| 1. |
- Li, Jingmei, et al.
(author)
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Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers
- 2015
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In: Annals of Oncology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0923-7534. ; 26:3, s. 517-522
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Journal article (peer-reviewed)abstract
- Background: Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. Patients and methods: A 77-SNP polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen-receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. Results: PRS weighted by breast cancer overall estimates was found to be differentially associated with 1,865 screen-detected and 782 interval cancers in the LIBRO-1 study (age-adjusted ORperSD [95% confidence interval]=0.91 [0.83-0.99], p=0.023). The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates (ORperSD=0.90 [0.82-0.98], p=0.011). This result was corroborated by two independent studies (combined ORperSD=0.87 [0.76-1.00], p=0.058) with no evidence of heterogeneity. When enriched for “true” interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced (ORperSD=0.74 [0.62-0.89], p=0.001), with a significant interaction effect between PRS and mammographic density (pinteraction=0.017). Conclusion: To our knowledge, this is the first report looking into the genetic differences between screendetected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.
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| 2. |
- Aaltonen, K. E., et al.
(author)
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Gene expression of breast cancer related genes in circulating tumour cells (CTCs) from patients with metastatic breast cancer
- 2015
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 26:Suppl. 3, s. 15-15
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Journal article (peer-reviewed)abstract
- Introduction: Detection of circulating tumour cells (CTCs) in peripheral blood has an established prognostic significance in patients with metastatic breast cancer. Change in the number of detected CTCs is also an indication of response to therapy. Characterisation of CTCs could provide easily accessible treatment predictive information of present cancer cells within the patient and could reveal important knowledge about the metastatic process. The aim of this pilot study was to characterize CTCs with regard to both treatment predictive and more experimental markers by analysing the expression of genes associated with breast cancer.Methods: Blood samples from twelve patients with metastatic breast cancer included in the ongoing CTC-MBC study at Lund University, Sweden (Clinical Trials Id. NCT01322893) were analysed in this pilot study. Systemic treatment included endocrine, targeted and chemotherapy regimen. Blood samples were collected before start of 1st line therapy and at four time points. If progression occurred, a new round of samples was taken. CTCs were isolated from whole blood using the commercial kits AdnaTest EMT1/stem cell and AdnaTest EMT2/stem cell (AdnaGen AG, Langenhagen, Germany). With this method, CTCs are captured using antibodies directed against EpCAM and MUC-1 (EMT1-kit) or EpCAM, HER2 and EGFR (EMT2-kit). Gene expression analyses from CTCs at each time point was performed by TATAA Biocenter (Gothenburg, Sweden) using qPCR. 38 breast cancer related genes were analysed including the oestrogen receptor (ESR), HER2, VEGFR2, ALDH1, PI3K, PTEN and TWIST1.Results: Using positive expression of pseudo-markers EpCAM, MUC1 and HER2 as definition of CTCs, 6 of 12 patients were positive for CTCs. However, gene expression of additional markers in potential CTCs suggests complex patterns such as an increase in TWIST1, ALDH1 and SATB1 at time of progression.Conclusions: We present gene expression data from CTCs isolated before and during therapy in metastatic breast cancer patients. This type of characterisation could provide information of importance for treatment response and clinical outcome.Clinical trial identification: NCT01322893, March 24 2011
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| 3. |
- Aapro, M, et al.
(author)
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Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel
- 2008
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 19:3, s. 420-432
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Journal article (peer-reviewed)abstract
- Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.
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| 10. |
- 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. |
- Ahlstedt Karlsson, Susanne, et al.
(author)
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Experiences of endocrine therapy after breast cancer surgery
- 2019
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In: Annals of Oncology. Abstract Book of the 44th ESMO Congress (ESMO 2019) 27 September – 1 October 2019, Barcelona, Spain. Vol. 30, Suppl. 5, s. v840. - : Elsevier BV. - 0923-7534.
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Conference paper (peer-reviewed)abstract
- Background For patients diagnosed with hormone-receptor-positive breast cancer, endocrine therapy (ET) is prescribed, which reduces recurrence and mortality rates (Early Breast Cancer Trialists’ Collaborative Group, 2011). Despite the prognostic benefits of ET, the adherence to treatment varies, and 30%–70% of the patients discontinue their treatment within five years (Daly et al., 2017; Tinari et al., 2015; Ursem et al., 2015), often during their first year of treatment (He et al., 2015), due to the fact that ET is associated with adverse side-effects (Regan et al., 2011). Methods The study was conducted in a surgical out-patient care unit at a hospital in Sweden. Inclusion criteria were women diagnosed with breast cancer and treated with ET after surgery. Forty-eight patients were invited to participate, of which 23 declined, thus 25 women were included. Seven focus group interviews, with two to five participants in each group, were conducted using an interview guide according to Krueger’s (2014) strategy. The interview guide contained six open-ended questions aiming to explore the women’s experiences of ET after breast cancer surgery. Inductive qualitative content analysis was used (Graneheim & Lundman, 2004). Results The analysis resulted in three categories that described the women’s experiences: the treatment “creates discomfort”; “promotes levels of management”; and “causes feelings of abandonment”. Women’s experiences of treatment could at first glance be seen as positive, as perceived protection, but after further analysis, a deeper meaning was identified: protection with reservation. When experiencing discomfort, the women were urged to manage the situation, although the mode of management sometimes varied. The women reported that they needed support, but when the support did not appear, they felt as though they had been abandoned. Moreover, knowledge about side-effects became an obstacle. The participants described feeling abandoned, but they also described their disease as “cancer light”. Conclusions Professionals need to explore the pre-knowledge and preconceptions that patients might have. This could be achieved by listening to the patient before providing them with information. The information needs to be customized specifically to each person. Funding Assar Gabrielsson’s Foundation, Herbert and Karin Jacobsson’s Foundation, and the Swedish Society of Nursing. Disclosure All authors have declared no conflicts of interest.
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| 14. |
- Al-Haidari, Amr, et al.
(author)
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Neutrophil extracellular traps promote surgery-induced peritoneal carcinosis of metastatic colorectal cancer via modulation of CXCR2 and αv integrin
- 2017. - Suppl 3
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 28, s. 87-88
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Conference paper (peer-reviewed)abstract
- Introduction: Peritoneal carcinosis (PC) is the third common site of metastatic colorectal cancer which characterized by a very low survival rate. Surgical trauma has been identified as an important factor in the progression of PC, postulated to be caused by the inflammatory response to tissue injury. The mechanism behind tumor metastasis remains poorly understood. However, existing evidence indicates that neutrophils, via Neutrophil Extracellular Traps (NETs), are implicated in the development of metastatic disease and recently identified as one of the most significant key players in promoting tumor progression. In this study, we highlight the mechanism by which NETs promote surgery-induced colon cancer cell peritoneal metastasis through regulation of key receptors, CXCR2 and αvβ3 integrin.Methods: We developed a murine model of surgical stress-induced PC by post-surgery inoculation of CT-26 murine colon cancer cell line. Surface expression of CXCR2 and αvβ3 on CT-26 cells were evaluated by flow cytometry live staining. Gene expression of extracellular matrix (ECM) proteins from wound incision wall was quantified using qRT-PCR. Function of CXCR2 and αvβ3 in tumor cell migration, proliferation, and adhesion were assessed by blocking assays using CXCR2 antagonist SB225002 and anti-CD51 in vitro and in vivo. Role of neutrophils in promoting cancer cell migration and adhesion was demonstrated using in vitro co-cultured migration and adhesion assays. NET formation was measured using modified ELISA technique of Histone-DNA complex. Depletion of NETs were achieved by daily intraperitoneal administration of 2mg/kg DNase I to mice for 10 days and tumor growth was evaluated by counting macroscopic nodules number on the peritoneum.Results: Blocking CXCR2 and Targeting αv integrin reduced tumor nodules number in vivo by 70% and 65% respectively and decreased cancer cell migration, proliferation, and adhesion in vitro. Incision wound tissue displayed pronounced reduction in ECM proteins mRNAs in treated mice with both CXCR2 antagonist and αv antibody. Mice treatment with DNase I significantly reduced tumor nodules number more than 90% compared to tumor control. Anti-CD51 decreased NET-induced CT-26 cell adhesion. Neutrophils stimulation with MIP-2 exhibits dose-dependent increase of NETosis. Co-culture of neutrophils and cancer cells provoked NETs formation and increased capacity of colon cancer cell migration while DNase I treatment abolished neutrophils NETs-induced tumor cell migration in vitroConclusion: Our novel findings implicate NETs in the development of PC due to surgical stress, suggesting that blocking NET formation might be an interesting potential therapeutic approach.
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| 17. |
- Alkner, Sara, et al.
(author)
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AIB1 is a predictive factor for tamoxifen response in premenopausal women
- 2010
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In: ANNALS OF ONCOLOGY. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 21:2, s. 238-244
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Journal article (peer-reviewed)abstract
- Background: Clinical trials implicate the estrogen receptor ( ER) coactivator amplified in breast cancer 1 (AIB1) to be a prognostic and a treatment-predictive factor, although results are not unanimous. We have further investigated this using a controlled randomised trial of tamoxifen versus control. Materials and methods: A total of 564 premenopausal women were entered into a randomised study independent of ER status. Using a tissue microarray, AIB1 and ER were analysed by immunohistochemistry. Results: AIB1 scores were obtained from 349 women. High AIB1 correlated to factors of worse prognosis (human epidermal growth factor receptor 2, Nottingham histological grade 3, and lymph node metastases) and to ER negativity. In the control arm, high AIB1 was a negative prognostic factor for recurrence- free survival (RFS) (P = 0.02). However, ER-positive patients with high AIB1 responded significantly to tamoxifen treatment (P = 0.002), increasing RFS to the same level as for systemically untreated patients with low AIB1. Although ER-positive patients with low AIB1 had a better RFS from the beginning, this was not further improved by tamoxifen (P = 0.8). Conclusions: In the control group, high AIB1 was a negative prognostic factor. However, ER-positive patients with high AIB1 responded significantly to tamoxifen. This implicates high AIB1 to be an independent predictive factor of improved response to tamoxifen and not, as has previously been discussed, a factor predicting tamoxifen resistance.
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| 19. |
- Alkner, Sara, et al.
(author)
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The role of AIB1 and PAX2 in primary breast cancer: validation of AIB1 as a negative prognostic factor.
- 2013
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:5, s. 1244-1252
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Journal article (peer-reviewed)abstract
- BackgroundThe steroid-receptor coactivator amplified in breast cancer one (AIB1) is implicated to be a prognostic factor, although the results are not unanimous. Recently its effect was suggested to be modified by paired box 2 gene product (PAX2).Patients and methodsUsing immunohistochemistry (IHC) AIB1 and PAX2 were investigated in two cohorts of early breast cancer, including systemically untreated premenopausal lymph-node-negative women and pre- and postmenopausal women receiving tamoxifen.ResultsAIB1 scores were available for 490 patients and PAX2 scores were available for 463 patients. High AIB1 was a negative prognostic factor for distant disease-free survival (DDFS, P = 0.02) and overall survival (OS, P < 0.001) in systemically untreated women, while no prognostic effect was seen in the tamoxifen-treated cohort, indicating AIB1 to be a predictor of tamoxifen response. In systemically untreated patients, PAX2 was not a prognostic factor, nor did it modify the effect of AIB1. However, in ER-positive patients receiving tamoxifen, PAX2 appeared to be a positive prognostic factor in premenopausal patients, while a negative factor in postmenopausal. The interaction between the menopausal status and PAX2 was significant (P = 0.01).ConclusionsIn an independent cohort of low-risk premenopausal patients, we validate AIB1 as a negative prognostic factor, indicating AIB1 to be an interesting target for new anti-cancer therapies. The effect of PAX2 warrants further studies.
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| 23. |
- Andersson, G., et al.
(author)
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Stromal progesterone receptor expression and long-term survival in patients with resected periampullary adenocarcinoma
- 2018
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In: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 29:Suppl. 8, s. 262-263
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Conference paper (other academic/artistic)abstract
- Background: Early trials have reported a beneficial effect from tamoxifen treatment in patients with unresectable pancreatic cancer, in particular in women. However, the presence and prognostic significance of female hormone receptors in pancreatic or other periampullary cancers has not yet been described. Methods: Immunohistochemical screening of normal and malignant pancreatic tissue revealed that the predominantly expressed female hormone receptor was the progesterone receptor (PgR), in particular in the cancer-associated stroma. The impact of PgR expression on overall survival (OS) was further examined on tissue microarrays with primary tumours from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinoma. Results: Median follow-up time was 29.7 (range 1.9–185.1) months. Stromal PgR positivity (PgR+), allover denoted in 31% of the cases, was significantly higher in pancreatobiliary-type than in intestinal-type tumours (38.7% vs 19.0%, p = 0.008), with an equal distribution between sexes. Stromal PgR+ was significantly associated with a prolonged OS in KRAS-mutated tumours, whereas the opposite was seen in KRAS wild-type tumours (p for interaction =0.015). This association was particularly evident in women, with a median OS of 60.5 months for PgR+/KRAS mutated tumours and 9.9 months for PgR+/KRAS wild-type tumours (p for interaction <0.001). PgR expression was not prognostic in male patients. Conclusions: The finding of stromal PgR expression, and its link to clinical outcome in a considerable proportion of pancreatic and other periampullary cancers is novel. The concept of tamoxifen treatment for patients with unresectable disease, in particular elderly women, should be pursued, and PgR and KRAS may be relevant biomarkers for improved patient stratification.
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| 24. |
- Andersson, J., et al.
(author)
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Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF
- 2005
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In: Ann Oncol. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 16:5, s. 743-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.
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