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| 3. |
- Colleoni, M, et al.
(author)
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Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.
- 2005
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In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 16:5, s. 716-25
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Journal article (peer-reviewed)abstract
- BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.
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| 4. |
- Karlsson, Per, 1963, et al.
(author)
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Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 23:11, s. 2852-2858
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Journal article (peer-reviewed)abstract
- Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Ten-year cumulative incidence for chest wall recurrence of > 15% was seen in patients aged < 40 years (16.1%), with >= 4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures > 10%: >= 4 positive nodes (10.2%); for axillary failures of > 5%: aged < 40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of > 15% were age < 40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. PMRT to the chest wall and supraclavicular fossa is supported in patients with >= 4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged < 40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
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| 5. |
- Rabaglio, M, et al.
(author)
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Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.
- 2009
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In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 1569-8041. ; 20:9, s. 1489-98
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Journal article (peer-reviewed)abstract
- BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.
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| 6. |
- Wallgren, Arne, 1940, et al.
(author)
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Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.
- 2003
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 21:7, s. 1205-13
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Journal article (peer-reviewed)abstract
- PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.
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| 7. |
- Erdelyi, Mate, 1975, et al.
(author)
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The Binding Mode of Side Chain- and C3-Modified Epothilones to Tubulin
- 2010
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In: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 5:6, s. 911-920
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Journal article (peer-reviewed)abstract
- The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3-modified analogues investigated. In particular, 3-deoxy- (compound 2) and 3-deoxy-2,3-didehydro-Epo A (3) were found to adopt similar conformations in the tubulin-binding cleft as Epo A, thus indicating that the 3-OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin-epothilone complex is able to fully recapitulate the differences in tubulin-polymerizing activity and microtubule-binding affinity between C20-modified epothilones 6 (C20-propyl), 7 (C20-butyl), and 8 (C20-hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline-based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of -His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule-binding data for 4, 5, and Epo B.
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| 8. |
- Fjerdingstad, E J, et al.
(author)
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The relationship between multiple mating by queens, within-colony genetic variability and fitness in the ant Lasius niger
- 2003
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In: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 16:5, s. 844-853
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Journal article (peer-reviewed)abstract
- Multiple mating has been suggested to benefit social insect queens because high genetic variation within colonies might decrease the load imposed by sterile diploid males, enhance resistance to parasites and pathogens, and lead to a more effective division of labour and/or a wider range of tolerable environmental conditions. We tested these hypotheses in the ant Lasius niger with three population samples from Switzerland and Sweden. We found no diploid males in young or mature colonies suggesting a lack of diploid male load. Colonies with multiply-mated queens were not larger nor did they produce more sexuals than colonies with singly-mated queens. We did find a significantly lower frequency of multiple mating among newly mated queens than among the queens heading mature colonies in one population sample (Switzerland 1997). However, this result was not repeated in the other study population, or in the following year in the Swiss population.
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| 9. |
- Gadau, J, et al.
(author)
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Oligogyny by unrelated queens in the carpenter ant, Camponotus ligniperdus
- 1998
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In: BEHAVIORAL ECOLOGY AND SOCIOBIOLOGY. - : SPRINGER VERLAG. - 0340-5443. ; 44:1, s. 23-33
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Journal article (other academic/artistic)abstract
- Multilocus DNA fingerprinting and microsatellite analysis were used to determine the number of queens and their mating frequencies in colonies of the carpenter ant, Camponotus ligniperdus (Hymenoptera: Formicidae). Only 1 of 61 analyzed queens was found t
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| 10. |
- Gruber, G, et al.
(author)
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Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer.
- 2008
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In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 1569-8041. ; 19:8, s. 1393-401
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Journal article (peer-reviewed)abstract
- BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.
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| 11. |
- Aebi, S, et al.
(author)
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Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: Long-term follow up on IBCSG Trial IX
- 2011
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In: ANNALS OF ONCOLOGY. - 0923-7534. ; 22:9, s. 1981-1987
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Journal article (peer-reviewed)abstract
- Abstract: Background: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)positive lymph node-negative breast cancer is being reassessed. Patients and methods: After stratification by ER status, 1669 postmenopausal patients with operable lymph nodenegative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF/tamoxifen) or to tamoxifen alone for 5 years. Results: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF/tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. Conclusion: CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.
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| 12. |
- Gertsch, Pia J.
(author)
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Adaptive significance of queen mating frequency in ants : In search of benefits of genetic variability
- 2000
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Doctoral thesis (other academic/artistic)abstract
- Fitness effects of polyandry, multiple mating by females, were studied on two ant speciesLasius niger and Formica truncorum. Particular emphasis was put on evaluating diploid male load, which happens when homozygosity in the sex determination locus leads to intendedfemales developing into sterile, diploid males. It has been hypothesised that under certainconditions diploid male load selects for polyandry.The power of spermatheca-PCR (genotyping stored sperm in the spermatheca of a femaleinsect) in identifying multiply mated females was scrutinised. Microsatellite amplificationsfrom artificial sperm mixes with known composition showed that alleles at and above 10%representation are reliably amplified and detected.Microsatellite markers were developed for L. niger and female survival and fecundityin relation to her mate number were studied in two populations: Uppsala, Sweden and Lausanne, Switzerland. Annual sexual production did not correlate with higher female mating frequency in either population. Colony survival appeared to be higher for multiple mated females in Lausanne but not in Uppsala. The possible higher survival of multiple mated queens is unlikely to be due to diploid male load as there was no sign of diploid males among broods of 479 queens which were kept in laboratory.Diploid male load in the colonies of the ant Formica truncorum was measured. Thecolony size was significantly negatively affected by diploid male production. However, theobserved frequencies of diploid males in the colonies did not comply with the theoreticalpredictions. Until the determinants of diploid male production in F.truncorum are clarified itis not possible to settle whether diploid male load selects for multiple mating in this species.A theoretical model was constructed to examine how the selection on mating frequencyfrom diploid male load changes when allelic diversity in the sex determination locus increases.Fitness of single and double mated females was compared. The fitness difference between themate number classes rapidly decreases when the number of alleles in the sex determinationlocus increases. Moreover, even when the selection pressure from diploid male production ismost extreme, the fitness differences between single and double mated females are small.Diploid male load probably is not strong enough a force to drive mating frequency evolutionin eusocial insects.
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| 13. |
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| 14. |
- Villesen, P, et al.
(author)
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Evolutionary transition from single to multiple mating in fungus-growing ants
- 1999
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In: MOLECULAR ECOLOGY. - : BLACKWELL SCIENCE LTD. - 0962-1083. ; 8:11, s. 1819-1825
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Journal article (peer-reviewed)abstract
- Queens of leaf cutter ants exhibit the highest known levels of multiple mating (up to 10 mates per queen) among ants. Multiple mating may have been selected to increase genetic diversity among nestmate workers, which is hypothesized to be critical in soci
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