MRI-guided vacuum-assisted breast biopsy performed at 3 T with a 9-gauge needle: preliminary experience.

OBJECTIVE: The purpose of this study was to test the feasibility of 3-T vacuum-assisted large-bore core biopsy of lesions detected with MRI of the breast. CONCLUSION: Our preliminary experience revealed that 3-T MRI-guided vacuum-assisted biopsy is a safe and effective interventional method that enables accurate biopsy of lesions identified with a 3-T MRI system. Artifacts on 3-T images did not result in failed biopsy; therefore, 3-T MRI systems can be used reliably for both diagnostic and interventional breast studies.

A germline variation in the progesterone receptor gene increases transcriptional activity and may modify ovarian cancer risk.

Recently, we and others have detected a haplotype of the human progesterone receptor gene (PR). This haplotype consists of a 320-bp insertion in intron G together with point mutations in exons 4 and 5 and was named PROGINS. Whereas the exon 5 mutation is silent, the mutation in exon 4 results in a V660L substitution. Interestingly, this genetic polymorphism was seen to cosegregate with an increased risk of sporadic ovarian cancer in different ethnic groups. Our data provide evidence for the existence of an epidemiological link between a mutated progesterone receptor allele and ovarian cancer (odds ratio, 3.02; 95% confidence interval, 1.86-4.91). Functional characterization of the mutated receptor protein revealed a greater transcriptional activity compared with the wild-type receptor. By contrast, hormone binding and hormone dissociation rates were similar in both receptor proteins. We found that the increased transcriptional activity was due to increased stability resulting in higher expression of the mutant protein. Thus, the long-lasting hyperactivation of progesterone receptor-driven genes secondary to the increased transcriptional activity of the mutated progesterone receptor may participate in ovarian carcinogenesis. This is of special interest, because only a few genetic markers are available for the majority of women diagnosed with sporadic ovarian cancer.

Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells.

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3-positive (Foxp3(+)) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3(+) Treg cells are poorly understood. Here, we found that the majority of Foxp3(+) Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3(+) Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS(+) Foxp3(+) Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS(+) Foxp3(+) Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS(+) Treg cell subset being a stronger predictor than total Foxp3(+) Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS(+) Foxp3(+) Treg cells, leading to tumor progression in ovarian cancer.

Nodal endosalpingiosis in ovarian serous tumors of low malignant potential with lymph node involvement: a case for a precursor lesion.

Lymph node involvement (LNI) in ovarian serous tumors of low malignant potential (OSLMP) upstages 22% of patients. The origin of LNI has been a subject of debate in the literature. The purpose of this study was to investigate the role of nodal endosalpingiosis in the pathogenesis of this entity. We first examined the frequency of nodal endosalpingiosis in 30 OSLMP cases, 30 cervical adenocarcinoma cases, and 30 endometrial endometrioid adenocarcinoma cases. The rate of nodal endosalpingiosis was significantly higher in OSLMP cases (33%) compared with both cervical (0%, P<0.0001) and endometrial tumor cases (3%, P=0.0015). We then compared the frequency of nodal endosalpingiosis in 36 cases of OSLMP with LNI and 36 cases of OSLMP without LNI. The rate of nodal endosalpingiosis was significantly higher in OSLMP with LNI (66%) than in OSLMP without LNI (14%, P<0.0001). We further investigated the cohort cases of OSLMP with LNI by recording the presence of nodal endosalpingiosis and LNI in each individual lymph node in every case. This analysis revealed that nodal endosalpingiosis and LNI appear together in the same lymph nodes at a much higher rate than would be expected by random chance alone (OR=71.2, P<0.0001). Lastly, in OSLMP cases with LNI, we recorded the types of LNI patterns. We found that the intraglandular pattern was present in a higher percentage of cases with nodal endosalpingiosis (50%) than in cases without nodal endosalpingiosis (8%, P=0.0253). Overall, the intraglandular pattern of LNI appeared in 36% of OSLMP cases with LNI. In this study, we show that nodal endosalpingiosis not only occurs more commonly in OSLMP compared with other Müllerian malignancies, but also in OSLMP with LNI compared with OSLMP without LNI. For the first time, we demonstrate a statistically significant association between endosalpingiosis and the intraglandular pattern of LNI, and we propose that in up to a third of patients with OSLMP and LNI, nodal foci of serous tumor of low malignant potential may derive independently, from nodal endosalpingiosis. This result contributes to the understanding of the pathogenesis of extraovarian disease in cases of OSLMP and has important implications for patient management and follow-up.

Phase 2 trial of mifepristone (RU-486) in advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma.

BACKGROUND: : The objective of this study was to determine the efficacy of mifepristone (RU-486) in women with advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma (LGESS). METHODS: : Mifepristone (RU-486; 200 mg orally) was given daily to patients with progesterone receptor-positive advanced or recurrent endometrioid adenocarcinoma or LGESS. Patients were evaluated every 4 weeks for toxicity and response. Quality-of-life data were obtained using the Memorial Symptom Assessment Scale and Functional Assessment for Cancer Therapy. RESULTS: : Twelve of 13 enrolled patients were evaluable in the first phase of accrual. Stable disease was noted in 3 of 12 patients (at 8 weeks, 12 weeks, and > or =77 weeks, respectively), and the median time to disease progression was 48 days. Among the patients who had stable disease, 2 women had endometrioid endometrial cancer, and 1 woman had LGESS. No partial or complete responses were observed. The most frequent grade 1 and 2 toxicities were anorexia, fatigue, and mood alterations observed in 50%, 50%, and 58% of patients, respectively. The most common grade 3 toxicities were fatigue and dyspnea observed in 25% and 17% of patients, respectively. One patient experienced grade 4 dyspnea. Thirty-three percent of patients had asymptomatic elevations of corticotropin. No serious treatment-related adverse events occurred. There were no significant changes in quality of life. CONCLUSIONS: : Single-agent mifepristone used in the treatment of recurrent endometrioid adenocarcinoma or LGESS resulted in a stable disease rate of 25%. One patient who had a biopsy-positive disease recurrence remained stable at 77 weeks. Although mifepristone was tolerated well, as a single agent, it provided limited response as a single agent in women with progesterone receptor-positive uterine tumors. Recently, was been recognized that biologic agents used as single agents may result only in stable disease unless they are combined with cytotoxic agents. The authors concluded that further research into the best mode of application for mifepristone in the treatment of endometrial cancer is needed. Cancer 2009. (c) 2009 American Cancer Society.

A phase II trial of oral capecitabine in patients with platinum--and taxane--refractory ovarian, fallopian tube, or peritoneal cancer.

PURPOSE: To determine the efficacy, toxicity, and quality of life of capecitabine (Xeloda), an oral 5-fluorouracil derivative, in patients with chemorefractory recurrent mullerian cancers. PATIENTS AND METHODS: Patients with chemorefractory persistent or recurrent ovarian, fallopian tube, or peritoneal cancer with measurable disease were enrolled. Capecitabine was administered beginning at 2000 mg/m2/day orally in two divided doses with meals on a 21-day cycle: 14 days of capecitabine followed by a 7-day rest period. One dose escalation or reduction was allowed. Response was assessed after cycle 2 and cycle 4 and every third cycle thereafter. Standard evaluation included two-dimensional measurement of evaluable disease. Standard criteria for response were used. Therapy was discontinued if progression occurred after at least two cycles of therapy. Quality of life and symptoms were assessed. RESULTS: Forty-one patients were enrolled. Ninety-two percent of patients had >2 previous chemotherapy regimens. All patients had platinum- and taxane-resistant disease. Thirty-six patients were evaluable for response. Three patients had a partial response, with a median response duration of five cycles. Twenty-two patients had stable disease for 3 to 11 cycles (median, 6 cycles). Eleven had progressive disease. The only grade 4 toxicity was abdominal pain (n = 2). The most common grade 3 toxicities were fatigue (n = 19), hand-foot syndrome (n = 11), abdominal pain (n = 7), and diarrhea (n = 4). One patient had a grade 3 hematologic toxicity (anemia). CONCLUSION: Capecitabine at the dosages used in this study is well tolerated and has minimal hematologic toxicity.