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ABSTRACT: Clinical trials have demonstrated an increased risk of breast cancer during estrogen/norethisterone (NET) therapy. With this in mind, the effects of estrogen/NET combination on the proliferation of breast cancer cells overexpressing the progesterone receptor membrane component 1 (PGRMC1) were examined. The same combination was used for the first time in a mouse xenograft model to determine its effects on tumor development.
MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12 cells) or empty vector control (pcDNA-3HA). NET, medroxyprogesterone acetate (MPA), and progesterone were tested alone and sequentially and continuously combined with estradiol (E2). Six-week-old nude mice were inoculated with E2 pellets 24 hours before the injection of tumor cells into both flanks (n = 5-6 mice per group). After 8 days, animals were inoculated with a NET pellet or with placebo pellets, and tumor volumes were recorded twice a week.
NET alone significantly increased the proliferation of WT-12 cells, MPA was effective only at the two highest concentrations, and progesterone had no effect. The twofold to threefold E2-induced increase (10 M) was not significantly influenced by the addition of the various progestogens. In contrast, 10 M E2 had no effect; however, addition of MPA and NET triggered a significant proliferative response. In vivo, a sequential combination of NET and E2 also significantly increased the tumor growth of WT-12 cells; empty vector cells did not respond to NET.
We have demonstrated for the first time that an E2/NET combination increases the proliferation of PGRMC1-overexpressing breast cancer cells, both in vivo and in vitro. Our results suggest that undetected tumor cells overexpressing PGRMC1 may be more likely to develop into frank tumor cells in women undergoing E2/NET hormone therapy.
Menopause (New York, N.Y.) 05/2013; 20(5):504-10. · 3.08 Impact Factor
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ABSTRACT: Detection of circulating tumor cells (CTCs) in the peripheral blood of patients with primary breast cancer is associated with poor clinical outcome. Recent studies have found evidence for immunological influence on tumor cell dormancy. We therefore investigated the relationship between peripheral T-cells and CTCs, as immunological factors may contribute to the fate of CTCs.
The peripheral blood immune status of 116 patients with primary breast cancer was analyzed by flow cytometry. Results were correlated with the presence of CTCs and clinicopathological parameters of these patients.
Appearance of CTCs was significantly associated with grade III tumors (p<0.05). Interestingly, CTC-positive patients presented with a significant increase of peripheral CD95(FAS)-positive T-helper cells. As immune response is regulated by CD95(APO-1/FAS)-CD95ligand interaction and tumor cells induce apoptosis via the CD95/CD95L (ligand) pathway, this might lead to tumor cell escape by apoptotic T-helper cells.
Absence of T-cell help at the time of priming may result in a loss of long-term antigen-activation of CD8 lymphocytes and could lead to an ineffective anti-tumor cell response. This might contribute to systemic immunosuppression and open the door for tumor cell dormancy.
Anticancer research 05/2013; 33(5):2233-8. · 1.73 Impact Factor
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ABSTRACT: Detection of disseminated tumor cells (DTCs) in bone marrow and of circulating tumor cells (CTCs) in the blood has become a major focus of translational cancer research. DTC presence is a common phenomenon seen in 30-40% of primary breast cancer patients and is strongly associated with poor clinical outcome. Since bone marrow biopsy is an invasive procedure, evaluation of CTCs might become a desired alternative. Recent clinical trials have shown CTC detection to be a promising prognostic tool in both primary and metastatic setting. Evaluation of CTCs might be useful for therapy monitoring and their characterization might help to identify novel targets for biological therapies aimed at disrupting earliest steps of metastatic cascade.
Clinica chimica acta; international journal of clinical chemistry 04/2013; · 2.54 Impact Factor
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Frédéric Amant,
Gunter von Minckwitz,
Sileny N Han,
Marijke Bontenbal,
Alistair E Ring,
Jerzy Giermek,
Hans Wildiers, Tanja Fehm,
Sabine C Linn,
Bettina Schlehe, [......],
Kristel Van Calsteren,
Brigitte Rack,
Valentina Nekljudova,
Nadia Harbeck,
Michael Untch,
Petronella O Witteveen,
Kathrin Schwedler,
Christoph Thomssen,
Ben Van Calster,
Sibylle Loibl
[show abstract]
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ABSTRACT: PURPOSEWe aimed to determine the prognosis of patients with breast cancer diagnosed during pregnancy (BCP). PATIENTS AND METHODS
In this cohort study, a multicentric registry of patients with BCP (from Cancer in Pregnancy, Leuven, Belgium, and GBG 29/BIG 02-03) compiled pro- and retrospectively between 2003 and 2011 was compared with patients who did not have associated pregnancies, using an age limit of 45 years. Patients with a diagnosis postpartum were excluded. The main analysis was performed using Cox proportional hazards regression of disease-free survival (DFS) and overall survival (OS) on exposure (pregnant or not), adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status, histology, type of chemotherapy, use of trastuzumab, radiotherapy, and hormone therapy.ResultsThe registry contained 447 women with BCP, mainly originating from Germany and Belgium, of whom 311 (69.6%) were eligible for analysis. The nonpregnant group consisted of 865 women. Median age was 33 years for the pregnant and 41 years for the nonpregnant patients. Median follow-up was 61 months. The hazard ratio of pregnancy was 1.34 (95% CI, 0.93 to 1.91; P = .14) for DFS and 1.19 (95% CI, 0.73 to 1.93; P = .51) for OS. Cox regression estimated that the 5-year DFS rate for pregnant patients would have increased from 65% to 71% if these patients had not been pregnant. Likewise, the 5-year OS rate would have increased from 78% to 81%. CONCLUSION
The results show similar OS for patients diagnosed with BCP compared with nonpregnant patients. This information is important when patients are counseled and supports the option to start treatment with continuation of pregnancy.
Journal of Clinical Oncology 04/2013; · 18.37 Impact Factor
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ABSTRACT: Backround: The incidence of abnormal cytological results in pregnant women is as much as 7%. Often there is need to advise pregnant women with an abnormal cervical cytology result and monitor them throughout pregnancy, without endangering the mother or child. PATIENTS AND METHODS: We retrospectively analyzed all pregnant women with an abnormal cervical cytology or condyloma in our dysplasia clinic between 01/2008 and 12/2011. Classification of the cervical cytological results was performed according to the Munich II nomenclature and a biopsy was obtained from most patients. Groups were defined in order to assess regression, persistence and progression. Particular attention was paid to the mode of delivery and the postpartum consultation. RESULTS: A total of 65 pregnant women were treated in the dysplasia clinic. The reason for referral was Pap IIID in 46.2%, Pap IVa in 40% and Pap III or Pap II with condyloma in 6.2% patients. Only one patient presented with a Pap IVb finding. The pregnancy was continued in all but one cases. Postpartum, a total of 40% of cases, were in remission. A partial remission occurred in 4.6%. Persistence of the abnormalities was observed in 26.2%. Progression was documented in 3% and 71.1% were able to have a vaginal delivery. A caesarean section was performed in 22.2%. A total of 4.4% suffered a miscarriage, which was not caused by the colposcopy. Discussion: The distinctive feature of the present study is the high number of follow-up examinations, which showed that even women with highly dysplastic changes in pregnancy, who are regularly monitored can be advised to continue pregnancy. Vaginal delivery is possible in most cases.
Anticancer research 02/2013; 33(2):711-5. · 1.73 Impact Factor
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Menopause 12/2012; · 3.76 Impact Factor
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ABSTRACT: OBJECTIVE: Clinical trials have demonstrated an increased risk of breast cancer during estrogen/norethisterone (NET) therapy. With this in mind, the effects of estrogen/NET combination on the proliferation of breast cancer cells overexpressing the progesterone receptor membrane component 1 (PGRMC1) were examined. The same combination was used for the first time in a mouse xenograft model to determine its effects on tumor development. METHODS: MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12 cells) or empty vector control (pcDNA-3HA). NET, medroxyprogesterone acetate (MPA), and progesterone were tested alone and sequentially and continuously combined with estradiol (E2). Six-week-old nude mice were inoculated with E2 pellets 24 hours before the injection of tumor cells into both flanks (n = 5-6 mice per group). After 8 days, animals were inoculated with a NET pellet or with placebo pellets, and tumor volumes were recorded twice a week. RESULTS: NET alone significantly increased the proliferation of WT-12 cells, MPA was effective only at the two highest concentrations, and progesterone had no effect. The twofold to threefold E2-induced increase (10 M) was not significantly influenced by the addition of the various progestogens. In contrast, 10 M E2 had no effect; however, addition of MPA and NET triggered a significant proliferative response. In vivo, a sequential combination of NET and E2 also significantly increased the tumor growth of WT-12 cells; empty vector cells did not respond to NET. CONCLUSIONS: We have demonstrated for the first time that an E2/NET combination increases the proliferation of PGRMC1-overexpressing breast cancer cells, both in vivo and in vitro. Our results suggest that undetected tumor cells overexpressing PGRMC1 may be more likely to develop into frank tumor cells in women undergoing E2/NET hormone therapy.
Menopause (New York, N.Y.) 12/2012; · 3.08 Impact Factor
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François-Clément Bidard, Tanja Fehm,
Michail Ignatiadis,
Jeffrey B Smerage,
Catherine Alix-Panabières,
Wolfgang Janni,
Carlo Messina,
Costanza Paoletti,
Volkmar Müller,
Daniel F Hayes,
Martine Piccart,
Jean-Yves Pierga
[show abstract]
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ABSTRACT: In 2004, circulating tumor cells (CTC) enumeration by the CellSearch® technique at baseline and during treatment was reported to be associated with prognosis in metastatic breast cancer patients. In 2008, the first evidence of the impact of CTC detection by this technique on survival of cM0(i+) patients were reported. These findings were confirmed by other non-interventional studies, whereas CTC were also investigated as a surrogate for tumor biology, mainly for HER2 expression/amplification. The aim of this report is to present the current prospective large interventional studies that have been specifically designed to demonstrate that CTC enumeration/characterization may improve the management of breast cancer patients: STIC CTC METABREAST (France) and Endocrine Therapy Index (USA) assess the CTC-guided hormone therapy vs chemotherapy decision in M1 patients; SWOG0500 (USA) and CirCe01 (France) assess the CTC count changes during treatment in metastatic patients; DETECT III (M1 patients, Germany) and Treat CTC (cM0(i+) patients, European Organization for Research and Treatment of Cancer/Breast International Group) assess the use of anti-HER2 treatments in HER2-negative breast cancer patients selected on the basis of CTC detection/characterization. These trials have different designs in various patient populations but are expected to be the pivotal trials for CTC implementation in the routine management of breast cancer patients.
CANCER AND METASTASIS REVIEW 11/2012; · 9.35 Impact Factor
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ABSTRACT: Objectives: Dienogest (DNG) is already used in hormone therapy, since recently being also the progestogenic component of the first estradiol based contraceptive pill. Data on breast cancer risk are currently not available. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in tissues of breast cancer patients and has already been proposed as a predictor for breast cancer risk. Methods: MCF-7 cells overexpressing PGRMC1 were stimulated with DNG, medroxyprogesterone acetate (MPA), norethisterone (NET) and progesterone (P) as well as sequentially and continuously combined with estradiol (E2). Results: DNG and MPA alone elicited a significant proliferation at 10(-6) and 10(-5) M. NET increased cell proliferation at all concentrations tested whereas P showed no effect. E2 alone elicited a significant increase at 10(-10) M, no effect was seen at 10(-12) M. Addition of the progestins (10(-6) M) to E2 at 10(-10) M had, compared to E2 only, no additional proliferating effect. However, at the low E2 concentration, DNG, MPA and NET significantly increased the E2-stimulated cell proliferation. Conclusion: DNG increased proliferation alone and in combination with low E2 concentrations. Thus a progestogen-derived breast cancer risk in the presence of low E2 concentrations cannot be excluded at least in women overexpressing PGRMC1.
Gynecological Endocrinology 11/2012; · 1.58 Impact Factor
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Siwei Wei,
Lingyan Liu,
Jian Zhang,
Jeremiah Bowers,
G A Nagana Gowda,
Harald Seeger, Tanja Fehm,
Hans J Neubauer,
Ulrich Vogel,
Susan E Clare,
Daniel Raftery
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ABSTRACT: Breast cancer is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. As an example, only some women will benefit from chemotherapy. Identifying patients who will respond to chemotherapy and thereby improve their long-term survival has important implications to treatment protocols and outcomes, while identifying non responders may enable these patients to avail themselves of other investigational approaches or other potentially effective treatments. In this study, serum metabolite profiling was performed to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy for breast cancer. Metabolic profiles of serum from patients with complete (n = 8), partial (n = 14) and no response (n = 6) to chemotherapy were studied using a combination of nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography-mass spectrometry (LC-MS) and statistical analysis methods. The concentrations of four metabolites, three (threonine, isoleucine, glutamine) from NMR and one (linolenic acid) from LC-MS were significantly different when comparing response to chemotherapy. A prediction model developed by combining NMR and MS derived metabolites correctly identified 80% of the patients whose tumors did not show complete response to chemotherapy. These results show promise for larger studies that could result in more personalized treatment protocols for breast cancer patients.
Molecular oncology 10/2012; · 4.10 Impact Factor
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ABSTRACT: Mutations of components of the mitogen-activated protein kinase pathway, mainly BRAF, are common in serous ovarian borderline tumors, whereas high-grade serous ovarian carcinomas rarely show this feature. With the advent of specific kinase inhibitors active against BRAF-mutated cancers, rapid and sensitive detection of the BRAF V600E, by far the most common mutation of this gene, is of great practical relevance. Currently, BRAF mutations are detected by DNA-based techniques. Recently, a monoclonal antibody (VE1) specific for the BRAF V600E protein suitable for archival tissues has been described. In this study, we compared detection of the V600E mutation in serous ovarian tumors by VE1 immunostaining and by allele-specific polymerase chain reaction. All 141 cases of high-grade serous ovarian cancer showed negative or rarely weak, diffuse background VE1 immunostaining, and BRAF wild type was confirmed by molecular analysis in all tested cases. In contrast, 1 (14%) of 7 low-grade serous carcinomas and 22 (71%) of 31 serous borderline tumors revealed moderate to strong VE1 positivity. Immunostaining was clearly evaluable in all cases with sufficient tumor cells, and only rare cases with narrow cytoplasm were difficult to interpret. The V600E mutation was confirmed by allele-specific polymerase chain reaction and sequencing in all VE1-positive cases. Two VE1-positive cases with low epithelial cell content required repeat microdissection to confirm the presence of the mutation. Immunohistochemistry with the VE1 antibody is a specific and sensitive tool for detection of the BRAF V600E mutation in serous ovarian tumors and may provide a practical screening test, especially in tumor samples with low epithelial content.
Human pathology 10/2012; · 3.03 Impact Factor
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Sibylle Loibl,
Sileny N Han,
Gunter von Minckwitz,
Marijke Bontenbal,
Alistair Ring,
Jerzy Giermek, Tanja Fehm,
Kristel Van Calsteren,
Sabine C Linn,
Bettina Schlehe, [......],
Volkmar Müller,
Liesbeth Heyns,
Brigitte Rack,
Ben Van Calster,
Nadia Harbeck,
Miriam Lenhard,
Michael J Halaska,
Manfred Kaufmann,
Valentina Nekljudova,
Frederic Amant
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ABSTRACT: Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child.
We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833.
From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1-105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76-1·69]; p=0·539).
Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance.
BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium.
The lancet oncology 08/2012; 13(9):887-96. · 14.47 Impact Factor
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Volkmar Muller,
Sabine Riethdorf,
Brigitte Rack,
Wolfgang Janni,
Peter Fasching,
Erich Solomayer,
Bahriye Aktas,
Sabine Kasimir-Bauer,
Klaus Pantel, Tanja Fehm,
The Detect Study Group
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ABSTRACT: INTRODUCTION: There is a multitude of assays for the detection of circulating tumor cells (CTC) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies. METHODS: A total of 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTC were assessed using both the AdnaTest Breast Cancer and the CellSearch assay according to the manufacturers' instructions. RESULTS: Using the CellSearch assay, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTC. The median OS was 18.1 months in CTC-positive patients. (95%-CI: 15.1 - 22.1 months) compared to 27 months in CTC-negative patients (23.5 - 30.7 months; p<0.001). This prognostic impact for overall survival (OS) was also significant in the subgroups of patients with triple negative, HER2-positive and hormone receptor-positive/HER2-negative primary tumors. The progression free survival (PFS) was not correlated with CTC status in our cohort receiving different types and lines of systemic treatment (p=0.197). In multivariate analysis, the presence of CTC was an independent predictor for overall survival (HR: 2.7, 95%-CI: 1.6 - 4.2). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC-positive. CTC-positivity assessed by the AdnaTest Breast had no association with PFS or OS. CONCLUSIONS: The prognostic relevance of CTC detection in metastatic breast cancer patients depends on the test method. The present results indicate that the CellSearch assay is superior to the AdnaTest Breast Cancer in predicting clinical outcome in advanced breast cancer. Trial registration: Current Controlled Trials Registry no. ISRCTN59722891.
Breast cancer research: BCR 08/2012; 14(4):R118. · 5.24 Impact Factor
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ABSTRACT: Numerous studies have shown that the presence of clinically occult disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients is associated with an unfavourable clinical outcome. Immunocytochemistry (ICC) remains the gold standard for their detection. Assays based on RT-PCR are available; however so far they have not been used for routine detection of DTC. Therefore, the purpose of this study was to evaluate a newly established molecular method for the detection of DTC.
BM aspirates from 405 patients were examined. Half of the samples were immediately inserted into ICC and the other half was examined with our newly established molecular method based on RT-PCR. Immunocytochemistry was performed according to the Consensus Recommendations of the German, Austrian, and Swiss Societies of Senology and ISHAGE Working Group (A45B-B3 antibody). RT-PCR was conducted as a one-step real-time assay Cytokeratin 19-mRNA was amplified.
In 142 of 405 (35%) aspirates disseminated tumor cells were detected by RT-PCR. In 34% of patients DTC were detected by ICC. 48% of the BM samples were positive by at least one method. In 73% of the patients identical results were obtained (p<0,001).
Our newly established molecular assay for the detection of disseminated tumor cells, and thus minimal residual disease, is sensitive, fast and reproducible, and has a potential to be used as a confirmatory or alternative test for DTC detection.
Ginekologia polska 08/2012; 83(8):590-7. · 0.41 Impact Factor
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ABSTRACT: The NeoAzure study has demonstrated that the use of the bisphosphonate zoledronic acid (Zol) in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity. The purpose of this study was to compare the antitumor effect of Zol with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA).
Breast cancer specimens were obtained from patients with breast cancer who underwent primary breast cancer surgery at the Department of Obstetrics and Gynecology, Tübingen, Germany, between 2006 through 2009. Antitumor effects of Zol, TAC (Docetaxel, Adriamycin, Cyclophosphamide) and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50), for IC90 and for the sensitivity index (IndexSUM). Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC) derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls.
The median IndexSUM value was lower for Zol than for the combined regimen FEC (36.8%) and TAC (12.9%), respectively, indicating increased antitumor activity of Zol in primary breast cancer cells. The difference regarding Zol and FEC was significant (p < 0.05). The median IC50 value for Zol (8.03% TDC) was significantly lower than the IC50 values for FEC (33.5% TDC) and TAC (19.3% TDC) treatment (p < 0.05). However, the median IC90 value for Zol (152.5% TDC) was significantly higher than the IC90 value obtained with TAC (49.5% TDC; p < 0.05), but similar to the IC90 value for FEC (180.9% TDC). In addition a significant positive correlation was observed for the IndexSum of Zol and the ER status (p < 0.01).
Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer.
BMC Cancer 07/2012; 12:308. · 3.01 Impact Factor
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ABSTRACT: To study whether the ovarian reserve in female lymphoma patients is already reduced before the start of chemotherapy.
Age-matched control study.
Women's university hospital.
Female patients aged <40 years with the initial diagnosis of lymphoma (study group) were compared with age-matched healthy volunteers (control group). Eighty-four female patients with breast cancer and 64 patients with lymphoma who underwent ovarian hormonal stimulation as a fertility-preserving method before the start of chemotherapy.
Measurement of antimüllerian-hormone (AMH) levels. Ovarian hormonal stimulation to retrieve oocytes.
AMH levels of the lymphoma patients and the healthy volunteers were compared. Numbers of retrieved oocytes after hormonal stimulation in patients with breast cancer and those with lymphoma were compared.
Female lymphoma patients have significantly lower AMH levels than healthy age-matched controls: mean value of AMH was 2.06 ng/mL in the study group versus 3.20 ng/mL in the control group. Analysis of the stimulation results showed that in significantly younger patients with lymphoma, significantly fewer oocytes could be retrieved in comparison to those with breast cancer.
Ovarian reserve is reduced in female patients affected by lymphoma even before the start of chemotherapy. Proper counseling and implementation of fertility-preserving methods is highly recommended.
Fertility and sterility 05/2012; 98(1):141-4. · 3.97 Impact Factor
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ABSTRACT: Objectives: Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a progestogen dependent risk of breast cancer. Methods: MCF-7 cells were transfected with PGRMC1 expression plasmid, and were stimulated with estradiol (E2, 10(-12) and 10(-10) M). NOM, progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) (each 10(-7) M) were added sequentially or continuously. Results: E2 at 10(-10) M elicited a significant increase of cell proliferation from 150 to 200%. No effect was seen at 10(-12) M. Addition of the progestogens to E2 at 10(-10) M had no significant effect. However, at an E2 10(-12) M, NET significantly stimulated cell proliferation more pronounced in the continuous combined model. No effect was seen for NOM, P and MPA. The E2/NET combined effect could be abrogated by the addition of an estrogen receptor (ER) antagonist. Conclusion: Since NOM did not increase proliferation it may be concluded that it will be neutral in terms of breast cancer risk when combined with E2 at least in women overexpressing PGRMC1.
Gynecological Endocrinology 04/2012; 28(11):863-6. · 1.58 Impact Factor
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02/2012; , ISBN: 978-953-307-812-0
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ABSTRACT: The detection of disseminated tumor cells in bone marrow is a common phenomenon seen in 30-40% of primary breast cancer patients. The presence of disseminated tumor cells at diagnosis as well as the persistence of disseminated tumor cells is strongly associated with poor clinical outcome. Since bone marrow biopsies are not well tolerated by many patients, the evaluation of circulating tumor cells in the blood might become a desired alternative. Circulating tumor cells are routinely detected, depending on stage of the disease and methodology, in 10-80% of breast cancer patients. Recent studies have shown a prognostic potential of circulating tumor cells in both primary and metastatic settings. The evaluation of circulating tumor cells may become one of the crucial markers for prediction of survival and therapy monitoring, and its characterization might enable specific targeting of minimal residual, and metastatic disease.
Biomarkers in Medicine 02/2012; 6(1):109-18. · 0.86 Impact Factor
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Gunter von Minckwitz,
Holger Eidtmann,
Mahdi Rezai,
Peter A Fasching,
Hans Tesch,
Holm Eggemann,
Iris Schrader,
Kornelia Kittel,
Claus Hanusch,
Rolf Kreienberg, [......],
Georg Kunz,
Jens-Uwe Blohmer,
Jens Huober,
Maik Hauschild, Tanja Fehm,
Berit Maria Müller,
Carsten Denkert,
Sibylle Loibl,
Valentina Nekljudova,
Michael Untch
[show abstract]
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ABSTRACT: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer.
We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk.
Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P=0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P=0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P=1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications.
The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.).
New England Journal of Medicine 01/2012; 366(4):299-309. · 53.30 Impact Factor
