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.

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).

BACKGROUND: The ESHO protocol 1-85 is a multicenter randomized trial initiated by the European Society for Hyperthermic Oncology with the aim to investigate the value of hyperthermia (HT) as an adjuvant to radiotherapy (RT) in treatment of locally advanced breast carcinoma. The trial is one of the largest studies of hyperthermia in radiotherapy but has not been previously published.
METHODS: Between February 1987 and November 1993, 155 tumors in 151 patients were included. Tumors were stratified according to institution and size (T2-3/T4) and randomly assigned to receive radiotherapy alone (2 Gy/fx, 5 fx/wk) to a total dose of 65-70 Gy, incl. boost, or the same radiotherapy followed once weekly by hyperthermia (aimed for 43 °C for 60 min). Radiation was given with high voltage photons or electrons. The primary endpoint was persistent complete response (local control) in the treated area.
RESULTS: A total of 146 tumors in 142 patients were evaluable, with a median observation time of 19 (range 1-134) months. Seventy tumors were randomized to RT alone and 76 to RT + HT. Size was T4 in 92, and T2-3 in 54 tumors, respectively. The compliance to RT was good with all but 4 patients fulfilling the planned RT treatment. The tolerance to HT was fair, but associated with moderate to severe pain and discomfort in 15 % of the treatments. In 84 % of the heated patients a least one heat treatment achieved the target temperature, but the temperature variation was large. Addition of heat did not significantly increase the acute nor late radiation reactions. Overall, the 5-year actuarial local failure rate was 57 %. Univariate analysis showed a significant influence of hyperthermia (RT alone 68 % versus RT + HT 50 %, p = 0.04, and T-size (T4 75 % versus T2-3 36 %, p < 0.01). A Cox multivariate analysis showed the same factors to be the only significant prognostic parameters: hyperthermia (HR: 0.61 [0.38-0.98], and small tumor strata (HR: 0.46 [0.26-0.92]. Consequentially, more patients given RT + HT (36 %) survived without disease (DFS), than after RT alone (19 %), p = 0.021) CONCLUSION: A randomized multicenter trial investigating the addition of a weekly hyperthermia treatment to radiotherapy of patients with locally advanced breast cancer significantly enhanced the 5-year tumor control and yielded more patients surviving free from cancer. The results substantiate the potential clinical benefit of hyperthermic oncology.

BACKGROUND: Breast carcinoma is one of the most common cancers in present-day women worldwide, hence surgical intervention for the same is inevitable. General anesthesia being the preferred technique, the selection of appropriate postoperative pain management is a major concern in which superficial fascial plane chest wall blocks play a pivotal role. We aimed to prove the efficacy of peripheral nerve stimulator-guided pectoral nerve-1 (PEC 1) block and serratus anterior plane (SAP) block for postoperative analgesia in modified radical mastectomy.
METHODS: This prospective randomized controlled clinical study comprised 60 females undergoing modified radical mastectomy and was randomly allocated to two groups. Group A patients received general anesthesia while, in addition to general anesthesia, group B patients received PEC 1 and SAP blocks. Postoperatively the active and passive visual analog score (VAS), duration of analgesia, cumulative requirement of rescue analgesics in the first 24 hours and associated perioperative complications were noted. All quantitative data were analyzed by student t-test and qualitative data by chi-square test using MedCalc software 12.5.
RESULTS: VAS score for first 24 hours in group B was lower at rest, on pressure over the surgical site as well as on movements compared with the patients in group A with the p-value being < 0.0001 at all time intervals. Time for receiving first rescue analgesia was shorter (1.25±0.56hour vs 20.05±7.78hour, p<0.001) with the significantly higher requirement of cumulative doses of tramadol in the first 24 hours in patients belonging to group A (233.33±47.95mg vs 110±31.62 mg, p<0.001).
CONCLUSIONS: PEC 1 and SAP blocks given under peripheral nerve stimulator guidance have a high success rate and are reliable in providing adequate postoperative analgesia for patients undergoing modified radical mastectomy.

OBJECTIVE: A false positive (FP) referral after screening mammography may influence a woman\'s likelihood to re-attend the screening program. The impact of having a FP result in the first or subsequent screening round on re-attendance after a FP result was investigated. In addition, we aimed to study differences in re-attendance rates between women who underwent non-invasive and invasive additional examinations as part of the diagnostic work-up following a FP referral.
METHODS: A consecutive series of 13,597 women with a FP referral following biennial screening mammography in the south of the Netherlands between 2009 and 2019 was included.
RESULTS: The screening re-attendance rate was 81.2% after a FP referral, and 91.3% when also including women who had clinical mammographic follow-up. Women who received a FP referral in the first screening round were less likely to re-attend the screening programme in the following three years, compared to those with a FP test in any subsequent round (odds ratio (OR): 0.59, 95%-confidence interval (CI): 0.51-0.69). Women with a FP referral who underwent invasive examinations after referral were less likely to re-attend the screening programme than those who only received additional imaging (OR, 0.48; 95% CI 0.36-0.64).
CONCLUSIONS: Women with a FP referral are less likely to re-attend the screening programme if this referral occurs at their first screening round or when they undergo invasive diagnostic workup. Hospitals and screening organizations should prioritize informing women about the importance of re-attending the programme following a FP referral.

In Pakistan, the death rate for post-menopausal women with breast cancer is significant due to late detection and delayed referral to proper facilities. There are a few reports on Pakistan\'s epidemiology and breast cancer risk factors. There are modifiable and non-modifiable risk factors associated with the development of breast carcinoma; of which body mass index (BMI), central obesity, and lipid profile are considered as major risk markers.
This was a cross-sectional analytical study. A total of 384 women constituted the present study sample. Purposive sampling was used to collect 192 confirmed new breast cancer cases throughout the study. By using basic random sampling, an equal number of controls were chosen. Studied parameters included age, fasting blood sugar, cholesterol, triglyceride, serum high-density lipoprotein, cholesterol, serum low-density lipoprotein cholesterol, weight, height, BMI, waist circumference, and waist-to-hip ratio. The inclusion criteria of this study were post-menopausal women (45-65 years) in Pakistan. The confirmation of breast carcinoma was done through histopathology. Breast cancer occurrence was taken as a dependent variable, whereas BMI, central obesity, and lipid profile were taken as independent variables.
Studied risk factors (cholesterol, BMI, and central obesity) significantly correlated with breast cancer. Cholesterol has a significantly high positive correlation (0.646) with breast cancer. BMI has a positive significant correlation (0.491) with breast cancer, and central obesity has a low but positive significant correlation (0.266) with breast cancer. Moreover, the binary logistic regression model also showed a significant association between biochemical factors and breast cancer occurrence. Regression analysis depicted a linear relationship between a dependent variable (breast cancer occurrence) and independent variables (central obesity, cholesterol, BMI).
Postmenopausal overweight (central obesity), increased BMI and high cholesterol levels are major risk factors for breast cancer. Moreover, high total cholesterol proved to be the most significant risk marker for the occurrence of breast cancer in post-menopausal women of Pakistan.

Human epidermal growth factor receptor 2 (HER2) status is used for decision-making in breast carcinoma treatment. The status is obtained through immunohistochemistry or in situ hybridization. These two methods have the disadvantage of necessitating tissue sampling, which is prone to error due to tumor heterogeneity or interobserver variability. Whole-body imaging might be a solution to map HER2 expression throughout the body. Methods: Twenty patients with locally advanced or metastatic breast carcinoma (5 HER2-positive and 15 HER2-negative patients) were included in this phase II trial to assess the repeatability of uptake quantification and the extended safety of the [68Ga]Ga-NOTA-anti-HER2 single-domain antibody (sdAb). The tracer was injected, followed by a PET/CT scan at 90 min. Within 8 d, the procedure was repeated. Blood samples were taken for antidrug antibody (ADA) assessment and liquid biopsies. On available tissues, immunohistochemistry, in situ hybridization, and mass spectrometry were performed to determine the correlation of HER2 status with uptake values measured on PET. If relevant preexisting [18F]FDG PET/CT images were available (performed as standard of care), a comparison was made. Results: With a repeatability coefficient of 21.8%, this imaging technique was repeatable. No clear correlation between PET/CT uptake values and pathology could be established, as even patients with low levels of HER2 expression showed moderate to high uptake. Comparison with [18F]FDG PET/CT in 16 patients demonstrated that in 7 patients, [68Ga]Ga-NOTA-anti-HER2 shows interlesional heterogeneity within the same patient, and [18F]FDG uptake did not show the same heterogeneous uptake in all patients. In some patients, the extent of disease was clearer with the [68Ga]Ga-NOTA-anti-HER2-sdAb. Sixteen adverse events were reported but all without a clear relationship to the tracer. Three patients with preexisting ADAs did not show adverse reactions. No new ADAs developed. Conclusion: [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT imaging shows similar repeatability to [18F]FDG. It is safe for clinical use. There is tracer uptake in cancer lesions, even in patients previously determined to be HER2-low or -negative. The tracer shows potential in the assessment of interlesional heterogeneity of HER2 expression. In a subset of patients, [68Ga]Ga-NOTA-anti-HER2-sdAb uptake was seen in lesions with no or low [18F]FDG uptake. These findings support further clinical development of [68Ga]Ga-NOTA-anti-HER2-sdAb as a PET/CT tracer in breast cancer patients.

Sumeet SidhuObjectives  Breast cancer is the leading cause of cancer-related deaths in women. Estrogen (ER) and progesterone receptor (PR) status and Her2 overexpression are major determinants in therapeutic decision making. Triple-negative breast cancers (TNBCs) have limited treatment options. Androgen receptor (AR) expression opens up therapeutic avenues for these patients. The aim of this article was to study the immunohistochemical expression of ARs in ER and PR Negative breast carcinomas and to correlate AR expression with various clinical, histopathological, and other immunohistochemical parameters. Materials and Methods  It is a cross-sectional study including 105 ER and PR Negative cases of breast carcinoma. Clinical parameters, histopathology, and immunohistochemical expression of AR, Her2, and Ki67 were analyzed in all cases. Results  AR expression was observed in 63.8% of ER and PR Negative breast cancers. In this group, AR expression was strongly associated with Her2 co-expression (89.2%) as compared to TNBCs (45.8%); p -value = 0.0002. Significant correlation was also observed between AR expression and tumor necrosis ( p -value = 0.034) and postmenopausal status ( p  = 0.007). Conclusion  Our study shows that significant proportion of ER and PR Negative breast carcinomas (ER- PR- Her2+ and TNBCs) show AR expression. We strongly recommend routine evaluation of all hormone receptor-negative breast carcinomas for AR status by immunohistochemistry.

UNASSIGNED: Mast cells influence tumour growth, neo-angiogenesis and the propensity for metastasis by contributing to innate and adaptive immune responses in the tumour microenvironment. The number of mast cells has increased in various malignant tumours and their abundance has been associated with either a favourable or unfavourable prognosis. This study investigated the significant difference in stromal mast cell density among multiple prognostic factor groups in invasive breast carcinoma.
UNASSIGNED: CD117 (c-KIT) antibodies were used to stain 160 formalin-fixed and paraffin-embedded invasive breast carcinoma tissues to demonstrate the presence of mast cells. Then the labelled mast cells were counted in 10 fields at 400× magnification and the mean value was used to represent the mast cell density.
UNASSIGNED: The demographic distribution revealed that most patients were 40 years old or older (92.5%) and of Malay ethnicity (66.3%). With regard to prognostic factors, the most prevalent subtype was invasive carcinoma of no special type (80.6%), followed by tumour grade 3 (41.3%), T2 tumour size (63.1%), N0 lymph node stage (51.3%), presence of lymphovascular invasion (59.4%), positive oestrogen (64.4%) and progesterone receptors (53.1%), and negative human epidermal growth factor receptor 2 (HER2) expression (75.0%). However, there was no significant difference in stromal mast cell density among the different demographic and prognostic factor groups in invasive breast carcinoma.
UNASSIGNED: The findings from this study suggest that stromal mast cells do not play a significant role in preventing or promoting tumour growth in invasive breast carcinoma.

BACKGROUND: The early diagnosis of breast carcinoma is of paramount importance in its management. Fine-needle aspiration cytology (FNAC) has the potential to play a pivotal role in providing the relevant information on the aggressiveness of this tumor. But there is no gold standard when it comes to cytological grading of breast carcinoma as there is no consensus between the pathologists and also the clinicians as to which grading is as par with the gold standard Elston-Ellis modification of Scarff-Bloom-Richardson (SBR) histological grading. This study was undertaken to study seven cytological 3-tier grading systems, namely, Robinson\'s, Fisher\'s, Mouriquand\'s, Dabbs\', Khan\'s, Taniguchi\'s, and Howells\'s and to correlate them with the Elston-Ellis modification of SBR histological grading system so as to determine the finest cytological grading system which could be reliably used in our routine practice.
METHODS: A total of 117 breast carcinoma cases diagnosed on FNAC were graded using seven 3-tier cytological grading systems and were correlated with Elston-Ellis modification of SBR histological grading system. Concordance, kappa measurement, and various correlation studies were done using SPSS software version 2021.
RESULTS: Robinson\'s method showed a better concordance (84.61%), a better correlation (Spearman = 0.750, τ = 0.731, p < 0.001), and a substantial kappa value of agreement (κ = 0.701) with SBR grading system compared to other system closely followed by Fisher\'s system.
CONCLUSIONS: Even though all the seven 3-tier cytological grading systems positively correlated with the SBR histologic grading of breast carcinoma, Robinson\'s method showed better concordance and correlation with a substantial kappa value of agreement in comparison to other 3-tier cytology grading systems. Hence, Robinson\'s grading which is simpler and also feasible should be incorporated in the routine cytology reporting of breast carcinoma.