 3.9). CONCLUSIONS. Benign proliferative breast disease recognized in biopsy specimens is associated with an increased risk of future breast cancer, but fine distinctions among levels of hyperplasia and atypia did not significantly distinguish risk among patients in this study.

Reproducibility and validity of pathologic classifications of benign breast disease and implications for clinical applications.

Bodian CA, Perzin KH, Lattes R, Hoffmann P. Department of Biomathematical Sciences, Mount Sinai Medical Center, New York, NY 10029.

Cancer 1993c Jun 15; 71(12): 3908-13.

BACKGROUND. Research studies on the relationship between benign breast diseases and cancer risk typically identify certain conditions as risk factors, and others as carrying no prognostic significance. This study addresses several issues concerning the relevance of such research results for advising individual patients in a clinical setting. METHODS. Data were obtained as part of a "blinded" retrospective pathology review of benign breast biopsies. A random sample of cases was reviewed twice, providing information about reliability. Comparisons with diagnoses that used information from the operative reports and gross pathology descriptions as well as microscopic histology were used to assess validity. RESULTS. Among cases that were reviewed twice, excellent agreement was achieved for diagnosing carcinoma and lobular neoplasia, good agreement for adenosis and intraductal papilloma, and relatively poor agreement about levels of hyperplasia and atypia, and whether ducts or lobules were involved. Distinctions among levels of hyperplasia also apparently were influenced by the number of slides available for review. The "blinded" review diagnoses frequently differed from the diagnoses that used all information available at the time of surgery in detecting the presence or absence of gross cystic disease, and in distinguishing solitary from multiple papillomas. CONCLUSIONS. Problems with reliability of precise distinctions among levels and sites of hyperplasia and atypia seem to limit the usefulness of such classifications as guidelines for individual patient care. For conditions with some clinical manifestations, diagnoses based exclusively on histologic review of biopsy specimens often are not accurate.

Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy.

Boyd NF, McGuire V, Shannon P, Cousins M, Kriukov V, Mahoney L, Fish E, Lickley L, Lockwood G, Tritchler D. Ludwig Institute for Cancer Research, Toronto Branch, Ontario, Canada.

Lancet 1988 Jul 16;2(8603):128-32

21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.

Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group.

Boyd NF, Greenberg C, Lockwood G, Little L, Martin L, Byng J, Yaffe M, Tritchler D. Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Canada.

J Natl Cancer Inst 1997 Apr 2;89(7):488-96

BACKGROUND: The appearance of breast tissue on mammography varies according to its composition. Fat is radiolucent and appears dark on mammography, while stromal and epithelial tissue has greater optical density and appears light. Extensive areas of radiologically dense breast tissue seen on mammography are associated with an increased risk of breast cancer. PURPOSE: The purpose of the present study was to determine whether the adoption of a low-fat, high-carbohydrate diet for 2 years would reduce breast density. METHODS: Women with radiologic densities in more than 50% of the breast area on mammography were recruited and randomly allocated to an intervention group taught to reduce intake of dietary fat (mean, 21% of calories) and increase complex carbohydrate (mean, 61% of calories) or to a control group (mean, 32% of calories from fat and 50% of calories from carbohydrates). Mammographic images from 817 subjects were taken at baseline and compared with those taken 2 years after random allocation by use of a quantitative image analysis system, without knowledge of the dietary group of the subjects or of the sequence in which pairs of images had been taken. The effects of the intervention on the mammographic features of breast area, area of dense tissues in the breast, and the percent of the breast occupied by dense tissue were examined using t tests. Multiple regression was used to examine these effects while accounting for age at trial entry, weight change, and menopausal status. RESULTS: After 2 years, the total area of the breast was reduced by an average of 233.7 mm2 (2.4%) (95% confidence interval [CI] = 106.9-360.6) in the intervention group compared with an average increase of 26.3 mm2 (0.3%) (95% CI = -108.0-160.5) in the control group (P = .01). The area of density was reduced by 374.4 mm2 (6.1%) (95% CI = 235.1-513.8) in the intervention group compared with an average of 127.7 mm2 (2.1%) (95% CI = 8.6-246.7) in the control group (P = .01). Weight loss was associated with a reduction in breast area. The effect of the intervention on breast area was only marginally statistically significant after weight change, menopausal status, and age at trial entry were taken into account (P = .06). Greater weight loss and becoming postmenopausal were associated with statistically significant reductions in the area of density on the mammographic image at 2 years (P = .04 and < 001, respectively). Age at entry into the trial was marginally significant in the same direction (P = .06). The effect of the intervention on area of density remained statistically significant after controlling for weight loss, age at entry, and menopausal status (P = .03). The change in the percentage of dense tissue in the mammographic image was not significantly different between the two groups (P = .71). CONCLUSIONS AND IMPLICATIONS: These results show that after 2 years, a low-fat, high-carbohydrate diet reduced the area of mammographic density, a radiographic feature of the breast that is a risk factor for breast cancer. Longer observation of a larger number of subjects will be required to determine whether these effects are associated with changes in risk of breast cancer.

Caffeine consumption and fibrocystic breast disease: a case-control epidemiologic study.

Boyle CA, Berkowitz GS, LiVolsi VA, Ort S, Merino MJ, White C, Kelsey JL.

J Natl Cancer Inst 1984 May;72(5):1015-9

In a hospital-based case-control study that included 634 women with fibrocystic breast disease and 1,066 comparison women in Connecticut, the occurrence of fibrocystic breast disease was positively associated with average daily consumption of caffeine. Women who consumed 31-250 mg of caffeine/day had a 1.5-fold increase in the odds of disease, whereas womitant papillomatosis or papillary hyperplasia, both of which have been associated with an increased breast cancer risk. The association was specific to fibrocystic breast disease in that there was no association of cafen who drank over 500 mg/day had a 2.3-fold increase in the odds. The association with caffeine consumption was especially high among women with atypical lobular hyperplasia and with sclerosing adenosis with concomfeine consumption with fibroadenoma or other forms of benign breast disease.

Long-term responses of women to indole-3-carbinol or a high fiber diet.

Bradlow HL, Michnovicz JJ, Halper M, Miller DG, Wong GY, Osborne MP. Institute for Hormone Research, New York, New York 10021-4004.

Cancer Epidemiol Biomarkers Prev 1994 Oct-Nov;3(7):591-5

We test the hypothesis that the estrogen metabolite ratio 2-OH-estrone:estriol can be raised via dietary indole-3-carbinol (I3C) and that this higher ratio can be sustained over a 3-month test period. We also explore the possible role of pure fiber on estradiol metabolism. Using a randomized clinical trial with three arms, each containing 20 subjects, arm 1 received 400 mg/day of I3C daily for 3 months, arm 2 received 20 g of alpha-cellulose daily for the same time period as a source of added fiber, and arm 3 received a placebo dose. Blood levels of a variety of biochemical parameters were measured. The urinary 2-OH-estrone:estriol estrogen metabolite ratio was measured monthly at the same time of the menstrual cycle. While no changes were observed in the control and alpha-cellulose-treated arms, a substantial mean increase in the ratio was observed in the I3C-treated arm at month 1; that increase was maintained over the 3-month time period. Three of the 20 subjects in this I3C-treated group differed from the others in that no significant change in the metabolite ratio was observed at any time point. The results suggest that I3C can serve to increase the 2-OH-estrone:estriol metabolite ratio in a sustained manner without detectable side effects and that some individuals may be resistant to such change.

Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent.

Bradlow HL, Sepkovic DW, Telang NT, Osborne MP. Strang Cancer Research Laboratory, New York, New York 10021, USA. leon@rockvax.rockefeller.edu

Ann N Y Acad Sci 1999;889:204-13

Previous studies from this laboratory have suggested that 2-hydroxyestrone is protective against breast cancer, whereas the other principal metabolite, 16 alpha-hydroxyestrone, and the lesser metabolite quantitatively, 4-hydroxyestrone, are potent carcinogens. Attempts to directly decrease the formation of the 16-hydroxylated metabolite were either unsuccessful or required such high levels of the therapeutic agent as to be impractical. On the other hand the concentration of the protective metabolite, 2-hydroxyestrone, proved to be readily modulated by a variety of agents, both in the direction of increased protection and the opposite direction, increased risk by a variety of agents and activities. We have focussed our attention on indole-3-carbinol, a compound found in cruciferous vegetables, and its further metabolites in the body, diindolylmethane (DIM) and indolylcarbazole (ICZ), because of its relative safety and multifaceted activities. It has been shown that it induces CyP4501A1, increasing 2-hydroxylation of estrogens, leading to the protective 2-OHE1, and also decreases CyP1B1 sharply, inhibiting 4-hydroxylation of estradiol, thereby decreasing the formation of the carcinogenic 4-OHE1. In addition to these indirect effects as a result of altered estrogen metabolism, indole-3-carbinol has been shown to have direct effects on apoptosis and cyclin D, resulting in blockage of the cell cycle. In addition to its antitumor activity in animals, it has also been shown to be effective against HPV-mediated tumors in human patients. All of these responses make the study of its behavior as a therapeutic agent of considerable interest.

Phytochemicals as modulators of cancer risk.

Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. Strang Cancer Research Laboratory, New York, NY 10021, USA.

Adv Exp Med Biol 1999;472:207-21

These results, describing antitumor activity of some of the phytochemicals that have been actively studied, suggest that dietary changes could play a role in decreasing the incidence of a variety of tumors. 13C and the other compounds discussed may well be only prototypes for other as yet unexplored phytochemicals present in the diet. There have been no attempts to explore the possibilities of synergistic action among the various phytochemicals, 13C, limonene, curcumin, epigallocatechin gallate, sulforaphene, or genistein. Mixtures of these compounds might well show potency at lower doses for each of the compounds and show even greater promise than that already demonstrated.

Is there an increased risk of breast cancer in women who have had a breast cyst aspirated?

Bundred NJ, West RR, Dowd JO, Mansel RE, Hughes LE. Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, UK.

Br J Cancer. 1991 Nov;64(5):953-5.

A consecutive series of 644 women who presented with breast nodularity between 1976 and 1982 have been followed up to determine their rate of subsequent breast cancer. Fifteen women have developed breast cancer, 14 of these were among 352 women with an aspirated cyst (relative risk 4.4). Women with multiple cysts had the highest risk and women with breast nodularity had no excess risk. Review of histology specimens from those women who had undergone biopsy showed an excess of florid epithelial hyperplasia in women who subsequently developed breast cancer and women with multiple aspirated cysts were more likely to have florid epithelial hyperplasia. Multiple cysts are clinical markers of histological breast proliferation and women who have had multiple breast cysts aspirated have an increased risk of breast cancer and should be advised to practice regular self examination.

Identifying the Breast Cancer Target for Indole-3-Carbinol (unpublished).

Chatterji, U.

Postdoctorate Fellowship 2001-2002. Berkeley, CA: University of California.

Management of cyclical mastalgia in oriental women: pioneer experience of using gamolenic acid (Efamast) in Asia.

Cheung KL. Department of Surgery, The University of Hong Kong, Queen Mary Hospital and Tung Wah Hospital. mszklc@msnl.surgery.nottingham.ac.uk

Aust N Z J Surg. 1999 Jul;69(7):492-4.

BACKGROUND: In most Western countries gamolenic acid is the first-line treatment for women with cyclical mastalgia. METHODS: A prospective study was carried out in the breast referral clinic of the Department of Surgery, University of Hong Kong to evaluate the treatment of cyclical mastalgia using gamolenic acid provided in evening primrose oil (Efamast, Scotia Pharmaceuticals Ltd, Scotia House, Stirling, Scotland) as a pioneer experience in Asia. In addition, the features of cyclical mastalgia in Oriental women were studied by conducting a survey using anonymous questionnaires. RESULTS: Sixty-six women with disturbing cyclical mastalgia seen by one breast surgeon were followed up with a breast pain diary. Thirty-four women had persistently disturbing mastalgia and were commenced on Efamast. Responses were measured at 3 and 6 months according to a standardized protocol. An overall useful response rate of 97% was observed at 6 months. Side-effects were found in 12% but all were insignificant. CONCLUSIONS: Efamast may be recommended as a first-line specific treatment for Oriental women with disturbing cyclical mastalgia.

Alternation of hepatic antioxidant enzyme activities and lipid profile in streptozotocin-induced diabetic rats by supplementation of dandelion water extract.

Cho SY, Park JY, Park EM, Choi MS, Lee MK, Jeon SM, Jang MK, Kim MJ, Park YB. Department of Food and Nutrition, Yeungnam University, Kyongsan 712-749, South Korea.

Clin Chim Acta. 2002 Mar;317(1-2):109-17.

BACKGROUND: Dandelion water extract (DWE), an herbal medication, may have an effect on the activity and mRNA expression of hepatic antioxidant enzymes and lipid profile in streptozotocin (STZ)-induced diabetic rats. METHODS: Male Sprague-Dawley rats were divided into nondiabetic (control), diabetic, and diabetic-DWE-supplemented groups. Diabetes was induced by injecting streptozotocin (55 mg/kg BW, i.p.) in a citrate buffer. The extract was supplemented in 2.4 g of a DWE/kg diet. RESULTS: The DWE supplement significantly decreased the serum glucose concentration in the diabetic rats. The hepatic superoxide dismutase and catalase activities significantly increased and the GSH-Px activity decreased in the diabetic rats, compared with the control group. When the DWE supplement was given to the diabetic rats, the antioxidant enzyme activity reverted to near-control values. However, there was no difference in the mRNA expression concentrations of these enzymes between the groups. With regard to the hepatic lipid peroxidation product, the malondialdehyde (MDA) content was significantly higher in the diabetic group than in the nondiabetic group. However, the DWE supplement lowered the hepatic MDA concentration in the diabetic-induced rats. The DWE supplement also lowered the total cholesterol and triglyceride concentrations in the serum and hepatic tissue, while increasing the serum HDL-cholesterol in the diabetic rats. CONCLUSIONS: A DWE supplement can improve the lipid metabolism and is beneficial in preventing diabetic complications from lipid peroxidation and free radicals in diabetic rats.

Nutrient intake, adiposity, plasma total cholesterol, and blood pressure of rural participants in the (Vermont) Nutrition Program for Older Americans (Title III).

Clarke RP, Schlenker ED, Merrow SB.

Am J Clin Nutr. 1981 Sep;34(9):1743-51.

The interrelationships of obesity, hypertension, elevated plasma cholesterol (risk factors), and intakes of selected nutrients were examined among elderly subjects attending a congregate meal program in Vermont. Mean nutrient intakes were significantly higher for 22 males compared to 69 females. Mean plasma cholesterol levels were higher in females. Age, systolic and diastolic blood pressure, and indices of adiposity showed no sex differences. Intakes of total fat and animal protein increased in males but plasma cholesterol decreased with age. Systolic blood pressure in females increased while body mass index decreased with age. A higher proportion of females had plasma cholesterol levels greater than or equal 260 mg/100 ml and a higher proportion of females than males greater than 73 yr of age had blood pressures at risk level. There was a greater proportion of females than males with both elevated plasma cholesterol levels and adiposity. Similarly the females had greater incidence of the combination of any two risks. No males, compared to 9% of females, were in the all three risk category.

In vivo dehydroepiandrosterone restores age-associated defects in the protein kinase C signal transduction pathway and related functional responses.

Corsini E, Lucchi L, Meroni M, Racchi M, Solerte B, Fioravanti M, Viviani B, Marinovich M, Govoni S, Galli CL. Department of Pharmacological Sciences, University of Milan, Milan, Italy. emanuela.corsini@unimi.it

J Immunol 2002 Feb 15;168(4):1753-8

Elderly subjects are at increased risk of pneumonia, influenza, and tuberculosis. Besides the known age-related decrease in mechanisms for mechanical clearance of the lungs, impaired alveolar macrophage function contributes to the increased risk of illness in the elderly. We have previously shown that age-induced macrophage immunodeficiencies are associated with a defective system for anchoring protein kinase C. Castration of young male rats produces effects on alveolar macrophages similar to those of aging, suggesting a relationship between circulating sex hormones, particularly androgens, and the decreases in the receptor for activated C kinase (RACK-1) and macrophage function observed. The aging process in humans and rats is associated with a decline in the plasma concentrations of dehydroepiandrosterone (DHEA) and its sulfate, among other steroid hormones. We report here that in vitro and in vivo administration of DHEA to rats restores the age-decreased level of RACK-1 and the LPS-stimulated production of TNF-alpha in alveolar macrophages. DHEA in vivo also restores age-decreased spleen mitogenic responses and the level of RACK-1 expression. These findings suggest that the age-related loss in immunological responses, linked to defective pathways of signal transduction, are partially under hormonal control and can be restored by appropriate replacement therapy.

Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells.

Cover CM, Hsieh SJ, Cram EJ, Hong C, Riby JE, Bjeldanes LF, Firestone GL. Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, 94720-3200, USA.

Cancer Res 1999 Mar 15;59(6):1244-51

The current options for treating breast cancer are limited to excision surgery, general chemotherapy, radiation therapy, and, in a minority of breast cancers that rely on estrogen for their growth, antiestrogen therapy. The naturally occurring chemical indole-3-carbinol (I3C), found in vegetables of the Brassica genus, is a promising anticancer agent that we have shown previously to induce a G1 cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. Combinations of I3C and the antiestrogen tamoxifen cooperate to inhibit the growth of the estrogen-dependent human MCF-7 breast cancer cell line more effectively than either agent alone. This more stringent growth arrest was demonstrated by a decrease in adherent and anchorage-independent growth, reduced DNA synthesis, and a shift into the G1 phase of the cell cycle. A combination of I3C and tamoxifen also caused a more pronounced decrease in cyclin-dependent kinase (CDK) 2-specific enzymatic activity than either compound alone but had no effect on CDK2 protein expression. Importantly, treatment with I3C and tamoxifen ablated expression of the phosphorylated retinoblastoma protein (Rb), an endogenous substrate for the G1 CDKs, whereas either agent alone only partially inhibited endogenous Rb phosphorylation. Several lines of evidence suggest that I3C works through a mechanism distinct from tamoxifen. I3C failed to compete with estrogen for estrogen receptor binding, and it specifically down-regulated the expression of CDK6. These results demonstrate that I3C and tamoxifen work through different signal transduction pathways to suppress the growth of human breast cancer cells and may, therefore, represent a potential combinatorial therapy for estrogen-responsive breast cancer.

[Risk factors associated with obesity: a metabolic perspective] [Article in French]

Despres JP, Pascot A, Lemieux I. Institut de cardiologie de Quebec, Centre de recherche de l'Hopital Laval, Pavillon Mallet, 2e etage, 2725, chemin Sainte-Foy, Sainte-Foy (Quebec), GIV 4G5. jean-pierre.depres@crchul.ulaval.ca

Ann Endocrinol (Paris) 2000 Dec;61 Suppl 6:31-38

Obesity, especially visceral obesity, is associated with a cluster of metabolic complications increasing the risk of type 2 diabetes and coronary heart disease. It has been shown that obese patients characterized by a high accumulation of visceral adipose tissue have increased glycemic and insulinemic responses to an oral glucose load compared to normal weight individuals or to obese individuals with a low accumulation of visceral adipose tissue. Viscerally obese patients are also characterized by an unfavourable plasma lipid profile which includes elevated triglyceride and apolipoprotein B concentrations, reduced HDL-cholesterol levels as well as an increased proportion of small, dense LDL particles. Such alterations in the lipid profile are often observed even in the absence of elevated LDL-cholesterol concentrations. Our work has clearly shown that this cluster of metabolic abnormalities found among viscerally obese patients was associated with a substantial increase in coronary heart disease risk. Our work has also shown that the "metabolic triad" of non-traditional risk factors (hyperinsulinemia, elevated apolipoprotein B levels, increased proportion of small, dense LDL particles) was associated with a 20-fold increase in the risk of coronary heart disease. In this regard, we have been interested in developing simple tools which would allow clinicians to identify at an early stage and at low cost individuals who would be carriers of the atherogenic metabolic triad. We have noted that the measurement and interpretation of waist circumference and of fasting plasma triglyceride levels could allow the identification of a high proportion of carriers of the metabolic triad. Indeed, less than 10% of men with a waist circumference below 90 cm and triglyceride concentrations below 2 mmol/l were characterized by the features of the metabolic triad. However, more than 80% of individuals with a waist circumference above 90 cm and triglyceride levels above 2 mmol/l were carriers of the metabolic triad. Finally, an elevated visceral adipose tissue accumulation has also been associated with a thrombogenic and a pro-inflammatory metabolic profile which would be predictive of an unstable atherosclerotic plaque. Therefore, the stabilisation of the atherosclerotic plaque may represent a legitimate therapeutic objective to reduce the risk of coronary heart disease among patients with visceral obesity. It is proposed that a rather modest weight loss (approximately 10%) could contribute to substantially improve the risk profile of these patients.

Treatment of fibrocystic mastopathy with hydrolytic enzymes

Ditmar F.-W.; Luh W. Dept. Obstetrics and Gynecology, District Hospital Starnberg, Osswaldstr 1,D-82319 Starnberg Germany

International Journal of Experimental and Clinical Chemotherapy (Germany) 1993, 6/1 (9-20)

Fibrocystic mastopathy affects about 50 % of all women in the course of their lives. Because of subjective symptoms, the risk of malignant degeneration (5 % of all cases), and ensuing physical and psychological stress, treatment of fibrocystic mastopathy is indispensable. So far, there is no causal therapy. Most common therapeutical regimens are associated with severe side effects. Therefore, the effect of treatment with an enzyme combination preparation was compared with that of placebo in a randomized double blind study in 96 patients with mastopathy over a study period of 6 weeks. At the start of the study both groups were well comparable with respect to all relevant study parameters. At the end of the study period there were significant differences regarding the parameters of effectiveness 'diameter of the largest cyst' (p = 0.003), 'subjective disturbance by symptoms' (p = 0.001) and 'cumulative score of complaints (< 0.001). As far as the number of cysts is concerned, there was no significant difference at the end of the study period (p = 0.695). Bearing in mind, however, that the initial condition was somewhat worse in the group treated with enzymes, a tendency towards better effectiveness of the enzyme combination preparation was observed with respect to this criterion, too. The difference of absolute change was significant (p = 0.008). The assessment of effectiveness by physician and patient showed clear advantages of the enzyme therapy over placebo. There was a higher number of mostly mild side effects in the enzyme group, but only stomach complaints and loose stool. Since tolerance was also comparable with that of placebo, the results obtained lead to the conclusion that the enzyme combination preparation lends itself to the symptomatic treatment of fibrocystic mastopathy. Further longer-term studies, including biopsies and determination of hormonal parameters, will clarify whether causal treatment of fibrocystic mastopathy is possible.

The epidemiology of benign breast disease.

Ernster V.L.

Epidemiol. Rev. 1981; 3: 184-202.

No abstract available.

Mastodynia due to fibrocystic disease of the breast controlled with thyroid hormone.

Estes NC.

Am J Surg 1981 Dec;142(6):764-6

Nineteen patients were evaluated for breast pain and nodularity associated with fibrocystic disease. Rapid pain relief occurred in 73 of patients, with total relief in 47 percent after daily treatment with 0.1 mg of levothyroxine. Softening of breast tissue and decreased nodularity occurred within 3 months in many patients. Three patients had elevated levels of serum prolactin before treatment, with dramatic pain relief and normalization of prolactin levels after treatment. Further trials of levothyroxine in patients with mastodynia due to fibrocystic disease appear justified.

Double-blind controlled trial of tamoxifen therapy for mastalgia.

Fentiman IS, Caleffi M, Brame K, Chaudary MA, Hayward JL.

Lancet 1986 Feb 8;1(8476):287-8

60 patients with severe mastalgia of more than 6 months' duration were randomly selected for treatment with either tamoxifen 20 mg daily or placebo for 3 months. As measured by linear analogue scoring, pain relief was achieved in 22/31 (71%) of those receiving tamoxifen and 11/29 (38%) of those taking placebo. Patients who did not respond to the first course of treatment were allocated to the alternative treatment for 3 months. Pain control was achieved in 8/12 (75%) of those receiving tamoxifen and 2/6 (33%) of those receiving placebo. The commonest side-effects were hot flushes (27% of patients receiving tamoxifen and 11% of those receiving placebo) and vaginal discharge (17% tamoxifen, 7% placebo). Side-effects caused 6 patients in each group to discontinue treatment. Tamoxifen is of value in the management of severe cyclical and non-cyclical mastalgia, and relief can be achieved without undue side-effects in the majority of patients.

A prospective study of the removal rate of imaged breast lesions by an 11-gauge vacuum-assisted biopsy probe system.

Fine RE, Israel PZ, Walker LC, Corgan KR, Greenwald LV, Berenson JE, Boyd BA, Oliver MK, McClure T, Elberfeld J. The Breast Center, 702 Canton Rd., Marietta, GA 30060, USA.

Am J Surg 2001 Oct;182(4):335-40

BACKGROUND: More than 1,000,000 breast biopsies are performed each year as a result of abnormalities identified by imaging techniques. This prospective study was designed to determine whether complete removal of the imaged evidence of an abnormal mammogram or ultrasonogram could be achieved with percutaneous image-guided procedures using an 11-gauge vacuum-assisted biopsy probe. METHODS: Forty-five women over the age of 18 years entered the study; 50 breast lesions were identified by ultrasonography or mammography. Biopsies were obtained using an 11-gauge vacuum-assisted probe. At 6 months after biopsy, ultrasonography or mammography examinations of the biopsy site were performed. RESULTS: Forty-five lesions (90%) were completely removed. At 6 months after biopsy, 82% of the sites were lesion free. The percentage of nonrecurring lesions at 6 months after surgery was inversely related to the size of the original lesion. CONCLUSION: This device allows biopsies to be successfully combined with complete removal of the imaged lesion in a one-step minimally invasive procedure.

Retinoid antagonism of estrogen-responsive transforming growth factor alpha and pS2 gene expression in breast carcinoma cells.

Fontana JA, Nervi C, Shao ZM, Jetten AM. Department of Medicine, University of Maryland Cancer Center, Baltimore.

Cancer Res 1992 Jul 15;52(14):3938-45

Exposure of MCF-7 breast carcinoma cells to estradiol results in an increase in transforming growth factor alpha (TGF-alpha) synthesis and secretion. Since TGF-alpha is a potent inducer of proliferation in MCF-7 cells, the increase in TGF-alpha production by estradiol is thought to play an important role in the estrogen stimulation of growth of these cells. Retinoic acid inhibits the proliferation of MCF-7 cells and antagonizes the estrogen stimulation of growth. Addition of retinoic acid resulted in a greater than 70% inhibition of estradiol-induced TGF-alpha synthesis and secretion in MCF-7 cells. The increase in TGF-alpha mRNA expression by estradiol was also inhibited by exposure of the cells to retinoic acid. Pretreatment of the cells with retinoic acid for 24 or 72 h caused more than 50 and 90% inhibition, respectively, of the estradiol-enhanced expression of TGF-alpha mRNA. Expression of pS2 mRNA in MCF-7 cells was stimulated approximately 8-fold by estradiol. Retinoic acid treatment suppressed by greater than 80% both the basal and estradiol-induced pS2 mRNA expression. Retinoic acid modulation of the estrogen receptor gene mRNA was not responsible for the retinoic acid inhibition of the stimulation of pS2 and TGF-alpha gene expression by estradiol, since estrogen receptor gene expression was increased rather than decreased in the presence of retinoic acid. The nuclear retinoic acid receptors alpha and gamma mRNA were expressed in MCF-7 cells and its retinoic acid-resistant derivative RROI. Addition of estradiol to MCF-7 cells resulted in a decreased expression of retinoic acid receptor gamma mRNA; this reduction is prevented by the presence of retinoic acid. These results indicate that retinoic acid can inhibit estradiol-induced TGF-alpha and pS2 mRNA expression in MCF-7 cells. The suppression of TGF-alpha expression may represent one possible mechanism by which retinoic acid antagonizes the stimulation of MCF-7 proliferation by estradiol.

Intake of macronutrients and risk of breast cancer.

Franceschi S, Favero A, Decarli A, Negri E, La Vecchia C, Ferraroni M, Russo A, Salvini S, Amadori D, Conti E, et al. Servizio di Epidemiologia, Centro di Riferimento Oncologico, Aviano, Italy.

Lancet 1996 May 18;347(9012):1351-6

BACKGROUND: The association between risk of breast cancer and dietary fat and intakes of other energy sources remains controversial. The Italian population offers special opportunities to assess the influence of high intakes of unsaturated fat and starch and, because the population has low awareness of diet and cancer issues, there is less scope for recall bias. We have assessed the relations of various macronutrient intakes with risk of breast cancer. METHODS: In this case-control study, 2569 women with incident breast cancer (median age 55 years) and 2588 control women (median age 56 years) in hospital with acute, non-neoplastic diseases, were interviewed in six different areas of Italy between 1991 and 1994. A validated food-frequency questionnaire was used. It included questions on 78 foods and recipes grouped into six sections, as well as specific questions on individual fat intake pattern. FINDINGS: The risk of breast cancer decreased with increasing total fat intake (trend p 0.01) whereas the risk increased with increasing intake of available carbohydrates (trend p = 0.002). The odds ratios for women in the highest compared with the lowest quintile of energy-adjusted intake were 0.81 for total fat and 1.30 for available carbohydrates. Starch was the chief contributor to the positive association with available carbohydrates. High intakes of polyunsaturated and unsaturated fatty acids (i.e., polyunsaturated fatty acids plus oleic acid) were associated with a decreased risk of breast cancer (odds ratios for highest vs lowest quintile 0.70 and 0.74, respectively). Conversely, the intakes of saturated fatty acids, protein, and fibre were not significantly associated with breast-cancer risk. INTERPRETATION: This case-controls study shows that unsaturated fatty acids protect against breast cancer, possibly because intake of these nutrients is closely correlated with a high intake of raw vegetables. The findings also suggest a possible risk in southern European populations, of reliance on a diet largely based on starch.

Plasma fatty acid profiles in benign breast disorders.

Gateley CA, Maddox PR, Pritchard GA, Sheridan W, Harrison BJ, Pye JK, Webster DJ, Hughes LE, Mansel RE. University Department of Surgery, University of Wales College of Medicine, Cardiff, UK.

Br J Surg 1992 May;79(5):407-9

Breast pain (mastalgia) and macroscopic breast cysts present commonly. Mastalgia may be improved by dietary manipulation to reduce saturated fat or supplement essential fatty acid intake. Fatty acid profiles were measured in women with mastalgia and breast cysts, before and during treatment with evening primrose oil, a rich source of essential fatty acids. The fatty acid profiles of both groups of patients were abnormal, with increased proportions of saturated fatty acids and reduced proportions of essential fatty acids. Treatment with evening primrose oil improved the fatty acid profiles towards normal, but this was not necessarily associated with a clinical response.

Management of cyclical breast pain.

Gateley CA, Mansel RE. University of Wales College of Medicine, Cardiff.

Br J Hosp Med 1990 May;43(5):330-2

Cyclical breast pain or mastalgia occurs in up to 70% of the female population. After exclusion of breast cancer and proper reassurance, only 15% of patients initially presenting will require drug treatment. Using bromocriptine, danazol and evening primrose oil some 77% of patients treated can obtain useful relief of their symptoms.

Management of the painful and nodular breast.

Gateley CA, Mansel RE. University Department of Surgery, University Hospital of South Mancheser, UK.

Br Med Bull 1991 Apr;47(2):284-94

Mild breast pain and nodularity are common and may be considered normal. Only when symptoms are severe enough to affect the patient's lifestyle should drug treatment be considered. Using danazol, bromocriptine or evening primrose oil a clinically useful improvement in pain can be anticipated in 77% of patients with cyclical mastalgia and 44% with non-cyclical mastalgia. Benign nodularity should not be biopsied surgically as it is unnecessary and makes subsequent assessment of the breast difficult.

Iodine replacement in fibrocystic disease of the breast.

Ghent WR, Eskin BA, Low DA, Hill LP. Department of Surgery, Queen's University, Hotel Dieu Hospital, Kingston, Ont.

Can J Surg 1993 Oct;36(5):453-60

OBJECTIVE: To determine the response of patients with fibrocystic breast disease to iodine replacement therapy. DESIGN: Review of three clinical studies beginning in 1975: an uncontrolled study with sodium iodide and protein-bound iodide; a prospective, control, crossover study from iodide to molecular iodine; and a prospective, control, double-blind study with molecular iodine. SETTING: University affiliated breast-treatment clinics. PATIENTS: Study 1: 233 volunteers received sodium iodide for 2 years and 588 received protein-bound iodide for 5 years. Study 2: the treatment of 145 patients from study 1 treated with protein-bound iodide for several months who still had symptoms was switched to molecular iodine 0.08 mg/kg; 108 volunteers were treated initially with molecular iodine. Study 3: 23 patients received molecular iodine, 0.07 to 0.09 mg/kg body weight; 33 received an aqueous mixture of brown vegetable dye and quinine. The numbers in study 2 increased over the review period so that 1365 volunteers were being treated with molecular iodine by 1989. INTERVENTIONS: All patients in study 3 had pre- and post-treatment mammography and measurement of serum triiodothyronine, thyroxine and thyroid-stimulating hormone levels. MAIN OUTCOME MEASURES: Subjective evaluation--freedom from pain--and objective evaluation--resolution of fibrosis. RESULTS: Study 1: 70% of subjects treated with sodium iodide had clinical improvement in their breast disease, but the rate of side effects was high; 40% of patients treated with protein-bound iodide had clinical improvement. Study 2: 74% of patients in the crossover series had clinical improvement, and objective improvement was noted in 72% of those who received molecular iodine initially. Study 3: in the treatment group 65% had subjective and objective improvement; in the control group there was a subjective placebo effect in 33% and an objective deterioration of 3%. CONCLUSIONS: The fibrocystic breast reacts differently to sodium iodide, protein-bound iodide and molecular iodine. Molecular iodine is nonthyrotropic and was the most beneficial.

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