Breast cancer in women younger than 35 years old.

PURPOSE: Women ≤ 35 years old with breast cancer constitute a special group. Considering the impact of the disease and its prognosis, these patients face some specific problems that are not present in older women. What are the prognostic features of the survival rate in very young women with breast cancer? METHODS: Retrospective analysis of very young women with breast cancer from the Surgical-Oncologic Breast Cancer Department at "Theagenio" Anticancer Hospital, 2003-2016. Patient and tumor characteristics, treatment options and follow-up information were collected. Univariate-multivariate analyses were conducted and survival rates were calculated. RESULTS: The median age was 34 years old. 53 patients (41%) had T1, 36 (28%) had T2, 7 (5.4%) had T3 and 33 (25.6%) had T4 stage tumors. Most women, 114 (88.4%), had ductal carcinoma in their histology. Furthermore, positive axillary lymph nodes were present in 62 women (48%). In the immunochemistry report, 91 patients (70.5%) were hormone receptor positive, HER2 was overexpressed in 32 patients (24.8%) and 27 patients presented with triple-negative subtype. Out of 65 patients tested for Ki-67, 51 (78.5%), had a high expression (cut-off value of 20%). After adjusting for all possible factors, the risk of recurrence and death was six times higher in the positive lymph node group, (p < 0.001). The median disease-free and overall survival was 133 and > 173 months, respectively. CONCLUSION: Breast cancer in very young women appears with large size and high-grade tumors, high incidence of infiltrated axillary lymph nodes, high Ki-67 expression and intrinsic subtypes with poor prognosis. As a result, these women need to be treated by a multidisciplinary team.

Split Hand Foot Malformation Syndrome: A Novel Heterozygous FGFR1 Mutation Detected by Next Generation Sequencing.

BACKGROUND: Split-hand/foot malformation syndrome is a rare, clinically and genetically het-erogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. It may occur as an isolated abnormality or it may be associated with a genetic syn-drome. CASE REPORT: In the present case, isolated split-hand/split-foot malformation was diagnosed by prenatal ultrasound at 24 weeks in a male singleton fetus, with deep median cleft of the right hand, syndactyly and hypoplasia of phalanges in both hands, and oligodactyly of the right foot. During consultation, the father of the fetus revealed that he also had an isolated right foot dysplasia. The parents chose elective termination and autopsy confirmed prenatal ultrasound findings. Genetic testing of the aborted fetus with QF-PCR analysis for common aneuploidies and array comparative genomic hybridization (aCGH) showed a male genomic pattern, without aneuploidies or chromosomal imbalances. Further investigation with next generation sequencing of 49 clinically relevant genes revealed a novel heterozygous FGFR1 mutation c.787_789del (p.Ala263del) in the fetus; the father was heterozygous to the same mutation. CONCLUSION: A novel heterozygous FGFR1 mutation causing split-hand/foot malformation syndrome is reported. Accurate genetic diagnosis allowed detailed counseling to be provided to the couple, including the underlying cause, recurrence risks, and detailed management plan with preimplantation genetic diag-nosis for future pregnancies.

Protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) in endometriosis and normal endometrium.

Given the involvement of different extracellular matrix (ECM) metalloproteinases (MMPs) in endometriosis, the protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) was analyzed in this study in endometriosis and normal endometrium. Tissue samples were collected prospectively from 64 premenopausal patients undergoing operative laparoscopy. Protein expression of TIMP3 was analyzed immunohistochemically in endometriotic lesions (n = 30) and normal eutopic endometrium from patients with (n = 35) and without (n = 29) endometriosis. Comparison between the three different groups of tissue samples showed that TIMP3 was differentially expressed between the three groups (p = .04). Pair-wise comparisons showed that TIMP3 expression was lower in endometriotic lesions as compared with normal eutopic endometrium from controls (p = .006); the same non-significant trend was found, in the comparison between endometriosis lesions and matched eutopic endometrium. There were no differences in TIMP3 expression in the normal eutopic endometrium between patients with and without endometriosis. In conclusion, TIMP3 seems to be involved in the pathogenesis, pathophysiology, and maintenance of endometriosis and it might be useful as a diagnostic and prognostic marker of endometriosis. Future studies should further investigate this issue, as well as the interplay between TIMPs and different extracellular MMPs in endometriosis.

Amniotic Fluid and Maternal Serum Metabolic Signatures in the Second Trimester Associated with Preterm Delivery.

Preterm delivery (PTD) represents a major health problem that occurs in 1 in 10 births. The hypothesis of the present study was that the metabolic profile of different biological fluids, obtained from pregnant women during the second trimester of gestation, could allow useful correlations with pregnancy outcome. Holistic and targeted metabolomics approaches were applied for the complementary assessment of the metabolic content of prospectively collected amniotic fluid (AF) and paired maternal blood serum samples from 35 women who delivered preterm (between 29 weeks + 0 days and 36 weeks +5 days gestation) and 35 women delivered at term. The results revealed trends relating the metabolic content of the analyzed samples with preterm delivery. Untargeted and targeted profiling showed differentiations in certain key metabolites in the biological fluids of the two study groups. In AF, intermediate metabolites involved in energy metabolism (pyruvic acid, glutamic acid, and glutamine) were found to contribute to the classification of the two groups. In maternal serum, increased levels of lipids and alterations of key end-point metabolites were observed in cases of preterm delivery. Overall, the metabolic content of second-trimester AF and maternal blood serum shows potential for the identification of biomarkers related to fetal growth and preterm delivery.

Fetal nasal bone length in the second trimester: comparison between population groups from different ethnic origins.

OBJECTIVE: To compare normal ranges of ultrasonographically measured fetal nasal bone length in the second trimester between different ethnic groups. METHOD: A prospective, non-interventional study in order to establish normal ranges of fetal nasal bone length in the second trimester in a Greek population was conducted in 1220 singleton fetuses between 18 completed weeks and 23 weeks and 6 days of gestation. A literature search followed in order to identify similar studies in different population groups. Fetal nasal bone length mean values and percentiles from different population groups were compared. RESULTS: Analysis of measurements in the Greek population showed a linear association, i.e., increasing nasal bone length with increasing gestational age from 5.73 mm at 18 weeks to 7.63 mm at 23 weeks. Eleven studies establishing normal ranges of fetal nasal bone length in the second trimester were identified. Comparison of fetal nasal bone length mean values between the 12 population groups showed statistically significant differences (P<0.0001). CONCLUSION: Normal ranges of fetal nasal bone length in the second trimester vary significantly between different ethnic groups. Hence, distinct ethnic nomograms of fetal nasal bone length in the second trimester should be used in a given population rather than an international model.

Quality-of-life changes over time in breast cancer patients undergoing breast-conserving surgery: a prospective study in Greece.

AIM: The aim of the present study was to evaluate quality of life (QL) over time in patients undergoing breast-conserving surgery, due to primary operable breast cancer, in Greece. MATERIALS AND METHODS: This was a prospective, questionnaire-based study in women with primary operable breast cancer. A Greek version of the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire was used. Patients filled out all six subscales of FACT-B, initially 24 h prior to and then 3-7 days and 9-12 months after breast-conserving surgery. All participants received standard adjuvant therapy. Patients with metastatic disease, psychiatric comorbidities and those treated with neoadjuvant therapy were excluded. Data were statistically analyzed using parametric and nonparametric tests as indicated. RESULTS: In total, 155 women, with a mean age of 59.2 years (range 30-80 years), filled out the study questionnaire. Patients' social/family well-being improved 3-7 days and 9-12 months after the operation as compared with the preoperative period (p < 0.05). Patient-doctor relationship and functional well-being deteriorated (p < 0.05), while physical well-being improved (p < 0.05) 9-12 months after surgery than prior to or 3-7 days postoperatively. Finally, emotional well-being and "additional concerns" and overall QL were all better 3-7 days postoperatively than prior to or 9-12 months after the operation (p < 0.05). Among demographic factors, patient age and place of residence did not appear to have any effect on QL, in contrast to marital status, with married women having better QL in the social/family subscale (p < 0.05). With respect to histopathological factors, patients with ER- and/or PR-positive tumors had better QL in the physical well-being but worse in the functional subscale, 9-12 months after surgery. No significant correlation was found between QL and other histopathological factors. CONCLUSION: In the long term, patients' QL deteriorates with respect to functional and emotional well-being, "additional concerns" and patient-doctor relationship. Hence, specific interventions should aim to improve these aspects of QL in breast cancer patients undergoing breast-conserving surgery.

Distinct demographic factors influence the acceptance of vaccination against HPV.

PURPOSE: To investigate the possible effect of demographic factors on HPV vaccination acceptance in Greece. METHODS: Analysis was performed on data from the "LYSISTRATA" project, a prospective, cross-sectional study, focusing on questions regarding the acceptance of HPV vaccination among Greek women for themselves, and their 13-year-old daughter or son. In total, 5,379 women participated in the study, between 2005 and 2011. RESULTS: Women born and raised in Greece were more likely to accept HPV vaccination for themselves (aOR = 4.1, 95 % CI 2.9-5.8), their daughter (aOR = 3.3, 95 % CI 2.3-4.7) and son (aOR = 3.3, 95 % CI 2.3-4.8), compared with immigrants. Similarly, women who had a Papanicolaou's test were more likely to accept vaccination for themselves (aOR = 1.8, 95 % CI 1.4-2.3), their daughter (aOR = 1.5, 95 % CI 1.2-1.9) and son (aOR = 1.4, 95 % CI 1.1-1.7) than those never tested. Smokers were less likely to accept HPV vaccination for themselves (aOR = 0.8, 95 % CI 0.6-0.9); however, such an association was not documented concerning their children. Educational level had a rather inconsistent impact on HPV vaccination acceptance. The effect of womens' age, monthly income, residence, profession and marital status on HPV vaccination acceptance for themselves was different than that for their daughters, and even more for their sons. CONCLUSIONS: There are distinct demographic factors that influence HPV vaccination acceptance. Women's perception that male vaccination is not as necessary may lead to lower acceptance of HPV vaccination for young boys and men.

Transcultural Adaptation of the Breast Cancer Awareness Measure in a Rural Border Area of Greece.

BACKGROUND: Breast cancer awareness is a concept suggesting that awareness of signs and symptoms and early seeking of medical advice may decrease mortality, especially in limited resource settings. METHODS: A modified questionnaire based on the breast cancer awareness measure (BCAM) by Cancer Research UK was translated into Greek and used for the first time. Participants were women residing in a rural border area in Greece. For statistical analysis the χ2 goodness-of-fit and Cramer's V test for categorical comparisons were used and Cronbach's alpha for reliability analysis. RESULTS: In total, 110 women filled out and returned the questionnaire. Respondents appeared to be inappropriately informed regarding the less common warning signs of breast cancer, the most common age of breast cancer occurrence, the national screening program, and the less important risk factors of breast cancer. On the other hand, most women appeared to be confident in recognizing breast changes and seeking medical advice if needed. CONCLUSIONS: The translated modified BCAM tool can be used to evaluate breast cancer awareness in Greek women. Future campaigns developed by policymakers should focus on improving breast cancer awareness, especially in socioeconomically deprived areas.

Sonographic vascularity indices' study in ectopic pregnancies, after methotrexate treatment.

Objectives: Ectopic pregnancy is a crucial problem in Gynaecology. Previous studies concerning the medical treatment of ectopic pregnancies, have used only ß-hCG (beta- human chorionic gonadotropin) values, to monitor the successful response to treatment. The current study was a PhD (Doctorate of Philosophy) thesis research, which has evaluated the vascularity indices' changes. The values of vascularity indices could be used, in combination with ß-hCG values and the gestational sac dimensions, in every medically treated ectopic pregnancy. The results could be used, for monitoring the course of all medically treated ectopic pregnancies. Study design: 72 women of reproductive age have taken part in the study. They have been admitted due to secondary amenorrhea, positive ß-hCG test, with or without vaginal bleeding. The participants took part voluntarily and were allocated in two groups. The first group consisted of 37 women, who were possible normal or threatened intrauterine pregnancies (control group). The second group consisted of 35 women, whose sonographic findings suggested ectopic pregnancy, and qualified for methotrexate treatment (study group). Sonographic control and measurement of the vascularity indices (PI - RI) (Pulsatility index - Resistance index) of the ectopic pregnancy was conducted, in combination with ß-hCG values for every admitted or outpatient woman.The dimensions of the gestational sac of both groups were measured during four consecutive periods of time. The control group has shown progressively increasing sac dimensions, whereas, in the study group sac dimensions were more stable or growing gradually smaller. The exception where those ectopic pregnancies that ruptured, which have also shown a gradual enlargement of the sac. Results: The endometrial thickness of the study group was gradually decreasing up to 76 % per day, and the more eminent, but not statistically significant decrease, was observed in the single dose regiment of methotrexate. Moreover, the quantitative PI and RI were evaluated, and the main finding was that there were no statistically significant decreases in any of the two groups. Concerning the study group, methotrexate treatment was successful, since there was a decrease of up to 80 %, whereas a clearly significant correlation was found between the ß-hCG levels and the RI. Conclusion: The vascularity indices could be used safely, in combination with ß-hCG levels and the decrease of the gestational sac dimensions, as criteria for the evaluation of response to medical treatment of ectopic pregnancies.

Prenatal diagnosis of thoracic kidney in the 2nd trimester with delayed manifestation of associated diaphragmatic hernia.

Ectopic kidney is a rare congenital malformation, caused by renal malpositioning during embryogenesis. We report a rare case of ectopic kidney located in the left hemithorax of a male fetus. The unique features in this case were early sonographic prenatal diagnosis of thoracic kidney at 22 weeks' gestation, which was confirmed by fetal MRI, and delayed sonographic manifestation of the associated congenital diaphragmatic hernia at 27 weeks.

Cervical, uterine corpus, and ovarian cancer mortality in Greece during 1980 to 2005: a trend analysis.

INTRODUCTION: The aim of the present study was to analyze cervical, uterine corpus, and ovarian cancer mortality, between 1980 and 2005, in Greece. METHODS: Mortality data and population age distribution were provided by the National Statistical Service of Greece. Time trends of mortality were calculated for each tumor type per 100,000 women in the whole female population of Greece, and 2 different age groups, that is, women aged 49 years and younger and those 50 years and older. Joinpoint regression was used for further analysis of mortality trends. RESULTS: Overall, cervical and uterine corpus cancer mortality in the whole female population of Greece had a slightly decreasing trend between 1980 and 2005, whereas ovarian cancer mortality rates increased steadily throughout the period studied. Subgroup analyses according to age showed that cervical cancer mortality decreased very slightly only in women older than 50 years, whereas it remained steady in younger women. Uterine corpus cancer mortality decreased slightly in both age groups, but increased during the last years of the study period in the older age group. Ovarian cancer mortality increased in women older than 50 years, whereas it remained steady in the younger age group. Joinpoint regression analysis showed that only the increase after 1997 in the mortality trend for uterine corpus cancer in women 50 years and older was statistically significant (P = 0.0044). CONCLUSIONS: Although our findings regarding cervical cancer mortality in Greece are encouraging, still more efforts are needed, particularly in preventing cervical cancer in younger women. The increasing trend of uterine corpus and ovarian cancer mortality in older women suggests that development of well-organized tertiary centers for the implementation of modern therapeutic modalities is urgently needed.

Levonorgestrel-releasing intrauterine system vs. endometrial thermal ablation for menorrhagia.

OBJECTIVE: To evaluate the efficacy of a Levonorgestrel-releasing Intrauterine System (LNG-IUS) in controlling menorrhagia in comparison with endometrial thermal rollerball ablation. DESIGN: Seventy-nine consecutive patients with menorrhagia underwent either LNG-IUS insertion (n=42) or hysteroscopical endometrial thermal rollerball ablation (n=37) in a prospective, observational, comparative study. Women reported duration of uterine bleeding in days prior to, and six and 12 months after each intervention. Prior to each intervention, endometrial, cervical or other pathological conditions of the genital tract were excluded. GnRH analogues for endometrial suppression were given for ten weeks before endometrial ablation but not prior to LNG-IUS insertion. RESULTS: There were no differences in duration of uterine bleeding before each intervention in the two groups. The duration of uterine bleeding was lower in the LNG-IUS group as compared with endometrial ablation at six (p<0.001) and 12 months (p<0.001) after each intervention. Furthermore, the effect on reduction of bleeding was stronger in the LNG-IUS group as compared with the endometrial ablation group at six (p<0.001) and 12 months (p<0.001). CONCLUSIONS: The LNG-IUS was more efficacious than endometrial thermal ablation in reducing duration of uterine bleeding at six and 12 months post-intervention.

Cavernous Breast Hemangioma Mimicking an Invasive Lesion on Contrast-Enhanced MRI.

Hemangiomas are vascular lesions, which are only rarely located in the breast. Larger breast hemangiomas may be detected by clinical examination, mammography, and breast ultrasound, whereas smaller lesions are usually incidental findings. We present a rare case of a 43-year-old woman with a cavernous hemangioma of the breast, presenting only on MRI and evading mammographic and ultrasonographic imaging. On breast MRI, a small lesion with irregular margins was detected in the right breast, and following gadolinium contrast medium administration, a type 3 curve, with rapid initial rise, followed by reduction in enhancement (washout) in the delayed phase was noted, raising suspicion for malignancy. The lesion could not be visualized on second-look targeted breast ultrasound and full-field digital mammography. A wide local excision was performed after 3 T MRI-guided hook wire localization and diagnosis of cavernous hemangioma was established histologically. Cavernous hemangioma is a rare breast lesion, with only few cases reported in the literature, and this is the first case with a presentation mimicking an invasive tumor on contrast-enhanced MRI.

Enhancer of the rudimentary gene homologue (ERH) expression pattern in sporadic human breast cancer and normal breast tissue.

BACKGROUND: The human gene ERH (Enhancer of the Rudimentary gene Homologue) has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1) via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. METHODS: The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN) on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH). RESULTS: Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test); the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1). These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. CONCLUSION: ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian cancer, ERH overexpression may be implicated in the initiation and/or progression of certain human malignancies. Further studies on large breast cancer tissue cohorts should determine whether ERH could function as a prognostic factor or even a drug target in the treatment of human breast cancer.

Genome-wide microarray gene expression, array-CGH analysis, and telomerase activity in advanced ovarian endometriosis: a high degree of differentiation rather than malignant potential.

The aim of the present study was to investigate whether endometriosis and cancer share common molecular characteristics. Tissue samples were collected prospectively during diagnostic laparoscopy of patients with primary infertility. Using high-density oligonucleotide microarrays, (Affymetrix Gene Chip HG-U133 Set) the genome-wide gene expression profile of advanced ovarian endometriosis was analyzed compared with matched normal endometrium. Expression of TERT, the gene encoding the telomerase reverse transcriptase subunit, and telomerase activity were analyzed in eutopic and ectopic endometrium. Genome-wide, high-resolution array-CGH was used to screen for genomic aberrations in endometriosis. Expression microarray data were validated quantitatively with RT-PCR. The genes RARRES1 and RARRES2 (retinoic acid receptor responder 1 and 2) were found to be up-regulated in endometriosis, suggesting a high degree of differentiation. Consistently, down-regulated genes included those involved in the cell cycle, cell metabolism and homeostasis. Expression of TERT and telomerase activity were present in eutopic but absent in ectopic endometrium. Array-CGH revealed a normal genomic pattern without gross amplifications and deletions. In conclusion, these data suggest that advanced ovarian endometriosis represents a highly differentiated tissue with minimal or no malignant potential.

Expression analysis and RNA localization of PAI-RBP1 (SERBP1) in epithelial ovarian cancer: association with tumor progression.

OBJECTIVE: The plasminogen activator system (PA) plays an important role in invasion and metastasis of solid tumors. The PA Inhibitor type 1 (PAI-1) is the main physiologic regulator of plasminogen activation. A recently characterized protein, PAI-RBP1 (PAI-1 mRNA Binding Protein 1), appears to regulate the stability of PAI-1 mRNA. Expression of PAI-RBP1 (the new, approved gene symbol is SERBP1) has not been previously analyzed in human tumors. We present herein for the first time expression analysis of PAI-RBP1 in epithelial ovarian cancer. METHODS: PAI-RBP1 was identified as gene overexpressed in ovarian cancer by an in silico approach using EST database mining. A thorough expression analysis of PAI-RBP1 and PAI-1 was performed in normal ovary (n=4), benign (n=6) and malignant (n=42) ovarian lesions using non-radioactive RNA in situ hybridization and immunohistochemistry, respectively. RESULTS: PAI-RBP1 mRNA and PAI-1 were significantly overexpressed in tumor epithelial cells as compared to benign and normal ovarian tissue. A significant correlation between PAI-RBP1 expression and advanced disease stage (FIGO) was found (p=0.042). CONCLUSION: In ovarian cancer, PAI-RBP1 is significantly overexpressed in tumor epithelial cells, suggesting a biological role in tumor invasion and metastasis. Its expression is higher in advanced disease, thus the prognostic significance of PAI-RBP1 in ovarian cancer remains to be evaluated in further studies.

Regulation of basal metabolic rate in uncomplicated pregnancy and in gestational diabetes mellitus.

Basal metabolic rate (BMR) is one of the major components of total energy expenditure (TEE). It is affected by various factors, such as body weight, body composition, age, race/ethnicity, gender, biochemical parameters, physical activity, and health status. Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy and it increases the risk for health complications, such as stillbirth, diabetes mellitus, and cardiovascular disease in later life. Both BMR and GDM have been linked with gestational weight gain (GWG), a fact suggesting a possible association between them. However, assessing BMR is a complex procedure, which becomes more complicated when additional parameters, such as pregnancy and GDM, are taken into consideration. The present review summarizes the current knowledge on factors affecting BMR and its regulation in relation to pregnancy and GDM. Future research addressing these associations should thoroughly consider other factors that affect BMI when designing such studies and/or discussing the BMR outcome results.

Expression analysis of mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2) in more than 300 human tumors and matching normal tissues reveals their co-expression in gynecologic malignancies.

BACKGROUND: Mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2), two members of the secretoglobin superfamily, are known to be co-expressed in breast cancer, where their proteins form a covalent complex. Based on the relatively high tissue-specific expression pattern, it has been proposed that the mammaglobin A protein and/or its complex with lipophilin B could be used in breast cancer diagnosis and treatment. In view of these clinical implications, the aim of the present study was to analyze the expression of both genes in a large panel of human solid tumors (n = 309), corresponding normal tissues (n = 309) and cell lines (n = 11), in order to evaluate their tissue specific expression and co-expression pattern. METHODS: For gene and protein expression analyses, northern blot, dot blot hybridization of matched tumor/normal arrays (cancer profiling arrays), quantitative RT-PCR, non-radioisotopic RNA in situ hybridization and immunohistochemistry were used. RESULTS: Cancer profiling array data demonstrated that mammaglobin A and lipophilin B expression is not restricted to normal and malignant breast tissue. Both genes were abundantly expressed in tumors of the female genital tract, i.e. endometrial, ovarian and cervical cancer. In these four tissues the expression pattern of mammaglobin A and lipophilin B was highly concordant, with both genes being down-, up- or not regulated in the same tissue samples. In breast tissue, mammaglobin A expression was down-regulated in 49% and up-regulated in 12% of breast tumor specimens compared with matching normal tissues, while lipophilin B was down-regulated in 59% and up-regulated in 3% of cases. In endometrial tissue, expression of mammaglobin A and lipophilin B was clearly up-regulated in tumors (47% and 49% respectively). Both genes exhibited down-regulation in 22% of endometrial tumors. The only exceptions to this concordance of mammaglobin A/lipophilin B expression were normal and malignant tissues of prostate and kidney, where only lipophilin B was abundantly expressed and mammaglobin A was entirely absent. RNA in situ hybridization and immunohistochemistry confirmed expression of mammaglobin A on a cellular level in endometrial and cervical cancer and their corresponding normal tissues. CONCLUSION: Altogether, these data suggest that expression of mammaglobin A and lipophilin B might be controlled in different tissues by the same regulatory transcriptional mechanisms. Diagnostic assays based on mammaglobin A expression and/or the mammaglobin A/lipophilin B complex appear to be less specific for breast cancer, but with a broader spectrum of potential applications, which includes gynecologic malignancies.

Sorafenib in breast cancer treatment: A systematic review and overview of clinical trials.

AIM: To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer. METHODS: An extensive search of the literature until March 2016 was carried out in Medline and clinicaltrials.gov, by using the search terms "sorafenib" and "breast cancer". Papers found were checked for further relevant publications. Overall, 21 relevant studies were found, 18 in advanced breast cancer (16 in stage IV and two in stages III-IV) and three in early breast cancer. RESULTS: Among studies in advanced breast cancer, there were two trials with sorafenib as monotherapy, four trials of sorafenib in combination with taxanes, two in combination with capecitabine, one with gemcitabine and/or capecitabine, one with vinorelbine, one with bevacizumab, one with pemetrexed and one with ixabepilone, three trials of sorafenib in combination with endocrine therapy and two trials in women with brain metastases undergoing whole brain radiotherapy. In addition, there was one trial of sorafenib added to standard chemotherapy in the adjuvant setting, and two trials in the neoadjuvant setting. In general, sorafenib was well tolerated in breast cancer patients, though its dosage had to be adjusted in some trials, and discontinuation rates were high, particularly for the combination of sorafenib with anastrozole. Sorafenib monotherapy and combinations with taxanes, bevacizumab and ixabepilone showed inadequate efficacy, while efficacy results from combinations with gemcitabine and/or capecitabine and possibly tamoxifen were more promising. CONCLUSION: At present, sorafenib should not be used for the treatment of breast cancer outside of clinical trials and more clinical data are needed in order to support its standard use in breast cancer therapy.