Leptin induces a proliferative response in breast cancer cells but not in normal breast cells.

Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, a hormone excessively produced during obesity, is suggested to be involved in breast cancer. The aim of the study was to investigate procarcinogenic potential of leptin by evaluating influence of leptin on cell proliferation, cell cycle, apoptosis, and signaling on numerous breast cells lines, including 184B5 normal cells, MCF10A fibrocystic cells and MCF-7, MDA-MB-231, and T47D cancer cells. Expressions of leptin and Ob-R were analyzed using qRT-PCR and immunohistochemistry, proliferation using fluorimetric resazurin reduction test and xCELLigence system, apoptosis and cell cycle by flow cytometry, and effect of leptin on different signalling pathways using qRT-PCR and Western blot. Cells were exposed to increasing concentrations of leptin. All cell lines expressed mRNA and protein of leptin and Ob-R. Leptin stimulated proliferation of all cell lines except for 184B5 and MDA-MB-231 cells. Leptin inhibited apoptosis but didn't alter proportion of cells within cell cycle in MCF7 cells. Leptin induced overexpression of leptin, Ob-R, estrogen receptor, and aromatase mRNA in MCF-7 and T47D cells. Autoregulation induced by leptin, relationship with estrogen pathway, and proliferative and antiapoptic activity in breast cancer cells may explain that obesity-associated hyperleptinemia may be a breast cancer risk factor.

Endometrial cancer in a 14-year-old girl with Cowden syndrome: a case report.

The appearance of endometrial cancer in adolescence is uncommon and warrants investigation for an hereditary cancer syndrome. Cowden syndrome is an autosomal dominant cancer syndrome associated with a germline PTEN mutation and increased risk of breast, thyroid, endometrial and colon cancer. In this report we present a case of a 14-year-old nulligravid female diagnosed with grade 1 endometrial adenocarcinoma. She subsequently developed fibrocystic breast disease and colon polyps and was diagnosed with Cowden syndrome at age 20. We therefore recommend formal evaluation for Cowden syndrome to be considered when endometrial cancer is diagnosed in adolescence.

Six-year analysis of treatment-related toxicities in patients treated with accelerated partial breast irradiation on the American Society of Breast Surgeons MammoSite Breast Brachytherapy registry trial.

BACKGROUND: The American Society of Breast Surgeons (ASBrS) enrolled women in a registry trial to prospectively study patients treated with the MammoSite RTS device. This report presents 6-year data on treatment-related toxicities from the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated with accelerated partial breast irradiation (APBI) using the MammoSite device (34 Gy in 10 fractions) in 1440 women. Of these, 1255 case (87%) had invasive breast cancer (IBC) (median size = 10 mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS) (median size = 8 mm). Median follow-up was 59 months. Fisher exact test was performed to correlate categorical covariates with toxicity. RESULTS: Breast seromas were reported in 28% of cases (35.5% with open cavity and 21.7% with closed cavity placement). Also, 13% of all treated breasts developed symptomatic seromas, and 77% of these seromas developed during the 1st year after treatment. There were 172 cases (11.9%) that required drainage to correct. Use of chemotherapy and balloon fill >50 cc were associated with the development of symptomatic seromas. Also, 2.3% of patients developed fat necrosis (FN). The incidence of FN during years 1 and 2 were 0.9% and 0.8%, respectively. Seroma formation, use of hormonal therapy, breast infection, and A/B cup size were associated with fat necrosis. There were 138 infections (9.5%) recorded; 98% occurred during the 1st year after treatment. Chemotherapy and seroma formation were associated with the development of infections. CONCLUSIONS: Treatment-related toxicities 6 years after treatment with APBI using the MammoSite device are similar to those reported with other forms of APBI with similar follow-up.

Is hyperandrogenemia protective for fibrocystic breast disease in PCOS?

The aim of this study is to evaluate the fibrocystic breast disease rates and its association with different clinical, endocrine and metabolic parameters between main polycystic ovary syndrome (PCOS) phenotypes. One hundred thirty two consecutive women were included in the study. Body mass index, serum follicle-stimulating hormone, luteinizing hormone (LH), progesterone, estradiol, testosterone, dehydroepiandrosterone sulphate, fasting glucose, low density lipoprotein (LDL-C), total cholesterol, high density lipoprotein, insulin, insulin sensitivity and fibrocystic breast disease rates were compared among different phenotypes of PCOS. Group 1: Polycystic ovaries (PCO)-anovulation (n = 32), Group 2: Hyperandrogenemia (HA)-anovulation (n = 28), Group 3: HA-PCO (n = 29), Group 4: HA-PCO-anovulation (n = 43). There were statistically significant differences between the different phenotype groups in terms of waist-hip ratio (p = 0.006), serum LDL-C (p = 0.008), LH (p = 0.002), estradiol (p = 0.022), fasting glucose (p = 0.001), progesterone (p = 0.007), free testosterone levels (p < 0.001) and Ferriman-Gallwey (FG) scores (p < 0.001). Different phenotype groups had significantly different fibrocystic breast disease rates. (p = 0.016). Higher free testosterone >3 pg/dl was protective for fibrocystic disease (RR = 0.316, 95:% CI 0.109-0.912, p = 0.033). Higher FG scores were more protective for fibrocystic disease (RR = 0.005, 95:% CI 0.001-0.042, p < 0.001). Group 3 ovulatory PCOS patients with PCO and hyperandrogenemia phenotype had lower risk to develop fibrocystic disease, while higher rates were observed in group 1 anovulatory-normoandrogenemic PCOS patients. Hyperandrogenemia is protective for fibrocystic diseases in PCOS.

[Association of polymorph variants of CYP1A2 and CYP1A1 genes with reproductive and thyroid diseases in female workers of petrochemical industry].

The article presents results obtained in study of relationship between polymorph variants of CYP1A1 and CYP1A2 genes with reproductive and thyroid diseases risk in female workers of petrochemical industry, when compared with reference group females. Variants TD and DD of CYP1A2 gene appeared to be associated with nodes formation in uterus and breast in female workers and reference group females. Following liability markers are obtained: homozygous in rare allele genotype CC of CYP1A1 gene for reproductive and thyroid diseaes (fibrous cystic mastopathy and nodular goitre), heterozygous genotype AG of CYP1A1 gene in uterine myoma and fibrous cystic mastopathy, homozygous in deleted T genotype of CYP1A2 gene in autoimmune thyroiditis. Occupational hazards and long length of service at hazardous industries increase effects of rare alleles of the genes studied.

ESR1 gene variants affect FSHR-depended risk of fibrocystic mastopathy in infertile women.

BACKGROUND: The infertile women have an increased risk of developing benign and malignant tumors, in particular, breast cancer. Most studies have examined the role of gene variants in the risk of developing breast cancer, but there is little evidence of genetic risk factors for benign tumors. AIM: To assess the combined genetic risk of developing mastopathy in women with FSHR (rs6165, rs6166) and ESR1 (rs9340799, rs2234693) gene variants. MATERIALS AND METHODS: The study included 87 infertile women (45 with concomitant fibrocystic mastopathy and 42 without mastopathy). RESULTS: For rs9340799 and rs2234693 variants of the ESR1 gene, we did not find any significant differences in the distribution of genotypes in infertile women with or without mastopathy. In patients with mastopathy, there was a reliable increase in the frequency of 307Ala/Ala and 680Ser/Ser genotypes of FSHR gene (χ2 = 6.39, p = 0.012, OR = 4.49 (1.48-13.65)) as compared to patients without mastopathy. In the presence of 307Thr/Thr and 680Asn/Asn genotypes of the FSHR gene, a 4.88-fold reduction of mastopathy risk (χ2 = 8.06, p = 0.005, OR = 0.21(0.07-0.59)) was observed. The frequency of the FSHR and the ESR1 genotypes combinations - 307Thr/Thr+680Asn/Asn+351AG+397TC was significantly decreased in patients with mastopathy. CONCLUSIONS: Our study did not find an association of ESR1 gene variants with the risk of developing of mastopathy in infertile women although heterozygous variants of the ESR1 gene enhanced the "protective" effect of FSHR gene variants and reduced the risk of mastopathy.

[Microglandular adenosis of the breast in a patient with a history of mediastinal radiotherapy]. / Adenosis microglandular mamaria en paciente con antecedente de radioterapia mediastínica.

The risk of secondary tumors in patients who have received mediastinal radiation therapy is well-known. Microglandular adenosis of the breast is a rare lesion that is considered benign, although its possible role as a precursor of invasive breast carcinoma has been considered. We present a case of microglandular adenosis in a patient who received mediastinal radiation therapy in childhood for Hodgkin's lymphoma. To our knowledge, this is the first reported case of microglandular adenosis in a patient with mediastinal radiotherapy which may shed light on its pathogenesis.

Increased bone mineral density in aged rats with spontaneous mammary dysplasia.

Spontaneous mammary tumors were seen in seven of the 12 breeding female rats aged 2 years. All mammary tumors were diagnosed as mammary dysplasia (MD). Bone mineral contents (BMC) and bone mineral density (BMD) of their lumbar vertebrae and femur were determined using dual energy X-ray absorptiometry (DXA). In rats with MD, body weight (BW), BMD of the lumbar vertebrae and BMC of the femur were significantly higher than in the rats without MD. Although corpus luteum (CL) and follicles were seen in the ovaries of all animals, the number of CL in rats with MD was significantly lower than the rats without MD. It was suggested that high BMD, BW and decreased CL promoted mammary tumors.

Some fibrocystic breast change may be caused by sexually transmitted H. pylori during oral nipple contact: supporting literature and case report of resolution after gut H. pylori eradication treatment.

OBJECTIVES: To briefly review previously published evidence for Helicobacter pylori (Hp), colonization of extra-intestinal sites and suggest an hypothesis that breast acini and ducts be added to this list, concluding such breast colonization is not rare and is a sexually transmitted infection. METHODS: PubMed literature search and review with a case report. CONCLUSIONS: (1) Evidence indicates oral Hp is common and can remain in the mouth after successful eradication in stomach and duodenum. (2) Evidence indicates that the breast is also occasionally colonized by Hp. (3) Hp may be injected retrograde up into ducts of the breast during oral nipple stimulation during sexual activity and this Hp may give rise to some cases of fibrocystic breast change. (4) A case of painful fibrocystic change that had been present for two years in a 27 year old female, resolved after gastrointestinal Hp treatment.

[Study on mental stress life events in patients with cyclomastopathy of liver stagnation syndrome type].

OBJECTIVE: To observe the changes of mental stress life events (MSLE) in patients with cyclomastopathy of liver stagnation syndrome type (LSS). METHODS: Clinical epidemiological research method was adopted, the changes of MSLE were observed in cyclomastopathy patients of LSS or non-LSS, classified by syndrome differentiation of TCM. RESULTS: Not only the mean age (33.38 +/- 6.76 years) of patients with LSS was obviously lower than that of patients with non-LSS (38.36 +/- 9.89 years, P < 0.01), but also the mean age of patients with moderate and serious symptoms of LSS (33.96 +/- 7.31 and 37.43 +/- 7.38 years) were higher than that of patients with mild symptoms of LSS (31.67 +/- 5.39 years, P < 0.05 and P < 0.01). MSLE score of patients with LSS (32 scores) was significantly higher than that of patients with non-LSS (22 scores, P < 0.01). MSLE score of patients with moderate and serious LSS was 34.69 +/- 17.78 scores and 51.65 +/- 20.75 scores respectively, both were significantly higher than that of patients with mild LSS (26.57 +/- 15.85 scores, P < 0.05 and P < 0.01). CONCLUSION: The high incidence age of cyclomastopathy is under 40 years, and most of cyclomastopathy patients are classsified to LSS by TCM syndrome differentiation. So age and life event scores may be the objective bases for syndrome typing and liver stagnation syndrome grading in patients with cyclomastopathy.

[A follow-up study about 52 cases of atypical lobular hyperplasia and lobular carcinoma in situ of the breast].

OBJECTIVE: To evaluate the biological behavior and treatment method for the breast atypical lobular hyperplasia (ALH) and breast lobular carcinoma in situ (LCIS). METHODS: Seventeen cases of ALH and thirty-five cases of LCIS were reviewed from July 1982 to January 1996. All cases were followed by physical examination, mammography and B-ultrasound for an average of 146.6 months (range, 3 - 257 months). RESULTS: Most cases of ALH and LCIS occurred before menopause (about 69.2%). Fifty-two cases of ALH and LCIS were occasionally verified pathologically after surgery for benign diseases. The microcalcification with ALH and LCIS had been detected in 25 cases, accounted for 48.1%. Eight cases of ALH/LCIS became invasive carcinoma. There were 5 cases in the same breast, 3 cases in the contralateral breast; The subsequent breast cancer occurred longer than nine years after ALH/LCIS was diagnosed. The family history of breast carcinoma and ovary carcinoma occurred in 4 cases of breast carcinoma, accounted for 50%, but it was no significant (P > 0.05). Also, there was no difference between LCIS and ALH, which occurred the breast carcinoma (P > 0.05). CONCLUSION: The excisional biopsy might be necessary to ALH and LCIS.

An uncommon case of diabetic mastopathy in type II non-insulin dependent diabetes mellitus.

Diabetic mastopathy is an uncommon tumor-like proliferation of fibrous tissue of the breast that usually occurs in a patient who has suffered from type I diabetes mellitus of long duration. Here we report a rare case of diabetic mastopathy that occurred in type II non-insulin dependent diabetes mellitus. This patient was a 63-year-old postmenopausal woman. Mammography, ultrasonography and MR imaging could not distinguish it from breast cancer. Although the core needle biopsy specimen showed fibrosis without evidence of malignancy, excisional biopsy was performed. Histological findings demonstrated typical diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. These lymphocytes were composed predominantly of B-cells. Five months after surgical biopsy, a nodular formation approximately 4 cm in diameter recurred adjacent to the resected end of the biopsy.

Oral contraceptive use and fibrocystic breast disease of different histologic classifications.

The relationship between oral contraceptive (OC) use and occurrence of fibrocystic breast disease (FBD) of different histologic classifications was evaluated with data from a cohort study. Biopsy specimens from 232 women with FBD were classified into different atypia categories. In 96 matched pairs of OC users and nonusers, atypia scores were lower in users than in nonusers. Women without breast diseases (500 OC users and 500 nonusers) were sampled from the original cohort to form a two-stage "anamorphic" study with the 232 cases of FBD. The previously shown inverse association between OC use and FBD occurrence was present and increased with increased length of OC use. However, the "protective effect" of OC use did not vary for different histologic classifications of FBD. The findings from both paired and anamorphic analyses of the data are not consistent with the hypothesis that the use of OC is associated with decreased frequency only of FBD with minimal epithelial atypia.

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

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

Risk factors for fibrocystic breast disease and its histopathologic components.

The relationship between various sociodemographic, reproductive, and other factors to the occurrence of fibrocystic breast disease was evaluated in a case-control study undertaken at five Connecticut hospitals from 1979 to 1981. The study groups comprised 590 women with biopsy-proven fibrocystic breast disease and 1,018 women with other surgical conditions. Among the premenopausal women, multivariate analysis suggested that high socioeconomic status, Jewish religion, low parity, a history of benign breast disease, a history of breast cancer in the mother or a sister, and low Quetelet index were associated with increased odds ratios (OR) for fibrocystic breast disease. Similar analysis for the postmenopausal women revealed increased OR for women with high socioeconomic status, a late age at menopause, and a history of benign breast disease. Current smokers as well as those who had had a tubal sterilization had significantly reduced odds of fibrocystic disease. There was no convincing evidence of linear trends according to degree of epithelial atypia for any of the variables considered. Although some variation in the OR emerged in the analysis according to selected histologic components, the results provided little evidence that women with biopsy specimens exhibiting gross cysts, sclerosing adenosis, papillary hyperplasia, or papillomatosis showed epidemiologic similarities with breast cancer patients.

Lhermitte-Duclos disease and Cowden's syndrome. Report of two cases.

OBJECTIVE AND IMPORTANCE: Lhermitte-Duclos disease, or dysplastic cerebellar gangliocytoma is a rare entity characterized by a hamartomatous lesion in the posterior fossa. Cowden's syndrome, or hamartoma-neoplasia syndrome is a rare underdiagnosed autosomal dominant genodermatosis with high incidence of malignant tumors. Several recent reports suggest that Lhermitte-Duclos disease may be a component of Cowden's syndrome. CLINICAL PRESENTATION: We report two cases of Lhermitte-Duclos and Cowden disease occurring in adult patients. A 40-year-old woman had symptoms of raised intracranial pressure and macrocephaly. She displayed the stigmata of fibrocystic breast disease, thyroid goitre. Clinical examination showed mucocutaneous lesions. Her mother, brother and uncle had manifestations of Cowden's disease. An asymptomatic 38-year-old male had bilateral optic nerve drusen related to a cerebellar neoplasm. He exhibited manifestations of Cowden's syndrome and his familial history confirmed this hypothesis. INTERVENTION: The first patient was operated on for Lhermitte-Duclos disease. A conservative strategy was performed for the second patient and the clinical and imaging follow-ups were uneventful over 5 years. CONCLUSION: We stress the possibility that Lhermitte-Duclos and Cowden disease might be a peculiar form of phakomatosis. A conservative strategy can be chosen without neurological signs because of slow tumor growth. However, these patients should be carefully examined and followed up because of the risk of future malignancy.

Detection of ductal dysplasia in mammary outgrowths derived from carcinogen-treated virgin female BALB/c mice.

These studies were undertaken to determine if altered growth potential of mammary epithelial cells could be detected in outgrowths derived from monodispersed mammary cells of virgin female BALB/c mice previously exposed to ionizing radiation or 7, 12-dimethylbenz(a)anthracene (DMBA). Monodispersed mammary epithelial cells were obtained by enzymatic dissociation of mammary tissues of 12-week-old virgin female BALB/c mice. Twenty-four hr prior to cell dissociation, donor animals were exposed to either 100 rads of gamma-ray irradiation, 0.25 mg of DMBA, or 0.075 mg of DMBA. Control donors were untreated. Mammary outgrowths were then derived from these donor cells by injecting either 10(5) or 10(4) cells into the gland-free mammary fat pads of three-week-old virgin female BALB/c mice. Ten weeks after the injection of cells, the outgrowths were examined and classified. Mammary outgrowths were classified either as having a normal ductal architecture or as having ductal dysplasia. Ductal dysplasias were further classified on the basis of an index of severity, which was an arbitrary index based on the number of abnormal ductal structures within each lesion. The data indicated that treatment of donor animals with either gamma-radiation or DMBA increased the frequency of ductal lesions over control levels; however, both the frequency and severity of the lesions depended on the number of cells which were injected into the fat pad. When outgrowths were derived by injection of 10(5) cells into the gland-free fat pads, lesion frequencies in outgrowths from control and treated cells were: 3.3%, control; 15.7%, gamma-rays; 5.3%, 0.25 mg DMBA; in these groups only a few severe lesions were detected. In outgrowths derived from 10(4) cells, less severe lesions (Class I lesions) were common in all groups and occurred in approximately 10 to 15% of the outgrowths. The frequency of severe (Class II and III) ductal dysplasia, however, was increased by treatment in these groups, occurring in 4.5% of control outgrowths in 15.6, 14.9, an 14.3% of the outgrowths derived from donor cells treated with 100 rads gamma-rays, 0.075 mg DMBA, nd 0.25 mg DMBA, respectively. Thus, these data indicated that ductal dysplasias were more common and more severe in outgrowths derived from 10(4) rather than 10(5) cells. The ductal lesions observed in this study resembled both morphologically and histologically ductal abnormalities which have been associated with the pathogenesis of mammary carcinoma in both rats and mice.

[About correlation of dysfunction of the thyroid gland with fibrocystic diseases in women].

The reference data contain a lot of information on the interrelation between destroying of a thyroid gland and fibrocystic diseases. However contradictions in these data proves that this issue is not solved completely. The aim of the given study was the investigation of interrelations between frequency of occurrence of pathology of a functional condition of the thyroid gland and the frequency of occurrence of fibrocystic diseases. 90 women aged 23-50 were investigated. Concentration of thyroxin (FT4), thyrotrophic hormone (TSH), titers of antibodies to thyreoperoxidase, microsomal fraction of thyreocytes and thyreoglobulin were measured by ELISA. Palpation and ultrasonic investigations of thyroid and mammary glands were used, morphology of central formations of mammary glands according to indications was also carried out. A special questionnaire was completed for each patient. Our investigations showed that along with the declining of function of thyroid gland and the increased level of TSH in the blood, the risk of development of fibrocystic diseases is increased twice.

Is contrast-enhanced spectral mammography (CESM) helpful in differentiating diabetic mastopathy from breast carcinoma?

Diabetic mastopathy (DM) is a rare benign inflammatory disease of the breast, which nevertheless gives suspicious image of malignancy by breast ultrasound and mammography. MRI studies of this disease have indicated both nonspecific enhancement and non-enhancement of the lesion, depending on its degree of lymphocytic infiltration. This is the first case report discussing the appearances of DM on CESM, a novel mammographic technique.