| 91. |
- Strell, Carina, et al.
(författare)
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High PDGFRb Expression Predicts Resistance to Radiotherapy in DCIS within the SweDCIS Randomized Trial.
- 2021
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - : American Association For Cancer Research (AACR). - 1557-3265 .- 1078-0432. ; 27:12, s. 3469-3477
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Tidskriftsartikel (refereegranskat)abstract
- This study analyzes the potential of stromal platelet-derived growth factor receptor-beta (PDGFRb) expression as biomarker for radiotherapy (RT) benefit on ipsilateral breast events (IBE) in ductal carcinoma in situ (DCIS). Improved identification of DCIS patients refractory to adjuvant whole-breast RT is needed. Predictive biomarker studies in DCIS have focused on tumor cell features rather than the tumor-associated stroma, despite growing evidence of its influence on therapy efficiency.Samples from the Swedish randomized radiotherapy DCIS trial (SweDCIS) were subjected to IHC analysis for stromal PDGFRb expression. IBE incidence at 10 years after breast-conserving surgery was the primary endpoint. Interactions between marker and treatment were analyzed.PDGFRb score was predictive for RT benefit with regard to IBE (Pinteraction = 0.002 and Pinteraction = 0.008 adjusted multivariably). Patients of the PDGFRblow group had a strong benefit from RT regarding IBE risk [HR, 0.23; 95% confidence interval (CI), 0.12-0.45; P < 0.001] with an absolute risk reduction of 21% (cumulative risk 7% vs. 28%) at 10 years. No significant risk reduction by RT was observed for patients of the PDGFRbhigh group (HR, 0.83; 0.51-1.34; P = 0.444; cumulative risk 22% vs. 25%). The RT response-predictive effect of stromal PDGFRb was equally strong in analyses for in situ and invasive IBE when analyzed separately (in situ IBE: P = 0.029; invasive IBE: P = 0.044).Results suggest high stromal PDGFRb expression as a novel biomarker identifying DCIS patients who are refractory to standard whole-breast adjuvant RT. The data imply previously unrecognized fibroblast-mediated modulation of radiosensitivity of DCIS, which should be further explored from mechanistic and targeting perspectives.
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| 92. |
- Strell, Carina, et al.
(författare)
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Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:9, s. 983-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal-epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases. Methods: Stromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided. Results: PDGFR alpha((low))/PDGFR beta((high)) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype. Conclusions: A PDGFR alpha((low))/PDGFR beta((high)) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma-epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial-stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.
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| 93. |
- Sun, Yibao, et al.
(författare)
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Detection of Breast Tumour Tissue Regions in Histopathological Images using Convolutional Neural Networks
- 2018
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Ingår i: 2018 IEEE International Conference on Image Processing, Applications and Systems (IPAS). - : IEEE. - 9781728102474 ; , s. 98-103
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Konferensbidrag (refereegranskat)abstract
- Ductal carcinoma in situ (DCIS) is considered a pre-invasive breast cancer and sometimes it can develop into an invasive ductal carcinoma. The analysis of histopathological images to detect tumour border of DCIS could provide important information for better diagnosis of patients. We present a deep learning based system to automatically identify DCIS in histopathological images. Specifically, a convolutional neural network (CNN) is first trained to predict labels of small patches cropped out of a histopathological whole slide image. Next, a sliding window method is used to produce a probability map of DCIS. Finally, given the probability map, a tumor border of DCIS is produced and delineated with the method of Marching Cubes to facilitate pathologists' review and assessment. Evaluation of cross validation demonstrates that the CNN model of GoogleNet performs well in histology image patch classification with an overall accuracy of (98.46 +/- 0.40)% and identifies the DCIS tissue patches with a Fl-score of (97.40 +/- 1.18)% (mean +/- variance). Moreover, around 95.6% tumour tissue within the enclosed tumour regions can be identified by our developed method. Finally, the goal of tumor border detection can be well achieved with a few post-processing steps.
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| 94. |
- Svee, Andreas, 1984-
(författare)
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Deep inferior epigastric perforator flap breast reconstruction after mastectomy : An analysis of long-term outcomes and potential complications
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis evaluated the long-term effects and satisfaction with outcomes following deep inferior epigastric perforator (DIEP)-based breast reconstruction after mastectomyPaper I is a retrospective cohort study of women who received a unilateral DIEP in 2000–2009 (n = 225) in Uppsala. These women were compared with individually matched women who underwent mastectomy without autologous reconstruction (n = 450). Recurrence and survival were primary endpoints. Both groups demonstrated a similar risk of recurrence. However, the DIEP group had a significant survival advantage not persisting after adjusting for tumor characteristics.Paper II examined whether breast reconstruction using a DIEP flap is associated with volume changes or arm lymphedema symptoms. It hypothesized that compared with DIEP reconstructions without using the cephalic vein (CV), that using CV is not associated with ipsilateral lymphedema. Patients completed the Lymphedema Quality of Life Inventory questionnaire to assess postoperative lymphedema symptoms. CV was found to be potentially useful as an extra venous outflow in DIEP breast reconstructions without increasing the risk of ipsilateral arm swelling or lymphedema symptoms.Paper III evaluated the aesthetic outcome and satisfaction with the appearance of abdominal-based breast reconstruction in the long-term. Patients responded to the postoperative BREAST-Q model, and their photographs were at a mean of 11 years postoperatively. The outcomes of the BREAST-Q and available normative scales were compared. The photographs were assessed by two panels, comprising eight professionals and lay individuals, respectively. According to patients, professionals, and lay observers, abdominal-based breast reconstructions yielded good term aesthetic outcomes.Paper IV is a retrospective study of long-term changes in the donor site after harvesting the DIEP flap. Patients were invited to complete BREAST-Q questionnaires regarding the abdomen. The follow-up period was >8 years. Most participants reported no abdominal pain and expressed satisfaction with their abdominal appearance. The outcomes were compared between women with DIEP and women who underwent mastectomy for breast cancer without abdominal-based breast reconstruction. DIEP breast reconstruction did not cause donor site morbidity and women with DIEP reconstruction were more likely satisfied with their abdominal appearance.Briefly, DIEP flap breast reconstruction yields long-lasting favorable outcomes for women undergoing mastectomy.
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| 95. |
- Svee, Andreas, et al.
(författare)
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Survival and risk of breast cancer recurrence after breast reconstruction with deep inferior epigastric perforator flap
- 2018
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 105:11, s. 1446-1453
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women who undergo autologous breast reconstruction have been reported to have an increased risk of breast cancer recurrence compared with those who have mastectomy alone. It has been suggested that more extensive surgery possibly activates dormant micrometastases. The aim of this study was to evaluate whether delayed unilateral deep inferior epigastric perforator (DIEP) flap reconstruction after mastectomy increases the risk of breast cancer recurrence or affects mortality among women previously treated for breast cancer. Methods: This was a matched retrospective cohort study including women with a previous unilateral invasive breast cancer who received a delayed DIEP flap breast reconstruction and a control cohort of individually matched women with unilateral breast cancer who underwent mastectomy but no autologous breast reconstruction. Matching criteria comprised: year of diagnosis (+/–3 years), age at diagnosis (+/–5 years), type of cancer and demographic region. The primary endpoints were local recurrence or distant metastasis, and overall mortality was a secondary endpoint. Absolute risk of recurrent disease and mortality was analysed, and relative risks were estimated using Cox proportional hazards analysis. Results: There were 225 women in the DIEP cohort and 450 in the no-DIEP cohort. The median follow-up time was 125 months. There was no difference in absolute risk of recurrence between the cohorts. The hazard ratio for breast cancer recurrence in DIEP versus no-DIEP cohorts was 0·76 (95 per cent c.i. 0·47 to 1·21). Conclusion: There is no increased risk in breast cancer recurrence after delayed DIEP flap reconstruction compared with mastectomy alone.
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| 96. |
- Söderberg, Emma, et al.
(författare)
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Association of clinicopathologic variables and patient preference with the choice of surgical treatment for early-stage breast cancer : A registry-based study
- 2024
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Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 73
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Observational studies suggest that breast conserving surgery (BCS) and radiotherapy (RT) offers superior survival compared to mastectomy. The aim was to compare patient and tumour characteristics in women with invasive breast cancer <= 30 mm treated with either BCS or mastectomy, and to explore the underlying reason for choosing mastectomy.Methods: Women registered with breast cancer <= 30 mm and <= 4 positive axillary lymph nodes in the Swedish National Breast Cancer Register 2013-2016 were included. Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy vs. BCS.Results: Of 1860 breast cancers in 1825 women, 1346 were treated by BCS and 514 by mastectomy. Adjuvant RT was given to 1309 women (97.1 %) after BCS and 146 (27.6 %) after mastectomy. Variables associated with receiving a mastectomy vs. BCS included clinical detection (Odds Ratio (OR) 4.15 (95 % Confidence Interval (CI) 3.35-5.14)) and clinical stage (T2 vs. T1 (OR 3.68 (95 % CI 2.90-4.68)), N1 vs. N0 (OR 2.02 (95 % CI 1.38-2.96)). Women receiving mastectomy more often had oestrogen receptor negative, HER2 positive tumours of higher histological grade. The most common reported reason for mastectomy was large or multifocal tumours (53.5 %), followed by patient preference (34.5 %).Conclusion: Choice of surgery is strongly associated with key prognostic factors among women undergoing BCS with RT compared to mastectomy. Failure to control for all relevant confounders may bias results in outcome studies in favour of BCS.
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| 97. |
- Thekkinkattil, D., et al.
(författare)
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Assessing variability in breast cancer management across the world: results of a questionnaire survey amongst global international experts in breast cancer management
- 2022
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Ingår i: Ecancermedicalscience. - : Ecancer Global Foundation. - 1754-6605. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer is the most common cancer in women worldwide with an estimated 2.3 million breast cancer cases diagnosed annually. The outcome of breast cancer management varies widely across the globe which could be due to a multitude of factors. Hence, a blanket approach in standardisation of care across the world is neither practical nor feasible.Aim: To assess the extent and type of variability in breast cancer management across the globe and to do a gap analysis of patient care pathway.Method: An online questionnaire survey and virtual consensus meeting was carried out amongst 31 experts from 25 countries in the field of breast cancer surgical management. The questionnaire was designed to understand the variability in diagnosis and treatment of breast cancer, and potential factors contributing to this heterogeneity.Result: The questionnaire survey shows a wide variation in breast surgical training, diagnosis and treatment pathways for breast cancer patients. There are several factors such as socioeconomic status, patient culture and preferences, lack of national screening programmes and training, and paucity of resources, which are barriers to the consistent delivery of high-quality care in different parts of the world.Conclusion: On-line survey platforms distributed to global experts in breast cancer care can assess gaps in the diagnosis and treatment of breast cancer patients. This survey confirms the need for an in-depth gap analysis of patient care pathways and treatments to enable the development of personalised plans and policies to standardise high quality care.
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| 98. |
- Unukovych, Dmytro, et al.
(författare)
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Breast reconstruction patterns from a Swedish nation-wide survey
- 2020
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 46:10, s. 1867-1873
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe overall aim of the Swedish Breast Reconstruction Outcome Study was to investigate national long-term outcomes after mastectomy with or without breast reconstruction. The current report evaluates breast reconstruction (BR) patterns in Sweden over time.Materials and methodsThis is a cross-sectional, registry-based study where all women operated with mastectomy 2000, 2005, 2010 were identified (N = 5853). Geographical differences in type of BR were investigated using heatmaps. Distribution of continuous variables were compared using the Mann-Whitney U test, categorical variables were compared using the chi-square test.ResultsMean age at survey was 69 years (SD=±11.4) and response rate was 50%, responders were on average six years younger than the non-responders and had a more favourable tumor stage (both p < 0.01). Of the 2904 responders, 31% (895/2904) had received a BR: implant-based in 58% (516/895)autologous in 31% (281/895). BR was immediate in 20% (176/895) and delayed in 80% (719/895) women.Women with BR were on average one year older, more often had a normal BMI, reported to be married or had a partner, had a higher educational level and a higher annual income when compared to those without BR (all p < 0.001). The independent factors of not receiving BR were older age and given radiotherapy.ConclusionsTo our knowledge, this is the first national long-term follow-up study on women undergoing mastectomy with and without BR. Around 30% of the survey responders have had a BR with a significant geographical variation highlighting the importance of information, availability and standardisation of indications for BR.
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| 99. |
- Vallon-Christersson, Johan, et al.
(författare)
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Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Multigene expression signatures provide a molecular subdivision of early breast cancer associated with patient outcome. A gap remains in the validation of such signatures in clinical treatment groups of patients within population-based cohorts of unselected primary breast cancer representing contemporary disease stages and current treatments. A cohort of 3520 resectable breast cancers with RNA sequencing data included in the population-based SCAN-B initiative (ClinicalTrials.gov ID NCT02306096) were selected from a healthcare background population of 8587 patients diagnosed within the years 2010-2015. RNA profiles were classified according to 19 reported gene signatures including both gene expression subtypes (e.g. PAM50, IC10, CIT) and risk predictors (e.g. Oncotype DX, 70-gene, ROR). Classifications were analyzed in nine adjuvant clinical assessment groups: TNBC-ACT (adjuvant chemotherapy, n = 239), TNBC-untreated (n = 82), HER2+/ER- with anti-HER2+ ACT treatment (n = 110), HER2+/ER+ with anti-HER2 + ACT + endocrine treatment (n = 239), ER+/HER2-/LN- with endocrine treatment (n = 1113), ER+/HER2-/LN- with endocrine + ACT treatment (n = 243), ER+/HER2-/LN+ with endocrine treatment (n = 423), ER+/HER2-/LN+ with endocrine + ACT treatment (n = 433), and ER+/HER2-/LN- untreated (n = 200). Gene signature classification (e.g., proportion low-, high-risk) was generally well aligned with stratification based on current immunohistochemistry-based clinical practice. Most signatures did not provide any further risk stratification in TNBC and HER2+/ER- disease. Risk classifier agreement (low-, medium/intermediate-, high-risk groups) in ER+ assessment groups was on average 50-60% with occasional pair-wise comparisons having <30% agreement. Disregarding the intermediate-risk groups, the exact agreement between low- and high-risk groups was on average ~80-95%, for risk prediction signatures across all assessment groups. Outcome analyses were restricted to assessment groups of TNBC-ACT and endocrine treated ER+/HER2-/LN- and ER+/HER2-/LN+ cases. For ER+/HER2- disease, gene signatures appear to contribute additional prognostic value even at a relatively short follow-up time. Less apparent prognostic value was observed in the other groups for the tested signatures. The current study supports the usage of gene expression signatures in specific clinical treatment groups within population-based breast cancer. It also stresses the need of further development to reach higher consensus in individual patient classifications, especially for intermediate-risk patients, and the targeting of patients where current gene signatures and prognostic variables provide little support in clinical decision-making.
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| 100. |
- Vichapat, Voralak, et al.
(författare)
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Tumor stage affects risk and prognosis of contralateral breast cancer : results from a large Swedish-population-based study
- 2012
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:28, s. 3478-3485
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEThe number of breast cancer survivors at risk of developing contralateral breast cancer (CBC) is increasing. However, ambiguity remains regarding risk factors and prognosis for women with CBC.PATIENTS AND METHODSIn a cohort of 42,670 women with breast cancer in the Uppsala/Örebro and Stockholm regions in Sweden in 1992 to 2008, we assessed risk factors for and prognosis of metachronous CBC by using survival analysis. Breast cancer-specific survival for women with CBC was evaluated and compared with results for women with unilateral breast cancer (UBC) by using time-dependent Cox-regression modeling.RESULTSAn increased risk for CBC was observed among women who had primary breast cancer with ≥ 10 involved lymph nodes compared with node-negative women (adjusted hazard ratio [HR], 1.8; 95% CI, 1.2 to 2.7). The prognosis was poorer in women with CBC than with UBC. The hazard of dying from breast cancer was especially high for women with a short interval time to CBC (adjusted HR, 2.3; 95% CI, 1.8 to 2.8 for CBC diagnosed ≤ 5 years v UBC) and gradually decreased with longer follow-up time but remained higher than the hazard originating from the primary tumor for ≥ 10 years.CONCLUSIONWomen with advanced-stage primary breast cancer had an increased risk of developing CBC. CBC is associated with an increased risk of dying from breast cancer throughout a long period of follow-up after the primary tumor. Our findings suggest that the event of CBC marks a new clinical situation in terms of investigations for metastases, treatment considerations, and follow-up strategy.
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