| 1. |
- Humphries, Matthew P., et al.
(författare)
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A case-matched gender comparison transcriptomic screen identifies eIF4E and eIF5 as potential prognostic markers in male breast cancer
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 23:10, s. 2575-2583
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.
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| 2. |
- Lundgren, Claudia, et al.
(författare)
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Cyclin E1 is a strong prognostic marker for death from lymph node negative breast cancer : A population-based case-control study
- 2015
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 54:4, s. 538-544
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Tidskriftsartikel (refereegranskat)abstract
- Background. A large proportion of women with lymph node negative breast cancer treated with systemic adjuvant treatment do not benefit from such therapy since the patient is already cured by local treatment. Several studies have suggested that proliferation markers are strong prognostic factors in early breast cancer. Cyclins are probably the most specific markers of cell proliferation. Previously high expression of cyclin E has been associated with breast cancer recurrence.Materials and methods. In this study we investigate the prognostic value of cyclin E1 in node negative breast cancer patients. In a population-based cohort 186 women who died from breast cancer were defined as cases and 186 women alive at the corresponding time as controls. Inclusion criteria were tumour size ≤ 50 mm, no lymph node metastases and no adjuvant chemotherapy. The study was designed to detect an odds ratio of 2.5 with a power of 90% and significance level of 0.05. Cyclin E1 was determined with immunohistochemistry (IHC) on tissue microarray (TMA).Results. High expression of cyclin E1 was significantly associated with breast cancer death, in both uni- and multivariate analyses with odds ratios (OR) 2.3 [univariate, 95% confidence interval (CI) 1.5-3.6] and 2.1 (multivariate, 95% CI 1.2-3.5).Discussion. Cyclin E1 is a strong prognostic factor for breast cancer death in a population-based and node negative patient cohort and can identify high-risk patients in this group.
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| 3. |
- Ahlin, Cecilia, et al.
(författare)
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High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 164:3, s. 667-678
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Tidskriftsartikel (refereegranskat)abstract
- Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case-control study. Immunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression. Expression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5-6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (rho 0.19, p = 0.006) and B (rho 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4-4.4). We confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.
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| 4. |
- Börjesson, Susanne, 1956-, et al.
(författare)
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Colored body images reveal the perceived intensity anddistribution of pain in women with breast cancer treated with adjuvant taxanes: : a prospective multi-method study of pain experience
- 2018
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Ingår i: Scandinavian Journal of Pain. - Berlin/Boston : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; , s. 581-591
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Forskningsöversikt (refereegranskat)abstract
- Background and aims:Breast cancer is the most prevalent adult cancer worldwide. A broader use of screening for early detection and adjuvant systemic therapy with chemotherapy has resulted in improved survival rates. Taxane-containing chemotherapy is one of the cornerstones of the treatment. However, taxane-containing chemotherapy may result in acute chemotherapy-induced nociceptive and neuropathic pain. Since this pain may be an additional burden for the patient both during and after taxane chemotherapy, it is important to rapidly discover and treat it. There is yet no gold standard for assessing taxane-induced pain. In the clinic, applying multiple methods for collecting information on pain may better describe the patients’ pain experiences. The aim was to document the pain during and after taxane through the contribution of different methods for collecting information on taxane-induced pain. Fifty-three women scheduled for adjuvant sequential chemotherapy at doses of ≥75 mg/m2 of docetaxel and epirubicin were enrolled in the study.Methods:Prospective pain assessments were done on a visual analog scale (VAS) before and during each cycle of treatment for about 5 months, and using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire’s (EORTC-QLQ-C30) two pain questions at baseline, 3 months, and 12 months. Participants scoring pain on the VAS >30 and undergoing an interview also colored their pain on a body image during treatment and at 12 months.Results:Surprisingly widespread, intense pain was detected using a multi-method approach. The colored body image showed pain being perceived on 51% of the body surface area during treatment, and on 18% 12 months after inclusion. In general, the pain started and peaked in intensity after the first cycle of taxane. After Cycle 3, most women reported an increase in pain on the VAS. Some women continued to report some pain even during the epirubicin cycles. The VAS scores dropped after the last chemotherapy cycle, but not to the baseline level. At baseline, 3 months and 12 months after inclusion, the women who estimated VAS >30 reported higher levels of pain on the pain questions of the EORTC-QLQ-C30.Conclusions:This study contributes information on how different pain assessment tools offer different information in the assessment of pain. The colored body image brings another dimension to pain diagnostics, providing additional information on the involved body areas and the pain intensities as experienced by the women. A multi-method approach to assessing pain offers many advantages. The timing of the assessment is important to properly assess pain.Implications:Pain relief needs to be included in the chemotherapy treatment, with individual assessment and treatment of pain, in the same way as is done in chemotherapy-triggered nausea. There is a time window whereby the risk of pain development is at its highest within 24–48 h after receiving taxane chemotherapy. Proper attention to pain evaluation and treatment should be in focus during this time window.
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| 5. |
- Grönberg, Malin, 1980-, et al.
(författare)
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Ghrelin expression is associated with a favorable outcome in male breast cancer
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin and obestatin are two gastrointestinal peptides, derived from a common precursor. Expression of both peptides have been found in breast cancer tissue and ghrelin has been associated with breast cancer development. Ghrelin expression is associated with longer survival in women diagnosed with invasive and node negative breast cancer. The clinical implications of the peptide expression in male breast cancer are unclear. The aim of this study was to investigate the role and potential clinical value of ghrelin and obestatin in male breast cancer. A tissue microarray of invasive male breast cancer specimens from 197 patients was immunostained with antibodies versus the two peptides. The expression of the peptides was correlated to previously known prognostic factors in breast cancer and to the outcome. No strong correlations were found between ghrelin or obestatin expression and other known prognostic factors. Only ghrelin expression was statistically significantly correlated to breast cancer-specific survival (HR 0.39, 95% CI 0.18-0.83) in univariate analyses and in multivariate models, adjusted for tumor size and node status (HR 0.38, 95% CI 0.17-0.87). HR for obestatin was 0.38 (95% CI 0.11-1.24). Ghrelin is a potential prognostic factor for breast cancer death in male breast cancer. Patients with tumors expressing ghrelin have a 2.5-fold lower risk for breast cancer death than those lacking ghrelin expression. Drugs targeting ghrelin are currently being investigated in clinical studies treating metabolic or nutritional disorders. Ghrelin should be further evaluated in forthcoming studies as a prognostic marker with the aim to be included in decision algorithms.
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| 6. |
- Grönberg, Malin, 1980-, et al.
(författare)
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Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size <= 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.
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| 7. |
- Hellerstedt Börjesson, Susanne, 1956-
(författare)
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Taxane-induced pain : Experiences of women with breast cancer and nurses providing their care
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer patients receiving taxane chemotherapy run a substantial risk of develop taxane-induced pain, but little is known about women’s experiences of such pain. The aim of this thesis was to explore women’s acute and longstanding experiences of taxane-induced pain, to evaluate the pain intensity and distribution using different assessment methods, and to study nurses´ perceptions of taxane-induced pain in people with breast cancer.The women experienced pain during chemotherapy with 37– 48% incidence of acute taxane-induced pain. The subjective burden of taxane-induced pain described by the women covered narratives from manageable pain to very difficult and disabling pain with a major impact on their lifeworld (Study I).Longstanding pain in the lifeworld of women with previous breast cancer, was explored through a retrospective reflection after 12 months. The descriptions of pain revealed a time perspective; as pain perceived at that specific time, currently ongoing pain, and pain expectations for the future. This resulted in the women sensing themselves of being somewhere between health and illness gazing into an uncertain future (Study II).A quantitative longitudinal assessment of taxane-induced pain using; the body image, the VAS, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) showed the women’s estimated pain; its intensity, distribution and occurrence - as it appeared during the actual taxane treatment and up to a year afterward. The baseline measurement on the VAS revealed low initial pain, VAS <10, which changed at treatment Cycle 1. The body image revealed intense and widespread pain, and pain after 12 months, as did the EORTC QLQ -C30 (Study III).The nurses’ estimations of taxane-induced pain varied to large extent in both prevalence and intensity. Large parts of the body were expected to be involved in the pain. Nurses lacked local and/or national guidelines reflecting a low level of generalized use of prophylaxis against taxane pain (Study IV).In conclusion, taxane-induced pain is a common debilitating symptom during taxane chemotherapy for women with breast cancer. Pain impacts women´s life during as well as long time after the completion of taxane treatment. Taxane pain can be accurately or successfully estimated using various pain assessment tools. Furthermore, guidelines for dealing with taxane-induced pain are needed.
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| 8. |
- Hellerstedt-Börjesson, Susanne, et al.
(författare)
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Women Treated for Breast Cancer Experiences of Chemotherapy-Induced Pain Memories, Any Present Pain, and Future Reflections
- 2016
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Ingår i: Cancer Nursing. - 0162-220X .- 1538-9804. ; 39:6, s. 464-472
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer survivors make up a growing population facing treatment that poses long-standing adverse effects including chemotherapy-related body function changes and/or pain. There is limited knowledge of patients' lived experiences of chemotherapy-induced pain (CHIP). Objective: The aim of this study was to explore CHIP and any long-standing pain experiences in the lifeworld of breast cancer survivors. Methods: Fifteen women participated in a follow-up interview a year after having experienced CHIP. They were interviewed from a lifeworld perspective; the interviews were analyzed through guided phenomenology reflection. Results: A past perspective: CHIP is often described in metaphors, leads to changes in a patient's lifeworld, and impacts lived time. The women become entirely dependent on others but at the same time feel isolated and alone. Existential pain was experienced as increased vulnerability. Present perspective: Pain engages same parts of the body, but at a lower intensity than during CHIP. The pain creates time awareness. Expected normality in relationships/daily life has not yet been achieved, and a painful existence emerges in-between health and illness. Future perspective: There are expectations of pain continuing, and there is insecurity regarding whom to turn to in such cases. A painful awareness emerges about one's own and others' fragile existence. Conclusions: Experiencing CHIP can impact the lifeworld of women with a history of breast cancer. After CHIP, there are continued experiences of pain that trigger insecurity about whether one is healthy. Implications for Practice: Cancer survivors would likely benefit from communication and information about and evaluation of CHIP.
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| 9. |
- Hellerstedt-Börjesson, Susanne, et al.
(författare)
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Women With Breast Cancer : Experience of Chemotherapy-Induced Pain: Triangulation of Methods
- 2015
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Ingår i: Cancer Nursing. - 0162-220X .- 1538-9804. ; 38:1, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDChemotherapy treatment for cancer diseases can cause body pain during adjuvant therapy.OBJECTIVEThe aim was to describe the perceived impact of adjuvant chemotherapy-induced pain (CHIP) on the daily lives of women with newly diagnosed breast cancer, using triangulation.METHODFifty-seven women scheduled for chemotherapy in doses of 75 mg/m2 or greater of epirubicin and/or docetaxel participated. Twenty-two of these women registered pain with values of 4 or more on the visual analog scale on day 10 following chemotherapy. Of these 22, 16 participated in an interview and colored a printed body image. A qualitative thematic stepwise analysis of the interviews was performed.RESULTSChemotherapy-induced pain had a profound impact on daily life. Ten women reported the worst possible pain, with visual analog scale scores of 8 to 10. Three different categories crystallized: perception (A) of manageable pain, which allowed the women to maintain their daily lives; perception (B) of pain beyond imagination, whereby the impact of pain had become more complex; and perception (C) of crippling pain, challenging the women's confidence in survival.CONCLUSIONSThe findings highlight the inability to capture CHIP with 1 method only; it is thus necessary to use complimentary methods to capture pain. We found that pain had a considerable impact on daily life, with surprisingly high scores of perceived pain, findings that to date have been poorly investigated qualitatively.IMPLICATIONS FOR PRACTICENurses need to (1) better identify, understand and treat CHIP, using instruments and protocols; and (2) provide improved communication about pain and pain management.
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| 10. |
- Johansson, Ida, et al.
(författare)
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Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes
- 2015
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 9:8, s. 1565-1579
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Tidskriftsartikel (refereegranskat)abstract
- Male breast cancer (hoc) is a rare disease that shares both similarities and differences with female breast cancer (FBC). The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC tumors revealed two stable epitypes, designated ME1 and ME2. The methylation patterns differed significantly between the groups and were closely associated with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group were more proliferative and aggressive than ME2 tumors, and showed a tendency toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2 target genes and high expression of EZH2, one of the core components of PRC2. Upon combined analysis of MBC and FBC tumors, ME1 MBCs clustered among luminal B FBC tumors and ME2 MBCs clustered within the predominantly luminal A FBC cluster. The majority of the MBC tumors remained grouped together within the clusters rather than being interspersed among the FBC tumors. Differences in the genomic location of methylated CpGs, as well as in the regulation of central canonical pathways may explain the separation between MBC and FBC tumors in the respective clusters. These findings further suggest that MBC is not readily defined using conventional criteria applied to FBC.
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