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13 result(s) for "Buhari, Shaik Ahmad"
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High-Throughput Mutation Profiling Changes before and 3 Weeks after Chemotherapy in Newly Diagnosed Breast Cancer Patients
Changes in tumor DNA mutation status during chemotherapy can provide insights into tumor biology and drug resistance. The purpose of this study is to analyse the presence or absence of mutations in cancer-related genes using baseline breast tumor samples and those obtained after exposure to one cycle of chemotherapy to determine if any differences exist, and to correlate these differences with clinical and pathological features. Paired breast tumor core biopsies obtained pre- and post-first cycle doxorubicin (n = 18) or docetaxel (n = 22) in treatment-naïve breast cancer patients were analysed for 238 mutations in 19 cancer-related genes by the Sequenom Oncocarta assay. Median age of patients was 48 years (range 32-64); 55% had estrogen receptor-positive tumors, and 60% had tumor reduction ≥25% after cycle 1. Mutations were detected in 10/40 (25%) pre-treatment and 11/40 (28%) post-treatment samples. Four mutation pattern categories were identified based on tumor mutation status pre- → post-treatment: wildtype (WT)→WT, n = 24; mutant (MT)→MT, n = 5; MT→WT, n = 5; WT→MT, n = 6. Overall, the majority of tumors were WT at baseline (30/40, 75%), of which 6/30 (20%) acquired new mutations after chemotherapy. Pre-treatment mutations were predominantly in PIK3CA (8/10, 80%), while post-treatment mutations were distributed in PIK3CA, EGFR, PDGFRA, ABL1 and MET. All 6 WT→MT cases were treated with docetaxel. Higher mutant allele frequency in baseline MT tumors (n = 10; PIK3CA mutations n = 8) correlated with less tumor reduction after cycle 1 chemotherapy (R = -0.667, p = 0.035). No other associations were observed between mutation pattern category with treatment, clinicopathological features, and tumor response or survival. Tumor mutational profiles can change as quickly as after one cycle of chemotherapy in breast cancer. Understanding of these changes can provide insights on potential therapeutic options in residual resistant tumors. ClinicalTrials.gov NCT00212082.
Ultrasound-guided photoacoustic (US-PA) tomography of the breast: Biochemical differentiation using intrinsic tissue markers—lipids, collagen and hemoglobin with histopathologic correlation
In this pilot study, we investigated the utility of handheld ultrasound-guided photoacoustic (US-PA) imaging probe for analyzing ex-vivo breast specimens obtained from female patients who underwent breast-conserving surgery (BCS). We aimed to assess the potential of US-PA in detecting biochemical markers such as collagen, lipids, and hemoglobin, and compare these findings with routine imaging modalities (mammography, ultrasound) and histopathology results, particularly across various breast densities. Twelve ex-vivo breast specimens were obtained from female patients with a mean age of 59.7 ± 9.5 years who underwent BCS. The tissues were illuminated using handheld US-PA probe between 700 and 1100 nm across all margins and analyzed for collagen, lipids, and hemoglobin distribution. The obtained results were compared with routine imaging and histopathological assessments. Our findings revealed that lipid intensity and distribution decreased with increasing breast density, while collagen exhibited an opposite trend. These observations were consistent with routine imaging and histopathological analyses. Moreover, collagen intensity significantly differed ( P  < 0.001) between cancerous and normal breast tissue, indicating its potential as an additional biomarker for risk stratification across various breast conditions. The study results suggest that a combined assessment of PA biochemical information, such as collagen and lipid content, superimposed on grey-scale ultrasound findings could aid in distinguishing between normal and malignant breast conditions, as well as assist in BCS margin assessment. This underscores the potential of US-PA imaging as a valuable tool for enhancing breast cancer diagnosis and management, offering complementary information to existing imaging modalities and histopathology.
Cohort profile: The Singapore Breast Cancer Cohort (SGBCC), a multi-center breast cancer cohort for evaluation of phenotypic risk factors and genetic markers
This article aims to provide a detailed description of the Singapore Breast Cancer Cohort (SGBCC), an ongoing multi-ethnic cohort established with the overarching goal to identify genetic markers for breast cancer risk, prognosis and treatment response, as well as to understand the ethnic differences in disease risk and outcome in an Asian setting. The cohort comprises of breast cancer patients aged 21 years and above from six public hospitals which diagnose and treat nearly 76% breast cancer cases in Singapore. Self-reported data on sociodemographic and lifestyle, reproductive risk factors, medical history and family history of breast or ovarian cancer is collected using a structured questionnaire. Clinical data on tumour characteristics, and treatment modalities are obtained through medical record. Bio-specimens (blood or saliva) is collected at recruitment. Follow-up on survival information is done through routine linkage with the Registry of Births and Deaths. As of 31 December 2016, 7,768 subjects have been recruited to the study with 76% subjects contributed bio-specimens. The SGBCC provides a valuable platform which offers a unique, large and rich resource for new research ideas on breast cancer related phenotypic risk factors and genetic markers.
Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results
Background: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients. Methods: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t-tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls. Results: PRS distributions were not significantly different in any of the comparisons. Higher PRSoverall quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79–1.06]; FNc: 0.87 [0.73–1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRSER-pos) and ER-negative weighted PRS (PRSER-neg). Conclusion: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc.
Photoacoustic Tomography Appearance of Fat Necrosis: A First-in-Human Demonstration of Biochemical Signatures along with Histological Correlation
A 50-year-old woman with no past medical history presented with a left anterior chest wall mass that was clinically soft, mobile, and non-tender. A targeted ultrasound (US) showed findings suggestive of a lipoma. However, focal “mass-like” nodules seen within the inferior portion suggested malignant transformation of a lipomatous lesion called for cross sectional imaging, such as MRI or invasive biopsy or excision for histological confirmation. A T1-weighted image demonstrated a large lipoma that has a central fat-containing region surrounded by an irregular hypointense rim in the inferior portion, confirming the benignity of the lipoma. An ultrasound-guided photoacoustic imaging (PA) of the excised specimen to derive the biochemical distribution demonstrated the “mass-like” hypoechoic regions on US as fat-containing, suggestive of benignity of lesion, rather than fat-replacing suggestive of malignancy. The case showed the potential of PA as an adjunct to US in improving the diagnostic confidence in lesion characterization.
Accelerated partial breast irradiation in an Asian population: dosimetric findings and preliminary results of a multicatheter interstitial program
Accelerated partial breast irradiation (APBI) using the multicatheter method has excellent cosmesis and low rates of long-term toxicity. However, there are few studies looking at the feasibility of this procedure and the outcomes in an Asian population. This study aims to look at outcomes at our hospital. We identified 121 patients treated with APBI at our center between 2008 and 2014. The median follow-up for our patient group was 30 months (range 3.7-66.5). The prescribed dose per fraction was 3.4 Gy in 10 fractions. In this study population, 71% of the patients were Chinese while 15% (n=19) were of other Asian ethnicity. In this study, the median breast volume was 850 cc (range 216-2,108) with 59.5% (n=72) patients with a breast volume of <1,000 cc. The average planning target volume was 134 cc (range 28-324). The number of catheters used ranged from 8 to 25 with an average of 18 catheters used per patient. We achieved an average dose homogeneity index of 0.76 in our patients. The average D90(%) was 105% and the average D90(Gy) was 3.6 Gy per fraction. The median volume receiving 100% of the prescribed dose (V100) was 161.7 cc (range 33.9-330.1), 150% of the prescribed dose (V150) and 200% of the prescribed dose (V200) was 39.4 cc (range 14.6-69.6) and 14.72 cc (range 6.48-22.25), respectively. Our dosimetric outcomes were excellent even in patients with breast volume under 1,000 cc. There were no cases of grade 3 skin toxicity or acute pneumonitis. Two patients had a postoperative infection and two patients had fat necrosis postprocedure. Multicatheter high dose rate APBI is a safe and feasible procedure that can be carried out with minimal toxicity in Asian patients with breast volumes under 1,000 cc.
Multi-catheter interstitial accelerated partial breast irradiation – tips and tricks for a good insertion
Adjuvant radiotherapy is recommended post breast conserving surgery. Accelerated Partial Breast Irradiation (APBI) offers a more attractive shorter course of treatment over 5 days compared to standard conventional external beam radiotherapy, which is often protracted. Multi-catheter interstitial APBI offers excellent dosimetric coverage. This article describes two insertion techniques for multi-catheter interstitial APBI, the operator dependent freehand technique, and the easier to learn template technique. The indications, benefits, and drawbacks of these two techniques are discussed.
Impact of contrast-enhanced mammography in surgical management of breast cancers for women with dense breasts: a dual-center, multi-disciplinary study in Asia
Objective To evaluate the impact of pre-operative contrast-enhanced mammography (CEM) in breast cancer patients with dense breasts. Methods We conducted a retrospective review of 232 histologically proven breast cancers in 200 women (mean age: 53.4 years ± 10.2) who underwent pre-surgical CEM imaging across two Asian institutions (Singapore and Taiwan). Majority (95.5%) of patients had dense breast tissue (BI-RADS category C or D). Surgical decision was recorded in a simulated blinded multi-disciplinary team setting on two separate scenarios: (i) pre-CEM setting with standard imaging, and clinical and histopathological results; and (ii) post-CEM setting with new imaging and corresponding histological findings from CEM. Alterations in surgical plan (if any) because of CEM imaging were recorded. Predictors CEM of patients who benefitted from surgical plan alterations were evaluated using logistic regression. Results CEM resulted in altered surgical plans in 36 (18%) of 200 patients in this study. CEM discovered clinically significant larger tumor size or extent in 24 (12%) patients and additional tumors in 12 (6%) patients. CEM also detected additional benign/false-positive lesions in 13 (6.5%) of the 200 patients. Significant predictors of patients who benefitted from surgical alterations found on multivariate analysis were pre-CEM surgical decision for upfront breast conservation (OR, 7.7; 95% CI, 1.9-32.1; p = 0.005), architectural distortion on mammograms (OR, 7.6; 95% CI, 1.3–42.9; p = .022), and tumor size of ≥ 1.5 cm (OR, 1.5; 95% CI, 1.0-2.2; p = .034). Conclusion CEM is an effective imaging technique for pre-surgical planning for Asian breast cancer patients with dense breasts. Key Points • CEM significantly altered surgical plans in 18% (nearly 1 in 5) of this Asian study cohort with dense breasts. • Significant patient and imaging predictors for surgical plan alteration include (i) patients considered for upfront breast-conserving surgery; (ii) architectural distortion lesions; and (iii) tumor size of ≥ 1.5 cm. • Additional false-positive/benign lesions detected through CEM were uncommon, affecting only 6.5% of the study cohort.