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ABSTRACT: Objective: Receptor discordances between primary and recurrent breast cancer have been described for years, but only a few analyses have elucidated the factors that influence receptor changes. Methods: Explorative analyses of prospective data from a breast cancer database of a tertiary breast cancer unit. Results: Recurrent tumours that had expressed oestrogen (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) as primary tumours were negative for the respective receptor in 22.8, 41.4 and 40.8% of cases. ER, PR and HER2 expression was found in 19.8, 16.7 and 11.5% of recurrent tumours, although no expression had been observed in primary tumours. Receptor discordances in recurrent disease leading to different therapeutic approaches were noted in 126 of 411 patients (30.7%). In patients with tumours expressing primary ER and HER2, independent factors associated with discordance were endocrine therapy and treatment with trastuzumab. Conclusion: High rates of receptor discordance were found. The impact of factors that influence receptor changes is small so that no subgroup of patients with recurrent breast cancer should be excluded from biopsy. Whenever possible, a biopsy should be taken to confirm the diagnosis of a possible relapse as well as the receptor status of patients with breast cancer.
Oncology 04/2013; 84(6):319-325. · 2.27 Impact Factor
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ABSTRACT: OBJECTIVE: Retrospective analyses suggest that the treatment with beta blocker improves survival in patients with breast cancer and melanoma. The aim of this study was to investigate the impact of medication with beta blocker in patients with recurrent ovarian cancer. METHODS: Included patients received treatment within two prospective clinical trials: AGO-OVAR 2.4 phase I trial (Carboplatin/ Gemcitabine; N=25, protocol AGO-OVAR 2.4) and AGO led Intergroup phase III trial (Carboplatin vs Carboplatin/ Gemcitabine; N=356, protocol AGO-OVAR 2.5, EORTC-GCG, NCIC CTG). Concurrent medication was documented after every cycle and thorough monitoring was conducted. RESULTS: During the studies 38 patients (9.97%) received a beta blocker as co-medication. Patients treated with beta blockers were significant older than patients not treated with beta blockers. Response rates to chemotherapy were not different between patients treated with beta blockers and those who were not. After a median follow up of 17months, 349 (91.6%) patients had progressive disease and 267 (70.1%) patients had died. No difference in median progression-free survival (7.79 vs 7.62months (p=0.95)) and overall survival (21.2 vs 17.3months (P=0.18)) was recorded for patients treated with and without beta blocker. In multivariate analyses including age, platinum free-interval, study treatment and ECOG performance status beta blocker treatment was not associated with a significant impact on progression-free survival (HR: 0.92; 95%CI: 0.65-1.31; P=0.65) and overall survival (HR:0.74; 95%CI: 0.49-1.11; P=0.15). CONCLUSIONS: In this series of recurrent platin-sensitive ovarian cancer patients it could not be confirmed that beta blocker treatment was associated with better or worse outcome.
Gynecologic Oncology 03/2013; · 3.89 Impact Factor
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Andreas du Bois,
Nina Ewald-Riegler,
Nikolaus de Gregorio,
Alexander Reuss,
Sven Mahner,
Christina Fotopoulou,
Friedrich Kommoss,
Barbara Schmalfeldt,
Felix Hilpert,
Tanja Fehm, [......],
Klaus Baumann,
Ulrich Canzler,
Kerstin Wollschlaeger,
Dirk Forner,
Jacobus Pfisterer,
Willibald Schröder,
Karsten Münstedt,
Barbara Richter,
Stefan Kommoss,
Steffen Hauptmann
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ABSTRACT: BACKGROUND: Borderline ovarian tumours (BOTs) are recognised as a unique entity of ovarian tumours that do not exert infiltrative destructive growth or stromal invasion. Prognosis of BOT is much better compared to the more common invasive epithelial ovarian cancer. Information regarding prognostic factors is inconclusive and no prospective studies exist that evaluate therapeutic strategies. We therefore started a retrospective-prospective cohort study to better understand BOT and identify scenarios in which future studies could be developed. METHODS: Consecutive patients with BOT treated between 1998 and 2008 in 24 German centres were analysed. The retrospective part of the study retrieved patients' data from hospital records and clinical tumour registries while active follow-up and an independent central pathology review were carried out prospectively. FINDINGS: BOT was confirmed in 950 patients, two thirds had serous BOT and 30.5% mucinous BOT. Most were diagnosed in stage I (82.3%); 7.6% and 10.1% had stages II and III, respectively. Overall, 74 patients (7.8%) experienced relapse and 43 (4.5%) died within the observation period. Multivariate analysis revealed higher stage, incomplete staging, tumour residuals, and organ preservation as independent prognostic factors for disease recurrence. Neither microinvasion nor micropapillary growth pattern showed any significant impact. Of 74 relapsed patients, 30% had malignant transformation to invasive ovarian cancer with five-year progression-free survival and overall survival of 12% and 50%, respectively. INTERPRETATION: Prognosis of BOT correlates with tumour-related as well as surgery-related factors. The balance between recurrence risk and organ preservation and fertility-sparing surgery is an important issue deserving further research.
European journal of cancer (Oxford, England: 1990) 03/2013; · 4.12 Impact Factor
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Current Oncology Reports 02/2013; · 2.55 Impact Factor
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ABSTRACT: Advanced epithelial ovarian cancer, cancer of the fallopian tube and primary peritoneal cancer have a poor prognosis and a high rate of disease recurrence following primary therapy. Recurrent ovarian cancer is currently classified according to sensitivity to platinum-based chemotherapy. Data on targeted therapy provide evidence of improvement with systemic treatment in addition to chemotherapy. Other strategies, although not proven in randomized trials, offer interesting options for future research and therapeutic development. In this review, the covered treatment modalities include surgery, chemotherapy and targeted therapy, immunological approaches and irradiation.
Future Oncology 09/2012; 8(9):1135-47. · 3.16 Impact Factor
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ABSTRACT: Whilst cytoreductive surgery is the mainstay treatment for primary ovarian cancer, its role in relapse is still unclear. Surgery in platinum-sensitive recurrent ovarian cancer might be beneficial if it results in complete resection of the disease. Clinical scores could help to identify suitable patients. Level I evidence is still missing; however, two randomized trials (DESKTOP III and GOG 213) are ongoing.
Current Oncology Reports 08/2012; · 2.55 Impact Factor
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ABSTRACT: In the past decade there have been many attempts to improve systemic treatment and thus the outcome of patients with ovarian cancer. However, neither the sequential addition of non cross-resistant drugs to standard chemotherapy comprising carboplatin and paclitaxel, nor triplet combination therapies with conventional chemotherapeutic drugs have improved outcomes. Instead, such approaches have led to an increase in the incidence of side effects. We are currently experiencing a shift toward the addition of molecularly targeted and biological anticancer therapies to standard treatment. Vascular endothelial growth factor (VEGF), which improves vitally important tumor vasculature, is secreted by a range of tumors, and a high level of VEGF is known to be an independent risk factor for aggressive disease in ovarian cancer. This finding led to the development in the 1990s of bevacizumab, a humanized monoclonal antibody against VEGF.
Several phase II trials and four phase III trials have demonstrated that bevacizumab is active in patients with advanced and recurrent ovarian cancer. Both phase III trials of bevacizumab as first-line therapy in advanced ovarian cancer (ICON 7/AGOOVAR 11 and GOG-0218) have shown that the addition of bevacizumab to chemotherapy and as maintenance therapy improves progressionfree survival (PFS). The phase III trials in platinum-sensitive (OCEANS) and platinumresistant, relapsed disease (AURELIA) have also demonstrated a benefit for bevazicumab with respect to PFS. The administration of bevacizumab to improve survival in patients with ovarian cancer is not without side effects and a broad discussion on the cost-effectiveness of this approach is ongoing.
This article presents clinical trial data on bevacizumab in the treatment of ovarian cancer and discusses the indication and pitfalls in the application of bevacizumab in patients with this malignancy.
Advances in Therapy 08/2012; 29(9):723-35. · 2.11 Impact Factor
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Werner Meier, Andreas du Bois,
Jörn Rau,
Martina Gropp-Meier,
Klaus Baumann,
Jens Huober,
Kerstin Wollschlaeger,
Rolf Kreienberg,
Ulrich Canzler,
Barbara Schmalfeldt,
Pauline Wimberger,
Barbara Richter,
Willibald Schröder,
Antje Belau,
Anne Stähle,
Alexander Burges,
Jalid Sehouli
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ABSTRACT: This study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).
We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175 mg/m(2)) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.
105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm: median PFS was 11.5 months (95% CI: 7.4-14.2) compared with 16.4 (95% CI: 10.3-40.4) for TC (p=0.0141; HR=0.36 (95% CI: 0.15-0.84)) with median OS 20.6 months (95% CI: 13.1-31.0) and 43.4 months (95% CI: 15.7-) for the TC arm (p=0.012; HR=0.32 (95% CI: 0.13-0.8)).
The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.
Gynecologic Oncology 05/2012; 126(2):236-40. · 3.89 Impact Factor
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ABSTRACT: Prognosis in advanced ovarian cancer is largely determined by completeness of tumor resection achieved during primary surgery. Incomplete initial debulking occurs frequently in non-specialized centers and there is an ongoing discussion about the best time for re-surgery after referral to tertiary centers.
Patients with advanced epithelial ovarian cancer (FIGO IIIB-IV) admitted between 1999 and 2007 who had primary incomplete surgery including those with initiated chemotherapy at an outside institution were included. Surgical results, morbidity and prognosis were evaluated in patients with immediate re-operation before chemotherapy and those with interval debulking.
48 eligible patients were identified in our tumor registry. Self-referral by patient was the most frequent mode of admission (n=21, 43.8%). 22 patients (45.8%) underwent immediate re-surgery and 26 patients (54.2%) had an interval debulking after chemotherapy. In 12 patients (54.5%), macroscopically complete tumor removal could be achieved by immediate re-operation and in 17 patients (65.4%) after chemotherapy. Major complications were observed more frequently in patients with interval debulking (26.9 vs. 9.1%, p=0.324). Median overall survival time was 53 and 34 months (p=0.110) after immediate and delayed re-operation, respectively.
Upfront re-operation before start of chemotherapy is feasible and successful in an expertise referral center in more than half of patients with incomplete primary surgery elsewhere. Complete resection even after initial incomplete debulking could improve outcome. Therefore, referral to expertise centers in those patients should be considered. Progression-free survival and overall survival showed a non-significant trend and complication rate is a remarkable advantage in favor of upfront re-operation.
Gynecologic Oncology 03/2012; 126(1):54-7. · 3.89 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the feasibility of phase 0 trials in the setting of a routine surgical procedure. Logistic considerations, tissue sampling and tissue handling, and variability of a biomarker during surgery, in here PARP, were evaluated.
Patients with highly suspicious or proven diagnosis of advanced ovarian cancer, planned for debulking surgery were asked to allow sequential tumor biopsies during surgery. Biopsies were frozen immediately and PARP activity was measured subsequently.
Baseline biopsies were obtained from eight patients after a median time of 88 minutes (minimum of 50 to maximum of 123 minutes). Second and third biopsies were obtained after a median of 60 (32-96) and 101 (79-130) minutes, respectively. Mean tumor load was 44% (5%-100%), with a cellular viability of 98% (85%-100%). Median baseline PARP activity was 1035 pg/mL (range, 429-2663 pg/mL). The observed interpatient variability at baseline was large: SD was 0.59 after natural logarithm transformation.
Conducting phase 0 trials during surgery seems to be feasible in terms of logistic considerations. In preparation of a phase 0 trial during surgery, a feasibility study like this should be conducted to rule out major interactions of the surgical intervention with respect to the targeted biomarker.
Clinical Cancer Research 03/2012; 18(9):2632-7. · 7.74 Impact Factor
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ABSTRACT: The prognosis in borderline tumors of the ovary (BOT) is generally favorable. However, some patients experience recurrence, and mortalities occur. There is a need to better characterize prognostic factors to be considered for individualized treatment planning.
The data of 158 consecutive patients who underwent surgery for BOT at a tertiary referral center for gynecologic oncology between 1997 and 2008 were retrospectively analyzed.
Most patients had early stage disease, and advanced stages FIGO II/III only occurred in 23.4%. Serous histology was most frequent (68%), followed by mucinous histology (22%). All patients received surgery as initial treatment with no adjuvant systemic therapy. 37 patients (40.7% of the patients under the age of 50) had fertility-sparing surgery (FSS). Recurrent disease occurred in 18 (11.4%) patients, and 4 (2.5%) patients died. Independent risk factors for recurrence were FIGO stages > I (hazard ratio (HR) 37.1; 95% confidence interval (CI) 4.5-155.5), tumor rupture (HR 12.4; 95% CI 1.5-61.5), incomplete staging (HR 5.9; 95% CI 1.6-21.3), and FSS in patients < 50 years (HR 8.0; 95% CI 2.0-31.6).
Intraoperative tumor rupture, incomplete staging, and FSS - all influenced by the surgeon - may impose a substantial recurrence risk. Therefore, careful counseling and balancing of risk and benefit are mandatory before therapy is applied, especially if FSS is planned.
Onkologie 01/2012; 35(1-2):28-33. · 0.87 Impact Factor
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ABSTRACT: Age remains a negative prognostic factor in ovarian cancer (OC). 3 separate analyses by the AGO (Arbeitsgemeinschaft Gynaekologische Onkologie) give insight into the treatment of elderly patients (EPs) in the context of controlled clinical trials (CCTs).
1 retrospective study evaluated the reasons for non-enrolment into CCTs of patients with advanced OC in AGO centers. 2 other exploratory age-specific analyses of a phase III trial in advanced OC treated with platinum/ paclitaxel evaluated (1) feasibility, toxicity and quality of life (QoL) and (2) the clinical outcome.
Non-study patients were significantly older (66.7 vs. 57.2 years). Reasons for non-enrolment were predominantly predefined exclusion criteria, numeric age, and the patient's decision. The phase III trial confirmed an under-representation of EPs. Cycle delivery was significantly lower and discontinuation more frequent in EPs than in younger patients (YPs), although QoL, toxicity, cycle delays, and dose reductions were comparable. Delivery of cycles was prognostically significant in EPs but not YPs. The survival advantage of YPs remained significant even in completely debulked patients.
There is some kind of investigator reservation for the treatment of EPs, which not only applies for the enrolment into clinical trials but also for the treatment, even under CCT conditions, with impact on outcome.
Onkologie 01/2012; 35(3):76-81. · 0.87 Impact Factor
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Timothy J Perren,
Ann Marie Swart,
Jacobus Pfisterer,
Jonathan A Ledermann,
Eric Pujade-Lauraine,
Gunnar Kristensen,
Mark S Carey,
Philip Beale,
Andrés Cervantes,
Christian Kurzeder, [......],
Charlie Gourley,
Alain Lortholary,
Frédéric Selle,
Mansoor R Mirza,
Arto Leminen,
Marie Plante,
Dan Stark,
Wendi Qian,
Mahesh K B Parmar,
Amit M Oza
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ABSTRACT: Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.
We randomly assigned women with ovarian cancer to carboplatin (area under the curve, 5 or 6) and paclitaxel (175 mg per square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (7.5 mg per kilogram of body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease. Outcome measures included progression-free survival, first analyzed per protocol and then updated, and interim overall survival.
A total of 1528 women from 11 countries were randomly assigned to one of the two treatment regimens. Their median age was 57 years; 90% had epithelial ovarian cancer, 69% had a serous histologic type, 9% had high-risk early-stage disease, 30% were at high risk for progression, and 70% had stage IIIC or IV ovarian cancer. Progression-free survival (restricted mean) at 36 months was 20.3 months with standard therapy, as compared with 21.8 months with standard therapy plus bevacizumab (hazard ratio for progression or death with bevacizumab added, 0.81; 95% confidence interval, 0.70 to 0.94; P=0.004 by the log-rank test). Nonproportional hazards were detected (i.e., the treatment effect was not consistent over time on the hazard function scale) (P<0.001), with a maximum effect at 12 months, coinciding with the end of planned bevacizumab treatment and diminishing by 24 months. Bevacizumab was associated with more toxic effects (most often hypertension of grade 2 or higher) (18%, vs. 2% with chemotherapy alone). In the updated analyses, progression-free survival (restricted mean) at 42 months was 22.4 months without bevacizumab versus 24.1 months with bevacizumab (P=0.04 by log-rank test); in patients at high risk for progression, the benefit was greater with bevacizumab than without it, with progression-free survival (restricted mean) at 42 months of 14.5 months with standard therapy alone and 18.1 months with bevacizumab added, with respective median overall survival of 28.8 and 36.6 months.
Bevacizumab improved progression-free survival in women with ovarian cancer. The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression. (Funded by Roche and others; ICON7 Controlled-Trials.com number, ISRCTN91273375.).
New England Journal of Medicine 12/2011; 365(26):2484-96. · 53.30 Impact Factor
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Oncology (Williston Park, N.Y.) 09/2011; 25(10):940, 942, 944. · 1.03 Impact Factor
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ABSTRACT: Cytoreductive surgery is accepted as a major treatment of primary ovarian cancer. The role in recurrent ovarian cancer remains a field of discussion and controversy, mainly owing to missing data from prospective randomized trials and lack of universal definitions. Retrospective data indicate that complete resection of recurrent tumor formations should be aimed for, since survival prolongation is mainly seen for patients with no residual disease. Thus, it is most important to find predictors of complete resection, on the one hand to offer the best therapeutic chances to patients, but on the other hand to protect patients with limited life expectancy from additional surgical burden. The first prospective surgical trial in recurrent ovarian cancer, AGO-DESKTOP II validated a score ('AGO score') for complete resection. It was shown that patients with a good general condition (ECOG 0), no residual disease after surgery for primary ovarian cancer and absence of ascites in presurgical diagnostics have a 76% likelihood of undergoing complete resection. In this article, further recent data regarding surgery for recurrent ovarian cancer are going to be discussed and the advantages of incorporating these patients into randomized trials are highlighted.
Women s Health 09/2011; 7(5):529-35.
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ABSTRACT: The objective of this study was to determine the relationship between clinician-graded symptoms based on the common toxicity criteria (CTC) and patient-reported quality of life (QoL). We hypothesized that toxicity symptoms that are objective or observable would have a higher correlation with QoL than subjective data.
A retrospective analyses of data from three closed randomized chemotherapy trials was performed. A total of 2,110 patients with ovarian cancer (stage IIB-IV) who had complete toxicity and QoL data at cycles 3 and 6 were included. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria. Quality of life was assessed every other cycle by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
Correlations between CTC grading and the QLQ-C30 functioning scales were weak (<0.30); correlation coefficients between CTC ratings and the QLQ-C30 symptom scales including nausea, vomiting, constipation, pain, and dyspnea ranged from 0.32 to 0.49 except for constipation (0.55). On a symptom level exact agreement between clinician and patient reporting ranged from 54.2% (pain) to 80.8% (emesis/vomiting). When symptom grading differed, patients reported greater severity for pain, constipation, and dyspnea, whereas clinicians graded emesis/vomiting and nausea as more severe than the grading by patients.
Patient experience is not routinely captured by CTC toxicity scales. Therefore, clinicians should not entirely rely on the CTC grading but consider patient-reported outcomes as well.
Supportive Care in Cancer 09/2011; 19(9):1421-7. · 2.09 Impact Factor
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Gunter von Minckwitz,
Sibylle Loibl,
Christian Jackisch,
Stefan Paepke,
Caroline Nestle-Kraemling,
Michael P Lux,
Nico Maass,
Rita Schmutzler, Andreas du Bois,
Diethelm Wallwiener,
Sabine Vescia,
Kai Budischewski,
Manfred Kaufmann
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ABSTRACT: Genetic testing for inherited mutations in breast cancer genes provides valuable information for disease prevention. Today, premenopausal women with increased risk for breast cancer have only limited nonsurgical options to reduce their risk.
The GISS trial, a randomized, multicenter, open-label phase II trial, assessed the feasibility of a preventive treatment with goserelin and ibandronate for premenopausal women at increased risk for breast cancer. The primary endpoints were refusal to undergo randomization and discontinuation of treatment. Safety and quality of life were also evaluated.
Between the years 2001 and 2003, 31 of 322 eligible women participated in the trial; 15 received goserelin/ibandronate plus screening, 15 screening only, and 1 withdrew her consent after randomization. The treatment duration was 24 months. Here, mainly the results from the first 12 months were evaluated because of the low compliance thereafter. Hot flushes, headache, and vaginal dryness/discharge occurred more often in the goserelin arm. No difference was observed between the two arms in the agreement to randomization, compliance, or any other endpoints.
Acceptance of chemoprevention with goserelin and ibandronate was low. Premenopausal women at increased risk for breast cancer should be better informed about chemoprevention through physician counseling and a more feasible study design (e.g., oral medication) should be provided.
This is the first chemoprevention trial in premenopausal women at increased risk for breast cancer.
Cancer Epidemiology Biomarkers & Prevention 08/2011; 20(10):2141-9. · 4.12 Impact Factor
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Sibylle Loibl,
Berit Maria Müller,
Gunter von Minckwitz,
Michael Schwabe,
Marc Roller,
Silvia Darb-Esfahani,
Beyhan Ataseven, Andreas du Bois,
Annette Fissler-Eckhoff,
Bernd Gerber,
Uwe Kulmer,
Jens-Uwe Alles,
Keyur Mehta,
Carsten Denkert
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ABSTRACT: The androgen receptor (AR) has been shown to be of potential prognostic importance in retrospective cohorts. We evaluated immunohistochemical AR expression on a tissue microarray of 673 core biopsies from primary breast cancer patients treated with neoadjuvant docetaxel/doxorubicin/cyclophosphamide (TAC) chemotherapy in the prospective GeparTrio phase-III trial. AR was detected in 53.2% of tumours. Lowest AR expression was detected in triple-negative breast cancers (TNBC) with 21.2%. Highest AR expression was observed in Luminal A-like tumours with 67%. In AR-positive tumours, pathological complete response (pCR) rate was 12.8% compared to 25.4% in AR-negative tumours (P < 0.0001). In multivariate analysis, AR independently predicted pCR (OR 1.86; 95% CI [1.16-2.79] P = 0.0086). Overall patients with an AR-positive tumour had a significant better disease-free (DFS) (AR-positive 78.9% vs. AR-negative 72.5%; log-rank P = 0.0329) and overall survival (OS) (88.8% vs. 82.7%; log-rank P = 0.0234) than those with AR-negative tumours. Stratified analysis revealed that in the TNBC subgroup, but not in the other subgroups defined by ER, PgR and HER2, AR expression predicted a better DFS (AR-positive 85.7% vs. AR-negative 65.5% log-rank P = 0.0544) and OS (95.2% vs. 76.2%; log-rank P = 0.0355). Within the non-pCR subgroup, AR positivity selected a group with a significant better DFS (P = 0.045) and OS (0.021) but not within the pCR group. Patients with an AR-negative tumour have a higher chance of achieving a pCR than those with an AR-positive one. But, patients with AR-positive tumours have a better survival especially if they did not achieve a pCR.
Breast Cancer Research and Treatment 08/2011; 130(2):477-87. · 4.43 Impact Factor
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ABSTRACT: Minority vote to statement A5 of the Fourth Ovarian Cancer Consensus Conference, Vancouver 2010, on behalf of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Germany plus North-Eastern Society of Gyneco-Oncology and the AGO Austria.
International Journal of Gynecological Cancer 08/2011; 21(6):1165-8. · 1.65 Impact Factor
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Michael Untch,
Peter A Fasching,
Gottfried E Konecny,
Stephan Hasmüller,
Annette Lebeau,
Rolf Kreienberg,
Oumar Camara,
Volkmar Müller, Andreas du Bois,
Thorsten Kühn,
Elmar Stickeler,
Nadia Harbeck,
Cornelia Höss,
Steffen Kahlert,
Thomas Beck,
Werner Fett,
Keyur M Mehta,
Gunter von Minckwitz,
Sibylle Loibl
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ABSTRACT: To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.
Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m(2)) followed by four 3-week cycles paclitaxel (175 mg/m(2)) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue.
Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was 96% in patients with pCR compared to 86% in patients without pCR (P = .025). pCR was the only significant prognostic factor for DFS (hazard ratio [HR] 2.5; 95% CI, 1.2 to 5.1; P = .013) and OS (HR, 4.9; 95% CI, 1.4 to 17.4; P = .012) in multivariable analysis. Cardiac toxicity was reported in eight patients (3.7%) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure.
Neoadjuvant combination of trastuzumab and chemotherapy resulted in a high pCR rate in HER2-overexpressing primary breast cancer. Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome. Patients without a pCR had an increased risk for relapse and death.
Journal of Clinical Oncology 07/2011; 29(25):3351-7. · 18.37 Impact Factor
