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Background: Prostate cancer (PCa) shows racial disparity in clinical and genomic characteristics, and Asian patients with PCa often present with more aggressive phenotypes at diagnosis. The ability of TP53 to serve as a prognostic biomarker of PCa has been well studied in Western populations. However, no studies to date have examined the role of TP53 in the disparities of primary hormone-naïve prostate cancer (HNPC) between Chinese and Western populations., Methods: We collected prostate tumors and matched normal tissues or blood samples to perform targeted next-generation sequencing of 94 Chinese primary localized HNPC samples, and correlated these genomic profiles with clinical outcomes. The OncoKB knowledge database was used to identify and classify actionable alterations., Results: The aberrations of PTEN, CDK12, and SPOP in Chinese HNPC samples were similar to those in the Western samples. However, we demonstrated an association of a high frequency of TP53 alterations (21/94) with a relatively higher percentage of alterations in the Wnt signaling pathway (15/94) in Chinese HNPC. Additionally, we highlighted alterations of LRP1B as accounting for a high proportion of PCa and found more frequent alterations in CDH1 in Chinese PCa. Of these, only CDH1 alteration was associated with rapid biochemical recurrence (BCR). However, we verified that TP53 status was at the core of the genomic alteration landscape in Chinese HNPC with putative driver mutations because of the strong connections with other signaling pathways. The mutually exclusive relationship between alterations in TP53 and Wnt/CTNNB1 further molecularly characterizes subsets of prostate cancers. Moreover, the alteration of KMT2C was more likely to co-occur with TP53 alteration, indicating a more aggressive phenotype of PCa, which was associated with sensitivity to treatment with poly ADT-ribose polymerase (PARP) inhibitors., Conclusions: Detection of TP53 alterations has clinical utility for guiding precision cancer therapy for HNPC, especially in the Chinese population.

Introduction: Hormonal therapy with tamoxifen and aromatase inhibitors reduces breast cancer recurrence and mortality but represents a risk factor for thromboembolic events. Therefore, most surgeons discontinue hormonal agents before microvascular surgery and for a variable period thereafter. There are no guidelines regarding when therapy should be stopped (preoperatively) or when it should be resumed (post-operatively). We, therefore, audited our hospital practice with the objective of making recommendations for microvascular breast reconstruction patients., Patients and Methods: A review was performed of all free flap breast reconstructions between 2014 and 2019. Patients were classified according to hormone medication status at operation. Timings of drug cessation and recommencement were recorded. Thrombotic events, namely flap microvascular thrombosis, deep vein thrombosis, superficial vein thrombosis and pulmonary embolism, were compared., Results: A total of 240 patients had 275 free flaps over five years with 36 receiving hormone therapy within one month prior to surgery, which was discontinued 8.5 days (range: 0-28 days) before surgery. Intraoperative microvascular thromboses (HT 2.0%, NHT 0%, and p = 0.869) and post-operative microvascular complications/flap re-explorations (HT 6.6%, NHT 0%, and p = 0.234) were comparable between the two groups. Systemic venous thromboembolic events were also similar (HT 8.3%, NHT 6.1%, and p = 0.893). Age, BMI, smoking status and preoperative chemotherapy did not influence the incidence of thrombotic complications., Conclusion: Hormone therapy did not significantly increase the risk of thromboembolic events. Despite the widespread practice of withholding it for 2 weeks prior to reconstructive surgery, this study does not support such practice being beneficial in terms of thromboembolic events and flap viability. Large-scale trials are needed to establish definitive protocols., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: A positive margin after breast conserving surgery has consistently been shown to be a significant predictor for ipsilateral breast tumor recurrence. Currently, there is no standard for intraoperative margin assessment during lumpectomy, and up to 20% of cases result in positive margins. MarginProbe is a device that provides real-time evaluation of lumpectomy margins during surgery. The aim of this study was to evaluate the impact of MarginProbe as an adjunct to standard operating procedure (SOP)., Methods: Patients diagnosed with breast cancer scheduled for breast conserving surgery were consented for intraoperative use of MarginProbe. Shaved margins were excised based on margin assessment using the surgeon's SOP which included specimen radiography and gross pathologic examination, and feedback from the device. The primary endpoint was re-excision rate. Secondary endpoints included sensitivity, specificity, false-positive and negative rates., Results: Of the 60 breast cancers, initial histologically close/positive margins were identified in 18 patients (30%). The re-excision rate in the overall cohort was 6.6%, compared to a historical re-excision rate of 8.6% (p < 0.01). Based on 360 measurement sites, MarginProbe demonstrated a sensitivity of 67% and specificity of 60%, with a positive predictive value of 16%, and of negative predictive value of 94%, which was similar to the accuracy of SOP., Conclusions: MarginProbe performs equally as well as specimen radiography and gross pathologic examination. In this setting where the baseline re-excision rate was low, the use of MarginProbe as an adjunct to SOP resulted in a small 2% absolute reduction in re-excision rate.

COVID-19 has been officially declared as a pandemic by the WHO. Italy was the first European country to be strongly affected by this outbreak. All elective and health promotion activities were reduced. Accordingly, Italian Breast Units and breast cancer (BC) screening programs scaled down significantly their activities. The aim of this study was to evaluate measures that could potentially reduce the clinical impact of COVID-19 on BC patients. Temporary recommendations are needed that could assist specialists in preventing COVID-19 infection and optimizing resources for diagnosis and treatment of BC patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The addition of everolimus to exemestane is recommended in patients with HR+ advanced breast cancer with disease recurrence or progression following prior non-steroidal aromatase inhibitors. We report a case of radiation recall syndrome in a breast cancer patient, after introduction of everolimus. A woman with a right breast cancer underwent a mastectomy, then adjuvant chemotherapy, radiation therapy and hormonotherapy. In a phase III trial (UNIRAD protocol), she received everolimus 5 months after radiation therapy. Seven days after introduction, she was suffering from a radiation recall syndrome with exacerbation skin reactions. The exact pathophysiological mechanism of radiation recall syndrome is unknown. The combination of radiation therapy and mTor inhibitor, even sequentially, should be done with caution as several cases have already been reported., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer., Patients and Methods: Premenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2-negative breast cancer were randomly assigned to triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to first assessment of centrally assessed estradiol level ≤ 2.72 pg/mL [≤ 10 pmol/L] during neoadjuvant therapy). The trial had 90% power to detect a difference using a log-rank test with a two-sided α of .05. Secondary end points included response, tolerability, and patient-reported endocrine symptoms., Results: Between February 2014 and January 2017, 51 patients were enrolled (n = 26 received triptorelin plus letrozole; n = 25 received degarelix plus letrozole). Time to optimal OFS was three times faster for patients assigned to degarelix and letrozole than to triptorelin and letrozole (median, 3 v 14 days; hazard ratio, 3.05; 95% CI, 1.65 to 5.65; P < .001). Furthermore, OFS was maintained during subsequent cycles for all patients assigned to receive degarelix and letrozole, whereas 15.4% of patients assigned to receive triptorelin and letrozole had suboptimal OFS after cycle 1 (six events during 127 measurements). Adverse events as a result of both degarelix plus letrozole and triptorelin plus letrozole were as expected., Conclusion: In premenopausal women receiving letrozole for neoadjuvant endocrine therapy, OFS was achieved more quickly and maintained more effectively with degarelix than with triptorelin.

Background: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies., Methods: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 10 6 or 0.2 × 10 6 isogenic hormone sensitive Myc-Cap cells to establish synchronous grafts. Mice were treated with four intraperitoneal injections of anti-PD-1 (10 mg/kg), anti-CTLA-4 (1 mg/kg), or isotype control antibody with or without adjuvant cryoablation of the larger tumor graft and with or without neo-adjuvant androgen deprivation with degarelix (ADT). Mouse survival and growth rates of tumor grafts were measured. The immune dependency of observed oncological effects was evaluated by T cell depletion experiments., Results: Treatment with anti-CTLA-4 antibody and cryoablation delayed the growth of the distant tumor by 14.8 days (p = 0.0006) and decreased the mortality rate by factor of 4 (p = 0.0003) when compared to cryoablation alone. This synergy was found to be dependent on CD3 +  and CD8 +  cells. Combining PD-1 blockade with cryoablation did not show a benefit over use of either treatment alone. Addition of ADT to anti-PD1 therapy and cryoablation doubled the time to accelerated growth in the untreated tumors (p = 0.0021) and extended survival when compared to cryoablation combined with ADT in 25% of the mice. Effects of combining anti-PD1 with ADT and cryoablation on mouse survival were obviated by T cell depletion., Conclusion: Trimodal therapy consisting of androgen deprivation, cryoablation and PD-1 blockade, as well as the combination of cryoablation and low dose anti-CTLA-4 blockade showed that local therapies with cryoablation could be considered to augment the effects of checkpoint blockade in prostate cancer.

Introduction: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer., Case Description: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications., Conclusions: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.

Carcinoid tumor of the prostate is extremely rare. Here we report a unique case of prostate cancer that underwent complete transformation from conventional adenocarcinoma to carcinoid-like tumor shortly after androgen-deprivation treatment (ADT). The patient was a 59-year-old man who presented with lower urinary tract symptoms. His biopsy specimen demonstrated a high-grade prostatic adenocarcinoma with mixed acinar and ductal features. After ADT for 6months, the patient underwent radical prostatectomy. The post-ADT tumor showed monotonous neoplastic cells with fine granular chromatin forming rosette-like structures, resembling a carcinoid tumor. No residual conventional adenocarcinoma was present. On immunostain, the tumor cells were diffusely positive for synaptophysin and chromogranin and negative for prostate-specific antigen and prostein. Thus, the carcinoid-like tumor represented complete transformation from prostatic adenocarcinoma to well-differentiated neuroendocrine tumor after ADT. This unique case highlights the important role of ADT in neuroendocrine differentiation of prostate cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Isoform-specific tumor estrogen receptor β (ERβ) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ERβ isoform 1 (ERβ1) expression in relation to tumor characteristics, ESR2 genotypes, and prognosis in different treatment groups., Experimental Design: A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between October 2002 and June 2012 was followed until June 2014 (median 5 years). Associations between immunohistochemical ERβ1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed., Results: Tumor ERβ1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ERβ1 positivity, defined as >75% (ERβ1 75 + , 72.7%), was positively associated with established favorable tumor characteristics. Overall, ERβ1 75 + was associated with lower risk of breast cancer events [HR adj = 0.60; 95% confidence interval (CI), 0.41-0.89]. The magnitude of the association was larger in patients with ERα - tumors (HR adj = 0.30; 95% CI, 0.12-0.76), compared with ERα + tumors (HR adj = 0.66; 95% CI, 0.42-1.03). Among the 232 chemotherapy-treated patients, ERβ1 75 + tumors were associated with lower risk of breast cancer events compared with ERβ1 75 - tumors (HR adj = 0.31; 95% CI, 0.15-0.64). Among the 671 chemonaïve patients, ERβ1 75 status was not associated with the outcome., Conclusions: High ERβ1 expression was a favorable prognostic marker in this breast cancer cohort, especially in chemotherapy-treated patients, but not in endocrine therapy-treated patients. These results warrant confirmation, preferably via a biomarker study in a previously conducted randomized trial. Clin Cancer Res; 23(3); 766-77. ©2016 AACR., (©2016 American Association for Cancer Research.)

Purpose: Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy., Patients and Methods: In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment., Results: There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination:anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P = .03); for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression., Conclusion: Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer., (© 2016 by American Society of Clinical Oncology.)

Introduction: Tumor collision is the encounter of two tumors from two different topographical sites. Cases of metastatic lymph node collision are exceptional. We report the case of a metastatic lymph node collision of an urothelial carcinoma and a prostatic adenocarcinoma., Observation: A 61-year-old man was hospitalized for a right nephroureterectomy with peri-ureteral lymph node dissection. He was followed since 2004 for prostatic adenocarcinoma and treated with radical prostatectomy then radiation therapy 4 years later due to a new increase of PSA. In the follow-up, an urothelial carcinoma of the lower right ureter was discovered in 2014. Histological analysis of a peri-ureteral lymph node showed a double metastasis of urothelial and prostatic origin. The prostatic adenocarcinoma was composed of acinar and ductal subtypes. Immunohistochemical study including CK7, CK20, PSA, GATA3, P63 antibodies confirmed the distinct phenotype of the 2 tumors., Discussion: Metastatic collision of urothelial carcinoma and prostatic adenocarcinoma has been reported in 4 cases only. Our review of literature shows that prostatic adenocarcinoma always precedes the urothelial carcinoma. Immunohistochemical study, when carried out for distinguishing both tumors, should include CK7, CK20 and PSA. GATA3, androgen receptor and P63 could be added in a second time., (Copyright © 2015. Published by Elsevier Masson SAS.)

Although invasive and metastatic progression via the epithelial-mesenchymal transition (EMT) and acquisition of resistance to castration are both critical steps in prostate cancer, the molecular mechanism of this interaction remains unclear. In this study, we aimed to elucidate the interaction of signaling between castration resistance and EMT, and to apply this information to the development of a novel therapeutic concept using transforming growth factor-β (TGF-β) inhibitor SB525334 combined with androgen-deprivation therapy against prostate cancer using an in vivo model. This study revealed that an EMT inducer (TGF-β) induced full-length androgen receptor (AR) and AR variant expression. In addition, a highly invasive clone showed augmented full-length AR and AR variant expression as well as acquisition of castration resistance. Conversely, full-length AR and AR as well as Twist1 and mesenchymal molecules variant expression were up-regulated in castration-resistant LNCaP xenograft. Finally, TGF-β inhibitor suppressed Twist1 and AR expression as well as prostate cancer growth combined with castration. Taken together, these results demonstrate that Twist1/AR signaling was augmented in castration resistant as well as mesenchymal-phenotype prostate cancer, indicating the molecular mechanism of mutual and functional crosstalk between EMT and castration resistance, which may play a crucial role in prostate carcinogenesis and progression., (© 2015 Society for Endocrinology.)

Aim: The prognostic value of sentinel lymph node micrometastases in invasive breast cancer patients is still widely debated. Even if, in the absence of unequivocal guidelines, the axillary lynphadenectomy is not still performed in the routine clinical care of these patients., Method: We have retrospectively analyzed 746 patients with operable invasive breast cancer and clinically negative axillary lymph nodes. These patients underwent conservative surgery or total mastectomy with sentinel lymph node biopsy. Patients with micrometastases in the sentinel lymph node treated with axillary dissection has been checked and the involvement of the remaining lymph nodes analyzed. Patients with micrometastases in the SLN not followed by axillary dissection have been checked as well and the incidence of recurrences has been evaluated in both groups., Results: Micrometastases were found in 51 (6.83%) patients and isolated tumor cells in 8 (1.07%) patients at frozen section and confirmed at the final hystopathologic examination. Fifteen of these patients underwent complete axillary dissection: two of them (13.33%) had metastatic involvement of other axillary lymph nodes. The other 44 patients didn't receive further surgical axillary procedure. No axillary recurrences in these patients were found during a median follow up of 65.3±9.65 months (range 42-78 months)., Conclusion: Based on the results and according to some recent randomized trials we can say that axillary lynphadenectomy can be avoided when micrometastases are found in sentinel lynph nodes. It should be performed anyway, depending on the analysis of the biomedical profile of the tumor., Key Words: Breast carcinoma, Micrometases, Sentinel lymph node.

Background: Conservative surgery can be regarded as the standard treatment for most early stage breast tumors. However, a minority of patients treated with conservative surgery will present local or locoregional recurrence. Therefore, it is of interest to evaluate the possible factors associated with this recurrence., Methods: A population-based retrospective study using data from the Tumor Registry of Castellón (Valencia, Spain) of patients operated on for primary nonmetastatic breast cancer between January 2000 and December 2008 was designed. Kaplan-Meier curves and log-rank test to estimate 5-year local recurrence were used. Two groups of patients were defined, one with conservative surgery and another with nonconservative surgery. Cox multivariate analysis was conducted., Results: The total number of patients was 410. Average local recurrence was 6.8%. In univariate analysis, only tumor size and lymph node involvement showed significant differences. On multivariate analysis, independent prognostic factors were conservative surgery (hazard ratio [HR] 4.62; 95% confidence interval [CI]: 1.12-16.82), number of positive lymph nodes (HR 1.07; 95% CI: 1.01-1.17) and tumor size (in mm) (HR 1.02; 95% CI: 1.01-1.06)., Conclusions: Local recurrence after breast-conserving surgery is higher in tumors >2 cm. Although tumor size should not be a contraindication for conservative surgery, it should be a risk factor to be considered.

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m(2) daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller-Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aims of the Study: Autologous fat graft injection has been systematically used by our team since 2001 in order to enhance the esthetic outcome of breast reconstruction. However, this technique remains controversial, notably in France. This study evaluated oncologic outcomes at 3 years among 110 patients operated on and monitored by two surgeons., Patients and Methods: 116fat graft injections in 110 patients who required reconstructive breast surgery between January 2001 and December 2011 were included in the analysis of oncologic outcomes. The AJCC (American Joint Committee on Staging) stages were: stage 0 (18 %), stage I (44 %), stage II (26.7 %), and stage III (11.3 %). Mean follow-up was 6.3 years (9 months to 17 years) after initial breast cancer surgery, and 3 years (6 months to 9.5 years) after the last lipofilling procedure., Results: The majority of patients (91.8 %) are alive and recurrence-free. Remote metastases occurred in 8.2 % of patients: one patient had a local and systemic recurrence, one patient had a local, regional and systemic recurrence., Conclusion: Although confirmation is needed from multicenter randomized trials with longer follow-up, a larger group of patients and a control group matched for the cancer status of the lipofilling group, our results support the view that lipofilling has little or no effect on the risk of locoregional recurrence of breast cancer.

Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

The role of aromatase inhibitors combined with gonadotropin-releasing hormone analog in metastatic male breast cancer patients remains unknown. In this retrospective study we evaluated the activity of letrozole combined with a gonadotropin-releasing hormone analog as a first- or second-line therapy for metastatic male breast cancer patients. 19 men entered the study. We did not observe any grade 3 or 4 adverse events. 2 patients (10.5 %) had complete response, 7 patients (36.8 %) experienced a partial response, 7 patients (36.8 %) had stable disease lasting ≥ 6 months, and 3 patients (15.8 %) had progressive disease. Overall, the disease control rate was 84.2 %. Median progression-free survival was 12.5 months (95 % CI 8.2-16.9), median overall survival was 35.8 months (95 % CI 24.4-49.2), 1- and 2-year survival rates were 89.5 and 67 %, respectively. Interestingly, 3 out of 4 patients treated with the combination following disease progression while on aromatase inhibitor monotherapy confirmed or improved the best overall response observed in the first-line setting. The combination of letrozole and gonadotropin-releasing hormone analog is effective and safe in hormone-receptor positive, metastatic male breast cancer patients.

The case of a female patient of 35 years of age, with a pedunculated tumor dependent of the vagina, of approximately 25 x 12 x 8 cm, who had a wide resection. The report was consistent with myxoid aggressive angiomyxoma. This is a myxoid mesenchymal neoplasm of slow growth, which mainly appears in deep soft tissues of the pelvic, genital or perineal areas of adult women. It is usually diagnosed after surgical resection by histopathologic examination. Routine evaluation includes: complete physical examination, imaging and pathology report of diagnostic confirmation.

Objective: There is controversial evidence regarding preoperative testosterone (T) levels related to poor prognosis factors after radical prostatectomy (RP). The aim of this manuscript is to determine the relationship between preoperative T levels and final pathologic report together to biochemical recurrence after RP., Materials and Methods: We prospectively analysed 143 patients submitted to RP from February 2008 to June 2010 in our centre. Pretreatment T and sex hormone-binding globulin levels were determined as part of our clinical protocol. Free calculated (fT) and bioavailable (bioT) T were calculated using Vermeulen's formula. Low T levels were defined as 346 ng/dL or less. A comparative analysis with variables pTNM, positive margins, tumour burden, Gleason score, multifocality and biochemical recurrence (using both PSA>0.4 ng/dL and PSA>0.2 ng/dL as cut-off values) was performed, according to preoperative levels of T., Results: Variables Gleason score, rate and number of positive margins, tumour burden, tumour multifocality, time to biochemical recurrence and pathological stage were not related to preoperative hormonal levels. Preoperative T<346 ng/dL was not found to be related to PSA recurrence (PSA>0,4 ng/dL log-rank, P=.512), although a trend was observed when PSA>0,2 ng/dL (log-rank, P=.097)., Conclusion: Preoperative T levels were not related to final pathological report or to biochemical recurrence., (Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.)

Background: male breast cancer is a disease with low incidence, which is further reduced when it comes to bilateral synchronous presentation. There are few published cases in recent years. The aim is to establish guidelines for the management of this disorder that is so rare., Clinical Case: a 75-year-old with tumors in both breasts, which were completely resected with removal of palpable nodes. The histopathological study reported ductal carcinoma. The indicated treatment was adjuvant tamoxifen and radiotherapy. The patient is currently in a disease-free period., Conclusions: this is a rare disease, whose main treatment is surgery, hence the importance of early diagnosis. Most cases require adjuvant chemotherapy and radiotherapy because they are usually diagnosed at an advanced stage.

Purpose of Review: Four new therapies have been recently approved for the treatment of men with castration-resistant prostate cancer; still, more treatment options are needed. This review summarizes the data supporting a role for novel chemotherapies including epothilones and immunomodulators (IMiDs), as well as other novel agents within the new landscape of approved therapies., Recent Findings: Epothilones are a class of chemotherapy that target microtubule disassembly, similar to taxanes. Results from phase II studies demonstrating a positive impact on serum prostate-specific antigen for patupilone and sagopilone, current epothilones in development, along with those of ixabepilone, are comparable with historical response rates to docetaxel, the current first-line chemotherapy for castration-resistant disease. IMiDs, including lenalidamide and thalidomide, are also in active development in castration-resistant prostate cancer. A recent phase III study evaluating the combination of lenalidomide and docetaxel revealed decreased overall survival relative to docetaxel alone; however, additional trials are currently recruiting to investigate lenalidomide in various other combination regimens., Summary: Epothilones could be efficacious as an additional therapy in patients who respond to docetaxel chemotherapy. A role for IMiDs, perhaps in combination with chemotherapy or androgen pathway inhibitors, remains to be elucidated.

Purpose of Review: Treatment of all stages of prostate cancer has changed considerably in recent years, as our understanding of its biochemical pathways has improved. Testosterone, true to Huggin's original observation, remains a key player not only in newly diagnosed prostate cancer but also in castration-resistant prostate cancer, and our understanding of how to combine and sequence drugs that attack these pathways continues to grow. New US Food and Drugs Administration approved pharmaceutical agents further eliminate testosterone ligand or its activity via inhibition of key synthetic enzymes and through strong inhibition of the androgen receptor., Recent Findings: This review will briefly examine our knowledge of the complex relationship between testosterone, androgen receptor and advanced prostate cancer, discuss the limits of traditional androgen deprivation therapy in the form of gonadotropin-releasing hormone agonists and newer antagonists, examine combination therapies, including combined androgen blockade and newer studies with 5α-reductase inhibitors, and overview two new therapeutics that target hormonal pathways., Summary: This review provides guidance on trials that examine combination therapies in various prostate cancer disease states. Androgens and prostate cancer remain inexorably linked, and this review will shed light on renewed focus on eliminating activity of this trophic ligand.

Purpose of Review: Although the treatment of castration-resistant prostate cancer (CRPC) has benefited from the use of increasingly potent androgen synthesis inhibitors and androgen receptor (AR) antagonists, it is only marginally effective. There is therefore a critical need for a better understanding of the mechanisms underlying the CRPC development and more effective therapeutic approaches. Here, we focus on the advancements reported in the last 18 months, particularly with regard to the mechanisms of castration resistance and potential therapeutic targets emerging from the studies with in-vivo models., Recent Findings: Recent findings indicate that AR-dependent mechanisms, for example, increased expression of CYP17A1 and AR splice variants, play important roles in in-vivo castration resistance to new antiandrogens and androgen synthesis inhibitors. Whereas current therapeutic approaches focus on AR-dependent CRPC, studies based on genetically engineered mouse models indicate that castration resistance can develop in the absence of robust AR signaling. Furthermore, increasing evidence suggests that cellular plasticity of prostate adenocarcinoma allows AR-independent CRPC development via various adaptive mechanisms., Summary: Significant progress has been made in the understanding of AR-dependent and AR-independent mechanisms involved in the development of CRPC. This may lead to identification of new therapeutic targets and improved therapy.

Purpose of Review: Prior to 2010, docetaxel was the only treatment shown to prolong survival in metastatic castrate-resistant prostate cancer (CRPC). In the past 3 years, several therapeutic agents have demonstrated survival improvements for CRPC after the receipt of prior docetaxel, leading to multiple approvals by the US Food and Drug Administration., Recent Findings: The development of these novel agents, each with a distinct mechanism of action, is the fruition of sedulous preclinical research and well designed clinical trials. Cabazitaxel, a next generation taxane, was the first Food and Drug Administration-approved drug for the postdocetaxel setting. The recognition of sustained androgen dependence of CRPC has led to the identification of more potent and selective inhibitors of androgen synthesis and androgen-receptor signaling, such as abiraterone and enzalutamide, respectively. Radium-223, an α-emitting radionuclide still under regulatory review, recently showed a significant survival benefit for CRPC. Finally, sipuleucel-T, a form of immunotherapy, may benefit a subset of patients in the postdocetaxel setting., Summary: Post-docetaxel management of CRPC has undergone a dramatic yet welcome paradigm change in the past 3 years. With multiple life-prolonging agents available, it now becomes imperative to coordinate how and when these new therapies should be used and sequenced to achieve optimal patient outcomes.

Purpose of Review: Therapeutic options for men with metastatic prostate cancer are expanding. Here we discuss the scientific progress in this disease that led to approval of several agents in the last decade and highlight ongoing clinical investigation., Recent Findings: In androgen-sensitive disease, trials are evaluating the role of intermittent androgen-deprivation therapy, early chemotherapy, and novel targeted and hormonal therapies. For chemotherapy-naive, metastatic castration-resistant prostate cancer (mCRPC), abiraterone is effective. Trials with additional agents targeting androgen receptor (AR) signaling, such as TAK-700 and enzalutamide, are ongoing. Other agents in development target the endothelin pathway, angiogenesis, AR chaperones, and immune mechanisms. Docetaxel with prednisone remains the standard first-line chemotherapeutic regimen as trials incorporating novel agents with docetaxel have been negative. Postdocetaxel, enzalutamide improves survival. Early results with cabozantinib are encouraging, and phase III studies are ongoing. Denosumab and radium-223 reduce the risk of skeletal-related events (SREs), but only radium-223 improves survival., Summary: Progress in understanding the disease biology and mechanisms of castration resistance led to significant therapeutic advancements, particularly in the setting of mCRPC in which several phase III trials, each incorporating agents with different mechanisms of action, have improved survival. As a result, new options exist, and the standard of care has changed significantly. Further advances are anticipated.

Introduction: Tamoxifen is associated with a twofold increased risk of thromboembolic events. Third generation aromatase inhibitors (AIs), such as letrozole, anastrozole, and exemestane have therefore replaced tamoxifen in the adjuvant therapy of hormone receptor-positive breast cancer. A retrospective review was performed in patients who underwent delayed microvascular breast reconstruction and received tamoxifen at the time of surgery in order to assess the risk of both minor and major flap complications including thromboembolic events., Patients and Methods: Twenty-nine patients who underwent delayed microsurgical breast reconstruction with autologous tissue between 2006 and 2012 were included in the study. The overall complication rates were compared between patients who did versus those who did not receive tamoxifen at the time of microsurgical breast reconstruction., Results: Breast reconstruction was performed with a DIEP flap in 25 patients and with a TRAM flap in 4 patients. Overall, the complication rate was 37.9% (n=11) consisting of 5 major (including one total flap loss) and 6 minor complications. In patients receiving tamoxifen (n=5), we observed one minor complication and one major complication with a total flap loss due to thrombus formation at the anastomosis site. In one patient pulmonary embolism occurred without association to tamoxifen. The number of thromboembolic events was equivalent in both groups (p=0.642). No increase of major (p=0.858) or minor (p=0.967) complications in the tamoxifen group could be observed. Taking the overall complication rate into account there was no statistically difference between the two groups (p=0.917)., Conclusion: In our study we could not observe an increased risk for thromobembolic events in patients receiving tamoxifen while undergoing autologous microvascular breast reconstruction.

Background: The cross-sectional ONCOVIH study prospectively enrolled HIV-infected adults and children with newly diagnosed malignancies in France in 2006., Method: We report the characteristics HIV-infected patients with breast cancer from the ONCOVIH study. Standardised questionnaires included characteristics of HIV infection and malignancy. Survival was estimated using Kaplan-Meier estimates., Results: Overall, 21 patients with breast cancer (two men and 19 women) were included with a median age of 43.8 years, (range: 30.1-65.5). At time of tumour diagnosis, the median CD4 count was 384/mm(3) (range: 180-1039) the median duration of known seropositivity 7.7 years (range: 0-20.3); 14 patients were under combined antiretroviral therapy for a median duration of 5.7 years (range: 1.1-10.6), of whom 11 had a controlled viral load (<500 copies/mL). The median tumour size was 1.8 cm (range: 1.0-7.0). In women, 17 (89.5%) had invasive ductal carcinoma, 17 (89.5%) with HER2 negative receptors, 8 (42.1%) with ER+ expression, and 7 (36.8%) with PR+ expression. A majority of women received chemotherapy (73.7%), surgery (68.4%) and radiotherapy (57.9%). Their one-year survival rate was estimated as 77.8% (95%confidence interval (CI): 58.6-97.0%)., Conclusions: We discuss the risk of breast cancer in infected patients, and the importance of taking into account the different contributing factors for breast cancer in HIV-infected individuals., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Pathologic complete response (pCR) is a surrogate end-point for prognosis in neoadjuvant chemotherapy (NAC) for breast cancer. We aimed to report summary estimates of the proportion of subjects achieving pCR (pCR%) by tumour subtype, and to determine whether subtype was independently associated with pCR, in a study-level meta-analysis., Methods: We systematically identified NAC studies reporting pCR data according to tumour subtype, using predefined eligibility criteria. Descriptive, qualitative and quantitative data were extracted. Random effects logistic meta-regression examined whether pCR% was associated with subtype, defined using three categories for model 1 [hormone receptor positive (HR+/HER2-), HER2 positive (HER2+), triple negative (ER-/PR-/HER2-)] and 4 categories for model 2 [HER2+ further classified as HER2+/HR+ and HER2+/HR-]. Subtype-specific odds ratios (OR) were calculated and were adjusted for covariates associated with pCR in our data., Results: In model 1, based on 11,695 subjects from 30 eligible studies, overall pooled pCR% was 18.9% (16.6-21.5%), and in model 2 (20 studies, 8095 subjects) pooled pCR% was 18.5% (16.2-21.1%); tumour subtype was associated with pCR% (P<0.0001) in both models. Subtype-specific pCR% (model 2) was: 8.3% (6.7-10.2%) in HR+/HER2- [OR 1/referent], 18.7% (15.0-23.1%) in HER2+/HR+ [OR 2.6], 38.9% (33.2-44.9%) in HER2+/HR- [OR 7.1] and 31.1% (26.5-36.1%) in triple negative [OR 5.0]; pCR% was significantly higher for the HER2+/HR- compared with the triple negative subtype, however pCR% was very similar for these subtypes (and OR=5.0 both subtypes) when studies using HER2-directed therapy with NAC were excluded from the model. Neither sensitivity analysis (excluding unknown subtypes), nor adjustment for associated covariates, substantially altered our findings., Interpretation: This meta-analysis provides evidence of an independent association between breast cancer subtype and pCR; odds of pCR were highest for the triple negative and HER2+/HR- subtypes, with evidence of an influential effect on achieving pCR in the latter subtype through inclusion of HER2-directed therapy with NAC., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Castration resistant prostate cancer (CRPC) is defined clinically as a failure of castration to prevent an increase in circulating hormones which are associated with worsening prostate cancer. Published information on the frequency and characteristics of CRPC patients are lacking. This may be partly because there is no specific code which doctors can use to record CRPC, making research in existing data sources such as the General Practice Research Database (GPRD) difficult., Methods: The aim of this study was to firstly develop a method to accurately and thoroughly identify CRPC patients in the GPRD, using a combination of codes for treatments and diagnostic tests which these patients are likely to have received. Secondly, the anonymised electronic medical records were used to study the identified CRPC patient characteristics, such as age, treatments, comorbidity and expected survival., Results: After comprehensive exploratory research, the final algorithm was selected to identify patients' assumed recording on the GPRD of either a rising prostate specific antigen (PSA) value (clinical definition of CRPC) or evidence of a switch in treatment after castration. Using the algorithm, over the 1999-2009 study period, 11600 castrated prostate cancer patients were identified. Of these, 3277 (28%) developed CRPC during the study period, with an incidence rate of 8.3 per 100 person years in castrated prostate cancer patients, and 3.8 per 100 person years in all prostate cancer patients. Mean patient age at CRPC was 76.8 years, and mean survival duration from CRPC status was 13.5 months, and from first prostate cancer diagnosis was 48.2 months. The most common comorbidities among CRPC patients were hypertension, dyspnoea, and anaemia., Conclusions: Sensitivity analyses to test algorithms with differing inclusion criteria suggested that the primary algorithm was robust, reducing bias through missing data, while avoiding 'false positives' and retaining clinical credibility. Overall, our study has documented a reliable method for identifying CRPC patients in GPRD, and thus we have been able to characterise these patients more accurately., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aim: To analyse the correlation between (18)F-FDG uptake assessed by PET/CT in locally advanced breast tumours and histopathological and immunohistochemical prognostic factors., Material and Methods: Thirty-six women with breast cancer were prospectively evaluated. PET/CT was requested in the initial staging previous to adjuvant chemotherapy (multicentric study). All the patients underwent an (18)F-FDG PET/CT with a dual-time-point acquisition. Both examinations were evaluated qualitatively and semiquantitatively with calculation of SUVmax values in PET-1 (SUV-1) and in PET-2 (SUV-2) and the percentage variation of the standard uptake values (retention index) between PET-1 and PET-2. Clinical and metabolic stages were assessed according to TNM classification. The biological prognostic parameters, such as the steroid receptor status, p53 and c-erbB-2 expression, proliferation rate (Ki-67), and grading were determined from tissue of the primary tumour. Metabolic and biological parameters were correlated., Results: A positive relationship was found between semiquantitative metabolic parameters and biological parameters. SUV-1 and SUV-2 values did not show significant statistical correlation (p<.05) except for the clinical tumour size. About the biological parameters, retention index showed the best results with positive and significant relation (p<.05) with estrogen and progesterone receptor status and Ki-67. Isolated SUV values did not show significant relation to these parameters., Conclusion: Retention index showed the best relation with biological parameters compared to isolated SUVmax values. These data suggest that SUV change over time is a prognostic marker., (Copyright © 2011 Elsevier España, S.L. and SEMNIM. All rights reserved.)

Retroperitoneal sarcomas are rare and aggressive tumors with a negative prognosis as there is currently no satisfactory treatment for them. The only proven factor that can significantly increase the otherwise poor survival of sarcoma patients is the radically of resection. However, the completeness of resection is hindered by the hypervascularized nature of sarcomas and the frequent involvement of major blood vessels. In this context, we propose to operate on retroperitoneal sarcomas only with the use of extracorporeal circulation, applying vascular clamps above and below the tumor, even with short periods of hypothermic circulatory arrest in complex cases. This technique would allow the surgeon to achieve complete tumor resections, approach large blood vessels easier and perform sofisticated vascular reconstructions with no fear of hemorrhage which is fundamental to achieve a bloodless surgical field. Also, we speculate on the etiology of retroperitoneal sarcomas that appear mostly during the period of menopause/andropause. Although both estrogens and androgens have been incriminated in inducing various cancer types, including sarcomas, an endogenous estradiol cathabolyte has been shown to have anti-tumor effects. Considering that during menopause/andropause sex steroid levels actually decrease, our second working hypothesis is that the increasing follicle-stimulating hormone (FSH) and especially luteinizing hormone (LH) levels, together with the relative estrogen/androgen imbalance, may be the triggering cause. Also, a certain level of estrogens (Methoxyestradiol) may be essential in limiting tumor development and dedifferentiation. Given that extragonadal sarcomas appear to behave as endocrine tumors, a targeted hormonal therapy, together with controlled radical resections in complex cases of tumor vascular involvement, would certainly provide a strong link to both prevention and treatment of retroperitoneal sarcomas and even of cancer in general., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Patients with advanced prostate cancer initially respond very well to medical or surgical castration. Despite a good initial response, the disease progresses to a castration-resistant state. Castration-resistant prostate cancer (CRPC) remains addicted to androgen receptor signaling. The addition of conventional anti-androgen agents, such as bicalutamide, only provides a transient benefit. This has led to a search for further drug targets. Cytochrome P450 17 (CYP17) is an enzyme that is vital for the adrenal biosynthesis of androgens. The CYP17 inhibitor abiraterone acetate has a proven benefit in a phase III randomized trial and other CYP17 inhibitors are currently being evaluated. The novel antiandrogen MDV3100 is a small molecule androgen receptor antagonist with promising activity. Heat shock proteins (HSPs) bind to the androgen receptor and modify its activity. Several HSP inhibitors are under evaluation in clinical trials. This review explores the role of CYP17 inhibitors, MDV3100, and HSP inhibitors., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Genetic aberrations affecting the androgen receptor (AR) are rare in untreated prostate cancers (PCs) but have been found in castration-resistant prostate cancers (CRPCs). Further, successful treatment with novel endocrine therapies indicates that CRPCs remain androgen-sensitive. Known AR aberrations include amplification of the AR gene leading to the overexpression of the receptor, point mutations of AR resulting in promiscuous ligand usage, and constitutively active AR splice variants. Gain, or amplification, of the AR gene is one of the most frequent genetic alterations observed in CRPCs. Up to 80% of CRPCs have been reported to carry an elevated AR gene copy number, and about 30% have a high-level amplification of the gene. AR mutations are also commonly observed and have been found in approximately 10-30% of the CRPC treated with antiandrogens; however, the frequency and significance of AR splice variants is still unclear. Because AR aberrations are found almost exclusively in CRPC, these alterations must have been selected for during therapy. Interestingly, these aberrations lead to activation of the receptor, despite treatment-induced emergence of therapy-resistant tumor clones. Therefore, future novel treatment strategies should focus on suppressing AR activity in CRPC., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Recent insights into mechanisms by which prostate cancer becomes castration resistant have allowed better and more rational therapeutic design. These novel therapies have complemented the modest success that chemotherapy has shown in recent years changing the landscape of this disease and leading to improved outcomes. Angiogenesis and immune deregulation are 2 pathways that have increasingly been shown to lead into castration resistant prostate cancer (CRPC). Thalidmide and lenalidomide are immunomodulatory agents with antiangiogenesis properties that have shown activity in this setting with acceptable safety profile. In this review, we discuss briefly the different mechanisms that render prostate cancer castration resistant and elaborate on thalidomide and lenalidomide data in CRPC after reviewing their theoretic mechanisms of action. This timely review coincides with the identification of newer therapies against CRPC affirming our steady movement toward better disease control., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Docetaxel (Taxotere®) is a well established anti-mitotic chemotherapy agent. Among other therapeutic indications, docetaxel plus prednisone is indicated for first-line chemotherapy in patients with castration-resistant prostate cancer (CRPC). Docetaxel every 3 weeks plus continuous prednisone has been standard first-line chemotherapy in CRPC since demonstrating improved survival compared with the previous standard regimen, mitoxantrone plus prednisone, in the phase III TAX 327 trial in 2004. Since that time, docetaxel has been combined with various agents that demonstrated additive or synergistic activity in preclinical studies in an effort to further improve outcomes, but to date, overall survival has not been extended compared with docetaxel plus prednisone. However, several promising agents are emerging with a potential role in docetaxel-based combinations based on efficacy and manageable toxicity, including bevacizumab, dasatinib and atrasentan. In the TAX 327 trial, neutropenia was relatively common in the group receiving 3-weekly docetaxel plus prednisone, but infection was rare. The tolerability of a weekly docetaxel regimen also administered in this trial was not significantly different to that of the 3-weekly regimen, except for a lower incidence of grade 3 or 4 neutropenia. However, weekly or 2-weekly docetaxel administration schedules may have a place in very elderly or frail patients in order to improve tolerability compared with the 3-weekly regimen. In conclusion, docetaxel every 3 weeks plus prednisone remains the optimum first-line chemotherapy for most patients with advanced CRPC until such time that ongoing research with docetaxel and emerging therapeutic agents can demonstrate improved survival.

Endocrine therapy by castration or anti-androgens is the gold standard treatment for advanced prostate cancer. Although it has been used for decades, the molecular consequences of androgen deprivation are incompletely known and biomarkers of its resistance are lacking. In this study, we studied the molecular mechanisms of hormonal therapy by comparing the effect of bicalutamide (anti-androgen), goserelin (GnRH agonist) and no therapy, followed by radical prostatectomy. For this purpose, 28 men were randomly assigned to treatment groups. Freshly frozen specimens were used for gene expression profiling for all known protein-coding genes. An in silico Bayesian modelling tool was used to assess cancer-specific gene expression from heterogeneous tissue specimens. The expression of 128 genes was > two-fold reduced by the treatments. Only 16% of the altered genes were common in both treatment groups. Of the 128 genes, only 24 were directly androgen-regulated genes, according to re-analysis of previous data on gene expression, androgen receptor-binding sites and histone modifications in prostate cancer cell line models. The tumours containing TMPRSS2-ERG fusion showed higher gene expression of genes related to proliferation compared to the fusion-negative tumours in untreated cases. Interestingly, endocrine therapy reduced the expression of one-half of these genes and thus diminished the differences between the fusion-positive and -negative samples. This study reports the significantly different effects of an anti-androgen and a GnRH agonist on gene expression in prostate cancer cells. TMPRSS2-ERG fusion seems to bring many proliferation-related genes under androgen regulation., (Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Unlabelled: The sentinel lymph node (SLN) biopsy is currently the procedure of choice for axillary node staging in initial stages of breast cancer. The purpose of this study is to establish our false negative rate within a 5-year follow-up period in 258 patients with breast cancer staged with this procedure., Methods: A retrospective study on 258 consecutive T1-T2<3 cm pN0 staged breast carcinomas treated from January 1, 2001 to December 31, 2005 was performed. The combined technique of isotope plus blue dye was used for detection. The subjects underwent a minimum follow-up of 5 years, mean 81 months, with an end of follow-up at December 31, 2010. Evidence of axillary recurrence, tumor recurrence in the breast and signs of disease progression or death were the events collected and analyzed., Results: Of the 258 patients, 3 false negatives (1.1%) with axillary recurrence were detected at 10, 11 and 29 months of the surgery. This did not have a significant repercussion in the survival analysis on the contrary to the existence of breast recurrence or the appearance of distant metastasis in 4.7% and 6.2% patients, respectively. Global survival related with the cancer was 93.0 (240/258) and disease free survival was 89.1% (230/258)., Conclusion: The risk of developing axillary recurrence after a negative SLN without axillary node dissection is low enough to consider the SLN procedure to be the best approach for axilla staging in early breast cancer. This staging technique also makes it possible to achieve local disease control without diminishing the survival of the patients., (Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.)

This article outlines the role of 16α-[(18)F]fluoro-17β-oestradiol ((18)F-FES) positron emission tomography (PET) combined with 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) in patients with oestrogen-related tumours for evaluating tumour phenotype. (18)F-FES-PET combined with (18)F-FDG is helpful in characterising the distinct phenotypic features of oestrogen-related tumours; that is, inter- and intrapatient tumour heterogeneity, which indicates its great potential as a determinant of individualised treatment and a prognostic predictor for patients with oestrogen-related tumours.

Background: Previous studies demonstrate that androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and orchiectomy for prostate cancer (PCa) is associated with cardiovascular disease. However, few studies have examined its effect on the peripheral vascular system., Objective: To study the risk of peripheral artery disease (PAD) and venous thromboembolism associated with ADT for PCa., Design, Settings, and Participants: This was a population-based observational study of 182 757 US men ≥ 66 yr of age who were diagnosed with nonmetastatic PCa from 1992 to 2007, with a median follow-up of 5.1 yr, of whom 47.8% received GnRH agonists and 2.2% orchiectomy., Measurements: We used Cox proportional hazards models with time-varying treatment variables to adjust for demographic and tumor characteristics in assessing whether treatment with GnRH agonists or orchiectomy were associated with PAD and/or venous thromboembolism., Results and Limitations: GnRH agonist use was associated with an increased risk of incident PAD (adjusted hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.12-1.21) and incident venous thromboembolism (adjusted HR: 1.10; 95% CI, 1.04-1.15). In addition, orchiectomy was associated with an increased risk of peripheral arterial disease (adjusted HR: 1.13; 95% CI, 1.02-1.26) and venous thromboembolism (adjusted HR: 1.27; 95% CI, 1.11-1.45). Limitations include the observational study design and the inability to assess the use of oral antiandrogens., Conclusions: ADT for nonmetastatic PCa is associated with an increased risk of PAD and venous thromboembolism. Additional research is needed to better understand the potential risks and benefits of ADT, so that this treatment can be targeted to patients for whom the benefits are clearest., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC., Methods: Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI., Results: Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density (VD), and vessel area fraction (VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores (AHS)--the proportion of hypoxia staining within 50 μm from perfusion staining--were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve (AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size (VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after pharmacokinetic modeling. Interestingly, such modeling also detected tumor necrosis very strongly., Conclusions: DCE MRI reliably allows non-invasive assessment of tumors' vascular function. The findings of increased tumor vascularization after ADT encourage further studies into whether these changes are beneficial for combined RT, or if treatment with anti-angiogenic therapy may be a strategy to improve the therapeutic efficacy of ADT in advanced PC.

Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. A total of 166 eligible patients were randomly assigned to receive adjuvant tamoxifen, exemestane, or anastrozole. FACT-B scores increased after treatment began and remained significantly higher in the tamoxifen group than in the exemestane group or anastrozole group during the first year (P = 0.045). FACT-B scores were similar in the exemestane group and anastrozole group. ES scores and CES-D scores were similar in all treatment groups. Arthralgia and fatigue were less frequent, but vaginal discharge was more frequent in the tamoxifen group than in the exemestane group or anastrozole group. HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole. HRQOL and AEs were similar with exemestane and anastrozole. Given the results of the TEAM trial, upfront use of tamoxifen followed by an aromatase inhibitor (AI) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women.