Breast Cancer Abstracts
Aromatization
Numerous studies have shown that human breast cancer tissue has the potential to synthesize estrogen through aromatization, which may act as a local growth factor of hormone-dependent cancer cells.
Aromatase expression in stromal or interstitial cells, including adipocytes, in breast cancer may be induced by carcinoma cells and locally synthesized estrogens could function as paracrine hormones. Intratumoral aromatase in human breast neoplasms correlated with malignant phenotypes but not with ER status or prognostic parameters, suggesting that other synthetic systems probably generate any biologically significant locally synthesized estrogens in hormone-dependent breast malignancy.
Immunolocalization of aromatase and other steroidogenic enzymes in human breast disorders. Sasano-H et al., Hum-Pathol. 1994 May; 25(5): 530-5.
Obesity & Breast Cancer
Obesity
Anthropometric measurements of 216 women with invasive breast cancer were compared with 432 controls. Patients with breast cancer had a significantly greater waist:hip circumference ratio and a significantly greater suprailiac:thigh skinfold ratio. Bicep and tricep skin fold measurements were greater in breast cancer patients. Obese women have a slightly greater risk of developing breast cancer, but for those who have android obesity there appears to be a significantly high risk for development of breast cancer.
"Abdominal Obesity and Breast Cancer Risk", Schapira, DB. et al, Annals of Internal Medicine, February 1, 1990;112(3):182-186.
Fine Needle Aspiration (FNA)
Fine-Needle Aspiration [FNA] (1)
Real-time US allowed continuous visualization of the needle during insertion and sampling, which resulted in pinpoint accuracy and safety. US-guided FNAB is recommended for needle biopsy in breasts with implants.
Masses in breasts with implants: diagnosis with US-guided fine-needle aspiration biopsy. Fornage-BD et al., Radiology. 1994 May; 191(2): 339-42.
Fine-needle aspiration [FNA] - (2)
FNA (fine-needle aspiration) describes the best degree of sensitivity and specificity but no procedure allows, by itself, the detection of all carcinomas. When considered in combination, clinical examination, mammography, and fine-needle aspiration have a sensitivity of 100% and a specificity of 49%, and are the best diagnostic tests for a correct assessment of mammary lesions.
Preoperative diagnostic accuracy of fine-needle aspiration in the management of breast lesions: comparison of specificity and sensitivity with clinical examination, mammography, echography, and thermography in 249 patients. Negri-S et al., Diagn-Cytopathol. 1994; 11(1): 4-8.
Nutrition & Breast Cancer
Nutrition (1)
Vitamin A, carotenoids, caloric restriction and exercise may help prevent breast cancer. Risk factors include alcohol intake, fat consumption, increased caloric consumption, elevated body mass, weight and stature.
"Nutrition and Breast Cancer", Kritchevsky, D. Cancer, September 15, 1990;66(6):1321-1324.
Nutrition (2) - Israel
Based on a lower reported incidence of breast cancer in the Arab population in Israel, nutritional levels were
The following results were obtained:
1. Calories of food consumption were significantly higher in Jewish and Arab patients than in their controls.
2. Jewish patients consumed significantly higher levels of monounsaturated fat; Arab patients consumed significantly higher levels of dietary fiber.
3. Animal protein intake was elevated in patients of both ethnic origins as compared with controls.
4. Vegetable fat and monounsaturated fatty acids were elevated in Arab patients as compared with Jewish patients.
5. Body weight of both Arab and Jewish patients was not significantly higher when compared with their controls.
6. Energy consumption and obesity were higher in breast cancer patients than in the controls. This supporting evidence suggests an association between obesity and breast cancer occurrence.
Nutritional risk factors and breast cancer in Jewish and Arab women. Henquin-N et al., Cancer-Nurs. 1994 Aug; 17(4): 326-33.
Nutrition (3) - Lifestyle
Breast cancer is the cause of death of more and more women each year. Many studies have tried to identify risk patterns and behaviors that, if altered, ultimately could decrease the incidence of breast cancer.
Several of those studies have looked into dietary or lifestyle patterns associated with risk. Some of the dietary factors that have been investigated include fats, vitamins, fiber, alcohol, meat and dairy products, fruits and vegetables, and pesticides.
Lifestyle factors have included breast-feeding and sunlight exposure. Although the information sometimes conflicts and some of the studies have weaknesses, certain patterns appear to emerge.
Tomlinson-SS: Dietary and lifestyle factors associated with breast cancer rates J of the American Academy of Physician Assistants. 1994 Oct; 7(9): 622-34. (92 ref)
Abdominal Obesity & Breast Cancer
Abdominal Obesity
Anthropometric measurements of 216 women with invasive breast cancer were compared with 432 controls. Patients with breast cancer had a significantly greater waist:hip circumference ratio and a significantly greater suprailiac:thigh skinfold ratio. Bicep and tricep skin fold measurements were greater in breast cancer patients. Obese women have a slightly greater risk of developing breast cancer, but for those who have android obesity there appears to be a significantly high risk for development of breast cancer.
"Abdominal Obesity and Breast Cancer Risk", Schapira, DB. et al, Annals of Internal Medicine, February 1, 1990;112(3):182-186.
Beta carotene & Breast Cancer
Beta-Carotene (1)
Breast cancer patients had lower concentrations of plasma beta-carotene than controls. Low plasma beta-carotene levels with high retinol levels are associated with increased risk of breast cancer. Retinol levels overall were not associated with breast cancer. Whether low carotene levels are a result of the disease or related to the cause of breast cancer is unknown.
"Breast Cancer and Dietary and Plasma Concentrations of Carotenoids and Vitamin A", Potischman, Nancy, et al, American Journal of Clinical Nutrition, 1990;52:909-15.
Beta-Carotene (2) - Female Cancers
Beta-carotene was measured in tissue samples of uterine leiomyomas and they were found to be significantly lower in fibroid tissue than in the normal myometrium. Beta-carotene tissue samples from cancers of the cervix, endometrium, ovary, breast, colon, lung, liver and rectum were also compared to normal adjacent tissue and found to be lower in all cancers. This suggests beta-carotene deficiency may have a role in the cause and/or pathogenesis of multiple types of cancers.
"Decreased B-Carotene Tissue Levels in Uterine Leiomyomas and Cancers of the Reproductive and Nonreproductive Organs", Palan, PR. et al, American Journal of Obstetrics and Gynecology, December 1989;161(6);Part I, 1649-1652.
Breast-Gut connection
The notion of a breast-gut connection was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines.
Intestinal bile acids rapidly gain access to cyst fluid..
Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid [published erratum appears in Lancet 1994 Apr 16;343(8903):986] Javitt-NB et al., Lancet. 1994 Mar 12; 343(8898): 633-5.
Biopsy & Breast Cancer
Biopsies
There is controversy in the literature regarding the effects of endogenous hormones on estrogen receptors (ER) and progesterone receptors (PR) in young women with breast cancer.
Studied 117 young women with primary breast cancer and assessed their breast biopsies for ER and PR.
The menstrual cycle was divided into 4 phases--early proliferative (days 1-7), late proliferative (days 8-15), early secretory (days 16-22), and late secretory (days 23-30).
There were lower levels of both ER and PR in biopsies excised during the early secretory phase than in other phases of the cycle; early proliferative phase receptor positive medians of ER = 77 fmol/mg protein and PR = 467 fmol/mg protein fell to ER = 28 fmol/mg and PR = 128 fmol/mg protein in the early secretory phase.
Smyth CM et al., Influence of the menstrual cycle on the concentrations of estrogen and progesterone receptors in primary breast cancer biopsies. Breast Cancer Res Treat, 1988 Apr, 11:1, 45-50.
Breast Imaging
Contents:
CT
MRI
Mammograms
Mammography
Screening
CT
The CT appearance of the normal breast, breast cancer, and several other abnormalities is demonstrated in this study. CT may occasionally allow for a precise diagnosis of a previously unsuspected breast lesion but a mammogram is usually required.
CT appearance of the normal and abnormal breast with mammographic correlation. Goldberg-PA et al., Clin-Imaging. 1994 Oct-Dec; 18(4): 262-72.
MRI
Study the architecture and enhancement characteristics of breast lesions with magnetic resonance imaging.
There is an overlap in the signal intensity characteristics and enhancement profiles of benign and malignant lesions. However, border characteristics, internal architecture, enhancement characteristics, and the presence of multiple tiny associated cysts may be important clues to lesion identification.
Suspicious breast lesions: MR imaging with radiologic-pathologic correlation. Orel-SG et al., Radiology. 1994 Feb; 190(2): 485-93.
Mammograms
The efficacy of breast carcinoma screening should be enhanced if false-negative mammography were reduced. [Canadian National Breast Screening Study.]
Examined whether menstrual cycle phase was associated with false-negative outcomes for mammographic screening. [women ages 40-44 years at the onset of screening.]
Comparing luteal with follicular mammograms in 6,989 patients who ever used estrogen, the unadjusted odds ratio for false-negatives versus true-negatives was 2.16 and the adjusted odds ratio was 1.47. In 1898 never-users, parallel odds ratios for luteal false-negatives were 0.55 (1.0) and 0.74 (1.0), respectively.
Menstruating women who have used hormones may have an increased risk of false-negative results for screening mammograms performed in the luteal phase of the menstrual cycle. An increased risk of false-negative mammography might adversely affect screening efficacy.
Baines CJ et al., Impact of menstrual phase on false-negative mammograms in the Canadian National Breast Screening Study. Cancer, 1997 Aug 15, 80:4, 720-4.
Mammography
Screening mammography improves carcinoma of the breast survival through early detection and treatment of nonpalpable, often noninvasive, carcinomas.
Age and irregular contour were independent significant predictors of malignancy for masses. Age, round, coarse, packed or scattered calcifications were significant independent predictors of benignity among calcifications. The radiologist correctly predicted malignant pathology in 60 percent of the patients and benign pathology in 78 percent.
Parity, age at menarche, age at first pregnancy, age at menopause, history of benign breast disease, history of carcinoma of the breast, family history of carcinoma of the breast, birth control pill exposure and smoking were not significantly associated with the diagnosis of malignant tumor.
Risk factors for carcinoma of the breast are insignificant for nonpalpable lesions because patients referred for needle localization are already selected for high risk. Roentgenologic patterns of masses are useful for predicting which lesions are invasive.
Multivariate analysis of roentgenologic characteristics and risk factors for nonpalpable carcinoma of the breast. Harkins-K et al., J-Am-Coll-Surg. 1994 Feb; 178(2): 149-54.
Screening
After seven years of breast cancer screening, there was no significant difference in mortality between the women who were screened and their controls, either in the 45-64 age group, or in the women aged 50 or over in a screening program in the United Kingdom. It is notable that Sweden, Iceland and Finland have begun national breast screening programs but they do not agree on which age group of women to screen. Norway and Denmark have no screening programs. A Norwegian conference concluded there was insufficient evidence to justify national screening. They encourage better mammography services for women with suspected breast disease. The question still remains "to screen or not to screen?"
"Breast Screening in Scandinavia", Westin, S. BMJ, February 10, 1990;300:352.
Dietary Factors & Breast Cancer
Contents:
Weight Gain
Dietary Factors
Dietary Fat
Weight Gain
Post menopausal weight gain may contribute significantly to development of post-menopausal breast cancer. Before menopause, however, higher body mass index is associated with a lower breast cancer incidence before and after menopause. In this study, more than 2,517 incident breast cancer cases were evaluated during 1,203,498 person-years, of which 60% were postmenopausal. The increased risk of breast cancer with weight gain was limited to women who had never used postmenopausal hormones. Before menopause, adiposity appears to reduce breast cancer incidence, but not mortality. After menopause, adult weight gain increases the risk of both breast cancer incidence and mortality. Avoiding weight gain during adult life may contribute significantly to the prevention of breast cancer incidence and mortality after menopause.
Huang, Zhiping, M.D., Ph.D., et al: Dual Effects of Weight and Weight Gain on Breast Cancer Risk, JAMA, November 5, 1997;278(17):1407-1411.
Dietary Factors
Reviewed 12 case-controlled studies of diet and breast cancer. There was a clear positive correlation between breast cancer risk and saturated fat intake in postmenopausal women. In premenopausal women there was little correlation with fat intake and breast cancer risk. Total caloric intake was not associated with an increased risk to breast cancer. There was a protective effect with consumption of fruit and vegetables. Vitamin C had the most consistent statistically significant inverse association with breast cancer risk in all women. If these dietary associations are indeed causal, then dietary modification in the North American population could prevent 24% of breast cancers in postmenopausal women and 16% in premenopausal women.
"Dietary Factors and The Risk of Breast Cancer: Combined Analysis of 12 Case-Controlled Studies", Howe, Geoffrey R. et al, Journal of The National Cancer Institute, 1990;82:561-569.
Dietary Fat
One in ten US women gets breast cancer. The incidence has been increasing steadily in women over the age of 44 by 2% per year since 1960. In a review of 1765 Kaiser Permanente patients from Portland, Oregon between 1960 and 1985, it was found the incidence of breast cancer rose on the average from 69.2 cases per 100,000 to 100.3, but only in those 45 years of age or older. The most dramatic change was seen in estrogen positive receptor cancers. The suggestion is more obese females have more circulating estrogens making dietary fat intake a risk factor for breast cancer. If North American women lowered their daily saturated fat consumption to 9% of the total calories, down 30% from today's standards, the breast cancer rate in postmenopausal women would fall 10%. Suggest eating enough produce to achieve vitamin C intake of 380 mg/d might reduce breast cancer incidence by another 16% among women over the age of 20.
"Breast Cancer Rise: Due to Dietary Fat?" Raloff, J., Science News, April 21, 1990.
Electricity & Breast Cancer
Contents:
Electric Blankets
Electrical potentials
Electric Blankets
There was a slight increased risk of breast cancer in electric blanket users. It has been suggested chronic exposure to electromagnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal rise in pineal melatonin.
"Electric Blankets Appear to Increase Risk of Breast Cancer", Vena, John E. et al, AFP, October 1990;1065.
Electrical potentials
Electrical potentials were measured for palpable breast masses. The tumor site was significantly electropositive compared with control sites only when the tumor was a cancer, as determined by a subsequent biopsy (the potentials were not influenced by age or menstrual cycle).
Electrical potentials may be suitable for diagnosis of individual patients if refinements are made in the measurement technique.
Electrical potential measurements in human breast cancer and benign lesions. Marino-AA et al., Tumour-Biol. 1994; 15(3): 147-52.
Fatty Acids & Breast Cancer
Contents:
Trans fat
Fatty Acids (2)
N-6 Polyunsaturated Fatty Acids
Trans fat
In the EURAMIC study, the relative risk of breast cancer was 1.4 for women in the highest quartile of trans fatty acids in adipose tissue. Produced when polyunsaturated fatty acids are artificially hydrogenated, trans fats comprise about 5 to 10% of the fat in the American diet, and about 5% of the fat stored in our American adipose tissue. Evidence over the years has suggested that trans fats increase the risk of coronary heart disease. In 1996, a joint task force of the American Society for Clinical Nutrition and the American Institute of Nutrition concluded that trans unsaturated fats have adverse effects on cholesterol, but they are not as severe as those of saturated fat. Reduction in intake of saturated fats should continue to be a nutritional priority. Reducing trans fat in the diet also seems to be a reasonable goal.
Byers, Tim, M.D., M.P.H.: Hardened Fats, Hardened Arteries? The New England Journal of Medicine, November 20, 1997;337(21):1544-1545.
Fatty Acids (1)
Epidemiologic evidence from the Japanese and the Eskimos suggests a low fat diet in combination with n-3/n-6 polyunsaturated fatty acid ratio of about .5 is associated with the lowest mortality from breast and colon cancer. N-6 fatty acids may have a tumor promoting effect while n-3 fatty acids (fish oil - EPA/DHA) may have an inhibitory effect on mammary and colon tumorogenesis.
"The Importance of N-6 and N-3 Fatty Acids in Carcinogenesis", Kromhout, Daan, Medical Oncology and Tumor Pharmacotherapy, 1990;7(2/3);173-176.
Fatty Acids (2)
High fat diets have been related to the risk of breast cancer. Five fatty acids were evaluated in breast cancer patients. These include palmitic, stearic, oleic, linoleic and arachidonic acids. There was a significant decrease in the risk of breast cancer associated with increased levels of linoleic acid in the red cell membranes in premenopausal women and of arachidonic acid in the postmenopausal group:
1) High fat diets are associated with a decreased risk to breast cancer especially if RBC fatty acid content is a reflection of dietary intake.
2) A diet high in polyunsaturated fatty acids protects against cancer.
3) RBC erythrocytes levels of fatty acids do not reflect dietary intake.
4) Low levels of arachidonic and linoleic acid in breast cancer patients could be the result of a loss due to enhanced lipid peroxidation.
This could explain lower levels of antioxidants in breast cancer patients. Metabolites of arachidonic acid are known to be tumor promoters and oxidant particles of these two fatty acids (arachidonic and linoleic) are involved in colon tumorigenesis.
"Fatty Acid Composition of Phospholipids in Erythrocyte Membranes and Risk of Breast Cancer", Zaridze, D.G., et al, International Journal of Cancer, 1990;45:807-810.
N-6 Polyunsaturated Fatty Acids
If levels of N-6 polyunsaturated fatty acids are lower than 28% of the total fatty acids in membrane phosphatidylethanolamine of the tumor, there is a high probability of early metastases. The quantity and quality of dietary fat intake appears to be associated with differences in post-treatment survivor rates.
"N-6 Fatty Acids in Human Breast Carcinoma Phosphatidylethanolamine and Early Relapse", Lanson, M., et al, British Journal of Cancer, 1990;61:776-778.
Hormones & Breast Cancer
Contents:
Endogenous sex hormones (2)
Hormone Levels
Salivary hormone levels
Endogenous sex hormones (1)
Studied the relation of endogenous sex hormones to breast carcinoma in premenopausal women.
During the follicular phase of the menstrual cycle, one overnight urine specimen was collected. During the luteal phase, urine and blood specimens were obtained. 17 beta-Estradiol, sex hormone-binding globulin, progesterone, and prolactin were measured in plasma, whereas estrogen metabolites (estrone, estradiol, and estriol) and pregnanediol were assessed in the urine.
Breast cancer was associated with high-plasma estradiol and prolactin and with low progesterone. Similar but weaker associations were observed for urinary estrogens and pregnanediol in the luteal phase.
Meyer F et al., Endogenous sex hormones, prolactin, and breast cancer in premenopausal women. J Natl Cancer Inst, 1986 Sep, 77:3, 613-6.
Endogenous hormones (2)
There is substantial evidence that high estrogen levels in postmenopausal women are associated with an increase in breast cancer risk, but such a relation has not yet been established in premenopausal women, despite biologic evidence that breast epithelial cell division rates are high during the luteal phase of the menstrual cycle when estradiol and progesterone levels are high.
Other hormones may play an important role in breast cancer development as well. Experimental data are particularly compelling for a role of progesterone and prolactin, but hormonal studies in women are not entirely convincing regarding the role of these hormones, nor is the literature nearly as extensive as it is for the estrogens.
Studies of various androgens are even less consistent. Moreover, such studies suffer from a lack of precise hypotheses regarding how these hormones might directly alter risk.
Bernstein L & Ross RK: Endogenous hormones and breast cancer risk. Epidemiol Rev, 1993, 15:1, 48-65.
Hormone Levels
Breast, endometrial and ovarian cancers account for 40% of all female cancers in the US These appear to be hormone related cancers. Oriental females have a decreased amount of ovarian steroid hormone production which may explain the four to six fold difference in breast cancer rates between Japanese and US women. A two year delay in menarche and low postmenopausal weight may lead to more than a 50% reduction in breast cancer and endometrial cancer. A two year delay in menarche is suggested to lead to an 18% reduction in ovarian cancer. Vegetarian diets, with a lower percentage of fat, result in lower levels of estradiol which may decrease cancer risk. The authors suggest there may be an estrogen contraceptive regime that could be created to help reduce breast cancer and ovarian cancer rates remarkably. Adding progestin to this contraceptive may significantly reduce endometrial cancer as well.
"Reducing Cancer in Women Through Lifestyle-Mediated Changes in Hormone Levels", Pike, Malcolm, C. Cancer Detection and Prevention, 1990;14(6):595-607.
Salivary hormone levels
The concentrations of estradiol and progesterone have been measured in salivary specimens collected daily over a complete menstrual cycle in 12 patients with operable breast cancer and normal control volunteers.
There was no significant difference for either hormone between these 2 groups. Both showed a mid-cycle rise in estradiol levels followed by a smaller but sustained increase during the luteal phase. The progesterone concentration increased markedly during the luteal phase of the cycle.
The amount of free estradiol in blood was about twice that found in saliva.
Wang DY et al., Salivary oestradiol and progesterone levels in premenopausal women with breast cancer. Eur J Cancer Clin Oncol, 1986 Apr, 22:4, 427-33.
Lipids & Breast Cancer
There was no association with cholesterol during the initial two year follow-up whereas there was a strong inverse relationship in cases diagnosed during the following four years. There is an inverse relationship between serum cholesterol and breast cancer risk among women diagnosed before the age of 51 years.
"Total Serum Cholesterol and Triglycerides and The Risk of Breast Cancer: A Prospective Study of 24,329 Norwegian Women", Vatten, Lars J. & Foss, Olav P., Cancer Research, April 15, 1990;50:2341-2346.
Melatonin & Breast Cancer
75 milligrams of melatonin has been utilized with a contraceptive pill in the hope that it would put a female into an anestrus type of situation. Melatonin can inhibit the growth of human breast cancer cell lines in vitro. Therefore, this pill may also be used to help protect against breast cancer.
"Melatonin: Hormone of Darkness", Editorial, British Medical Journal, 1993;307.
Oral Contraceptives & Breast Cancer
Contents:
Estrogens & progestagens
Oral contraceptives (2)
Estrogens & progestagens
The protective effect of early menopause shows that ovarian hormones increase the risk of breast cancer: it is likely that this is because they stimulate breast cell division.
The mitotic rate of breast cells is higher during the luteal phase of the menstrual cycle than during the follicular phase, suggesting either that progesterone and estrogen together induce more mitoses than estrogen alone (the 'estrogen plus progestagen hypothesis') or that estrogen alone induces breast cell mitoses in a dose-dependent manner and that progesterone has no effect (the 'estrogen alone hypothesis').
Both hypotheses are consistent with the known effects of reproductive history, obesity, combined oral contraceptives and estrogen replacement therapy (ERT) on breast cancer risk, but while the estrogen alone hypothesis predicts that hormone replacement therapy with estrogen and a progestagen (HRT) will cause the same increase in risk as ERT, the estrogen plus progestagen hypothesis predicts that HRT will cause a greater increase in risk than ERT.
Both hypotheses suggest that the risk of breast cancer could be reduced by delaying the onset of regular ovulatory menstrual cycles and by minimizing the therapeutic use of oestrogens, and possibly of progestagens, in postmenopausal women.
It may be possible to design hormonal contraceptives that will decrease breast cancer risk.
Key TJ & Pike MC: The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol, 1988 Jan, 24:1, 29-43.
Oral contraceptives (1)
Extensive use of oral contraceptives in New Zealand women has not increased their risk of breast cancer in middle age.
"Oral Contraceptives and Risk of Breast Cancer", Paul, C et al, International Journal of Cancer, 1990;46:366-373.
Oral contraceptives (2)
In young women undergoing curettage for benign uterine disorders (#65) a significant relationship was found between early oral contraceptive use (starting age less than 25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae.
Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results.
Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumors.
Olsson H et al., Permanent alterations induced in plasma prolactin and estrogen receptor concentration in benign and malignant tissue of women who started oral contraceptive use at an early age. Anticancer Res, 1987 Jul-Aug, 7:4B, 853-6.
Radiation & Breast Cancer
Concern about the risk to breast cancer in individuals who might be treated for refractory keloids by radiation therapy, since keloids on the trunk might expose breast tissue to undesirable amounts of radiation. This commentary notes three studies dealing with radiation exposure to the breast early on in life being a risk factor to breast cancer. The treatments were for conditions other than breast disorders (thymic irradiation, chest fluoroscopy and tinea capitis). In the latter there was an increased risk to breast cancer later in life in those who had been exposed from ages 5 to 9. Radiation doses were between 1 cGy and 10 cGy in the three reports.
"Radiation as a Risk Factor for Cancer of the Breast", Nusbaum, N J. NEJM, March 29, 1990;322(13): 937. {Letter]
Selenium & Breast Cancer
Breast cancer patients had serum selenium levels between 41-51 ug/L, those with mastopathy 67-76 ug/L and healthy subjects between 73-89 ug/L levels. Serum selenium is a noninvasive diagnostic parameter of malignant breast disease.
"Selenium in Serum as a Possible Parameter For Assessment of Breast Disease", Ksrnjavi, H & Beker, D. Breast Cancer Research and Treatment, 1990;16:57-61.
Timing of Surgery
Timing of surgery (1)
Patients with surgery performed during the luteal phase (d 14-23+) had an overall mean 5% benefit compared to those operated on the follicular phase determined by date of onset of their last menstrual period.
In reports from major cancer treatment centers, risk of recurrent cancer and/or death increased 5 to 6-fold after 10 years for women receiving surgery during d 7-14 of their cycle, compared to those resected during d 21-36.
Accurate menstrual histories should be included in the medical record for all premenopausal women receiving any surgical procedure upon the breast, preferably using an objective method of determining the date of last ovulation.
Lemon HM & Rodriguez-Sierra JF: Timing of breast cancer surgery during the luteal menstrual phase may improve prognosis. Nebr Med J, 1996 Apr, 81:4, 110-5.
Timing of surgery (2)
The timing of surgery during the menstrual cycle of premenopausal breast cancer patients was correlated with their disease-free survival (DFS) and overall survival (OS).
Two different surgery dates used for analysis were biopsy date and definitive surgery date.
Premenopausal breast cancer patients who have biopsy and/or definitive surgery during their perimenstrual phase (days 0 to 2 or after day 13) of the menstrual cycle may have a longer DFS than patients operated on during their midcycle phase (days 3 to 13); however, this may not affect overall survival.
Vanek VW et al., Correlation of menstrual cycle at time of breast cancer surgery to disease-free and overall survival. South Med J, 1997 Aug, 90:8, 780-8.
Timing of surgery (3)
The influence of the timing of surgery in relation to the menstrual cycle on the survival of breast cancer patients has been both advocated and disputed.
Consensus on the menstrual phase related to the expected best prognosis is still required.
Mondini G et al., Timing of surgery related to menstrual cycle and prognosis of premenopausal women with breast cancer. Anticancer Res, 1997 Jan-Feb, 17:1B, 787-90.
Timing of surgery (4)
Hormone measurements during the menstrual cycle were assessed to determine whether the stress of diagnosis and surgery influenced cycle characteristics. There was hormonal evidence for normal ovulation in all cancer and control women, although the length of the luteal phase of the cycle was prolonged because of a delay in menstruation in 2 cancer patients.
The timing of surgery in the cycle did not influence the hormonal data. The hormonal characteristics of the menstrual cycle thus appear to be normally preserved in women during the month in which breast cancer surgery is performed.
Holdaway IM et al., Characteristics of the menstrual cycle at the time of surgery for breast cancer. Br J Cancer, 1997, 75:3, 413-6.
Timing of surgery (5) - Growth factors
Measured tumour epidermal growth factor (EGF). No significant differences were seen in hormone receptor levels, pathological parameters or EGF levels between the two groups.
EGFR levels were significantly higher in women undergoing surgery during the follicular phase of their cycle, when classified by menstrual history. Patients operated on during this phase have previously been found to have a poorer prognosis, and these results may provide a basis for this finding. This may have implications for prognosis and timing of surgery, and further investigation is warranted.
Oliver DJ & Ingram DM: Timing of surgery during the menstrual cycle for breast cancer: possible role of growth factors. Eur J Cancer, 1995, 31A:3, 325-8.
Timing of surgery (6) - Lymph-node involvement
Prompted by a report of Hrushesky et al. stating that women operated upon for breast cancer during their perimenstrual period showed a higher risk for developing future metastases than women operated upon during their mid-cycle.
In contrast to the experience of Hrushesky et al., we found no significant differences in the survival curves.
These findings indicate that there might be certain cycle-related differences with respect to lymph node status but that they do not affect survival. Hence, timing surgery to the menstrual cycle is not mandatory for the time being.
Rageth JC et al., Timing of breast cancer surgery within the menstrual cycle: influence on lymph-node involvement, receptor status, postoperative metastatic spread and local recurrence [see comments]. Ann Oncol, 1991 Apr, 2:4, 269-72.
Timing of surgery (7) - Serum progesterone
Several studies have now shown that women with operable breast cancer undergoing tumor excision during the luteal phase of the menstrual cycle have a better prognosis than those having surgery during the follicular phase.
Cases with a progesterone level of 4 ng ml-1 or more had a significantly better survival than those with a level < 4 ng ml-1. This was especially clear in node-positive patients.
The possibility of misclassification of menstrual cycle status, because of misreported LMP, has been minimized by applying an independent hormonal measurement (P) of cycle activity. This parameter will also identify women who may be undergoing anovular cycles.
Confirmed that a raised level of progesterone at the time of tumor excision is associated with an improvement in prognosis for women with operable breast cancer.
Mohr PE et al., Serum progesterone and prognosis in operable breast cancer. Br J Cancer, 1996 Jun, 73:12, 1552-5.
Breast Conservation
Small Breast Cancer
The 10 year survival was 76% in the mastectomy group and 79% in the quadrantectomy. 13 year survival was 69% and 71% respectively. In small size (less than 2 cm) carcinomas total mastectomy is a treatment that should not be used.
"Breast Conservation is The Treatment of Choice in Small Breast Cancer: Long-Term Results of a Randomized Trial", Veronesi, Umberto, et al, European Journal of Cancer, 1990;26(6):668-670.
Fish consumption & Breast Cancer
There was a remarkable inverse association between percent calories from fish and breast cancer rates. This is in accord with animal data suggesting omega-III fatty acids (fish) may be protective against breast cancer.
"Fish Consumption and Breast Cancer Risk: An Ecological Study", Kaizer, Leonard, et al, Nutrition and Cancer, 1989;12:61-68.
Breast Heat cycle
There is substantial room for an improvement in breast cancer practice. The United Kingdom experience in the 1980s was a 50:50 survival to death ratio in the 10 years after diagnosis.
Preliminary analysis of the effects of mammographic screening suggests that there will be a real but small fall in overall mortality.
Existing practice involves 3 stages:
first, the 'earliest' detection of a lump by palpation or imaging;
second, diagnosis by histopathology; and
third, treatment by surgery, etc.
This limited success could be due, in part, to a failure to recognize the precancerous state of the mammary tissue as a whole in cancer cases; and a failure to exploit this state for earlier diagnosis.
There is a gross excess of focal hyperplasia in premenopausal cancer-associated breast tissue. Further, epidemiological data are consistent in that the tissue is subject to a sixfold increase in the risk of further primary carcinogenesis. A method is presented for detecting the cancer-associated breast. It exploits the breast menstrual cycle.
Physiologically the premenopausal mammary tissue goes into a monthly pregnancy rehearsal with glandular proliferation and increased blood supply. The latter effects a luteal heat cycle, which can be measured readily by an electronic thermometric bra as increased breast surface temperature (1 degree C).
The cancer-associated breasts exhibit an absent or altered response to endogenous progesterone during the luteal phase of the menstrual cycle. The abnormality in the luteal heat cycle is maximal during the few days just after ovulation.
Data indicate that a 1-h clinical test at this time achieves a sensitivity of 71% and a specificity of 80% for "clinically normal' yet cancer-associated breast tissue. Such patients would be candidates for increased surveillance and chemoprevention.
Simpson HW: Sir James Young Simpson Memorial Lecture 1995. Breast cancer prevention: a pathologist's approach. J R Coll Surg Edinb, 1996 Dec, 41:6, 359-70.
Early Menarche
Early menarche (1)
Early menarche is a risk factor for breast cancer.
Investigated the endocrine features of girls with early menarche (before 12).
Women who had early menarche had higher serum estradiol concentrations during the follicular phase of the menstrual cycle. The serum oestradiol concentrations increased rapidly at the beginning of cycle in these "early menarche" women.
If there is a threshold which serum estradiol concentrations must exceed to increase the risk of breast cancer, then these women have more days at risk than other women. In addition, the serum SHBG (sex-hormone-binding globulin) concentration was about 30% lower in the follicular-phase specimens of the women who had had their menarche before 12.0 years compared with those who had had their menarche at 13.0 years.
Data indicate that women with early menarche are subject to a high degree of estrogen stimulation at least until approximately 30 years of age. Our findings may have important consequences for the design of intervention programs for breast cancer prevention.
Apter D et al., Some endocrine characteristics of early menarche, a risk factor for breast cancer, are preserved into adulthood. Int J Cancer, 1989 Nov 15, 44:5, 783-7.
Early Menarche (2)
The search for major endocrine abnormalities as causes for breast cancer has not been successful.
There are, however, clear-cut differences in a number of variables in the pubertal development of girls with an early menarche: an early increase in serum concentrations of follicle stimulating hormone, higher circulating oestradiol concentrations before and for several years after menarche and lower serum sex hormone-binding globulin concentrations for several years after menarche, the last two leading to higher 'free estradiol indices' in the serum.
Early menarche was characterized by early onset of ovulatory cycles. We found that the times from menarche until 50% of the cycles were ovulatory were about 1, 3 and 4.5 years, when the ages at menarche were less than 12, 12-12.9 and more than or equal to 13 years, respectively.
In addition, the luteal phase of the menstrual cycles of subjects with an early menarche was adequate more frequently than that of subjects with a later menarche. These findings are compatible with the view that girls with an early menarche have a more profound decrease in the sensitivity of the hypothalamic-pituitary axis to the negative feedback of circulating steroids. The associations between endocrine variables and body weight and percentage of fat seem to be primarily determined by the endocrine variables.
Altogether the data on early menarche suggest that early-onset regular cyclic ovarian function is related to the increased risk of breast cancer that is associated with this category of women. Athletic activities may delay menarche, which may have relevance for reducing the risk of breast cancer.
Vihko RK & Apter DL: The epidemiology and endocrinology of the menarche in relation to breast cancer. Cancer Surv, 1986, 5:3, 561-71.
Vegetarians & Breast cancer
Seventh-Day Adventist vegetarians and controls, underwent measurement of their plasma hormone levels in the follicular and luteal phase of their menstrual cycles as well as dietary intake measured by 3-day food records, medical history, height, and weight.
There were no significant differences between vegetarians and nonvegetarians in average age of the girls, weight, body mass index, age at menarche, years since the onset of menstruation, or percentage of girls with ovulatory cycles.
Vegetarian girls had significantly higher levels of log follicular estradiol [2.00 +/- 0.27 (SD) versus 1.85 +/- 0.27 pg/ml] and luteal dehydroepiandrosterone sulfate (DHS) (1.88 +/- 0.71 versus 1.45 +/- 0.80 microgram/ml) than nonvegetarian girls.
There were no significant differences in testosterone or in percentage free estradiol levels between vegetarians and nonvegetarians.
Smoking was significantly associated with follicular and luteal DHS and with percentage free follicular estradiol, while alcohol use was significantly and inversely associated with percentage free follicular estradiol after controlling for other variables.
Persky VW et al., Hormone levels in vegetarian and nonvegetarian teenage girls: potential implications for breast cancer risk. Cancer Res, 1992 Feb 1, 52:3, 578-83.
Soya & Breast Cancer
Soybean consumption
Soybean consumption is associated with reduced rates of breast, prostate, and colon cancer, which is possibly related to the presence of isoflavones that are weakly estrogenic and anticarcinogenic.
Examined the effects of soya consumption on circulating steroid hormones in healthy females 22-29 years of age (# 6).
Starting within 6 days after the onset of menses, the subjects ingested a 12-oz portion of soymilk with each of 3 meals daily for 1 month on a metabolic unit.
Daily isoflavone intakes were approximately 100 mg of daidzein (mostly as daidzin) and approximately 100 mg of genistein (mostly as genistin).
Serum 17 beta-estradiol levels on cycle days 5-7, 12-14, and 20-22 decreased by 31%, 81%, and 49%, respectively, during soya feeding. Decreases persisted for 2 or 3 menstrual cycles after withdrawal from soya feeding.
The luteal phase progesterone levels decreased by 35% during soya feeding.
Dehydroepiandrosterone sulfate levels decreased progressively during soya feeding by 14-30%.
Menstrual cycle length was 28.3 +/- 1.9 days before soymilk feeding, increased to 31.8 +/- 5.1 days during the month of soymilk feeding, remained increased at 32.7 +/- 8.4 days at 1 cycle after termination of soymilk feeding, and returned to pre-soya diet levels 5 to 6 cycles later.
Results suggest that consumption of soya diets containing phytoestrogens may reduce circulating ovarian steroids and adrenal androgens and increase menstrual cycle length. Such effects may account at least in part for the decreased risk of breast cancer that has been associated with legume consumption.
Lu LJ et al., Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev, 1996 Jan, 5:1, 63-70.
Alcohol & Breast Cancer
Evaluated whether plasma hormone levels might mediate the reported positive relation between alcohol ingestion and breast cancer risk.
Alcohol ingestion was estimated using a drinking pattern questionnaire, a food frequency questionnaire, and 7-day food records.
Alcohol ingestion was not associated with plasma estrogens in the follicular, midcycle, or luteal phases of the menstrual cycle, nor with the level of SHBG or DHEAS in plasma averaged from the 3 phases of the cycle.
Alcohol, however, was significantly positively associated with the average level of plasma androstenedione. Based on these cross-sectional findings among premenopausal women, the increased risk of breast cancer related to alcohol ingestion does not appear to be mediated by elevated plasma estrogen levels. Androstenedione, however, may mediate the alcohol/breast cancer-association.
Dorgan JF et al., The relation of reported alcohol ingestion to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States). Cancer Causes Control, 1994 Jan, 5:1, 53-60.
Mastopathy
Cyclical mastopathy (CM) is a common clinical syndrome of premenstrual breast swelling and tenderness. Its symptoms are relieved by reduction in dietary fat intake and, because fat intake may be associated with breast cancer risk, it was hypothesized that CM may also be related to breast cancer risk. [Case-control study.]
A cyclical pattern of symptoms was identified in both groups; breast tenderness scores were similar postmenstrually but were significantly higher premenstrually in the case group.
Cases also had a greater premenstrual increase in breast tenderness than controls.
Identified an association of cyclical breast tenderness with breast cancer risk in premenopausal women.
Goodwin PJ et al., Cyclical mastopathy and premenopausal breast cancer risk. Results of a case-control study. Breast Cancer Res Treat, 1995, 33:1, 63-73.
Exercise & Breast Cancer
Investigated the behavior of C4-substituted estrogens, the so-called catecholestrogens, in response to acute exercise and training.
The 4-hydroxyestrogens are known to have both a strong estrogenic potency and affinity for catechol-O-methyltransferase (COMT), the enzyme that deactivates catecholamines.
Hormone measurements included follicular and luteal phase plasma E2, LH, catecholamines, PRL, total unconjugated and conjugated estrogens, total 4-hydroxyestrogens (4-OHE), and 4-hydroxyestrogen-monomethylethers (4-MeOE).
Because 4-OHE can control the hypothalamic gonadotropin oscillator and stimulate the luteolytic prostaglandin PGF2 alpha, the acute exercise-induced increases of 4-OHE and their positive correlation with lactate levels may indicate a key process in the pathogenesis of exercise-associated menstrual irregularities.
In addition, 4-OHE, when insufficiently O-methylated, are known to be capable of raising mutagenic superoxide free radicals and causing DNA damage that may lead to breast cancer.
Results may also be of significance for the apparent protective effects of sports participation against cancer of the breast.
De Cree C et al., 4-Hydroxycatecholestrogen metabolism responses to exercise and training: possible implications for menstrual cycle irregularities and breast cancer. Fertil Steril, 1997 Mar, 67:3, 505-16.
Chemotherapy & Breast Cancer
Studied changes in endocrine profile due to chemotherapy (CMF) in 70 pre-menopausal patients with axillary node positive, stage II and/or III breast carcinoma.
Cyclophosphamide and other alkylating agents suppress ovarian function in pre-menopausal women. However, endocrine details remain unknown regarding the influence of patients' age and obesity on CMF-induced hormonal changes.
After receiving therapy, 23% of the women continued to have regular menstrual cycles (non-amenorrheic group). In the remaining 77%, ovarian function was suppressed, as evidenced by the onset of amenorrhea within 0-11 months (amenorrheic group). The mean time to amenorrhea was 2.83 +/- 0.33 months (SE).
The time required to develop amenorrhea inversely correlated to the patient's age. Both incidence of amenorrhea and time to amenorrhea remained unaffected by either patient's obesity or the timing of chemotherapy initiation in relation to menstrual cycle phase (progestational, follicular). Plasma hormone levels fluctuated widely in both groups during the first three chemocycles. During chemocycle months 4 to 10, in the amenorrheic group, plasma E1, E2, and P declined to their baseline levels with a concomitant rise in LH levels. At this time, E1, E2, and P levels were significantly lower in amenorrheics, despite menstrual cycle associated fluctuations in the non-amenorrheic group. Estrogens (E1 and E2) gradually declined further following the onset of amenorrhea in subsequent months.
Host age or obesity did not influence CMF-induced changes in the plasma endocrine profile.
Mehta RR et al., Endocrine profile in breast cancer patients receiving chemotherapy. Breast Cancer Res Treat, 1992 Jan, 20:2, 125-32.
Cross-national Survey
A study from 66 countries concluded that the most significant risk factor was eating animal products; while the greatest protective effects were noted from eating: whole grains, legumes and fish.
Positive correlates:
Animal foods
Meats (total fat)
Saturated fats
Dairy
Refined sugar
Total calories
Alcohol
Negative correlates:
Whole grains
Legumes
Fish
Nuts
Cabbage
Vegetables
Fruits
Herbert, JR & Rosen, A: Nutritional, socioeconomic, and reproductive factors in relation to female breast cancer mortality: Findings from a cross-naitonal study. Cancer Detect. Prevent. 1996, 20:234-244.
Estrogen deficiency
Estrogen deficiency
Breast cancer therapy may interfere with the body's production of estrogen and may cause severe clinical depression among women. In a clinical study, the relationship between estrogen level and depression during breast cancer therapy was observed. During this study, these women lost their menses during chemotherapy, stopped estrogen replacement therapy or took tamoxifen. Eight out of 21 suffered severe depression. Ninety-five percent of the women had dysphoria and/or insomnia. Fourteen premenopausal women had hot flashes. Breast cancer therapy may induce similar symptoms of menopause as well as major depression. The researchers note a need for further studies into the association between estrogen-depletion and depression in breast cancer patients.
Duffy LS, Greenberg DB, Younger J, Ferraro MG: Iatrogenic acute estrogen deficiency and psychiatric syndromes in breast cancer patients, Psychosomatics 1999 Jul-Aug;40(4):304-8
Lycopene
Lycopene
Lycopene may significantly reduce the risk for breast cancer by inhibiting a pathway called IGF-I receptor signaling, which is necessary for growth of cancerous mammary cells (MCF7). Researchers found that treating MCF7 cells with lycopene reduced IGF-1 stimulation and delayed cell cycle progression, thereby inhibiting cell division and growth.
Karas M, et al: Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells, Nutr Cancer 2000;36(1):101-11
CHRT
CHRT
Use of estrogen/progestin combinations of hormone replacement therapy (CHRT) may increase the risk for lobular, rather than ductal, breast cancer. Researchers interviewed 537 women ages 50-64 who had been diagnosed with primary breast carcinoma between 1988 and 1990; and compared results to 492 women from the same area (King County, WA) without a history of breast cancer. Results indicated that women who took CHRT for at least 6 months had an elevated risk for lobular breast carcinoma. Risk for ductal breast carcinoma did not change.
Li CI, Weiss NS, Stanford JL, Daling JR: Hormone replacement therapy in relation to risk of lobular and ductal breast carcinoma in middle-aged women, Cancer 2000 Jun 1;88(11):2570-7
GLA & tamoxifen
GLA and Tamoxifen
Gamma linolenic acid (GLA) may work synergistically with tamoxifen to reduce tumor growth in breast cancer cell lines, according to this animal study. Female mice were implanted with a breast cancer cell line, and given one of four experimental diets: 1) control, 2) control and GLA, 3) control and tamoxifen, and 4) control, GLA, and tamoxifen. Both tamoxifen groups exhibited significantly slower tumor growth compared to control. The combined GLA/tamoxifen therapy resulted in markedly lower estrogen receptor expression (a measure of breast cancer progression) than either substance alone.
Kenny FS, et al: Effect of dietary GLA+/-tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts, Int J Cancer 2001 May 1;92(3):342-7
Resveratrol
Resveratrol
High concentrations of resveratrol - a natural chemical found in grapes and red wine -- may help to induce programmed cell death of breast cancer cells. Researchers tested the effect of resveratrol on human breast cancer cell lines. At low concentrations, resveratrol led to growth of estrogen-receptor-positive cancer cell lines. However, high concentrations of resveratrol suppressed growth of all three breast cancer cell lines, by inducing apoptosis (programmed cell death). This suppression also counteracted the breast cancer cell-stimulating effect of linoleic acid.
Nakagawa H, et al: Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator, J Cancer Res Clin Oncol 2001 Apr;127(4):258-64
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