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Peritumoral edema (PE) of breast cancer at T2-weighted MR images is considered a poor prognostic sign and may represent the microenvironment surrounding the tumor; however, its histopathological mechanism remains unclear. The purpose of the study was to identify and describe detailed histopathological characteristics associated with PE at preoperative breast MRI in breast cancer patients. This retrospective study included breast cancer patients who had undergone preoperative MRI and surgery between January 2011 and December 2012. Two radiologists determined the presence of PE in consensus based on the signal intensity surrounding the tumor at T2-weighted images. The following detailed histopathological characteristics were reviewed by two breast pathologists using four-tiered grades; lymphovascular invasion, vessel ectasia, stromal fibrosis, growth pattern, and tumor budding. Tumor necrosis and tumor infiltrating lymphocytes were assessed using a percent scale. Baseline clinicopathological characteristics, including age and histologic grade, were collected. The associations between detailed histopathologic characteristics and PE were examined using multivariable logistic regression with odds ratio (OR) calculation. A total of 136 women (median age, 49 ± 9 years) were assessed; among them 34 (25.0%) had PE. After adjustment of baseline clinicopathological characteristics that were significantly associated with PE (age, T stage, N stage, histologic grade, and subtype, all P s < 0.05), lymphovascular invasion ( P  = 0.009), vessel ectasia ( P  = 0.021), stromal fibrosis ( P  = 0.024), growth pattern ( P  = 0.036), and tumor necrosis ( P  < 0.001) were also associated with PE. In comparison with patients without PE, patients with PE were more likely to have a higher degree of lymphovascular invasion (OR, 2.9), vessel ectasia (OR, 3.3), stromal fibrosis (OR, 2.5), lesser degree of infiltrative growth pattern (OR, 0.4), and higher portion of tumor necrosis (OR, 1.4). PE of breast cancer at MRI is associated with detailed histopathological characteristics of lymphovascular invasion, vessel ectasia, stromal fibrosis, growth pattern, and tumor necrosis, suggesting a relevance for tumor microenvironment.

Emerging evidence suggests that the mammalian target of rapamcyin (mTOR) pathway is associated with radio-resistance in cancer treatment. We hypothesised that phosphorylated ribosomal S6 kinase 1 (p-S6K1), a major downstream regulator of the mTOR pathway, may play a role in predicting radio-resistance. Therefore, we evaluated the association of p-S6K1 expression with radio-resistance in breast cancer cell lines and patients. During median follow-up of 33 (range, 0.1–111) months for 1770 primary breast cancer patients who underwent surgery, patients expressing p-S6K1 showed worse 10-year loco-regional recurrence-free survival (LRFS) compared to that of p-S6K1-negative patients after radiotherapy (93.4% vs. 97.7%, p  = 0.015). Multivariate analysis revealed p-S6K1 expression as a predictor of radio-resistance (hazard ratio 7.9, 95% confidence interval 1.1–58.5, p  = 0.04). In vitro , CD44 high /CD24 low MCF7 cells with a radioresistant phenotype expressed higher levels of p-S6K1 than control MCF7 cells. Furthermore, the combination of radiation with treatment of everolimus, an mTOR-S6K1 pathway inhibitor, sensitised CD44 high /CD24 low MCF7 cells to a greater extent than MCF7 cells. This study provides in vivo and in vitro evidence for p-S6K1 expression status as an important marker for predicting the resistance to radiotherapy and as a possible target for radio-sensitization in breast cancer patients.

Background Paclitaxel resistance and recurrence are major obstacles in ovarian cancer, which is the leading cause of death among gynecologic cancers. During cancer cell progression, cyclin-dependent kinase 1 (CDK1) drives cells through the G2 phase and into mitosis. In this study, we demonstrated that CDK1 played a crucial role in switching paclitaxel-resistant ovarian cancer cells from mitotic arrest to apoptosis following combined treatment with paclitaxel and duloxetine, an antidepressant known as a serotonin-norepinephrine reuptake inhibitor (SNRI). Methods Cell viability was assessed by MTT assay. Apoptotic cell death and mitochondrial membrane potential (MMP) were detected by flow cytometry. Protein expression levels were explored using western blotting. Mitochondrial and cytosolic fractionation were performed to determine the mitochondrial localization of proteins. Immunofluorescence was used to detect protein expression levels and localization. Results Combined treatment with paclitaxel and duloxetine induced apoptotic cell death in paclitaxel-resistant ovarian cancer cells. We suggested that combined treatment of these drugs induced CDK1 activation and increased mitochondrial localization of activated CDK1, which caused phosphorylation of the antiapoptotic Bcl-2 and Bcl-xL proteins. Selective CDK1 inhibitors blocked Bcl-2 and Bcl-xL phosphorylation induced by paclitaxel and duloxetine, and strongly suppressed apoptotic cell death. Furthermore, we demonstrated that S6K is a potential upstream mediator of the proapoptotic activation of CDK1. Conclusion Taken together, switching CDK1 to a proapoptotic role through the combination of paclitaxel and duloxetine could overcome paclitaxel resistance in ovarian cancer cells, providing promising therapeutic strategies for treating paclitaxel-resistant ovarian cancer.

Background Preoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC). Methods A total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS ( n  = 199) and IDC ( n  = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans. Results Changes (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group ( P  <  0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different ( P  = 0.138). Conclusions Preoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.

Background Using the Latissimus dorsi (LD) muscle flap is one of the popular surgical technique for breast reconstruction. However, usually, long postoperative scar was remained on donor site which does not have disease. The authors applied the endoscopy-assisted surgery to harvest the LD muscle flap for breast reconstruction. Methods From July 2018 to July 2019, five consecutive patients with breast cancer underwent partial mastectomy with endoscopy-assisted LD muscle flap reconstruction. The clinic-pathologic factors were analyzed and the cosmetic outcomes were assessed with breast shape, scarring of breast and back. A 4–6 cm of lateral incision (donor site scar) was designed and LD muscle was harvested under endoscopic surgery without gas inflation. And the harvested LD muscle was inserted for partial breast reconstruction after the cancer surgery was done. Results Mean operative time was 116.4 min (range, 92–134) and there was no major postoperative complication. The satisfactory degree of cosmetic outcomes were shown better in patient’s survey than that of surgeon’s. Conclusions The endoscopy-assisted LD muscle flap harvesting would be useful technique to eliminate a large donor site incision in partial breast reconstruction.

We investigated whether tailored neoadjuvant therapy (chemotherapy [NCT] or endocrine therapy [NET]) guided by a 70-gene assay could improve breast-conserving surgery (BCS) rates among patients with ER-positive/HER2-negative breast cancer initially deemed ineligible for BCS. Of 130 prospectively enrolled patients (stage II–IIIA, across four Korean centers), 92 were analyzed. Patients classified as high genomic risk received NCT, while low-risk patients underwent NET (letrozole ± leuprolide for premenopausal women) for 16–24 weeks. The primary endpoint—achieving the surgeon-defined target tumor size for BCS—was reached in 69.6% (95% CI: 59.1–78.7%), significantly surpassing the predefined goal of 50.8% ( p  < 0.05). The actual overall BCS rate was 59.8% (64.7% NCT, 45.8% NET). Pathologic complete response occurred in 2.2%, exclusively in the NCT group. Thus, pretreatment genomic profiling effectively guided therapy selection, substantially increasing BCS eligibility while sparing low-risk patients unnecessary chemotherapy toxicity.

PURPOSE Neck ultrasonography (US), computed tomography (CT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are all known to be useful imaging modalities for detecting supraclavicular lymph node (SCN) metastasis in breast cancer. The authors compared the diagnostic values of neck US, CT, and PET/CT in the detection of SCN metastasis in breast cancer. METHODS SCN metastases identified in neck US, CT, or PET/CT during follow-up visits of patients with breast cancer were pathologically confirmed with the use of US-guided fine-needle aspiration cytology. The clinicopathological factors of the patients were analyzed, and the statistical parameters including sensitivity, specificity, positive and negative predictive values, false-positive and false-negative rates, and accuracy of neck US, CT, and PET/CT were compared. RESULTS Among 32 cases of suspicious SCNs, 24 were pathologically confirmed as metastasis of breast cancer. The sensitivity of US + CT was 91.7%, which was the same as that of PET/CT, while the sensitivity rates of US alone and CT alone were 87.5% and 83.3%, respectively. Accuracy was 99.8% in PET/CT alone and 98.1% in US + CT. The false-negative rate was 0.1% in US + PET/CT, while it was 0.2% in PET/CT and US + CT, 0.3% in US alone and 0.4% in CT alone. CONCLUSION PET/CT can be the first choice for detecting SCN metastases in breast cancer. However, if PET/CT is unavailable for any reason, US + CT could be a good second option to avoid false-negative results.

The fibroblast growth factor receptor (FGFR) signaling pathway is abnormally activated in human cancers, including breast cancer. Therefore, targeting the FGFR signaling pathway is a potent strategy to treat breast cancer. The purpose of this study was to find drugs that could increase sensitivity to FGFR inhibitor effects in BT-474 breast cancer cells, and to investigate the combined effects and underlying mechanisms of these combinations for BT-474 breast cancer cell survival. Cell viability was measured by MTT assay. Protein expression was determined by western blot analysis. mRNA expression was detected by Real-time PCR. Drug synergy effect was determined by isobologram analysis. Nebivolol, a third generation β1-blocker, synergistically increased the sensitivity of BT-474 breast cancer cells to the potent and selective FGFR inhibitors erdafitinib (JNJ-42756493) and AZD4547. A combination of nebivolol and erdafitinib markedly reduced AKT activation. Suppression of AKT activation using specific siRNA and a selective inhibitor further enhanced cell sensitivity to combined treatment with nebivolol and erdafitinib, whereas SC79, a potent activator of AKT, reduced cell sensitivity to nebivolol and erdafitinib. Enhanced sensitivity of BT-474 breast cancer cells to nebivolol and erdafitinib was probably associated with down-regulation of AKT activation. Combined treatment with nebivolol and erdafitinib is a promising strategy for breast cancer treatment.

Rictor is an adaptor protein essential for mTORC2, which regulates cell growth and survival. The aim of this study was to identify microRNAs (miR) that down-regulate Rictor and investigate their function on breast cancer cell survival. Trypan blue assay, MTT assay, polymerase chain reaction analysis, luciferase reporter assay and western blot analysis were carried out in breast cancer cell lines HCC1954, MDA-MB-231, SK-BR-3, and BT474. miR-3188 overexpression suppressed the expression of Rictor and inhibited cell viability in HCC1954 and MDA-MB-231, highly Rictor-expressing breast cancer cells. In addition, miR-3188 overexpression decreased the protein level of p-AKT at Ser473, a substrate of mTORC2. Moreover, miRNA-3188 overexpression sensitized breast cancer cells to ionizing radiation (IR) by down-regulating Rictor and p-AKT. miR-3188 enhances IR sensitivity by affecting the mTORC2/AKT signalling pathway by altering the expression of Rictor, which could be a promising therapeutic strategy for the future treatment of breast cancer.

To demonstrate a variety of MR imaging findings of orbital inflammatory pseudotumors with extraorbital extension. We retrospectively reviewed the MR features of five patients, who were diagnosed clinically and radiologically as having an orbital inflammatory pseudotumor with extraorbital extension. The types of orbital pseudotumors were a mass in the orbital apex (n = 3), diffuse form (n = 2), and myositis (n = 1). The extraorbital extension of the orbital pseudotumor passed through the superior orbital fissure in all cases, through the inferior orbital fissure in two cases, and through the optic canal in one case. The orbital lesions extended into the following areas: the cavernous sinus (n = 4), the middle cranial fossa (n = 4), Meckel's cave (n = 2), the petrous apex (n = 2), the clivus (n = 2), the pterygopalatine fossa and infratemporal fossa (n = 2), the foramen rotundum (n = 1), the paranasal sinus (n = 1), and the infraorbital foramen (n = 1). On MR imaging, the lesions appeared as an isosignal intensity with gray matter on the T1-weighted images, as a low signal intensity on the T2-weighted images and showed a marked enhancement on the post-gadoliniumdiethylene triamine pentaacetic acid (post-Gd-DTPA) T1-sequences. The symptoms of all of the patients improved when they were given high doses of steroids. Three of the five patients experienced a recurrence. MR imaging is useful for demonstrating the presence of a variety of extraorbital extensions of orbital inflammatory pseudotumors.