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Olofsson, Helena
Publications (4 of 4) Show all publications
Lundgren, C., Bendahl, P.-O., Borg, Å., Ehinger, A., Hegardt, C., Larsson, C., . . . Ekholm, M. (2019). Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer. Breast Cancer Research and Treatment, 178(2), 459-467
Open this publication in new window or tab >>Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer
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2019 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 178, no 2, p. 459-467Article in journal (Refereed) Published
Abstract [en]

Purpose: Oestrogen receptor-positive (ER+) and human epidermal receptor 2-negative (HER2-) breast cancers are classified as Luminal A or B based on gene expression, but immunohistochemical markers are used for surrogate subtyping. The aims of this study were to examine the agreement between molecular subtyping (MS) and surrogate subtyping and to identify subgroups consisting mainly of Luminal A or B tumours.

Methods: The cohort consisted of 2063 patients diagnosed between 2013-2017, with primary ER+/HER2- breast cancer, analysed by RNA sequencing. Surrogate subtyping was performed according to three algorithms (St. Gallen 2013, Maisonneuve and our proposed Grade-based classification). Agreement (%) and kappa statistics (kappa) were used as concordance measures and ROC analysis for luminal distinction. Ki67, progesterone receptor (PR) and histological grade (HG) were further investigated as surrogate markers.

Results: The agreement rates between the MS and St. Gallen 2013, Maisonneuve and Grade-based classifications were 62% (kappa = 0.30), 66% (kappa = 0.35) and 70% (kappa = 0.41), respectively. PR did not contribute to distinguishing Luminal A from B tumours (auROC = 0.56). By classifying HG1-2 tumours as Luminal A-like and HG3 as Luminal B-like, agreement with MS was 80% (kappa = 0.46). Moreover, by combining HG and Ki67 status, a large subgroup of patients (51% of the cohort) having > 90% Luminal A tumours could be identified.

Conclusions: Agreement between MS and surrogate classifications was generally poor. However, a post hoc analysis showed that a combination of HG and Ki67 could identify patients very likely to have Luminal A tumours according to MS.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Breast cancer, Intrinsic subtype, Molecular subtyping, Surrogate marker, Gene expression
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-396512 (URN)10.1007/s10549-019-05378-7 (DOI)000491200400022 ()31432367 (PubMedID)
Funder
The Breast Cancer Foundation
Available from: 2019-11-06 Created: 2019-11-06 Last updated: 2019-11-07Bibliographically approved
Vallon-Christersson, J., Häkkinen, J., Hegardt, C., Saal, L. H., Larsson, C., Ehinger, A., . . . Staaf, J. (2019). Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series. Scientific Reports, 9, Article ID 12184.
Open this publication in new window or tab >>Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12184Article in journal (Refereed) Published
Abstract [en]

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 similar to 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 group 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-393727 (URN)10.1038/s41598-019-48570-x (DOI)000481999500038 ()31434940 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society, CAN 2018/685The Crafoord FoundationBioCARE - Biomarkers in Cancer Medicine Improving Health Care Education and InnovationKing Gustaf V Jubilee Fund
Available from: 2019-09-30 Created: 2019-09-30 Last updated: 2019-09-30Bibliographically approved
Karakatsanis, A., Hersi, A.-F., Pistiolis, L., Bagge, R. O., Lykoudis, P. M., Eriksson, S., . . . Stålberg, P. (2019). Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study). British Journal of Surgery, 106(6), 720-728
Open this publication in new window or tab >>Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study)
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2019 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, no 6, p. 720-728Article in journal (Refereed) Published
Abstract [en]

Background: One-fifth of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) have invasive breast cancer (IBC) on definitive histology. Sentinel lymph node dissection (SLND) is performed in almost half of women having surgery for DCIS in Sweden. The aim of the present study was to try to minimize unnecessary SLND by injecting superparamagnetic iron oxide (SPIO) nanoparticles at the time of primary breast surgery, enabling SLND to be performed later, if IBC is found in the primary specimen.

Methods: Women with DCIS at high risk for the presence of invasion undergoing breast conservation, and patients with DCIS undergoing mastectomy were included. The primary outcome was whether this technique could reduce SLND. Secondary outcomes were number of SLNDs avoided, detection rate and procedure-related costs.

Results: This was a preplanned interim analysis of 189 procedures. IBC was found in 47 and a secondary SLND was performed in 41 women. Thus, 78.3 per cent of patients avoided SLND (P<0.001). At reoperation, SPIO plus blue dye outperformed isotope and blue dye in detection of the sentinel node (40 of 40 versus 26 of 40 women; P<0.001). Costs were reduced by a mean of 24.5 per cent in women without IBC (3990 versus 5286; P<0.001).

Conclusion: Marking the sentinel node with SPIO in women having surgery for DCIS was effective at avoiding unnecessary SLND in this study. Registration number: ISRCTN18430240 (http://www.isrctn.com).

Place, publisher, year, edition, pages
WILEY, 2019
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-383156 (URN)10.1002/bjs.11110 (DOI)000465082200009 ()30839104 (PubMedID)
Funder
The Breast Cancer Foundation
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-10Bibliographically approved
Wärnberg, F., Stigberg, E., Obondo, C., Olofsson, H., Abdsaleh, S., Wärnberg, M. & Karakatsanis, A. (2019). Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery.. Annals of Surgical Oncology, 26(5), 1247-1253
Open this publication in new window or tab >>Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery.
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2019 (English)In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 26, no 5, p. 1247-1253Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/OBJECTIVE: SPIO is effective in sentinel node (SN) detection. No nuclear medicine department is needed, and no allergic reactions have occurred. This study aimed to compare retro-areolar and peri-tumoral SPIO injections regarding skin staining, detection rates and number of SNs.

METHODS: Data on staining size, intensity and cosmetic outcome (0-5; 0 = no problem) were collected by telephone interviews with 258 women undergoing breast conservation. SN detection and the number of SNs were prospectively registered in 332 women.

RESULTS: After retro-areolar and peri-tumoral injections, 67.3% and 37.8% (p < 0.001) developed skin staining, with remaining staining in 46.2 vs. 9.4% after 36 months (p < 0.001). Initial mean size was 16.3 vs. 6.8 cm (p < 0.001) and after 36 months, 6.6 vs. 1.8 cm2 (p < 0.001). At 75.1% of 738 interviews, staining was reported paler. After retro-areolar injections, cosmetic outcome scored worse for 2 years. The mean (median) scores were 1.3(0) vs. 0.5(0) points, and 0.2(0) vs. 0.1(0) points, at 12 and 36 months, respectively. Overall detection rates were 98.3% and 97.4% (p = 0.43) and the number of SNs 1.35 vs. 1.57 (p = 0.02) after retro-areolar and peri-tumoral injections. Injection, regardless of type, 1-27 days before surgery increased detection rates with SPIO, 98.0% vs. 94.2% (p = 0.06) ,and SN numbers, 1.56 vs. 1.27 (p = 0.003).

CONCLUSION: SPIO is effective and facilitates planning for surgery. Peri-tumoral injection reduced staining with a similar detection rate. Staining was not considered a cosmetic problem among most women. Injecting SPIO 1-27 days before surgery increased the detection rate by 3.8% and increased the number of SNs by 0.3.

National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-380893 (URN)10.1245/s10434-019-07239-5 (DOI)000464726300019 ()30830536 (PubMedID)
Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-05-09Bibliographically approved
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