UNASSIGNED: While Heat Shock Protein 60 (HSP60) has been linked to human tumor, its clinic significance specifically in breast carcinoma is unclear. This investigation aims to retrospectively evaluate how HSP60 protein levels relate to survival outcomes among patients diagnosed with breast carcinoma.
UNASSIGNED: Evaluation of 206 patients diagnosed with breast carcinoma and receiving treatment from January 2012 to April 2018, carried out retrospectively. The protein level of HSP60 in breast carcinoma determined by immunohistochemical.
UNASSIGNED: The study provided evidence of a distinct upregulation of HSP60 expression in breast carcinoma tumor samples in contrast to adjacent normal tissue samples. Additionally, heightened HSP60 expression was linked to advanced T stage (P = 0.046), N stage (P = 0.034), tumor metastasis (P = 0.016), pathological grading (P = 0.012), and adjuvant therapy utilization (P = 0.004). Moreover, elevated levels of HSP60 proteins exhibited a significant inverse correlation with overall survival (OS) [hazard ratio (HR) 1.598, P = 0.018] and progression-free survival (PFS) (HR 1.600, P = 0.017) among breast carcinoma patients in univariate analyses. The results of multivariate analyses highlighted HSP60 may serve as an independent predictor for both OS and PFS in breast carcinoma patients (HR 1.525, P = 0.034; HR 1.528, P = 0.033, respectively).
UNASSIGNED: The involvement of HSP60 in breast carcinoma progression suggests its potential clinical relevance in treatment target validation and prognostic assessment of the disease.

This study evaluated the paracrine signaling between breast carcinoma-associated fibroblasts (CAFs) and breast cancer (BCa) cells. Resolving cell-cell communication in the BCa tumor microenvironment (TME) will aid the development of new therapeutics. Here, we utilized our patented TAME (tissue architecture and microenvironment engineering) 3D culture microphysiological system, which is a suitable pathomimetic avatar for the study of the BCa TME. We cultured in 3D BCa cells and CAFs either alone or together in cocultures and found that when cocultured, CAFs enhanced the invasive characteristics of tumor cells, as shown by increased proliferation and spread of tumor cells into the surrounding matrix. Secretome analysis from 3D cultures revealed a relatively high secretion of IL-6 by CAFs. A marked increase in the secretion of granulocyte macrophage-colony stimulating factor (GM-CSF) when carcinoma cells and CAFs were in coculture was also observed. We theorized that the CAF-secreted IL-6 functions in a paracrine manner to induce GM-CSF expression and secretion from carcinoma cells. This was confirmed by evaluating the activation of STAT3 and gene expression of GM-CSF in carcinoma cells exposed to CAF-conditioned media (CAF-CM). In addition, the treatment of CAFs with BCa cell-CM yielded a brief upregulation of GM-CSF followed by a marked decrease, indicating a tightly regulated control of GM-CSF in CAFs. Secretion of IL-6 from CAFs drives the activation of STAT3 in BCa cells, which in turn drives the expression and secretion of GM-CSF. As a result, CAFs exposed to BCa cell-secreted GM-CSF upregulate inflammation-associated genes such as IL-6, IL-6R and IL-8, thereby forming a positive feedback loop. We propose that the tight regulation of GM-CSF in CAFs may be a novel regulatory pathway to target for disrupting the CAF:BCa cell symbiotic relationship. These data provide yet another piece of the cell-cell communication network governing the BCa TME.

Background Breast cancer remains one of the most common malignancies affecting women globally, contributing significantly to the disease burden. The advent of neoadjuvant chemotherapy (NAC) has revolutionized the treatment for locally advanced breast cancer, allowing tumors to be downstaged and making breast-conserving surgery (BCS) feasible. Accurate localization of the tumor bed post-NAC is crucial for successful surgical removal of residual disease. While traditional single tissue marker placement has been effective, recent advances suggest multiple markers might provide superior localization by comprehensively delineating the entire tumor area. This study aims to compare the effectiveness of single versus multiple tissue marker placements in breast malignancy patients undergoing NAC. Materials and methods A prospective study was conducted in the Department of Radio-diagnosis at Saveetha Medical College over 18 months, including 10 patients diagnosed with breast carcinoma, selected through convenience sampling. Inclusion criteria involved patients diagnosed with breast cancer via mammography, sonography, and histological confirmation, referred for clip placement before NAC. Exclusion criteria were patients unwilling to participate. The procedure involved placing one to two surgical clips within the tumor using a 14/16-gauge coaxial guiding needle under USG guidance, with additional clips for larger or multiple tumors. Data collection included pre-procedural USG, post-procedural mammography (MG1), pre-operative mammography (MG2)/USG, and gross specimen histopathological examination/specimen mammography. Statistical analysis Demographic data, clipping distribution, receptor status, localization methods, surgical outcomes, operation diagnoses, and correlation analysis were statistically analyzed. Mean age, standard deviation, and p-values were calculated to determine the significance of differences between single and multiple clip groups. Results The study included 10 patients with a mean age of 52.5 years. Of these, five (50%) had a single clip, and two (20%) had four clips. The average time from clipping to the second mammogram (MG2) was 106.3 days, and from clipping to operation was 111.0 days, with longer follow-up times for multiple clip patients. Six (60%) of the patients were estrogen receptor (ER) positive, and six (60%) were human epidermal growth factor receptor 2 (HER2) negative. Localization methods were similar between single and multiple clip groups. However, multiple clip patients tended to undergo more extensive surgeries like modified radical mastectomy (MRM). Imaging responses showed no preoperative ultrasound lesions in single clip patients, while multiple clip patients had higher inconsistent diagnoses (10 (100%)) suggesting that multiple clips provide better tumor localization but are linked to increased complexity and longer follow-up times. Conclusion Patients with multiple clips experienced significantly longer follow-up times, reflecting more complex clinical scenarios. Despite no significant differences in receptor status distributions, multiple clip patients required more extensive surgeries, emphasizing the need for tailored surgical planning. The study underscores the importance of considering the number of clips in clinical decision-making. Future research should focus on larger, prospective studies to validate these findings and explore underlying mechanisms.

BACKGROUND: Mammary carcinoma is the most frequently diagnosed form of carcinoma in women worldwide. The organometallic compounds showed a prospective anticancer activity. This research explored the anticancer efficacy of taxifolin ruthenium-p-cymene counter to breast cancer.
METHODS: The anticancer efficacy of the novel organometallic compound was investigated via various in vitro and in vivo techniques using breast cancer cell lines and breast cancer model of rat.
RESULTS: Target proteins were identified via pharmacophore analysis, which revealed a high binding affinity towards AhR, EGFR, and β-catenin. The compound induced apoptotic events and prevented cancer cell colony formation. Furthermore, decreased expression of AhR, EGFR, and N-cadherin inhibited cancer cell growth, migration, and proliferation. The compound provoked the cell cycle arrest at sub G0/G1 phase, S phase and G2/M phase and inaugurated the caspase-3 dependent apoptotic events. The in-vivo experimentation displayed the fruitful restoration of breast tissue since the complex treatment in DMBA persuaded breast carcinoma in rat. Moreover, the upstream of p53 and caspase-3 expression along with substantially downstream of vimentin, β-catenin, m-TOR and Akt expression.
CONCLUSIONS: In conclusion, the compound repressed the cancerous cellular viability, migration, and EMT via modulating the AhR/EGFR/ PI3K transduction pathway and the expression of EMT biomarkers such as N-cadherin, E-cadherin, thus eventually revoked the EMT facilitated metastasis of malignant cells.

Gallium-68 ( 68 Ga)-fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) images the cancer-associated fibroblast that forms a vital component of the tumor microenvironment. It is known that 68 Ga-FAPI PET can aid in differentiating reactive lymph nodes from metastatic lymph nodes. 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is still the most commonly used PET radiopharmaceutical in the evaluation of a wide range of malignancies including breast carcinoma. Reactive lymph nodes may also show FDG uptake which can hinder optimal assessment for metastatic involvement. We report an interesting case of invasive ductal carcinoma of the right breast with associated World Health Organization clinical stage I acquired immunodeficiency syndrome for which 18 F-FDG PET/CT and 68 Ga-FAPI PET/CT were done.

Asparagine and glutamine depletion operated by the drug Asparaginase (ASNase) has revolutionized therapy in pediatric patients affected by Acute Lymphoblastic Leukemia (ALL), bringing remissions to a remarkable 90 % of cases. However, the knowledge of the proproliferative role of asparagine in adult and solid tumors is still limited. We have here analyzed the effect of ASNase on three adenocarcinoma cell lines (A549, lung adenocarcinoma, MCF-7, breast cancer, and 786-O, kidney cancer). In contrast to MCF-7 cells, 786-O and A549 cells proved to be a relevant target for cell cycle perturbation by asparagine and glutamine shortage. Indeed, when the cell-cycle was analyzed by flow cytometry, A549 showed a canonical response to asparaginase, 786-O cells, instead, showed a reduction of the percentage of cells in the G1 phase and an increase of those in the S-phase. Despite an increased number of PCNA and RPA70 positive nuclear foci, BrdU and EdU incorporation was absent or strongly delayed in treated 786-O cells, thus indicating a readiness of replication forks unmatched by DNA synthesis. In 786-O asparagine synthetase was reduced following treatment and glutamine synthetase was totally absent. Interestingly, DNA synthesis could be recovered by adding Gln to the medium. MCF-7 cells showed no significant changes in the cell cycle phases, in DNA-bound PCNA and in total PCNA, but a significant increase in ASNS and GS mRNA and protein expression. The collected data suggest that the effect observed on 786-O cells following ASNase treatment could rely on mechanisms which differ from those well-known and described for leukemic blasts, consisting of a complete block in the G1/S transition in proliferating cells and on an increase on non-proliferative (G0) blasts.

UNASSIGNED: p16 has different roles in the nuclear and cytoplasmic locations. The nuclear localization of the p16 protein explains its role in cell cycle regulation. Cytoplasmic expression was considered an artifact in the initial years, but there is evidence to prove that cytoplasmic localization is real and that p16 has different roles in the nuclear and cytoplasmic locations. We aimed to study the immunoexpression of p16 protein in the nuclear and cytoplasmic locations of the epithelial and stromal compartments of fibroadenoma, invasive breast carcinoma, and a select number of phyllodes tumors.
UNASSIGNED: The study included a total of 107 patients, comprising 51 cases of invasive breast carcinoma, 51 cases of fibroadenoma, 4 cases of benign phyllodes tumors, and 1 case of lobular carcinoma in situ (LCIS). The p16 immunohistochemistry was evaluated for nuclear and cytoplasmic localization in the epithelial and stromal compartments of the tumors.
UNASSIGNED: Of the 51 fibroadenoma cases, 23 showed strong nuclear p16 epithelial expression, but no case showed cytoplasmic expression. In 19/51 cases, stromal cells also showed strong p16 nuclear expression. Moderate stromal p16 expression was observed in 3 out of 4 cases of benign phyllodes. Out of the 51 cases of invasive carcinoma, 31 showed moderate to strong nuclear p16 immunopositivity, while 27 cases exhibited cytoplasmic p16 expression. We found a statistically significant correlation between moderate to strong nuclear p16 immunoexpression and the molecular subtype of breast carcinoma.
UNASSIGNED: The cytoplasmic localization of p16 immunohistochemistry is not seen in epithelial components of fibroadenoma, while it is seen frequently in breast carcinoma. Nuclear p16 expression has a statistically significant correlation with molecular subtypes of breast carcinoma.

BACKGROUND: The human cytochrome P450 (CYP) superfamily encompasses different categories of isoenzymes that contribute to multiple metabolic processes involving drug detoxification, cellular signaling, and the proliferation of malignant tissues. Using genetic technology, customized bioinformatic analysis, and meta-analysis design, the main goal of this study was to identify the association between the CYP1A2*rs762551 variant and the susceptibility to breast carcinoma (BRCA).
METHODS: The case-control study was conducted based on 104 BRCA women and 102 healthy controls. Using the TaqMan allelic discrimination assay, the CYP1A2 (rs762551; c.-9-154 C>A) variant was genotyped. Bioinformatic frameworks and logistic regression analysis were used to assess the involvement of this genetic variant in BRCA development. A meta-analysis design was accomplished based on our case-control study and other previously published records. Publication bias, heterogeneity between studies, and trial sequential analysis (TSA) were analyzed.
RESULTS: The CYP1A2*rs762551 variant conferred protection against BRCA development under allelic (OR = 0.48, p-value < 0.001), dominant (OR = 0.34, p-value < 0.001), and recessive (OR = 0.44, p-value = 0.011) models. However, this intronic variant was correlated with a decreased risk of BRCA among late-onset menopause women compared to other cases. Bioinformatic analysis confirmed that this genetic variant has a functional impact on the progression of tumorgenesis. Moreover, this meta-analysis design included 12922 BRCA women and 15603 healthy controls. Our findings disclosed the contribution of the CYP1A2*rs762551 variant with protection against cancer development among Caucasian females under allelic (OR = 0.75, p-value = 0.025), and dominant (OR = 0.58, p-value = 0.015) models.
CONCLUSIONS: This case-control study confirmed the contribution of the CYP1A2*rs762551 variant with decreased risk of BRCA development among Egyptian subjects. Moreover, BRCA women with late-onset menopause conferred protection against cancer progression compared to other subjects. Our findings identified that this meta-analysis design achieved protection against BRCA development among Caucasian women compared to other ethnicities.

UNASSIGNED: Breast cancer is the most common cancer in women and the second leading cause of cancer-related death. Breast cancer manifestations in the head and neck are relatively rare, have greater predilection for the jaws than for soft tissues. Metastasis in the oral cavity account for only 1 to 3 % of all oral malignant lesions. Regardless of the rare occurrence of metastatic lesions to the jaw, it should be taken into consideration in the individuals with a history of malignancy.
METHODS: The article reports a rare case of metastatic lesion of breast cancer to unilateral mandibular ramus region. The 66-year-old female patient was complaining of pain and swelling in the right mandible angle. She was referred to our department by her oncologist with the differential diagnosis of osteonecrosis or metastasis. She had undergone radical mastectomy for invasive lobular carcinoma of the left breast without adjuvant treatment. Oral cavity examination did not reveal the existence of any ulcer or fistula. Based on the patient\'s medical history and paresthesia of the lower lip and chin, the metastatic disease was highly suspected. The patient was referred to her oncologist for chemotherapy treatment before any invasive surgical management.
UNASSIGNED: Breast cancer (BC) is the most common cancer affecting women globally. Bone is the most common site of metastasis in BC patients, with up to 75 % of stage IV BC patients developing skeletal metastasis. The frequent metastatic sites of bone are spine, ribs, sternum, femur, pelvis. Breast carcinoma metastasizes to the jaw bones are uncommon.
CONCLUSIONS: The diagnosis of metastasis to the oral cavity is a significant challenge to the clinician due to the lack of pathognomonic signs and symptoms. The general dentist or dental specialist should maintain a high level of suspicion while dealing patients with a history of cancer.

OBJECTIVE: This study aimed to compare the outcomes of modified radical mastectomy (MRM) with the use of a harmonic scalpel versus electrocautery in patients with breast carcinoma.
METHODS: A prospective, non-randomized comparative study conducted from August 2022 to June 2024 on 40 female patients with stage II breast carcinoma undergoing MRM with electrocautery and harmonic scalpel.
RESULTS: Patients with MRM by harmonic scalpel exhibited significantly lower intraoperative blood loss (92.50 ± 9.67 mL) than by electrocautery (172.50 ± 30.76 mL) (p-value <.0001). The average operative time was significantly shorter for the harmonic scalpel (111.00 ± 10.71 minutes) than for the electrocautery (169.50 ± 19.32 minutes) (p-value <.0001). Postoperative pain was lower for the harmonic scalpel (visual analog scale (VAS) score 3.75 ± 0.79) than for the electrocautery (VAS score 6.10 ± 0.85) (p-value <.0001). The incidence of flap necrosis was not substantially different between the categories; seroma formation was significantly lower with the use of a harmonic scalpel (p-value <.0001). Subjects in the group of harmonic scalpels also had shorter hospital stays (8.35 ± 0.93 days) compared with the electrocautery group (12.20 ± 1.06 days) (p-value <.0001).