The impact of age on patient-reported outcomes after oncoplastic versus conventional breast cancer surgery.

PURPOSE: Some studies have indicated age-specific differences in quality of life (QoL) among breast cancer (BC) patients. The aim of this study was to compare patient-reported outcomes after conventional and oncoplastic breast surgery in two distinct age groups. METHODS: Patients who underwent oncoplastic and conventional breast surgery for stage I-III BC, between 6/2011-3/2019, were identified from a prospectively maintained database. QoL was prospectively evaluated using the Breast-Q questionnaire. Comparisons were made between women < 60 and ≥ 60 years. RESULTS: One hundred thirty-three patients were included. Seventy-three of them were ≥ 60 years old. 15 (20.5%) of them received a round-block technique (RB) / oncoplastic breast-conserving surgeries (OBCS), 10 (13.7%) underwent nipple-sparing mastectomies (NSM) with deep inferior epigastric perforator flap (DIEP) reconstruction, 23 (31.5%) underwent conventional breast-conserving surgeries (CBCS), and 25 (34.2%) received total mastectomy (TM). Sixty patients were younger than 60 years, 15 (25%) thereof received RB/OBCS, 22 (36.7%) NSM/DIEP, 17 (28.3%) CBCS, and 6 (10%) TM. Physical well-being chest and psychosocial well-being scores were significantly higher in older women compared to younger patients (88.05 vs 75.10; p < 0.001 and 90.46 vs 80.71; p = 0.002, respectively). In multivariate linear regression, longer time intervals had a significantly positive effect on the scales Physical Well-being Chest (p = 0.014) and Satisfaction with Breasts (p = 0.004). No significant results were found concerning different types of surgery. CONCLUSION: Our findings indicate that age does have a relevant impact on postoperative QoL. Patient counseling should include age-related considerations, however, age itself cannot be regarded as a contraindication for oncoplastic surgery.

Phosphorylated CXCR4 expression has a positive prognostic impact in colorectal cancer.

BACKGROUND: The CXCL12-CXCR4 chemokine axis plays an important role in cell trafficking as well as in tumor progression. In colorectal cancer (CRC), the chemokine receptor CXCR4 has been shown to be an unfavorable prognostic factor in some studies, however, the role of its activated (phosphorylated) form, pCXCR4, has not yet been evaluated. Here, we aimed to investigate the prognostic value of CXCR4 and pCXCR4 in a large cohort of CRC patients. PATIENTS AND METHODS: A tissue microarray (TMA) of 684 patient specimens of primary CRCs was analyzed by immunohistochemistry (IHC) for the expression of CXCR4 and pCXCR4 by tumor cells and tumor-infiltrating immune cells (TICs). RESULTS: The combined high expression of CXCR4 and pCXCR4 showed a favorable 5-year overall survival rate (68%; 95%CI = 59-76%) compared to tumors showing a high expression of CXCR4 only (48%; 95%CI = 41-54%). High expression of pCXCR4 was significantly associated with a favorable prognosis in a test and validation group (p = 0.015 and p = 0.0001). Moreover, we found that CRCs with a high density of pCXCR4+ tumor-infiltrating immune cells (TICs) also showed a favorable prognosis in a test and validation group (p = 0.054 and p = 0.004). Univariate Cox regression analysis for TICs revealed that a high density of pCXCR4+ TICs was a favorable prognostic marker for overall survival (HR = 0.97,95%CI = 0.96-1.00; p = 0.01). In multivariate Cox regression survival analyses a high expression of pCXCR4 in tumor cells lost its association with a better overall survival (HR = 0.99; 95%CI = 0.99-1.00, p = 0.098). CONCLUSION: Our results show that high densities of CXCR4 and pCXCR4 positive TICs are favorable prognostic factors in CRC.

Standardization of oncoplastic breast conserving surgery.

The emphasis on esthetic outcomes and quality of life after breast cancer surgery has motivated surgeons to develop oncoplastic breast conserving surgery (OPS). Training programs are still rare in most countries, and there is little standardization, which challenges the scientific evaluation of the techniques. The present article attempts to standardize OPS nomenclature, indications, and reconstruction choice selection embedded in a thorough review of the literature. We propose four breast conserving surgery (BCS) categories: Conventional tumorectomy, oncoplastic mastopexy, oncoplastic tumorectomy and oncoplastic reduction mammoplasty. The main volume displacement techniques are glandular re-approximation, use of tailored glandular or dermoglandular flaps and nipple-areola complex pedicles. We developed an indication algorithm based on the size and shape of the breast as well as the size and location of the tumor. A reconstruction algorithm suggests a selection of suitable tailored flaps and pedicles based on tumor location and vascular supply of the breast. The application of these algorithms results in known and novel OPS techniques, which are presented here with long-term results. We designed the algorithms to help tailor every operation to the individual patient in a standardized manner, since OPS is now on the rise, more than two decades after the publication of the first techniques. A rapidly increasing body of observational evidence suggests comparable rates of local recurrence between OPS and conventional BCS. Importantly, the rates of clear resection margins are in favor of OPS despite extended indications to larger tumors. Finally, OPS optimizes patient satisfaction by improving esthetic outcomes after BCS.

The immune system and cancer evasion strategies: therapeutic concepts.

The complicated interplay between cancer and the host immune system has been studied for decades. New insights into the human immune system as well as the mechanisms by which tumours evade immune control have led to the new and innovative therapeutic strategies that are considered amongst the medical breakthroughs of the last few years. Here, we will review the current understanding of cancer immunology in general, including immune surveillance and immunoediting, with a detailed look at immune cells (T cells, B cells, natural killer cells, macrophages and dendritic cells), immune checkpoints and regulators, sialic acid-binding immunoglobulin-like lectins (Siglecs) and other mechanisms. We will also present examples of new immune therapies able to reverse immune evasion strategies of tumour cells. Finally, we will focus on therapies that are already used in daily oncological practice such as the blockade of immune checkpoints cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) in patients with metastatic melanoma or advanced lung cancer, or therapies currently being tested in clinical trials such as adoptive T-cell transfer.

Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes.

Mammaglobin-A (MAM-A) is a secretory protein that is overexpressed in 80 % of human breast cancers. Its near-universal expression in breast cancer as well as its exquisite tissue specificity makes it an attractive target for a breast cancer prevention vaccine, and we recently initiated a phase 1 clinical trial of a MAM-A DNA vaccine. Previously, we have identified multiple MAM-A CD8 T cell epitopes using a reverse immunology candidate epitope approach based on predicted binding, but to date no attempt has been made to identify epitopes using an unbiased approach. In this study, we used human T cells primed in vitro with autologous dendritic cells expressing MAM-A to systematically identify MAM-A CD8 T cell epitopes. Using this unbiased approach, we identified three novel HLA-A2-restricted MAM-A epitopes. CD8 T cells specific for these epitopes are able to recognize and lyse human breast cancer cells in a MAM-A-specific, HLA-A2-dependent fashion. HLA-A2(+)/MAM-A(+) breast cancer patients have an increased prevalence of CD8 T cells specific for these novel MAM-A epitopes, and vaccination with a MAM-A DNA vaccine significantly increases the number of these CD8 T cells. The identification and translational validation of novel MAM-A epitopes has important implications for the ongoing clinical development of vaccine strategies targeting MAM-A. The novel MAM-A epitopes represent attractive targets for epitope-based vaccination strategies, and can also be used to monitor immune responses. Taken together these studies provide additional support for MAM-A as an important therapeutic target for the prevention and treatment of breast cancer.

Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer.

Recent studies in multiple epithelial cancers have shown that the inhibitory receptor programmed cell death 1 (PD-1) is expressed on tumor-infiltrating lymphocytes and/or programmed death ligand 1 (PD-L1) is expressed on tumor cells, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway. In addition, phase 1 clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 have shown promising results in several human cancers. The purpose of this study was to investigate the impact of PD-L1 expression in human breast cancer specimens. We conducted an immunohistochemistry study using a tissue microarray encompassing 650 evaluable formalin-fixed breast cancer cases with detailed clinical annotation and outcomes data. PD-L1 was expressed in 152 (23.4 %) of the 650 breast cancer specimens. Expression was significantly associated with age, tumor size, AJCC primary tumor classification, tumor grade, lymph node status, absence of ER expression, and high Ki-67 expression. In univariate analysis, PD-L1 expression was associated with a significantly worse OS. In multivariate analysis, PD-L1 expression remained an independent negative prognostic factor for OS. In subset analyses, expression of PD-L1 was associated with significantly worse OS in the luminal B HER2(-) subtype, the luminal B HER2(+) subtype, the HER2 subtype, and the basal-like subtype. This is the first study to demonstrate that PD-L1 expression is an independent negative prognostic factor in human breast cancer. This finding has important implications for the application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.

Nuclear expression of snail is an independent negative prognostic factor in human breast cancer.

BACKGROUND: Snail is a key regulator of epithelial-mesenchymal transition of tumor cells. Several studies have shown nuclear Snail expression to be a negative prognostic factor in human cancer, where it is generally associated with more aggressive tumor behavior and worse survival. OBJECTIVES AND METHODS: To further explore the role of Snail expression in breast cancer, we conducted a study on a tissue microarray, encompassing 1043 breast cancer cases. RESULTS: A total of 265 (25.4%) breast cancers were positive for Snail. Snail expression was significantly associated with greater tumor size, higher tumor stage and grade, positive lymph node status, and hormone receptor negative status and was differently expressed in the intrinsic subtypes of breast cancer, being the highest in the basal-like subtype and the lowest in the luminal A subtype. In multivariate analysis, Snail proved to be an independent negative prognostic factor for OS. In the intrinsic subtypes, Snail expression was a negative prognostic factor for OS in the luminal B HER2(-), the luminal B HER2(+), and the basal-like subtype. CONCLUSIONS: This is the first study demonstrating that nuclear Snail expression is an independent negative predictor of prognosis in breast cancer, thus suggesting that it may represent a potential therapeutic target.

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer.

Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1(+) TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1(+) TIL were present in 104 (15.8 %) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1(+) TIL was associated with a significantly worse overall survival (HR = 2.736, p < 0.001). In subset analyses, the presence of PD-1(+) TIL was associated with significantly worse overall survival in the luminal B HER2(-) subtype (HR = 2.678, p < 0.001), the luminal B HER2(+) subtype (HR = 3.689, p < 0.001), and the basal-like subtype (HR = 3.140, p < 0.001). This is the first study to demonstrate that the presence of PD-1(+) TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.

EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2(+), basal-like, and HER2 intrinsic subtypes of breast cancer.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is frequently expressed in breast cancer, and its expression has been associated with poor prognosis. Breast cancer can be subdivided into intrinsic subtypes, differing in prognosis and response to therapy. METHODS: To investigate the association between EpCAM expression and prognosis in the intrinsic subtypes of breast cancer, we performed immunohistochemical studies on a tissue microarray encompassing a total of 1365 breast cancers with detailed clinicopathological annotation and outcomes data. RESULTS: We observed EpCAM expression in 660 out of 1365 (48%) cases. EpCAM expression varied significantly in the different intrinsic subtypes. In univariate analyses of all cases, EpCAM expression was associated with a significantly worse overall survival. In the intrinsic subtypes, EpCAM expression was associated with an unfavourable prognosis in the basal-like and luminal B HER2(+) subtypes but associated with a favourable prognosis in the HER2 subtype. Consistently, specific ablation of EpCAM resulted in increased cell viability in the breast cancer cell line SKBR3 (ER(-), PR(-), and HER2(+)) but decreased viability in the breast cancer cell line MDA-MB-231 (ER(-), PR(-), and HER2(-) ). CONCLUSION: The differential association of EpCAM expression with prognosis in intrinsic subtypes has important implications for the development of EpCAM-targeted therapies in breast cancer.

[Embolization of hydrophilic guide wire coating]. / Embolisation von Katheterbeschichtung in das Myokard.

The number of interventional cardiovascular procedures has been rising steadily. Such procedures include the intravascular insertion of catheters and guide wires. These devices consist of a metallic core and coil that may be covered by hydrophilic coating to ease crossability and control for challenging lesions. We report two cases where insertion of a ChoICE® PT guide wire into the coronary artery led to embolization of the hydrophilic coating material with occlusion of small intramyocardial arteries.