池田正: 日本における乳腺症の概念と診断の現状に関するアンケート結果. 癌の臨床. 1997;43:1-5.
H Yoshida, A Kadota, R Fukunishi, K Matsumoto
Induction of mammary dysplasia and mammary carcinoma in neonatally androgenized female rats by 7,12-dimethylbenz[a]anthracene.
J Natl Cancer Inst. 1980 May;64(5):1105-12.
Abstract/Text
Effects of neonatal androgenization on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis infemale noninbred Sprague-Dawley rats are reported. Testosterone propionate (1.25 mg) was injected sc into 29 2-day-old rats. At 50 days of age, all rats were given 20 mg of DMBA through a stomach tube. In these androgenized rats, no corpora lutea were found in the ovaries and the induction of mammary carcinoma by DMBA was strongly suppressed, whereas the induction of mammary dysplasia was significantly accelerated in comparison with the neonatally intact controls. Mammary dysplasia in the androgenized group varied widely, with two kinds of macroscopically detectable tumor-forming lesions (solid and cystic) and with microscopic characteristics of acinar adenosis, fibrotic adenosis, fibrosis, intraductal papillary proliferative lesions, and epithelial cysts. The earliest lesions of mammary dysplasia observed were acinar adenosis nodules and microcysts, both of which appeared as multifocal phenomena as early as 25 days after administration of DMBA.
Krzysztof Sieja, Stanisław Stanosz
[The concentrations of prolactin and estrogens in women with fibrocystic changes in the breast].
Ginekol Pol. 2002 Jul;73(7):594-9.
Abstract/Text
OBJECTIVE AND STUDY DESIGN: To evaluate the concentrations of prolactin and estrogens in blood sera in women with fibrocystic changes in the breast (FCC).
MATERIAL AND METHODS: The control group consisted of 32 women without any pathological changes in the breast (mean age 44.9 +/- 4.4 y.). The studied group comprised 81 women having FCC (mean age 45.5 +/- 3.5 y.). Both groups were divided into two subgroups according to age: the first subgroup ranged 40-44 y. and the second 45-51 y. The hormonal profiles, namely: prolactin in basal conditions (PRL I), and after metoclopramide-test (PRL II), follitropin (FSH), lutropin (LH), estradiol (E2), progesterone (P) were assayed by means of "bioMerioux" kits. Estrone (E1) was assayed by means of "DBC Diagnostic kits.
RESULTS: In both subgroups of the study group (40-44 and 45-51 y.) a significantly higher (p < 0.001) concentration of prolactin was shown after metoclopramide test, as well as significantly higher percentage increase in prolactin after metoclopramide test (p < 0.001) were shown in comparison with the control group. In age compartment of 40-44 y. in the study group significantly lower (p < 0.05), progesterone-estradiol index (PEL) was found in comparison with the control group. In age compartment of 45-51 y. a progesterone-estradiol index (PEL) in study group was significantly lower (p < 0.05) in comparison with the control group.
CONCLUSION: Functional hyperprolactinemia and relative hyperestrogenism are risk factors of the development concerning fibrocystic changes in the breast.
秋山太, 坂元吾偉:乳腺症の病理診断の現状. 癌の臨床 1997;43(1):6-10.
坂元吾偉監修.乳腺症の臨床―その概念と診療のためのアトラス―. 篠原出版,1997.
L E Hughes, R E Mansel, D J Webster
Aberrations of normal development and involution (ANDI): a new perspective on pathogenesis and nomenclature of benign breast disorders.
Lancet. 1987 Dec 5;2(8571):1316-9.
Abstract/Text
A framework for understanding and management of benign breast disorders is presented, based on the notion that most breast complaints can be explained as minor aberrations of the normal processes of development, cyclical change, and involution. The generic term ANDI (aberrations of normal development and involution) is introduced to allow breast problems to be placed within an overall framework of pathogenesis; this concept also permits more detailed individual assessment with respect to normality and disease. Fibrocystic disease and its synonyms are discarded in favour of terms that are strictly descriptive of the clinical and/or histological picture.
Lynn C Hartmann, Thomas A Sellers, Marlene H Frost, Wilma L Lingle, Amy C Degnim, Karthik Ghosh, Robert A Vierkant, Shaun D Maloney, V Shane Pankratz, David W Hillman, Vera J Suman, Jo Johnson, Cassann Blake, Thea Tlsty, Celine M Vachon, L Joseph Melton, Daniel W Visscher
Benign breast disease and the risk of breast cancer.
N Engl J Med. 2005 Jul 21;353(3):229-37. doi: 10.1056/NEJMoa044383.
Abstract/Text
BACKGROUND: Benign breast disease is an important risk factor for breast cancer. We studied a large group of women with benign breast disease to obtain reliable estimates of this risk.
METHODS: We identified all women who received a diagnosis of benign breast disease at the Mayo Clinic between 1967 and 1991. Breast-cancer events were obtained from medical records and questionnaires. To estimate relative risks, we compared the number of observed breast cancers with the number expected on the basis of the rates of breast cancer in the Iowa Surveillance, Epidemiology, and End Results registry.
RESULTS: We followed 9087 women for a median of 15 years. The histologic findings were nonproliferative lesions in 67 percent of women, proliferative lesions without atypia in 30 percent, and atypical hyperplasia in 4 percent. To date, 707 breast cancers have developed. The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia.
CONCLUSIONS: Risk factors for breast cancer after the diagnosis of benign breast disease include the histologic classification of a benign breast lesion and a family history of breast cancer.
W D Dupont, D L Page
Risk factors for breast cancer in women with proliferative breast disease.
N Engl J Med. 1985 Jan 17;312(3):146-51. doi: 10.1056/NEJM198501173120303.
Abstract/Text
To assess the importance of various risk factors for breast cancer in women with benign proliferative breast lesions, we reevaluated 10,366 consecutive breast biopsies performed in women who had presented at three Nashville hospitals. The median duration of follow-up was 17 years for 3303 women, 1925 of whom had proliferative disease. This sample contained 84.4 per cent of the patients originally selected for follow-up. Women having proliferative disease without atypical hyperplasia had a risk of cancer that was 1.9 times the risk in women with nonproliferative lesions (95 per cent confidence interval, 1.2 to 2.9). The risk in women with atypical hyperplasia (atypia) was 5.3 times that in women with nonproliferative lesions (95 per cent confidence interval, 3.1 to 8.8). A family history of breast cancer had little effect on the risk in women with nonproliferative lesions. However, the risk in women with atypia and a family history of breast cancer was 11 times that in women who had nonproliferative lesions without a family history (95 per cent confidence interval, 5.5 to 24). Calcification elevated the cancer risk in patients with proliferative disease. Although cysts alone did not substantially elevate the risk, women with both cysts and a family history of breast cancer had a risk 2.7 times higher than that for women without either of these risk factors (95 per cent confidence interval, 1.5 to 4.6). This study demonstrates that the majority of women (70 per cent) who undergo breast biopsy for benign disease are not at increased risk of cancer. However, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer.
D P Rose, A P Boyar, C Cohen, L E Strong
Effect of a low-fat diet on hormone levels in women with cystic breast disease. I. Serum steroids and gonadotropins.
J Natl Cancer Inst. 1987 Apr;78(4):623-6.
Abstract/Text
For examination of the effect of a low-fat diet on serum estrogen, progesterone, and gonadotropin levels, 16 patients with cystic breast disease and cyclic mastalgia were studied before dietary intervention and at 2 and 3 months thereafter. Four-day food diaries indicated that total fat intake was reduced from a prediet average of 69 g (35% of total kilocalories/day) to an average of 32 g (21% of total kilocalories) after 3 months. Highly significant reductions (P less than .001) occurred in dietary cholesterol and less changes occurred in protein and total kilocalorie consumption (P less than .05); fiber intakes were not affected. After 3 months on this low-fat diet, there were significant reductions in luteal-phase serum total estrogens (P less than .001), estrone (P less than .005), and estradiol (P less than .01); progesterone, luteinizing hormone, and follicle-stimulating hormone levels were unchanged. Two of the 16 patients were excluded from the hormone statistical analyses because the serum progesterone levels were not consistent with sampling in the luteal phase of the menstrual cycle. It is concluded that a reduction of dietary fat intake to 20% of the total kilocalories will result in significant decreases in circulating estrogens in benign breast disease patients and that this effect is achievable without increasing dietary fiber consumption. Absence of changes in serum progesterone and gonadotropins during the dietary intervention is consistent with altered enterohepatic circulation of estrogens rather than with effects on the pituitary-ovarian axis.
N F Boyd, V McGuire, P Shannon, M Cousins, V Kriukov, L Mahoney, E Fish, L Lickley, G Lockwood, D Tritchler
Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy.
Lancet. 1988 Jul 16;2(8603):128-32.
Abstract/Text
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.
N F Boyd, M Cousins, M Beaton, E Fishell, B Wright, E Fish, V Kriukov, G Lockwood, D Tritchler, W Hanna
Clinical trial of low-fat, high-carbohydrate diet in subjects with mammographic dysplasia: report of early outcomes.
J Natl Cancer Inst. 1988 Oct 5;80(15):1244-8.
Abstract/Text
Despite evidence that dietary fat intake may influence breast cancer risk, there is little information about the effects of dietary fat on the human breast. We have studied the effects of dietary fat on the breast by examining the influence of dietary fat reduction on mammographic dysplasia (nodular or sheetlike areas of radiological density). Subjects with mammographic dysplasia were randomly allocated to a control group, in which they received advice about maintaining a balanced diet (36% of calories as fat), or an intervention group, in which they were taught to reduce dietary fat to a target of 15% of calories. A total of 295 patients consented to randomization, and after 1 year, 20% of the intervention group and 5% of the control group had dropped out (failed to keep appointments and provide nutrient data). The remaining patients closely adhered to the dietary goals of the study as assessed by food records, chemical analysis of duplicate meals, and serum cholesterol measurements. Comparison of mammograms before and after 1 year of dietary fat reduction shows no significant influence on the extent or density of mammographic dysplasia. Surgical biopsies performed in subjects after entry in the study showed five cancers in the control group and two cancers in the intervention group; this total of seven cancers is four times the number expected. These data show that clinical trials of the effects of dietary fat reduction on breast cancer risk are feasible and that long-term compliance with a low-fat diet can be achieved, and they confirm that the patients selected because they had mammographic dysplasia had increased risk of breast cancer.
N K Horner, J W Lampe
Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness.
J Am Diet Assoc. 2000 Nov;100(11):1368-80. doi: 10.1016/S0002-8223(00)00383-7.
Abstract/Text
Fibrocystic breast conditions, formerly referred to as fibrocystic breast disease, affect about half of all women and typically present as any combination of breast nodularity, swelling, and pain. We reviewed the literature to evaluate evidence supporting nutrition interventions commonly recommended for fibrocystic breast conditions by health care providers. Randomized, controlled studies of the effectiveness of caffeine restriction fail to support any benefit in fibrocystic breast conditions. Similarly, evidence supporting evening primrose oil, vitamin E, or pyridoxine as treatments for the discomforts of fibrocystic breast conditions is insufficient to draw conclusions about effectiveness. Dietary alterations that influence the intermediate markers for fibrocystic breast conditions include low-fat (15% to 20% energy), high-fiber (30 g/day), and soy isoflavone regimens. However, our findings provide no solid evidence for secondary prevention or treatment of fibrocystic breast conditions through a dietary approach. Health care providers should limit recommendations to proven diet therapies supported by randomized, placebo-controlled trials, given the instability inherent in fibrocystic breast conditions and the near 20% placebo effect associated with intervention. Because excessive estrogen or altered sensitivity to estrogen is the dominant theory of etiology, interventions that may modulate endogenous steroid hormones warrant further investigation as potential treatments for symptomatic fibrocystic breast conditions.
Thomas E Rohan, Abdissa Negassa, Bette Caan, Rowan T Chlebowski, J David Curb, Mindy Ginsberg, Dorothy S Lane, Marian L Neuhouser, James M Shikany, Sylvia Wassertheil-Smoller, David L Page
Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial.
Cancer Prev Res (Phila). 2008 Sep;1(4):275-84. doi: 10.1158/1940-6207.CAPR-08-0003. Epub 2008 Jul 9.
Abstract/Text
Modifiable factors, including diet, might alter breast cancer risk. We used the Women's Health Initiative Dietary Modification trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of, and considered to be on the pathway to, invasive breast cancer. The Women's Health Initiative Dietary Modification trial was a randomized, controlled, primary prevention trial conducted in 40 U.S. clinical centers from 1993 to 2005. A total of 48,835 postmenopausal women, ages 50 to 79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the dietary modification intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to > or =5 servings/d and intake of grain products to > or =6 servings/d, but resulted in smaller, albeit significant, changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between dietary modification and benign proliferative breast disease was 1.09 (95% confidence interval, 0.98-1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake do not alter the risk of benign proliferative breast disease.
J P Minton, H Abou-Issa, N Reiches, J M Roseman
Clinical and biochemical studies on methylxanthine-related fibrocystic breast disease.
Surgery. 1981 Aug;90(2):299-304.
Abstract/Text
The results of this study show that the consumption of methylxanthines through dietary sources appears to be associated with the etiologic development of benign fibrocystic disease in the American woman. Complete abstention from methylxanthine consumption resulted in complete resolution of the disease in 82.5% and significant improvement in 15% of those studied. Thus 97.5% showed clinical benefit from total methylxanthine abstention. The results of a clinical questionnaire answered by 500 women consuming methylxanthines, one half of whom had fibrocystic breast disease, suggest that women with fibrocystic disease may have a genetic predisposition for both benign breast disease and cancer. Biochemical studies implicate increased sensitivity of the adenylate cyclase system to catecholamines in patients with fibrocystic disease. Methylxanthines are known to increase circulating catecholamines.
V L Ernster, L Mason, W H Goodson, E A Sickles, S T Sacks, S Selvin, M E Dupuy, J Hawkinson, T K Hunt
Effects of caffeine-free diet on benign breast disease: a randomized trial.
Surgery. 1982 Mar;91(3):263-7.
Abstract/Text
There is considerable interest in the potential effect on benign disease of a diet free of methylxanthines (caffeine, theophylline, and theobromine) found in coffee, tea, colas, and chocolate. We randomly assigned 158 women who presented with a breast concern either to a group encouraged to abstain from methylxanthine-containing foods and beverages or to a group who received no dietary recommendations (controls). At the initial visit each patient's sociomedical history and data on methylxanthine consumption were obtained by interview, and clinically palpable breast findings were graded on a scale of 0 to 4 (no nodularity to confluent hard "dysplasia") for each quadrant of both breasts. On the follow-up visit approximately 4 months later similar information was obtained. Mammograms were taken at both visits for a subset of women in each group. We found a statistically significant reduction in clinically palpable breast findings in the abstaining group as compared with controls, but the absolute change was minor and may be of little clinical significance. Comparison of before-after mammograms offered little support for the methylxanthine hypothesis. There was no relation between clinically palpable breast finding scores at initial examination and caffeine consumption levels reported at that time.
S S Allen, D G Froberg
The effect of decreased caffeine consumption on benign proliferative breast disease: a randomized clinical trial.
Surgery. 1987 Jun;101(6):720-30.
Abstract/Text
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.
T E Rohan, M G Cook, A J McMichael
Methylxanthines and benign proliferative epithelial disorders of the breast in women.
Int J Epidemiol. 1989 Sep;18(3):626-33.
Abstract/Text
The relationship between methylxanthine intake (caffeine, theobromine and theophylline) and risk of benign proliferative epithelial disorders (BPED) of the breast was examined in a case-control study conducted in Adelaide, South Australia. The study involved 383 cases with biopsy-confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls individually matched to cases on age and area of residence. Overall, there was relatively little variation in risk of BPED with total methylxanthine intake, or with intake of caffeine or theophylline, while there was a positive association between theobromine intake and risk of BPED, but only when cases were compared with biopsy controls. Total methylxanthine intake was positively associated with risk of BPED showing severe atypia, but the trend in risk was statistically significant only when community controls formed the comparison group. These data do not provide strong support for an association between methylxanthine intake and risk of BPED.
W R Ghent, B A Eskin, D A Low, L P Hill
Iodine replacement in fibrocystic disease of the breast.
Can J Surg. 1993 Oct;36(5):453-60.
Abstract/Text
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.
Jack H Kessler
The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia.
Breast J. 2004 Jul-Aug;10(4):328-36. doi: 10.1111/j.1075-122X.2004.21341.x.
Abstract/Text
A randomized, double-blind, placebo-controlled, multicenter clinical trial was conducted with 111 otherwise healthy euthyroid women with a history of breast pain. Patients had to document moderate or severe breast pain by recording a score > or =5 on a visual analog scale (VAS) of pain for > or =6 days per cycle and had to present with fibrosis involving at least 25% of both breast surfaces. Subjects could not be effectively treated with more conservative measures such as local heat or nonprescription analgesics. There was not a statistically significant difference in the dropout rate for patients on placebo (11.8%), 1.5 mg/day (31.3%), 3.0 mg/day (18.4%), or 6.0 mg/day (25%) of molecular iodine for 6 months. Physicians assessed breast pain, tenderness, and nodularity each cycle; patients assessed breast pain and tenderness with the Lewin breast pain scale at 3-month intervals and with a VAS at each cycle. A statistically significant improvement (p < 0.01) associated with dose was observed in the Lewin overall pain scale for all treated groups compared to placebo. Reductions in all three physician assessments were observed in patients after 5 months of therapy in the 3.0 mg/day (7/28; 25%) and 6.0 mg/day (15/27; 18.5%) treatment groups, but not the 1.5 mg/day or placebo group. Patients recorded statistically significant decreases in pain by month 3 in the 3.0 and 6.0 mg/day treatment groups, but not the 1.5 mg/day or placebo group; more than 50% of the 6.0 mg/day treatment group recorded a clinically significant reduction in overall pain. All doses were associated with an acceptable safety profile. No dose-related increase in any adverse event was observed.
Lyn Patrick
Iodine: deficiency and therapeutic considerations.
Altern Med Rev. 2008 Jun;13(2):116-27.
Abstract/Text
Iodine deficiency is generally recognized as the most commonly preventable cause of mental retardation and the most common cause of endocrinopathy (goiter and primary hypothyroidism). Iodine deficiency becomes particularly critical in pregnancy due to the consequences for neurological damage during fetal development as well as during lactation. The safety of therapeutic doses of iodine above the established safe upper limit of 1 mg is evident in the lack of toxicity in the Japanese population that consumes 25 times the median intake of iodine consumption in the United States. Japan's population suffers no demonstrable increased incidence of autoimmune thyroiditis or hypothyroidism. Studies using 3.0- to 6.0-mg doses to effectively treat fibrocystic breast disease may reveal an important role for iodine in maintaining normal breast tissue architecture and function. Iodine may also have important antioxidant functions in breast tissue and other tissues that concentrate iodine via the sodium iodide symporter.
Jane Teas, Thomas G Hurley, James R Hebert, Adrian A Franke, Daniel W Sepkovic, Mindy S Kurzer
Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women.
J Nutr. 2009 May;139(5):939-44. doi: 10.3945/jn.108.100834. Epub 2009 Mar 25.
Abstract/Text
Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.
H Funahashi, T Imai, T Mase, M Sekiya, K Yokoi, H Hayashi, A Shibata, T Hayashi, M Nishikawa, N Suda, Y Hibi, Y Mizuno, K Tsukamura, A Hayakawa, S Tanuma
Seaweed prevents breast cancer?
Jpn J Cancer Res. 2001 May;92(5):483-7.
Abstract/Text
To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.
Sieja K.: Psychological characteristic of women with fibrocystic changes of the breast. Ginek Prakt 2004;12(2):27-31.
Mei Zhou, Natalia Wege, Huakang Gu, Li Shang, Jian Li, Johannes Siegrist
Work and family stress is associated with menstrual disorders but not with fibrocystic changes: cross-sectional findings in Chinese working women.
J Occup Health. 2010;52(6):361-6. Epub 2010 Oct 7.
Abstract/Text
OBJECTIVES: To explore the separate and combined effects of work and family stress on menstrual disorders and fibrocystic changes in Chinese working women.
METHODS: Data were obtained from a cross-sectional study of 1,642 female railway workers. The Effort-Reward Imbalance Questionnaire and Family Stress Scale were used to measure work stress and family stress, respectively; the menstrual and breast conditions were evaluated by gynecologic interview and a medical examination. Multivariate log-binomial regression was performed to analyze the associations.
RESULTS: Menstrual disorders were found in 59.3% of female workers, and 54.8% had fibrocystic changes. The risk of menstrual disorders was significantly elevated with respect to work and family stress. The highest risk was found in the group with combined exposure to both work and family stress (RR with 95% CI 1.33 (1.18-1.49)). No significant association between stress and fibrocystic changes was observed.
CONCLUSIONS: Menstrual disorders were associated with stress from work and family life, but not fibrocystic changes, in working women. Tailored intervention measures reducing the burden of stressful psychosocial work and family environment are needed to improve women's reproductive well-being.
G S Berkowitz, J L Kelsey, V A LiVolsi, M J Merino, T R Holford, N G Hildreth, S Ort, T Z O'Connor, C White
Exogenous hormone use and fibrocystic breast disease by histopathologic component.
Int J Cancer. 1984 Oct 15;34(4):443-9.
Abstract/Text
In a hospital-based case-control study of 590 women with biopsy-proven fibrocystic breast disease and 1,018 control women with other surgical conditions, no linear relationship was evident between the use of oral contraceptives or of estrogen replacement therapy and the degree of epithelial atypia of the fibrocystic lesions. Case-control and intracase comparisons suggested that oral contraceptive use might be associated with an increased occurrence of sclerosing adenosis among the premenopausal women and of gross cysts among the postmenopausal women. Estrogen replacement therapy, which was positively associated with fibrocystic breast disease as a whole among the post-menopausal women, was most frequently used among the cases whose biopsy specimens exhibited gross cysts, papillomatosis or papillary hyperplasia.
L J Hofseth, A M Raafat, J R Osuch, D R Pathak, C A Slomski, S Z Haslam
Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast.
J Clin Endocrinol Metab. 1999 Dec;84(12):4559-65. doi: 10.1210/jcem.84.12.6194.
Abstract/Text
The relative effects of postmenopausal hormone replacement therapy (HRT) with estrogen alone vs. estrogen+progestin on breast cell proliferation and on breast cancer risk are controversial. A cross-sectional observational study was carried out to examine the proliferative effects of HRT with estrogen or estrogen plus the progestin, medroxyprogesterone acetate, in breast tissue of postmenopausal women. Benign breast biopsies from 86 postmenopausal women were analyzed with antiproliferating cell nuclear antigen (anti-PCNA) and Ki67 antibodies to measure relative levels of cell proliferation. Epithelial density and estrogen and progesterone receptor status were also determined. The women were categorized either as users of: 1) estrogen (E) alone; 2) estrogen+medroxyprogesterone acetate (E+P); or 3) no HRT. Compared with no HRT, the breast epithelium of women who had received either E+P or E alone had significantly higher PCNA proliferation indices, and treatment with E+P had a significantly higher index (PCNA and Ki67) than treatment with E alone. Breast epithelial density was significantly greater in postmenopausal women treated with E and E+P, compared with no HRT. Thus, the present study shows that postmenopausal HRT with E+P was associated with greater breast epithelial cell proliferation and breast epithelial cell density than E alone or no HRT. Furthermore, with E+P, breast proliferation was localized to the terminal duct-lobular unit of the breast, which is the site of development of most breast cancers. Further studies are needed to assess the possible association between the mitogenic activity of progestins and breast cancer risk.
D Cyrlak, C H Wong
Mammographic changes in postmenopausal women undergoing hormonal replacement therapy.
AJR Am J Roentgenol. 1993 Dec;161(6):1177-83. doi: 10.2214/ajr.161.6.8249722.
Abstract/Text
Increasing numbers of postmenopausal women are undergoing hormonal replacement therapy. In this pictorial essay, we present the spectrum of mammographic changes seen in these women. These changes include symmetric and asymmetric increase in breast density, increase in size of fibroadenomas, and development or increase in size of cysts. Our examples illustrate that differentiation of hormonal therapy changes from neoplasm can occasionally be problematic when a focal density or mass is seen on mammograms. Furthermore, reexamination of published reports and our cases suggests that treatment with estrogen alone promotes enlargement of cysts and fibroadenomas, whereas treatment with a combination of estrogen and progesterone is more likely to be associated with diffuse increase in density.
