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Differences in intra-tumoral macrophage infiltration and radiotherapy response among intrinsic subtypes in pT1-T2 breast cancers treated with breast-conserving surgery.

ABSTRACT: Breast cancer (BC) intrinsic subtype classification is based on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation marker Ki-67. The expression of these markers depends on both the genetic background of the cancer cells and the surrounding tumor microenvironment. In this study, we explore macrophage traits in cancer cells and intra-tumoral M2-macrophage infiltration (MI) in relation to intrinsic subtypes in non-metastatic invasive BC treated with breast conserving surgery, with and without postoperative radiotherapy (RT). Immunostaining of M2-macrophage-specific antigen CD163 in cancer cells and MI were evaluated, together with ER, PR, HER2, and Ki-67-expression in cancer cells. The tumors were classified into intrinsic subtypes according to the ESMO guidelines. The immunostaining of these markers, MI, and clinical data were analyzed in relation to ipsilateral local recurrence (ILR) as well as recurrence-free (RFS) and disease-free specific (DFS) survival. BC intrinsic subtypes are associated with T-stage, Nottingham Histologic Grade (NHG), and MI. Macrophage phenotype in cancer cells is significantly associated with NHG3-tumors. Significant differences in macrophage infiltration were observed among the intrinsic subtypes of pT1-T2 stage BC. Shorter RFS was observed in luminal B HER2neg tumors after RT, suggesting that this phenotype may be more resistant to irradiation. Ki-67-expression was significantly higher in NHG3 and CD163-positive tumors, as well as those with moderate and high MI. Cancer cell ER expression is inversely related to MI and thus might affect the clinical staging and assessment of BC.

SUBMITTER: Garvin S

PROVIDER: S-EPMC6647441 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Differences in intra-tumoral macrophage infiltration and radiotherapy response among intrinsic subtypes in pT1-T2 breast cancers treated with breast-conserving surgery.

Garvin Stina S Vikhe Patil Eva E Arnesson Lars-Gunnar LG Oda Husam H Hedayati Elham E Lindström Annelie A Shabo Ivan I

Virchows Archiv : an international journal of pathology 20190326 2

Breast cancer (BC) intrinsic subtype classification is based on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation marker Ki-67. The expression of these markers depends on both the genetic background of the cancer cells and the surrounding tumor microenvironment. In this study, we explore macrophage traits in cancer cells and intra-tumoral M2-macrophage infiltration (MI) in relation to intrinsic subtypes in non ...[more]

PMID: 30915533

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Project description:The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012.A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms "breast cancer", "radiotherapy", and "breast conserving therapy". Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer.Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48-0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75-0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified.After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit.

Project description:PurposeSurgical clips are used as a target for postoperative breast radiotherapy, and displacement of surgical clips would result in inaccurate delivery of radiation. We investigated the displacement range of surgical clips in the breast during postoperative radiotherapy following breast-conserving surgery.MethodsA total of 178 patients who received breast-conserving surgery and postoperative radiation of 59.4 Gy in 33 fractions to the involved breast for 6.5 weeks were included. Surgical clips were used to mark the lumpectomy cavity during breast-conserving surgery. Patients undertook planning computed tomography (CT) scan for whole breast irradiation. Five weeks after beginning radiation, when the irradiation dose was 45 Gy, planning CT scan was performed again for a boost radiotherapy plan in all patients. The surgical clips were defined in both CT images and compared in lateromedial (X), anteroposterior (Y), superoinferior (Z), and three-dimensional directions.ResultsThe 90th percentile of displacement of surgical clips was 5.31 mm (range, 0.0-22.2 mm) in the lateromedial direction, 7.1 mm (range, 0.0-14.2 mm) in the anteroposterior direction, and 6.0 mm (range, 0.0-10.0 mm) in the superoinferior direction. The 90th percentile of three-dimensional displacement distance was 9.8 mm (range, 0.0-28.2 mm). On the multivariate analysis, seroma ≥15 mL was the only independent factor associated with the displacement of surgical clips. In patients with seroma ≥15 mL, the 90th percentile of displacement of surgical clips was 15.1 mm in the lateromedial direction, 12.7 mm in the anteroposterior direction, 10.0 mm in the superoinferior direction, and 21.8 mm in the three-dimensional distance.ConclusionA target volume expansion of 10 mm from surgical clips may be sufficient to compensate for the displacement of clips during postoperative radiotherapy after breast-conserving surgery. For patients who had a seroma, a replanning CT scan for a boost radiation should be considered to ensure exact postoperative radiotherapy in breast cancer.

Dataset Information

Differences in intra-tumoral macrophage infiltration and radiotherapy response among intrinsic subtypes in pT1-T2 breast cancers treated with breast-conserving surgery.

Publications

Differences in intra-tumoral macrophage infiltration and radiotherapy response among intrinsic subtypes in pT1-T2 breast cancers treated with breast-conserving surgery.

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