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Christian Jackisch

Publications and source records attributed to Christian Jackisch.

At least 19 recordsLinked to original sources
PubMed2006

Gefitinib in combination with tamoxifen in patients with ovarian cancer refractory or resistant to platinum-taxane based therapy--a phase II trial of the AGO Ovarian Cancer Study Group (AGO-OVAR 2.6).

BACKGROUND: Tamoxifen and gefitinib (IRESSA) combination therapy was studied in patients with ovarian cancer refractory or resistant to platinum- and taxane-based therapy. PATIENTS AND METHODS: In this phase II study, 56 patients with epithelial ovarian carcinoma or cancer of the fallopian tube or peritoneum received oral tamoxifen 40 mg/day and gefitinib 500 mg/day until progression or unacceptable toxicity. RESULTS: Seventeen patients (mean age: 59.6 years) had previously received first-line platinum/taxane treatment only, while 39 had received 2-8 (median 2) prior chemotherapy regimens. Gefitinib dose reduction to 250 mg/day was performed in 10 patients (14.9%), predominantly due to diarrhea (6 patients [10.7%]). Trial medication was discontinued in 6 patients (10.7%) due to adverse events (AEs). The most frequent drug-related AEs were diarrhea and acne-like skin rash. There were no tumor responses, but 16 patients had stable disease. Median time-to-progression was 58 days (95% CI, 55-71 days) and median survival was 253 days (95% CI, 137-355 days). CONCLUSION: Gefitinib plus tamoxifen did not appear to be efficacious in the treatment of patients with refractory/resistant ovarian cancer. The addition of tamoxifen did not worsen the known side effects of gefitinib, or induce additional side effects.

Adult↗
PubMed2006

Surgical procedures after neoadjuvant chemotherapy in operable breast cancer: results of the GEPARDUO trial.

BACKGROUND: Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery in patients with operable breast cancer. However, uncertainty remains regarding surgical procedures and predictors for successful breast-conserving surgery. METHODS: This study was an analysis of surgical data of a representative data subset of 607 patients enrolled in the GEPARDUO study. This prospective, multicenter, phase III study randomly assigned patients with operable breast cancer (> or = 2 cm) to neoadjuvant 8-week dose-dense doxorubicin plus docetaxel or a 24-week schedule of doxorubicin plus cyclophosphamide followed by docetaxel (AC-DOC). RESULTS: Breast conservation was attempted in 493 (81.2%) patients, but 43 patients eventually required mastectomy, thus resulting in a breast-conserving surgery rate of 74.1%. Breast-conserving re-excision was performed in 61 patients (12.4%). Factors associated with a significantly higher breast-conserving surgery rate were a prechemotherapy tumor size < or = 40 mm, nonlobular histological characteristics, treatment with AC-DOC, clinical response, postchemotherapy tumor size < or = 20 mm, and treatment in a larger center (>10 enrolled patients). Nonlobular histological characteristics and intraoperative frozen-section analysis for margin evaluation were associated with significantly lower reoperation rates (P = .015). CONCLUSIONS: Breast conservation after neoadjuvant chemotherapy is feasible in most patients with operable breast cancer. For surgical planning, tumor characteristics and response to neoadjuvant chemotherapy should be taken into account. Improved breast-imaging modalities are necessary to improve detection of residual disease after neoadjuvant chemotherapy, especially when breast cancer is of lobular invasive histology. Margin assessment by intraoperative frozen-section analysis is helpful to avoid reoperation. To achieve an optimal result, an interdisciplinary surgical approach is important.

Adult↗
PubMed2006

Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG.

PURPOSE: Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients. METHODS: Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS). RESULTS: Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted. CONCLUSION: Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.

Adult↗
PubMed2006

Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer.

PURPOSE: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. PATIENTS AND METHODS: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation. RESULTS: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. CONCLUSION: Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.

Adult↗
PubMed2006

Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO.

BACKGROUND: The combination of carboplatin and paclitaxel is the standard of care for the treatment of ovarian cancer, yet rates of recurrence and death remain high. We performed a prospective randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. METHODS: A total of 1308 patients with previously untreated ovarian cancer (International Federation of Gynecology and Obstetrics stages IIB-IV) were randomly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650 patients) on a 3-week per cycle schedule. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, response rate, toxicity, and quality of life. Time-to-event data were analyzed using the Kaplan-Meier method, and a stratified log-rank test was used to compare distributions between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. Categorical data were compared using a stratified Cochran-Mantel-Haenszel test. All statistical tests were two-sided. RESULTS: Median progression-free survival was 18.2 months in the TC-Top arm versus 18.5 months in the TC arm (stratum-adjusted HR = 0.97 [95% CI = 0.85 to 1.10]; P = .688). Median overall survival was 43.1 months for the TC-Top arm versus 44.5 months for the TC arm (stratum-adjusted HR = 1.01 [95% CI = 0.86 to 1.18]; P = .885). At 3 years, overall survival in both arms was 57% (58.5% in the TC arm and 55.7% in the TC-Top arm). Compared with patients in the TC arm, patients in the TC-Top arm had more grade 3-4 hematologic toxic effects (requiring more supportive care) and more grade 3-4 infections (5.1% versus 2.7%; P = .034) but did not have a statistically significant increase in febrile neutropenia (3.3% versus 3.1%; P = .80). Among patients who had measurable disease (TC, n = 147; TC-Top, n = 145), overall (i.e., complete or partial) response was 69.0% (95% CI = 61.4% to 76.5%) in the TC-Top arm and 76.2% (95% CI = 69.3% to 83.1%) in the TC arm (P = .166). CONCLUSIONS: The sequential addition of topotecan to carboplatin-paclitaxel did not result in superior overall response or progression-free or overall survival. Therefore, this regimen is not recommended as standard of care treatment for ovarian cancer.

Adult↗
PubMed2006

Neutropenic event risk and impaired chemotherapy delivery in six European audits of breast cancer treatment.

GOALS OF WORK: The aims of this study were to assess chemotherapy treatment characteristics, neutropenic event (NE) occurrence and related risk factors in breast cancer patients in Western Europe. MATERIALS AND METHODS: Six retrospective audits of breast cancer chemotherapy were combined into a dataset of 2,860 individuals. NEs were defined as neutropenia-related hospitalisation, dose reduction > or = 15% or dose delay > or = 7 days. Summation dose intensity (SDI) was calculated to compare different types of chemotherapy regimens on a single scale. Risk factors of NE occurrence and of low relative dose intensity (RDI) < or = 85% were identified by multiple logistic regression. MAIN RESULTS: Patient populations were comparable between audits. Until 1998, cyclophosphamide, methotrexate and fluorouracil regimens were most frequently used, but thereafter, anthracycline-based regimens were most common. NEs occurred in 20% of the patients and low RDI in 16%. NE occurrence predicted low RDI and was associated with higher age, bigger body surface area, lower body mass index, regimen type, more chemotherapy cycles planned, normal to high SDI, concomitant radiotherapy and year of treatment. First cycle NE occurrence predicted NEs from cycle 2 onwards. A risk score using age, SDI, number of planned chemotherapy cycles and concomitant radiotherapy differentiated patients with increasing NE risk (9-37%). An alternative score version not using concomitant radiotherapy performed moderately less well. CONCLUSIONS: NEs occurred frequently in this combined dataset and they affected treatment delivery. Identifying patients at high NE risk enables targeted prophylaxis and may avoid dose limitations.

Adult↗
PubMed2006

C-KIT expression in ductal carcinoma in situ of the breast: co-expression with HER-2/neu.

The proto-oncogene c-KIT (CD117) is highly expressed in normal breast epithelium and is decreased in invasive breast cancer. In this study, we analyzed the protein expression and the mutational status of c-KIT in ductal carcinoma in situ (DCIS) of the breast and correlated these findings with nuclear grade, architectural pattern, and expression of HER-2, estrogen receptor (ER)-alpha, and progesterone receptor (PR). C-KIT, HER-2, ER, and PR expression were analyzed immunohistochemically in 106 cases of paraffin-embedded DCIS (85 pure DCIS and 21 DCIS with concurrent carcinoma). Direct sequencing of exons 9 and 11 of the c-KIT gene was performed to analyze the hot spot mutational regions in representative cases. C-KIT expression was found in 55 (52.8%) of all DCIS, correlating with high nuclear grade (P < .0001), comedonecrosis (P < .0001), and solid growth pattern (P = .001). Furthermore, c-KIT expression was strongly associated with HER-2 positivity (P < .0001) and was significantly lower in ER- or PR-positive cases (P = .001 and P = .006, respectively). C-KIT expression alone or co-expression with HER-2 in pure DCIS did not differ significantly from DCIS with invasive component (P = .09). Mutational analysis in 6 c-KIT-positive DCIS revealed no activating mutations in exons 9 or 11. Our findings suggest that the expression of c-KIT protein might define a subset of poorly differentiated, HER-2-positive DCIS with decreased expression of steroid hormone receptors, comedonecrosis, and a solid growth pattern. The implications of c-KIT and HER-2 co-expression for breast carcinogenesis should be further evaluated.

Adolescent↗
PubMed2006

HER-2-positive metastatic breast cancer: optimizing trastuzumab-based therapy.

Trastuzumab with a taxane as first-line therapy is now the standard of care for patients with human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer (MBC). The search for additional and more effective trastuzumab-based therapies continues. Novel combinations of trastuzumab with chemotherapeutic agents, including vinorelbine, gemcitabine, and capecitabine, and hormonal therapy agents, such as tamoxifen and aromatase inhibitors, are currently under investigation in clinical trials. Available data suggest these combinations will provide additional treatment options that may ultimately lead to better outcomes for patients with HER-2-positive MBC. Evidence is growing for the use of trastuzumab treatment beyond disease progression and retreatment after (neo)adjuvant relapse is being explored to assist in clinical decision making. Already, the use of trastuzumab in the metastatic setting has changed HER-2-positive status from a marker of poor prognosis to one of better overall outcome, and ongoing studies should expand further the treatment options for patients with HER-2-positive MBC.

Anthracyclines↗
PubMed2005

Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.

BACKGROUND: Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial. METHODS: Patients with at least nine positive nodes were randomly assigned either two courses of accelerated (2-week intervals, with filgrastim support), conventionally dosed epirubicin and cyclophosphamide followed by two courses of high-dose chemotherapy (epirubicin, cyclophosphamide, and thiotepa supported by peripheral-blood progenitors) or four identical cycles of epirubicin and cyclophosphamide followed by three cycles of accelerated cyclophosphamide, methotrexate, and fluorouracil. The primary endpoint was event-free survival. Analyses were done both by intention to treat and per protocol. FINDINGS: 403 patients were enrolled; 201 were assigned high-dose chemotherapy and 202 conventional treatment. The mean number of positive nodes was 17.6, and median follow-up was 48.6 months. 4-year event-free survival (intention-to-treat analysis) was 60% (95% CI 53-67) in the high-dose chemotherapy group and 44% (37-52) in the control group (p=0.00069). The corresponding overall survival was 75% (69-82) versus 70% (64-77; p=0.02). There were no treatment-related deaths. INTERPRETATION: Our finding of significant improvements in both event-free and overall survival for high-dose chemotherapy compared with a dose-dense conventional regimen contrasts with the results of other studies. The discrepancy might be due partly to design differences (tandem, brief induction) between our regimen and those studied in other trials. This approach merits further study.

Adult↗
PubMed2005

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.

BACKGROUND: Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. METHODS: This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. RESULTS: Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. CONCLUSIONS: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)

Adult↗
PubMed2005

Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group.

PURPOSE: Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer. METHODS: This phase III study investigated 913 women with untreated operable breast cancer (T2-3, N0-2, M0) randomly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support (ADOC), or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each (AC-DOC). The primary end point was the incidence of pathologic complete (invasive and noninvasive) response (pCR) in the breast and axillary nodes. Secondary end points were predictors for pCR, clinical response, rate of breast conservation, and safety. RESULTS: A pCR was achieved in 94 patients (10.6%), but the likelihood was significantly greater with AC-DOC (14.3%; n = 63) than with ADOC (7.0%; n = 31) (odds ratio, 2.22; 90% CI, 1.52 to 3.24; P < .001). Independent predictors of attaining a pCR included the use of sequential therapy, high tumor grade, and negative hormone receptor status. The response rates detected by palpation and by imaging were significantly higher with AC-DOC (85.0% and 78.6%, respectively) than with ADOC (75.2% and 68.6%, respectively; both P values < .001). The rate of breast-conserving surgery was 63.4% for AC-DOC and 58.1% for ADOC (P = .05). Predominant grade 3/4 toxicities were leucopenia (AC-DOC, 74.2%; ADOC, 53.7%) and neutropenia (AC-DOC, 66.4%; ADOC, 44.7%) but were infrequently associated with fever (AC-DOC, 4.6%; ADOC, 3.1%). CONCLUSION: Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer.

Adult↗
PubMed2005

Androgen receptor expression in ductal carcinoma in situ of the breast: not a helpful marker for classification such as estrogen receptor alpha and progesterone receptor.

Androgen receptor (AR) is known to be expressed in approximately 70 to 90% of invasive breast cancers, but there are still conflicting data in terms of AR expression in ductal carcinoma in situ (DCIS). The aim of this study was to evaluate AR expression in DCIS and to compare these results with nuclear grading and with other common endocrine-related markers. On this basis the authors performed immunohistochemical staining for estrogen receptor (ER)-alpha and ER-beta, progesterone receptor (PR), pS2, her-2/neu, and AR in 59 cases of DCIS (24 low grade, 5 intermediate grade, 30 high grade). They found a strong correlation of expression of ER-alpha (P=0.003), PR (P<0.0001), and nuclear grading. For AR expression, 44.1% of all DCIS were positive, but there was no correlation between nuclear grading (P=0.535) and the expression of the other factors. The authors conclude that AR expression in DCIS is not correlated with nuclear grading and with the expression of other known endocrine-related markers such as ER-alpha and -beta, PR, pS2, and her-2/neu. The immunohistochemical assessment of AR status, therefore, may not help in providing a more objective way of classifying DCIS.

Adolescent↗
PubMed2005

[Healing in sight?].

Explore the source record for details and available documents.

Antibodies, Monoclonal↗
PubMed2004

Future options with trastuzumab for primary systemic and adjuvant therapy.

HER2 positivity can be detected early in breast cancer development and is associated with a poor outcome. Primary systemic therapy with trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) in combination with taxanes and other cytotoxic agents has been studied in phase II clinical trials in women with HER2-positive breast cancer. These combinations have achieved pathologic complete response rates of 12% to 42% and clinical complete response rates of 30% to 67%. These results compare favorably with those of primary systemic therapy using standard combinations in patients with unselected (HER2-positive or -negative) breast cancer. Consequently, larger studies are in progress in which trastuzumab is administered before surgery in combination with chemotherapy. Trastuzumab is continued as monotherapy afterward to complete 1 year of treatment or until disease progression. These studies aim to provide further proof of the clinical benefits associated with trastuzumab as primary systemic therapy. They will also investigate the molecular determinants of sensitivity and resistance. In addition, four major randomized trials, in more than 13,500 patients, are investigating the impact of adding trastuzumab to standard adjuvant therapy. Planned interim cardiac safety analyses have been passed without concerns. Recruitment to these studies has either recently been completed or continues as planned. Together, this extensive program, which includes analysis of predictive molecular and pathologic makers, will establish the efficacy, safety, and role of trastuzumab in early breast cancer.

Antibodies, Monoclonal↗
PubMed2004

Estrogen receptor alpha and beta, progesterone receptor, pS2 and HER-2/neu expression delineate different subgroups in ductal carcinoma in situ of the breast.

Antiestrogen therapy of ductal carcinoma in situ (DCIS) has become a more common option in reducing risk of developing invasive cancer. Previously, estrogen receptor alpha (ER-alpha) was evaluated as the only predictive factor. Immunohistochemical staining was performed for ER-alpha, estrogen receptor ER-beta, progesterone receptor (PR), pS2 and her-2/neu in 59 cases of ductal carcinoma in situ (DCIS). We observed a positive correlation between the expression of ER-alpha (p=0.003), PR (p<0.001) and histopathological grading. Of the DCIS, 61.5% of ER-beta positive (p=0.046) and 35.5% of PR positive samples showed a coexpression with pS2, whereas 72.1% of pS2 negative DCIS were also negative for ER-beta and 92.9% of PR negative DCIS were negative for pS2 (p=0.012). In contrast, 50.0% of her-2/neu negative DCIS expressed ER-beta receptor (p=0.052). We propose that there are subpopulations of DCIS which can be described by distinct endocrine-associated expression patterns.

Adolescent↗
PubMed2003

A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer.

BACKGROUND: Despite considerable improvement in the treatment of advanced ovarian cancer, the optimization of efficacy and tolerability remains an important issue. Therefore, we performed a randomized, phase III non-inferiority trial comparing paclitaxel plus cisplatin (PT) with paclitaxel plus carboplatin (TC) in patients with advanced ovarian cancer. METHODS: A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were randomly assigned to receive six courses of either PT or TC at 3-week intervals. The primary endpoint was the proportion of patients without progression at 2 years. Secondary endpoints included toxicity, response to treatment, quality of life, and overall and progression-free survival time. Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30, version 2.0. Survival curves were calculated using the Kaplan-Meier method, and hazard ratios were estimated using the Cox proportional hazards model. RESULTS: The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms (40.0% for PT versus 37.5% for TC, difference = 2.5%, one-sided 95% confidence interval [CI] = - infinity to 8.2%). Median progression-free survival time in the TC arm (17.2 months, 95% CI = 15.2 to 19.3 months) and the PT arm (19.1 months, 95% CI = 16.7 to 21.5 months) were also not statistically significantly different; the same was true of median overall survival time (43.3 months, 95% CI = 37.2 to 47.8 months versus 44.1 months, 95% CI = 40.2 to 49.4 months, for the TC and PT arms, respectively). The TC regimen was associated with a higher frequency of hematologic toxicity, but a lower frequency of gastrointestinal and neurologic toxicity, than the PT regimen. Mean global quality-of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm (65.25 versus 51.97, respectively; difference = -13.28, 95% CI = -18.88 to -7.68). CONCLUSION: The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life, and should, therefore, be considered as an important alternative for standard first-line chemotherapy in patients with advanced ovarian cancer.

Adult↗
PubMed2003

Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry.

Secretory carcinomas (SCA) are distinguished from infiltrating ductal carcinomas (IDC) of the breast by their characteristic histomorphology and more favorable prognosis and by the expression of a chimeric tyrosine kinase that is encoded by the ETV6-NTRK3 fusion gene. On this basis, we evaluated 13 SCAs (12 of them with ETV6-NTRK3 gene fusion) by molecular and immunohistochemical (IHC) methods. DNA was obtained from 8 of 13 microdissected SCAs and was analyzed for genetic alterations (GA) by comparative genomic hybridization (CGH). IHC staining was performed for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67 (MIB1) in all 13 cases. Molecular and immunohistochemical results in SCAs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. An average of 2.0 GAs (range: 0 to 6) were detected, including recurrent gains of chromosome 8q (37.5%) and 1q (25%) and losses of 22q (25%). Four of 13 (31%) SCAs were positive for ER, and 2 were positive for PR. The mean MIB1-labeling index was 11.4% (range: <1 to 34%). Her-2/neu protein overexpression was detected in 2 cases, including 1 with strong (score 3+) and 1 with weak HER2/neu expression (score 2+). Fluorescence in situ hybridization analysis of the latter case showed no evidence of HER-2/neu-gene amplification. Compared with previous findings in IDCs, SCAs are characterized by a relatively low number of GAs, a low proliferative rate, infrequent HER2/neu protein overexpression, decreased steroid hormone receptor expression, and expression of ETV6-NTRK3 fusion gene. These results support the hypothesis that SCAs have immunohistochemical and genetic features that distinguish them from IDCs of the usual type.

Adult↗