| 1. |
- Tufvesson Stiller, Helena, et al.
(author)
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Patient reported experiences of Swedish patients being investigated for cancer during the Covid-19 pandemic
- 2023
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In: Supportive Care in Cancer. - : Springer Nature. - 0941-4355 .- 1433-7339. ; 31:7
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Journal article (peer-reviewed)abstract
- Background: Patient reported experiences in individuals being investigated for cancer have been recorded in a nationwide survey in Sweden, providing an opportunity to assess the impact of the Covid-19-pandemic.Material and Methods: Questionnaires from 45920 patients were analyzed to assess the experience of being investigated for cancer. Data from before the Covid-19-pandemic (2018–2019) was compared to data acquired during the pandemic (2020–2021), using chi-square and Wilcoxon rank sum tests. Both, patients who were cleared from suspicion of cancer and those who were diagnosed with cancer were included.Results: Fewer patients in total visited health services during the pandemic. However, patients that did seek help did so to a similar extent during as prior to the pandemic. Patient waiting time was perceived to be shorter during the pandemic and judged as neither too long nor too short by most patients. The emotional support to patients improved during the pandemic, whereas the support to next of kin declined. A majority of patients received the results from the investigation in a meeting with the physician. Although there was a preference for receiving results in a meeting with the physician, the pandemic has brought an increasing interest in receiving results by phone.Conclusion: Swedish cancer healthcare has shown resilience during the Covid-19-pandemic, maintaining high patient satisfaction while working under conditions of extraordinary pressure. Patients became more open to alternatives to physical “in person” health care visits which could lead to more digital visits in the future. However, support to significant others demands special attention.
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| 2. |
- Chamalidou, Chaido, 1972, et al.
(author)
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Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up
- 2021
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In: Breast. - : Churchill Livingstone. - 0960-9776 .- 1532-3080. ; 59, s. 294-300
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Journal article (peer-reviewed)abstract
- Background: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. Purpose: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. Material and methods: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. Results: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. Conclusions: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 3. |
- El Ouali, Mourad, et al.
(author)
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A randomised approximation algorithm for the hitting set problem
- 2014
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In: Theoretical Computer Science. - : Elsevier. - 0304-3975 .- 1879-2294. ; 555, s. 23-34
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Journal article (peer-reviewed)abstract
- Let H = (V, epsilon) be a hypergraph with vertex set V and edge set epsilon, where n := vertical bar V vertical bar and m := vertical bar epsilon vertical bar. Let l be the maximum size of an edge and Delta be the maximum vertex degree. A hitting set (or vertex cover) in H is a subset of V in which all edges are incident. The hitting set problem is to find a hitting set of minimum cardinality. It is known that an approximation ratio of l can be achieved easily. On the other hand, for constant l, an approximation ratio better than l cannot be achieved in polynomial time under the unique games conjecture (Khot and Regev, 2008 [17]). Thus breaking the l-barrier for significant classes of hypergraphs is a complexity-theoretically and algorithmically interesting problem, which has been studied by several authors (Krivelevich, 1997 [18], Halperin, 2000 [12], Okun, 2005 [23]). We propose a randomised algorithm of hybrid type for the hitting set problem, which combines LP-based randomised rounding, graphs sparsening and greedy repairing and analyse it for different classes of hypergraphs. For hypergraphs with Delta = O(n1/4) and l = O (root n) we achieve an approximation ratio of l(1 - c/Delta), for some constant c greater than 0, with constant probability. For the case of hypergraphs where l and Delta are constants, we prove a ratio of l(1 - l-1/8 Delta). The latter is done by analysing the expected size of the hitting set and using concentration inequalities. Moreover, for quasi-regularisable hypergraphs, we achieve an approximation ratio of l(1 - n/8m). We show how and when our results improve over the results of Krivelevich, Halperin and Okun.
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| 4. |
- El Ouali, Mourad, et al.
(author)
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An approximation algorithm for the partial vertex cover problem in hypergraphs
- 2016
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In: Journal of combinatorial optimization. - : SPRINGER. - 1382-6905 .- 1573-2886. ; 31:2, s. 846-864
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Journal article (peer-reviewed)abstract
- Let be a hypergraph with set of vertices and set of (hyper-)edges . Let be the maximum size of an edge, be the maximum vertex degree and be the maximum edge degree. The -partial vertex cover problem in hypergraphs is the problem of finding a minimum cardinality subset of vertices in which at least hyperedges are incident. For the case of and constant it known that an approximation ratio better than cannot be achieved in polynomial time under the unique games conjecture (UGC) (Khot and Ragev J Comput Syst Sci, 74(3):335-349, 2008), but an -approximation ratio can be proved for arbitrary (Gandhi et al. J Algorithms, 53(1):55-84, 2004). The open problem in this context has been to give an -ratio approximation with , as small as possible, for interesting classes of hypergraphs. In this paper we present a randomized polynomial-time approximation algorithm which not only achieves this goal, but whose analysis exhibits approximation phenomena for hypergraphs with not visible in graphs: if and are constant, and , we prove for -uniform hypergraphs a ratio of , which tends to the optimal ratio 1 as tends to . For the larger class of hypergraphs where , is not constant, but is a constant, we show a ratio of . Finally for hypergraphs with non-constant , but constant , we get a ratio of for , leaving open the problem of finding such an approximation for k < m/4(.)
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| 5. |
- Fohlin, Helena, et al.
(author)
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Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer
- 2013
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49:6, s. 1196-1204
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Journal article (peer-reviewed)abstract
- IntroductionAkt is a signalling modulator for many cellular processes, including metabolism, cell proliferation, cell survival and cell growth. Three isoforms of Akt have been identified, but only a few studies have concerned the isoform-specific roles in the prognosis of breast cancer patients. The aim of this study was to investigate the prognostic value of v-akt murine thymoma viral oncogene homologue 1 (Akt1) and v-akt murine thymoma viral oncogene homologue 2 (Akt2) in oestrogen receptor positive (ER+) and oestrogen receptor negative (ER–) breast cancer with long-term follow-up.Material and methodsThe expression of Akt in tumour tissue was analysed with immunohistochemistry in a cohort of 272 postmenopausal patients with stage II breast cancer. The median follow-up time was 19 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox’s proportional hazards model.ResultsThe risk of distant recurrence was reduced for patients with ER+ tumours expressing Akt2 compared to patients with no Akt2 expression (HR = 0.49, 95% CI 0.29–0.82, p = 0.007). When adjusting for important clinical tumour characteristics and treatment, Akt2 was still an independent prognostic factor (HR = 0.38, 95% CI 0.21–0.68, p = 0.001) and the association remained long-term. The prognostic value of Akt2 increased with higher oestrogen receptor levels from no effect among patients with ER– tumours to 68% risk reduction for the group with high ER-levels (P for trend = 0.042). Akt1 showed no significant prognostic information.ConclusionOur results indicate that Akt2 expression is associated with a lower distant recurrence rate for patients with ER+ tumours and that this association remains long-term. The prognostic value of Akt2 increases with higher oestrogen receptor expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer.
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| 6. |
- Fohlin, Helena, 1979-
(author)
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Long-term prognostic and predictive factors in hormone receptor positive breast cancer
- 2018
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Doctoral thesis (other academic/artistic)abstract
- The breast cancer survival in Sweden is good (almost 90 % 5-year relative survival) and has increased over time. For women with hormone receptor negative tumors, most relapses occur within the first 5 years after diagnosis. Thereafter the recurrence risk decreases rapidly. For women with estrogen receptor positive (ER+) tumors the annual risk for late recurrences is 1 – 2 %, even after 5 years of endocrine therapy. This risk accumulates so that approximately 25 % of the patients that are recurrence-free after five years from diagnosis may experience a relapse within further 15 years of follow-up. The relatively high long-term risk calls for identification of prognostic and predictive markers with long-term effect. Though, the number of such markers with proven significance is limited. Of the clinical characteristics, only nodal status and to some extent tumor size and tumor grade have been shown to have long-term prognostic value. In this thesis, we propose long-term prognostic and predictive markers for breast cancer.In paper I, we suggest the protein v-akt murine thymoma viral oncogene homologue 2 (AKT2) as a long-term prognostic marker among patients with ER+ tumors. In our study, besides nodal status, AKT2 was the only factor with long-term prognostic value. This is in accordance with some other studies, though we also showed that the significance of AKT2 was limited to ER+ tumors and that the impact increased with higher ER expression.Approximately 75 – 85 % of the ER+ tumors are also progesterone receptor positive (PR+). ER+/progesterone receptor negative (PR-) tumors are considered to be more aggressive and patients with such tumors are often treated with chemotherapy. In this group, more specific subgroups for targeted therapy are needed.Whereas ER has long been established as a predictive factor regarding tamoxifen benefit, the role of PR has not been clarified to date. In paper II, we showed that PR status adds predictive value to ER considering the long-term benefit from tamoxifen.In paper III, we aimed to identify new prognostic markers among patients with ER+ tumors. Systemically untreated patients with ER+/PR- tumors and high expression of the Ras-related protein RAB6C (RAB6C) had reduced distant recurrence rate. Therefore, we suggest RAB6C as a candidate marker for subgroup division among patients with ER+/PR- tumors.According to the results from paper II, there might be subgroups of patients with ER+/PRtumors that do benefit from tamoxifen. The aim of paper IV was to identify such subgroups. Here, we suggest that patients with ER+/PR- tumors and low RAB6C expression do benefit from tamoxifen.The results from this thesis may encourage further studies for more specific subgroup divisions. Such studies may lead to changes in the management program, where some patients with ER+ tumors should receive prolonged or more intense treatment and others reduced treatment based on the pathological markers AKT2, PR and RAB6C.
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| 7. |
- Fohlin, Helena, 1979-, et al.
(author)
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Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor-positive/progesterone receptor-negative breast cancer
- 2020
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In: Molecular and clinical oncology. - : SPANDIDOS PUBL LTD. - 2049-9450 .- 2049-9469. ; 12:5, s. 415-420
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Journal article (peer-reviewed)abstract
- Over the last few decades, improved and more individualized treatment has contributed to the increased survival rate of patients with breast cancer. However, certain patients may receive excessive treatment resulting in undesired side effects. In a previous study, it was demonstrated that systemically untreated patients with estrogen receptor (ER)-positive/progesterone receptor (PR)-negative tumors with high Ras-related protein Rab-6C (RAB6C) expression levels (RAB6C(+)) had prolonged distant recurrence-free survival compared with that of patients exhibiting low RAB6C (RAB6C(-))-expressing tumors. The aim of the present study was to investigate whether RAB6C predicts the effectiveness of tamoxifen treatment. The present study used a dataset comprising 486 female patients with ER+ tumors from a randomized study conducted by the Stockholm Breast Cancer Study Group between November 1976 and August 1990. The patients were considered as low-risk if their tumor size was <= 30 mm and their lymph node status was negative. Patients were followed up until distant recurrence, mortality or when 25 years after randomization was achieved, whichever occurred first. For patients with ER+/PR-/RAB6C(+) tumors, prolonged distant recurrence-free survival could not be observed if the patients were treated with tamoxifen [hazard ratio (HR), 1.82; 95% confidence interval (CI), 0.69-4.79; P=0.23], whereas patients with ER+/PR-/RAB6C(-) tumors had 75% reduced distant recurrence risk (HR, 0.25; 95% CI, 0.09-0.70; P=0.008). In the ER+/PR+ subgroup, patients with RAB6C(-) and RAB6C(+) tumors benefited from tamoxifen treatment, though it was most evident in the RAB6C(+) group (HR, 0.27; 95% CI, 0.13-0.58; P=0.001). The results of the present study indicated that, for patients with ER+/PR- tumors, those with low RAB6C expression benefited from tamoxifen treatment, whereas no benefit was observed in patients with high RAB6C levels.
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| 8. |
- Fohlin, Helena, 1979-, et al.
(author)
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RAB6C is an independent prognostic factor of estrogen receptor-positive/progesterone receptor-negative breast cancer
- 2020
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In: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 19:1, s. 52-60
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Journal article (peer-reviewed)abstract
- The majority of breast cancer tumors are estrogen receptor-positive (ER+) and can be treated with endocrine therapy. However, certain patients may exhibit a good prognosis without systemic treatment. The aim of the present study was to identify novel prognostic factors for patients with ER breast cancer tumors using gene copy data, and to investigate if these factors have prognostic value in subgroups categorized by progesterone receptor status (PR). Public data, including the whole genome gene copy data of 199 systemically untreated patients with ER+ tumors, were utilized in the present study. To assess prognostic value, patients were divided into two groups using the median gene copy number as a cut-off for the SNPs that were the most variable. One SNP was identified, which indicated that the Ras-related protein Rab-6C (RAB6C) gene may exhibit prognostic significance. Therefore, RAB6C protein expression was subsequently investigated in a second independent cohort, consisting of 469 systematically untreated patients (of which 310 were ER+) who received long term follow-up. In the public data set, a distant recurrence risk reduction of 55% was determined for copy numbers above the median value of RAB6C compared with numbers below [multivariable adjusted hazard ratio (HR), 0.45; 95% CI 0.28-0.72; P=0.001)]. It was also more pronounced in the ER+/PR- subgroup (HR, 0.15; 95% CI, 0.05-0.46; P=0.001). In the second cohort, patients of the ER+/PR- subgroup who exhibited high RAB6C expression had a reduced distant recurrence risk (HR, 0.17; 95% CI, 0.05-0.60; P=0.006). However, this was not identified among ER+/PR- tumors (HR, 1.31; 95% CI, 0.69-2.48; P=0.41). The results of the present study indicated that RAB6C serves as an independent prognostic factor of distant recurrence risk in systemically untreated patients with an ER+/PR- tumor.
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| 9. |
- Hackshaw, Allan, et al.
(author)
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Long-term Effectiveness of Adjuvant Goserelin in Premenopausal Women With Early Breast Cancer
- 2009
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In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 101:5, s. 341-349
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Journal article (peer-reviewed)abstract
- Systematic reviews have found that luteinizing hormone-releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer.We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In Premenopausal Patients (ZIPP), which evaluated the LHRH agonist goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone, both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival (breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, and risk of dying from breast cancer, in the presence or absence of tamoxifen.Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin. However, among women who did take tamoxifen, there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with goserelin compared with those not treated with goserelin. The risk of dying from breast cancer was also reduced at 15 years: For every 100 women given goserelin, the number of breast cancer deaths was lower by 2.6 (95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen, respectively, although in the former group the difference was not statistically significant.Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit on these outcomes when goserelin was added.
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| 10. |
- Johansson, Henrik J, et al.
(author)
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Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer
- 2015
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In: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 12:1, s. 8-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.RESULTS: Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca(2+)) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.CONCLUSIONS: This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.
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