Benign Mastopathies Research Articles

Diagnostic and therapeutic features of invasive lobular carcinoma of the breast: a study of 30 cases

Le cancer lobulaire infiltrant (CLI) du sein représente 5 à 15% des cancers du sein, il est classé le deuxième type histologique le plus fréquent, après le cancer infiltrant de type non spécifique (CINS) et son incidence est en nette augmentation. Son diagnostic clinique et radiologique est difficile. Il est plus fréquemment bilatéral. C'est un cancer d'évolution plus lente que le CINS avec de meilleurs facteurs pronostiques notre étude vise à détailler les caractéristiques cliniques, radiologiques, thérapeutiques et pronostiques du CLI. Il s'agit d'une étude rétrospective descriptive de 30 cas de CLI du sein colligé au Centre de Maternité et Néonatologie Monastir sur une période de 10 ans. L'incidence du CLI était de 5,2%. L'âge moyen est de 53,43 ans. Dix pourcent avaient des antécédents personnels de mastopathies bénignes, 6,66% avaient des antécédents personnels du cancer du sein et 3,33% avaient des antécédents familiaux du cancer du sein. Le CLI était diagnostiqué à un stade tardif chez 18 cas. La masse était bifocale chez 5 patientes, multifocale chez 4 patientes et bilatérale chez 3 patientes. Une seule patiente avait présenté une métastase hépatique lors du diagnostic. La chirurgie radicale type Patey était réalisée d'emblée chez 63,33% des patientes. Des lésions multifocales étaient détectées dans 44,80% des cas lors de l'examen anatomopathologique. Le curage ganglionnaire était positif chez 21 patientes. Vingt-huit patientes soit 93,33% avaient bénéficié d'une radiothérapie et d'hormonothérapie adjuvante. La survie globale à 5 ans était estimée à 77,3%.

Stereotactic vacuum biopsy of calcifications with a handheld portable biopsy system: a validation study

To prospectively evaluate a compact portable 10-gauge handheld battery-operated biopsy system for stereotactic biopsy of microcalcifications. The ethics committee of the hospital approved this prospective multicentric study, and informed consent was obtained. Biopsy under stereotactic guidance was performed in 215 patients for 219 lesions consisting of microcalcifications without mass. The feasibility and the tolerance of the procedure were evaluated. The mean weight of the specimen was calculated. In patients with surgical diagnoses, the underestimation rate in biopsy diagnoses of atypical ductal hyperplasia and ductal carcinoma in situ were evaluated. The sampled specimens were separated according to the presence of calcifications on magnified specimen radiographs and to the probe the rotation number in order to evaluate the contribution of each rotation and the contribution of the specimen with and without calcifications on the radiographs. The macrobiopsy was feasible in 98.5% of the patients and was well tolerated in 82% of patients. It identified 4.6% invasive carcinomas, 18.5% ductal carcinomas in situ, 14.8% atypical ductal hyperplasias, 22.2% benign proliferative mastopathies and 39.8% benign non-proliferative mastopathies. The underestimation rate was 26.6% when an atypical ductal hyperplasia was diagnosed at biopsy, and 7.7% when a ductal carcinoma in situ was diagnosed. In the 77 patients with surgical correlation, the accurate diagnosis was obtained in specimens sampled during the first, second, and third in 69%, 9%, and 4% of the biopsies, respectively, and the analysis of specimens without microcalcification had an added value in 8% of patients. The compact portable battery-operated biopsy system can be used successfully for stereotactic biopsy of microcalcifications and constitutes a valid alternative to current systems.

Effects of tibolone on the breast

Objective: to evaluate the effect of hormone replacement therapy and tibolone on the breast. Study design: prospective, controlled, randomized study. Setting: Outpatient Menopause Clinic of the Second University of Naples. Participants: forty four women in spontaneous menopause without any risk factor for breast cancer were randomly allocated to three groups: 15 patients (group A) were treated with transdermal oestrogens 50 μg, 2 patches/week for 3 weeks per month, plus acetate nomegestrolo per os 5 mg/die for 12 days per cycle, 17 patients (group B) were treated with tibolone 2.5 mg/die. Twelve patients not given any medication represented the control group (group C). Methods: at the time of recruitment and after at least 12 months of therapy the patients were subjected to a questionnaire aimed at quantifying the slight, moderate or severe presence of the tension/mastodynia symptoms and to a mammographic test to assess the parenchymal pattern according to a quantitative method: type 1 (less than 25% of mammary gland covered by dense tissue), type 2 (from 25% to 75% of total glandular area covered by dense tissue), type 3 (more than 75% of mammary parenchyma covered by dense tissue). Statistical analysis was carried out by means of Fisher's exact test. Results: after at least 12 months of treatment in Group A 5 out of 15 patients (33%) showed a trend of increase in mammographic density not statistically significant ( P=0.22) when compared with group B in which one patient showed a swift from type 1 to type 2 and another from type 2 to type 3. The analysis of tension/mastodynia symptoms revealed a significantly difference between the two groups ( P=0.02): in group A mastodynia appeared in three previously asymptomatic women and increased in five women, with a total increase in the symptomatology in 8 out of 15 patients (53.3%), in group B only in one case (5%) mastodynia turned from slight to moderate. Conclusion: in postmenopausal women oestroprogestogenic replacement therapy may be associated with an increase in mammographic density and with the onset or increase in mastodynia. On the contrary tibolone does not seem to affect normostructured mammas and may be considered a first-rate replacement therapy in case of mammas showing particular density or benign mastopathies.

Variation of bcl-2 expression in breast ducts and lobules in relation to plasma progesterone levels: overexpression and absence of variation in fibroadenomas.

Some women with benign breast disease eventually develop breast cancer. The mammary gland undergoes tissue remodelling according to hormonal influences, involving a balance between quiescence, proliferation, and mechanisms of cell death. Proliferation and/or apoptotic events could therefore be investigated to help understand the mechanisms of benign lesion formation and identify mastopathies with a poor prognosis. bcl-2 expression was analysed by immunohistochemistry in 75 benign mastopathies. Protein levels were quantitated with an image analyser in various epithelial structures on frozen sections, including adenoses, fibroadenomas, ductal epithelial hyperplasias, cysts, and apparently normal surrounding lobules and ducts. bcl-2 levels were equivalent in apparently normal lobules and ducts, as well as in cysts and ductal hyperplasias. bcl-2 staining was significantly higher in fibroadenomas, known to be of lobular origin [mean = 10.1, quantitative immunochemistry score (QIC) arbitrary units (AU), n = 19], than in normal lobules (mean = 5.1 AU, n = 43, P = 7 x 10(-5). bcl-2 levels in normal lobules and ducts varied according to the menstrual cycle, being higher during the follicular than the luteal phase (P = 1.8 x 10(-2) and P = 1.7 x 10(-2), respectively). This was further supported by a statistical link (P = 5 x 10(-3) between high levels of circulating progesterone and weak bcl-2 staining in lobules and ducts. This progesterone-dependent variation was absent in fibroadenomas. No statistical correlation was found between bcl-2 expression and circulating levels of oestradiol, and follicle-stimulating or luteotrophic hormones. Although these are only preliminary results, they suggest an influence of progesterone on bcl-2 expression which might be lost in fibroadenomas. A hypothesis is proposed concerning the potential involvement of altered regulation of the apoptotic process in the formation of such benign lesions.

Clinical value of thymidine kinase and tissue polypeptide specific antigen in breast cancer.

Thymidine kinase (TK) and tissue polypeptide specific antigen (TPS) were determined in breast cancer (BC) patients (n = 83), normal healthy women (n = 30) and 18 women with different benign mastopathies. Mean serum levels of TK and TPS in BC patients showed significant increases from their corresponding levels in healthy women and those with benign breast diseases. Diagnostic sensitivity of TK and TPS was 47% and 58% respectively at the selected cut-off values 8 U/L for TK and 110 U/L for TPS (96% specificity). Pre-operative serum levels of TK and TPS showed significant correlation with the stage of disease and with other classical prognostic factors; clinical stage, tumour size, lymph node involvement and distant metastasis. Nineteen BC patients were followed-up by serial monthly measurements of TK and TPS (4-10 samples). Both markers seemed to be valuable in monitoring drug efficacy. TK and TPS were able to detect systemic recurrence before clinical diagnosis (average 2 months lead time). TPS was greatly affected by liver diseases.

The expression of tnf receptors at the materno/fetal interface in normal human pregnancy

Breast tissues from 59 patients were immunohistologically studied for transferrin and transferrin receptors. None of the 8 normal breasts or 22 benign mastopathies, and only 1 of 7 fibroadenomas were reactive for transferrin, but 16 (72·7%) of 22 carcinomas were positive and parallel sections showed histopathologically that the reactive areas were confined to tumour-cell membranes. That breasttumour transferrin is probably receptor-bound in vivo was indicated by its complete chemical removal in vitro and return to the same cells following reincubation with dilute solutions of transferrin. Similar binding is found on certain normal or transformed cells and at the maternofetal interface of human placentæ. It is suggested that this oncofetal receptor preferentially binds apotransferrin and may offer a novel approach to more specific therapy of certain breast cancers.

Expression of the Progestin-Induced Fatty Acid Synthetase in Benign Mastopathies and Breast Cancer as Measured by RNA In Situ Hybridization

We have shown previously that fatty acid synthetase (FAS) is specifically induced by progestins in human breast cancer cell lines. To test the potential value of FAS as a clinical marker in breast diseases, we measured FAS expression in frozen sections of 22 benign and 27 malignant mammary tumors using in situ hybridization with the [35S]UTP alpha S-labeled FAS anti-sense mRNA. The hybridized RNA was quantified with an IMSTAR computerized image analyzer. We found FAS RNA in epithelial cells, but no labeling was detected in the connective tissue. In breast cancer, we found no correlation between FAS expression and estrogen receptor and progesterone receptor concentrations or status. However, the level of FAS was significantly (P less than .02) higher in premenopausal than in post-menopausal patients and increased with the grade of tumor differentiation (P less than .005 between the poorly and well-differentiated tumors). In benign mastopathies, high levels of FAS RNA were found in some cysts (mostly with apocrine metaplasia). In lobules, the FAS RNA level increased proportionally to the degree of proliferation determined by histological examination (P less than .015) and correlated with the H4 histone level measured in an adjacent section using in situ hybridization (r = 0.85, P less than .001). In ductal structures, a lower correlation (r = 0.64, P less than .01) was found between FAS and H4 RNA levels. We conclude that FAS RNA is overexpressed in some mammary tumors and may be useful in predicting high-risk mastopathies and less aggressive breast cancers.

A two-site immunoenzymometric assay of 52-kDa pro-cathepsin D, and its use in human breast diseases.

After isolating monoclonal antibodies specific for the 52-kDa precursor of cathepsin D (cath-D), which is secreted in excess in both hormone-dependent and hormone-independent breast cancer, we developed a two-step double-determinant immunoenzymometric assay that is specific for this pro-enzyme. The assay combines the use of a monoclonal antibody specific for the precursor and bound to microtiter plates, and a second antibody directed against a smaller processed form of the mature enzyme, coupled to alkaline phosphatase. The specificity of the assay relies on separate and sequential additions of the antigen and the conjugated second antibody. It allows rapid measurement of the analyte in plasma and cytosols of normal and neoplastic mammary tissues, with a detection limit of 5 fmol and a maximal interassay coefficient of variation of 9%. This assay is particularly useful for tissue cytosol samples where the pro-enzyme form co-exists with large quantities of the mature processed forms of the enzyme. Comparative assays of 52-kDa pro-cath-D and total cath-D in cytosols of breast cancers and benign mastopathies indicate that the present assay better discriminates between benign and cancerous mammary tumors.

Prognostic value of concentration of pregnancy-specific beta 1-glycoprotein (SP1) in serum of patients with breast cancer.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle counting immunoassay in serum from 46 healthy female blood donors, 33 patients with benign mastopathy and 84 patients with breast cancer before operation and during follow-up. Values greater than 1 micrograms/1 were found more frequently with benign mastopathies (11/33) and in patients with breast cancer at stage 2 (20/48), 3 (4/9), and 4 (7/10) than in healthy female blood donors (3/46). The survival rate after 4 years was significantly lower in patients with SP1 level greater than 1 microgram/1 before tumor resection (52% vs. 87%). The difference remained significant when only patients in stage 2 were taken into account (57% vs. 85%). A highly significant (r = 0.64; N = 46) negative correlation was observed between the concentration of SP1 in serum and the concentration of estrogen receptor in the tumor. The longitudinal study of patients in stage 2 indicated that, of the 15 whose SP1 concentration fell below 1 microgram/1 after operation, 14 survived over 4 years whereas during the same period, 9 of the 10 patients whose SP1 value remained higher than 1 microgram/1 died.

TRANSFERRIN AND TRANSFERRIN RECEPTORS IN CARCINOMA OF THE BREAST

Breast tissues from 59 patients were immunohistologically studied for transferrin and transferrin receptors. None of the 8 normal breasts or 22 benign mastopathies, and only 1 of 7 fibroadenomas were reactive for transferrin, but 16 (72·7%) of 22 carcinomas were positive and parallel sections showed histopathologically that the reactive areas were confined to tumour-cell membranes. That breasttumour transferrin is probably receptor-bound in vivo was indicated by its complete chemical removal in vitro and return to the same cells following reincubation with dilute solutions of transferrin. Similar binding is found on certain normal or transformed cells and at the maternofetal interface of human placentæ. It is suggested that this oncofetal receptor preferentially binds apotransferrin and may offer a novel approach to more specific therapy of certain breast cancers.