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Comparison of age at first full-term pregnancy between women with breast cancer and women with benign breast diseases.

Benign breast diseases have a broadly similar risk profile to that of breast cancer, possibly reflecting a similar underlying endocrine milieu. We have hypothesized that a crucial distinction between breast cancer and benign breast diseases is that mammary gland terminal differentiation has not been successfully accomplished among women who tend to develop breast cancer. From October 2001 to December 2002, information concerning breast cancer risk factors and sociodemographic characteristics was collected from 174 women with breast cancer and 116 women with benign breast diseases, all 30 years old or older, who were histologically diagnosed at a major prevention center in Athens, Greece. Among the examined breast cancer risk factors, only age at first full-term pregnancy was significantly associated with the odds of having breast cancer rather than benign breast disease, and the association was evident among premenopausal [odds ratio (OR) per 5 years = 1.76, 95% confidence interval (CI) 1.10-2.93] and postmenopausal (OR = 2.10, 95% CI 1.16-3.71) women, as well as among all women (OR = 1.93, 95% CI 1.34-2.70). There was no evidence that any of the remaining breast cancer risk factors could discriminate between breast cancer and benign breast diseases. We conclude that early age at first pregnancy may convey substantial protection against breast cancer risk among women with benign breast diseases, probably operating through induction of terminal differentiation of mammary gland cells. The finding is accentuated by the fact that women with benign breast diseases are already at a relatively high risk for breast cancer.

Adult↗

Glycolytic enzymes in breast cancer, benign breast disease and normal breast tissue.

The activities of hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase were studied in breast cancer tissues, in comparison to benign breast disease and normal breast tissues. The enzyme activities in breast cancer were significantly increased compared to normal and benign breast tissues (p less than 0.001). Also the increase in activity in benign disease compared to normal was statistically significant (p less than 0.001). Within the group of benign diseases, fibroadenomas could be distinguished from fibrocystic disease, the former generally showing higher activities compared to the latter (p less than or equal to 0.05). Carcinoma subgroups, classified according to their histology, could not be recognized enzymologically. In addition, isozyme composition of pyruvate kinase and enolase was studied. We did not find a significant shift towards K type pyruvate kinase expression in benign disease compared to normal breast tissues. Also fibroadenomas did not differ from fibrocystic disease. However, the amount of K type pyruvate kinase in carcinomas proved to be significantly higher in comparison to benign disease and normal breast tissues (p less than 0.001). Expression of alpha gamma-enolase in normal breast tissue was virtually absent. In benign disease only a minority of specimens did show the hybrid alpha gamma-enolase. Nearly all carcinomas had alpha gamma-enolase expression and in 20% of the carcinomas gamma gamma-enolase could be detected (so-called neuron-specific enolase). By discriminant analysis, the function giving the best discrimination compared to the histological data was based on natural logarithm aldolase and the total of gamma-enolase subunits. Contrary to expectation, the regulator enzymes of glycolysis; i.e., hexokinase, phosphofructokinase and pyruvate kinase were not included in this discriminant function. The best fit produced a 90% correct classification in both benign and malignant disease. If these findings are confirmed to a larger series, the discrimination is sufficiently strong to form the basis of a clinically useful tool.

Biomarkers, Tumor↗

Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue.

Tyrosine specific protein kinase activity was determined in 70 specimens of the human mammary gland. These included 28 cancers of the breast, 21 benign breast diseases, and 21 normal breast tissues. We measured tyrosine kinase activity in the cytosol fraction and in the membrane fraction of the homogenates. In addition cytosolic aldolase activity was measured. Tyrosine kinase activity was determined using poly(glutamic acid:tyrosine = 4:1) as an artificial substrate. Cancers of the breast exhibited considerable higher tyrosine kinase activities in both cytosol and membrane fractions, compared to benign breast tumors (P less than or equal to 0.001). Benign tumors demonstrated increased activities in cytosol in comparison to normal breast tissues (P less than 0.001). Furthermore, there appears to be a strong association of an enhanced expression of activity of tyrosine kinase in cytosol of primary carcinomas and early systemic relapse. In combination with aldolase activity a nearly complete discrimination is achieved between malignant specimens on one hand and benign and normal tissues on the other.

Adult↗

Cytomorphology of fibrocystic change, high-risk proliferative breast disease, and premalignant breast lesions.

In a prospective study using mammographically guided fine needle aspirates in 100 nonpalpable breast lesions, the author's group assessed the reliability of a cytological grading system to define the cytological features of proliferative and nonproliferative breast disease and to differentiate between benign, premalignant and malignant breast lesions. We developed a cytological grading system evaluating the aspirates for the cellular arrangement, the degrees of cellular pleomorphism and anisonucleosis, presence of myoepithelial cells and nucleoli and the status of the chromatin pattern. This grading system, now recognized as the Masood Cytology Index, is commonly used as a surrogate end point biomarker in chemoprevention trials.

Breast Diseases↗

Immunohistochemical studies of S-100 protein expression in myoepithelial cells of benign breast diseases and normal breast tissues.

We studied benign breast diseases using polyclonal anti S-100 protein and monoclonal anti a-subunit or beta-subunit of S-100 protein antibodies. The antibody gave positive staining in most of the cytoplasms and nuclei of the myoepithelial cells of normal breast tissues, gynecomastia, fibroadenoma, intraductal papilloma and mastopathy. However, immunohistochemical methods using the monoclonal antibodies for them did not reveal positive staining in the myoepithelial cells.

Amino Acid Sequence↗

Histochemically demonstrable phosphotyrosyl-protein phosphatase in normal human breast, in benign breast diseases and in breast cancer.

The activity of phosphotyrosyl-protein phosphatase enzyme was investigated by a histochemical method in the normal human breast and in breast diseases in order to evaluate its possible significance in the genesis and in the growth of benign and malignant epithelial proliferative. In normal human breast tissue only a weak enzyme activity was present. The activity was elevated in benign disease in actively proliferative lesions and in 71% of the cases of breast cancers. When enzyme activity of breast cancers was compared with the content of receptors for epidermal growth factor and insulin-like growth factor-I, no association was found. It is concluded that phosphotyrosyl-protein phosphatase is increased in actively proliferating human breast diseases. Thus the putative increase in phosphotyrosyl-proteins mediating benign and malignant epithelial proliferations is rather caused by an increase in protein-tyrosine kinase activity than by a decrease in phosphotyrosyl-protein phosphatase activity.

Breast↗

Fibrocystic breast disease.

Fibrocystic breast disease is characterized by breast pain, lumpiness or cysts. The few patients who have atypia on breast biopsy are at substantially increased risk for the development of breast cancer. Management of fibrocystic breast disease involves monitoring for breast cancer by repeated physical and mammographic examinations. Alleviation of symptoms may be attempted by reassurance, reduction of methylxanthine intake and treatment with danazol.

Adult↗

Benign breast disease as a breast cancer risk in Japanese women.

A hospital-based retrospective cohort study of benign breast disease (BBD) as a risk factor of future breast cancer (BC) development was conducted. Four hundred and twenty-eight patients with biopsied BBD were followed-up for a median period of 8 years, together with age-matched women with normal breasts (normal control) and BC patients (cancer control), at the ratio of 1:2:2. Twenty-one breast cancers developed, 7 in the cases, 4 in the normal controls, and 10 in the BC controls, showing the relative risk (RR) with 95% confidence intervals (CI) to be 3.5 (1.03-11.9) in the cases with respect to the normal controls. The RR of the cases is not lower than that of contralateral breast cancer incidence. There were no significant differences in the risks of cancers in other organs among the groups. Pathological examination revealed that only atypical hyperplasia increased the RR of BC, as compared with the normal control breast group, or with non-proliferative disease. These results suggest that in a low-risk country, Japan, BBD is a definite risk factor for BC development as in high-risk countries.

Adult↗

[Steroid hormone receptors in benign breast diseases].

Benign breast diseases generally occur in women with progesterone insufficiency and an unopposed estrogen status. This hormonal imbalance is also a main risk factor for breast cancer in the long run. The presence of estradiol and progesterone receptors in benign breast disease are additional proof of their hormone dependence. The level of receptors is higher when the epithelial cellularity is high and also in more recent lesions, and younger women. The level and subcellular location of the receptors also depend on the endogenous secretion of steroids: their level varies throughout the menstrual cycle, and it is maximal at the end of the follicular phase, due to the high estradiol secretion. The cytosol and nuclear level and location of the receptors are also modified by hormonal therapy: estrogen-progestagens given as a contraceptive, or progestins given as a substitutive and antiestrogen therapy. These modifications constitute a biochemical basis for the hormonal progestagen treatment of benign breast diseases.

Adenofibroma↗

Benign breast disease.

Benign breast disease is common with an estimate of over half the female population at sometime seeking medical attention for a breast problem. The clinician must prove that the woman with a breast problem (ie, tenderness, lump, discharge) does not have a malignancy. This is done using a history and physical examination and, when indicated, mammography, ultrasonography, ductography, fine needle aspiration biopsy, or excisional biopsy. A comprehensive breast center allows for an efficient and cost-effective workup for women with a breast problem. In this context, benign breast disease and preinvasive breast cancer is presented.

Algorithms↗

[Breast diseases (fibroadenomas, mastopathies, breast cancers) in hormonal contraception].

282 female patients with histologically confirmed fibroadenomas (71), mastopathies (187) and breast carcinomas (24) were questioned for hormonal contraception. 144 women had taken oral steroid contraceptive pills, 138 denied such treatment. Statistically significant differences could not be observed in the occurrence of the breast diseases studied. Under hormonal contraception, fibroadenomas were found in 28% (without contraception in 22%), simple mastopathies in 41% (without in 40%), proliferative mastopathies in 22% (without in 30%) and mammary carcinomas in 9% (without in 8%) of the corresponding cases. The histological finding of a so-called apocrine metaplasia was found in all the diseases (except carcinomas) more frequent in the contraceptive group. Histometrically, the breast parenchyma showed a changing lobular hyperplasia under hormonal contraception in all the disease groups studied. An influence of questioned gynecological risk factors for a breast carcinoma was not striking in the women with and without hormonal contraception.

Adult↗

Benign breast diseases.

Benign breast diseases have always been neglected in comparison to cancer, despite the fact that there are many more patients with such diseases than patients presenting to a breast clinic for cancer. Like normal breast tissues, benign breast diseases are under a complex system of controls by both systemic hormonal and local factors. In this review, we attempt to present an overview of the latest knowledge concerning the epidemiology, classification, clinical presentation, management, and physiopathology of these disorders.

Adolescent↗

Evaluating benign breast disease.

Benign breast diseases are present in some form in nearly all women. A basic understanding of breast anatomy and physiology, underlying pathology and methods available for evaluating breast problems provides the ability to assess the client's breast complaint. Four common breast problems--fibrocystic disease, fibroadenoma, mammary duct ectasia, and intraductal papilloma--are described along with guidelines for assessment and referral or follow-up. Current breast-imaging options are discussed in terms of their usefulness and limitations. The value of consumer education regarding benign breast problems cannot be overstated. The National Cancer Institute offers free consumer information explaining benign breast diseases and evaluation techniques.

Adenofibroma↗