Association of estrogen receptor alpha (ERα) gene polymorphisms with endometrial thickness and lipid profile in women with breast cancer treated with aromatase inhibitors.

Aromatase inhibitors (AIs) provide an alternative to tamoxifen as an adjuvant therapy for post-menopausal, hormone-receptor positive breast cancer patients. The aim of the present study was to evaluate the effect of PvuII and XbaI polymorphisms of the ERα gene at ΑΙs treatment's adverse effects in post-menopausal women with breast cancer. The study included 87 post-menopausal women with ER-positive breast cancer treated with AIs and 80 healthy controls. The overall presence of ERα polymorphisms in all women with breast cancer was not different from the healthy controls. Endometrial thickness under AIs treatment was reduced from (mean value ± SD) 6,404 ± 2,901 mm to 3,666 ± 1,4656 mm. Moreover, the AA XbaI genotype was associated with greater reduction in endometrial thickness during therapy with AIs (p = 0.005). The presence of the CC PvuII and the AA XbaI genotypes were associated with elevated LDL levels and elevated triglycerides. In conclusion, the results of the present study showed that the genotype of women with breast cancer under AIs treatment might influence treatment's adverse effects, as, the presence of the CC PvuII and the AA XbaI genotypes of the ERα were associated with elevated LDL and triglycerides serum levels, while the AA XbaI genotype was associated with a greater reduction in endometrial thickness.

Fournier's gangrene, a urologic and surgical emergency: presentation of a multi-institutional experience with 45 cases.

OBJECTIVE: To review multi-institutional, multidisciplinary experience in the management of Fournier's gangrene (FG) in an attempt to identify etiologic parameters as well as to propose methods of efficient management. PATIENTS AND METHODS: Retrospective chart review of 45 patients diagnosed with FG and treated in three departments (general surgery and urology departments) was performed. RESULTS: Average patient age was 50 ± 15.8 (range 33-81) years. Five female and 40 male patients. Seven patients deceased due to the disease. In 26 and 6 cases, perianal or ischiorectal abscess was present, respectively. These abscesses were extending up to the level of rectovesical/Douglas pouch in 12 cases. Abscesses in the scrotum and perineum were revealed in 10 and 6 cases, respectively. A fistula to the rectum and 8 sinuses to the skin were observed. Colostomy was performed in 25 cases, diverting cystostomy in 17, and orchidectomy in 12 cases. In 18 patients (40%) repeat debridement was deemed necessary. Three patients required more than 3 debridement procedures. Average hospitalization time was 15.7 ± 11.6 (range 4-40) days. CONCLUSION: FG is a life-threatening form of necrotizing soft tissue infection. The disease is unpredictable and the currently proposed methods for prognosis are promising but still questionable.

Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial.

INTRODUCTION: The aim of this multicenter, phase III, prospective open label clinical trial was to investigate the effect of risedronate (R) on bone mineral density (BMD) in postmenopausal, early breast cancer (BC) patients scheduled to receive anastrozole (A). METHODS: Pre-treatment BMD of 213 patients with hormone receptor-positive BC was evaluated at lumbar spine (LS) and hip (HP). Patients were categorized according to their baseline BMD T-score as being at low, moderate and high risk of osteoporosis. Low risk patients received anastrozole only (A), moderate risk were randomized to anastrozole +/- risedronate (A+/-R) administration and high risk patients received anastrozole + risedronate (A+R). Anastrozole was given at a dosage of 1 mg/day while oral risedronate was given at 35 mg/week. BMD was then assessed at 12 and 24 months. All patients received daily supplements of calcium (1000 mg/day) and vitamin D (400 IU/day). RESULTS: At 24 months, in the moderate risk group, treatment with A+R resulted in a significant increase in BMD at LS and HP compared to treatment with A only (5.7% v -1.5%, Wilcoxon test P = 0.006, and 1.6% v -3.9% Wilcoxon test P = 0.037, respectively), while no significant difference was found at 12 months; 24.3% of the patients moved to normal BMD region. In the high risk group, a significant increase for LS was detected both at 12 and 24 months (6.3% and 6.6%, P < 0.001) but not for HP; BMD in 14% of patients improved to the osteopenic region. In the low risk group, a significant decrease of BMD was detected at 12 months for LS and HP (-5.3% P < 0.001 and -2.4% P < 0.001, respectively,); at 24 months, a significant decrease of BMD was detected only for LS (-2.5%, P < 0.001). However, 22% of patients became osteopenic and only 4% became osteoporotic. CONCLUSIONS: The addition of oral risedronate in post-menopausal breast cancer patients receiving anastrozole has a favorable effect on BMD. Patients with pre-treatment osteopenic to osteoporotic status should be treated with a combination of both therapies in order to avoid bone loss induced by aromatase inhibition. Patients with normal BMD before starting treatment with anastrozole have a very low risk to develop osteoporosis.

Extended adjuvant hormonal therapy with exemestane has no detrimental effect on the lipid profile of postmenopausal breast cancer patients: final results of the ATENA lipid substudy.

INTRODUCTION: Extended adjuvant endocrine therapy for breast cancer with aromatase inhibitors may potentially alter the lipid profile of postmenopausal patients and thus increase the risk of developing cardiovascular disease. In this study, a subprotocol of the ATENA (Adjuvant post-Tamoxifen Exemestane versus Nothing Applied) trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal patients with operable breast cancer, in the adjuvant setting, with that of observation alone after completion of 5 to 7 years of primary treatment with tamoxifen. METHODS: In this open-label, randomized, parallel-group study, 411 postmenopausal patients with operable breast cancer, who had been treated with tamoxifen for 5 to 7 years, were randomized to either 5 additional years of exemestane (25 mg/day; n = 211) or observation only (n = 200). Assessments of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total serum triglycerides (TRG) were performed at baseline and then during each follow-up visit, performed at either 6 or 12 months, according to the center's clinical practice, until completing 24 months in the study. RESULTS: TC and LDL levels increased significantly across time for both arms; TC increase was more pronounced for the observation arm, and that was sustained up to 24 months. HDL levels decreased significantly across time for the exemestane arm, whereas no significant change was detected across time for the observation arm. Triglyceride levels decreased significantly across time on both arms, with no difference detected in changes from baseline between the exemestane and the observation arms. CONCLUSIONS: Exemestane lacks the beneficial effect of tamoxifen on lipids; however, sequential adjuvant treatment with exemestane in postmenopausal breast cancer patients after cessation of 5 to 7 years of tamoxifen does not appear to alter the lipid profile significantly compared with that of an observational arm. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00810706.

Breast cancer section analysis correlates with sentinel lymph node biopsies: Precision and topographic anatomy.

BACKGROUND: The mainstream treatment of breast cancer is radical mastectomy accompanied with Axillary Lymph Node Dissection (ALND). Lately, more conservative methods accompanied by adjuvant radiotherapy have been gradually replacing radical modalities. The Sentinel Lymph Node Biopsy (SLNB) has been considered such a valuable alternative to surgery conservative approach. OBJECTIVE: To assess the agreement between SLNB in breast cancer patients and pathology results following ALND and to provide correlation between the sentinel lymph nodes (SLN) anatomical topography and biopsy positivity according to SLNBs. METHODS: Two hundred female breast cancer patients (31 to 83 years of age) underwent partial or simple mastectomy with or without subsequent ALND. All patients were randomized against selection criteria and underwent SLNB. RESULTS: In a set of 200 patients, 96.3% presented identical results between SLNB and pathology. 36% of them were confirmed with positive SLN through both approaches. Regarding the SLN topographic anatomical position, 67.3% of samples were located in the front axillary position, 24.5% in the front thoracic position, whereas 6.1% was located in the central axillary position. CONCLUSIONS: The correlation between the SLN topographic anatomical position and the pathology results, revealed that the majority of the SLN accumulates in the front axillary region. A larger patient population will statistically support this association.

Increased frequency of thyroid nodules and breast fibroadenomas in women with uterine fibroids.

Fibroids or leiomyomas or myomas of the uterus are the most common benign gynecologic disease, while fibroadenomas of the breast are most frequently seen in young women, usually within 20 years after puberty. Multiple tumors in one or both breasts are found in 10-15% of patients. Single thyroid nodules are much more common in women than in men, and their prevalence increases with age. The aim of the present study was to determine cross-sectionally the incidence of solitary thyroid nodules and fibroadenomas of the breast in women with uterine fibroids. In women with uterine adenomas, the frequency of fibroadenomas of the breast was 65% and of thyroid nodules was 38.7%, while in women with a normal uterus, the frequency was 35% and 20%, respectively. Therefore, women with uterine fibroids have an increased incidence of thyroid nodules (t = 4.68, p = 0.030) and of fibroadenomas of the breast (t = 11.74, p = 0.001).

Non-palpable breast carcinomas: correlation of mammographically detected malignant-appearing microcalcifications and epidermal growth factor receptor (EGFR) family expression.

Malignant-appearing microcalcifications (MAMCs) represent one of the earliest mammographic findings of non-palpable breast carcinomas (NPBCs). In the present study, we have evaluated the expression of all EGFR family members in NPBCs and its possible association with MAMCs. Three hundred and fifty patients with non-palpable suspicious breast lesions detected during screening mammography were studied. EGFR family proteins' expression was found to be present since the preclinical phase of breast carcinomas and was strongly correlated (except HER-3) with MAMCs. The co-expression pattern of EGFR family members combined with other molecular prognostic factors and the mammographic appearance might predict the natural history of NPBCs.

A web-based system for supporting collaboration towards resolving oncology issues.

The coordinated consideration of diverse perspectives and knowledge sources in medical decision-making contexts is undoubtedly of crucial importance, in that it augments the quality of both the overall process and decisions to be made. Towards this end, this study presents a web-based system that aims at the exploitation of personalized knowledge through a structured process of collaborative and argumentative resolution of issues raised in such settings. By using the system, a consensus emerges through the process of collaboratively considering alternative interpretations of the issue under consideration. Using an illustrative example of collaboration between a group of experts deciding on the most appropriate treatment for a particular case of breast cancer, we present the design rationale, features and functionality of the proposed system. Much attention is also paid to the associated knowledge management issues. The system can be used for distributed, asynchronous collaboration, allowing users to surpass the requirements of working at the same place and time.

Expression of p27KIP1, p21WAF1 and p53 does not correlate with prognosis in node-negative invasive ductal carcinoma of the breast.

The expressions ofp27Kip1 (p27) and p21waf1 (p21) cyclin-dependent kinase inhibitors and p53 were examined in a series of 170 node-negative breast carcinomas (NNBCs) to evaluate their prognostic significance. Low nuclear (p27TN) and cytoplasmic (p27TC) p27 expressions were noted in 66% and 81% of NNBCs, respectively. p21 and p53 overexpressions were detected in 56% and 26%, respectively. Low p27TN was significantly associated with high grade (p=0.001), age < or = 50 years (p=0.01), negative hormone receptors (p<0.001), low p27TC (p<0.001) and p53 overexpression (p=0.02). Low p27TC was associated with negative hormone receptors (p<0.001). p53 overexpression was associated with high grade (p<0.001) and negative hormone receptors (p<0.001). p21 overexpression, although not correlated with the examined parameters, was associated with increased disease-free survival in univariate analysis. In multivariate analysis, p27TN, p27TC, p21 and p53 were not associated with disease-free survival or overall survival. These findings argue against the prognostic value of p27, p21 and p53 in NNBC.

Age effect on bone mineral density changes in breast cancer patients receiving anastrozole: results from the ARBI prospective clinical trial.

PURPOSE: We investigated whether age at anastrozole (A) initiation influences the effect of treatment on bone mineral density (BMD). We conducted a post hoc analysis of the dataset of Arimidex Bone Mass Index Oral Bisphosphonates prospective trial, studying the effect of risedronate (R) on BMD of postmenopausal, early breast cancer patients receiving A. METHODS: Patients were stratified into those with normal BMD or mild osteopenia (T > -2) receiving A-only and patients with mild or severe osteopenia (T ≤ -2) or osteoporosis (T < -2.5) receiving A and per os R (A + R). Depending on age on treatment initiation, patients were grouped into two age cohorts, above and below 65 years. BMD change in lumbar spine (LS) and hip (HP) was evaluated at 12 months. An analysis of patients with normal BMD at baseline was additionally performed. RESULTS: Among patients receiving A-only, women ≤65 years were more likely to have a decrease in LS-BMD than older (p = 0.034). HP-BMD decrease at 12 months was not related to age (p = 0.182). In patients with mild or severe osteopenia or osteoporosis, treated with A + R, no age effect was observed for LS or HP (p = 0.099 and p = 0.939, respectively). Among patients with normal BMD at baseline, the age effect on LS-BMD change was more profound (p = 0.026). CONCLUSIONS: Our study suggests that younger postmenopausal women with normal BMD or mild osteopenia receiving A-only face an increased risk of bone loss in LS. Among patients with mild or severe osteopenia or osteoporosis treated with A + R, 12 months LS or HP BMD variations were configured regardless of age group.

Percutaneous minimally invasive management of iatrogenic ureteral injuries.

PURPOSE: To present experience with the percutaneous management of iatrogenic ureteral injuries. PATIENTS AND METHODS: Eighteen women and six men with a mean age of 59.3 years (range 33-80 years) received a diagnosis of ureteral injury sustained during gynecologic, urologic, and general surgical procedures. In a total of 25 injured ureters, 12 had interruption of continuity of their lumen, 10 were associated with contrast extravasation, and 3 were related to both. A standard percutaneous nephrostomy tract was established on the side of the afflicted kidney. Combined use of hydrophilic guidewires and balloon dilations were performed to achieve antegrade recanalization of the ureteral lesion. Then, a ureteral stent was inserted to assure patency. RESULTS: Average stricture length was 1.21 (range 0.5-1.9 cm). Success of the aforementioned technique was possible in 18 ureters. Successful management in one session took place in 14 ureters. Average hospitalization time was 1.8 days (range 0-5 d). The follow-up period ranged between 12 and 18 months, with mean follow-up time of 12.9 months. Ureteral patency was evident at 1 week follow-up in six patients with obstructed ureters. In the remaining patients, balloon dilation of the stricture was repeated, and another stent was placed. Extravasation of contrast was observed in two patients with extravasating ureters in the same period. Nephrostomy tubes were removed after a mean indwelling period of 5.9 weeks (range 1-12 wks). Two patients treated by the described method died during their hospitalization in the intensive care unit because of sepsis from peritonitis that was related to colon injury and multiple concomitant injuries. Major complications were not observed in the remaining 22 patients during the follow-up period. CONCLUSION: The minimally invasive management of ureteral injuries is a safe and efficient method for both ureteral obstruction and/or laceration in a wide range of iatrogenic ureteral injuries.

Estrogen receptor polymorphisms in tamoxifen-treated women with breast cancer.

In postmenopausal women with estrogen receptor (ER)-positive breast cancer, long-term tamoxifen administration has proved beneficial after surgical treatment and subsequent chemotherapy. One of the major adverse effects of tamoxifen is the development of endometrial pathology (polyps, endometrial hyperplasia and endometrial cancer). PvuII and XbaI polymorphisms of the estrogen receptor-alpha gene (ERalpha) and RsaI and AluI polymorphisms of the estrogen receptor-beta gene (ERbeta) have been associated with breast cancer. Thus the present study aimed to identify whether ER gene polymorphisms are associated with breast cancer stage or endometrial responsiveness to long-term tamoxifen treatment in 87 postmenopausal, tamoxifen-treated women with ER-positive breast cancer. The mean age of the patients was 58.7 +/- 4.7 years and the mean duration of tamoxifen treatment was 3.9 +/- 1.1 years. At diagnosis, the stage of breast cancer was determined as follows: 29 women (32%) at Stage I, 49 (58%) at Stage II and 9 (10%) at Stage III. The frequency distributions of the estrogen receptor polymorphisms in all women with breast cancer were not different from those predicted by the Hardy-Weinberg equilibrium hypothesis (p > 0.10). None of the ER polymorphisms studied was linked to either the presence of endometrial pathology or the stage of breast cancer.

Acute lymphoblastic leukemia relapse in the breast diagnosed with gray-scale and color Doppler sonography.

Extramedullary relapses of acute lymphoblastic leukemia (ALL) in children and young adults are rare and in most cases are localized in the central nervous system, testes, or both. We describe a rare case of extramedullary relapse of ALL in the breast of a 17-year-old girl. The patient, who had been diagnosed with ALL 1 year before and had been in complete remission for 5 months, was admitted to the hospital for investigation of a mass in her left breast. On clinical examination, she had a large, palpable, nontender mass in her left breast. Mammography revealed a very dense mass. On gray-scale and power Doppler sonography, the appearance of the mass was consistent with malignancy. Histopathologic examination of a surgical biopsy specimen permitted accurate diagnosis of ALL.

Non-palpable breast carcinomas: correlation of mammographically detected malignant-appearing microcalcifications and molecular prognostic factors.

Screening mammography has greatly increased the number of non-palpable breast carcinomas diagnosed in asymptomatic women. Malignant-appearing microcalcifications represent one of the earliest mammographic findings of non-palpable breast carcinomas. Many studies have attempted to correlate radiological and histological features of malignant-appearing microcalcifications. In the present study, we evaluated the association between mammographically detected malignant-appearing microcalcifications and the expression profile of selected biological markers in non-palpable breast carcinomas. Two hundred and eighty patients with non-palpable suspicious breast lesions that were detected during screening mammography were studied. All patients underwent mammographically-guided needle localization-excision breast biopsy. Histological examination showed 74 (26.4%) carcinomas of various subtypes. Immunohistochemistry was carried out in 58/74 carcinomas by using a panel of monoclonal and polyclonal antibodies against estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, Bcl-2, Bax, Fas and DNA fragmentation factor (DFF). Malignant-appearing microcalcifications was the major mammographic finding in 45/58 (77%) patients. Nuclear ER positivity (65.5%) and PR positivity (46.5%) of non-palpable breast carcinomas were statistically correlated with malignant-appearing microcalcifications (p < 0.01 and p < 0.05, respectively). Statistically significant associations were also found between malignant-appearing microcalcifications and HER-2/neu positivity (p < 0.01), Bax positivity (p < 0.01), Fas positivity (p < 0.05) and DFF positivity (p < 0.01), whereas no statistical correlation was found with Bcl-2 positivity (p > 0.05). Malignant-appearing microcalcifications detected during screening mammography represent a diagnostic, prognostic and therapeutic challenge. The mammographic/biological associations and their potential implications in the management of women with non-palpable breast carcinomas are thoroughly discussed.