Axillary lymph node dissection (ALND) has been the standard treatment of breast cancer axillary staging in Indonesia. The limited facilities of radioisotope tracer and isosulfan or patent blue dye (PBD) have been the major obstacles to perform sentinel node biopsy (SNB) in our country. We studied the application of 1% methylene blue dye (MBD) alone for SNB to overcome the problem. This prospective study enrolled 108 patients with suspicious malignant lesions or breast cancer stages I–III. SNB was performed using 2–5 cc of 1% MBD and proceeded with ALND. The histopathology results of sentinel nodes (SNs) were compared with axillary lymph nodes (ALNs) for diagnostic value assessments. There were 96 patients with invasive carcinoma from July 2012 to September 2014 who were included in the final analysis. The median age was 50 (25–69) years, and the median pathological tumor size was 3 cm (1–10). Identification rate of SNs was 91.7%, and the median number of the identified SNs was 2 (1–8). Sentinel node metastasis was found in 53.4% cases and 89.4% of them were macrometastases. The negative predictive value (NPV) of SNs to predict axillary metastasis was 90% (95% CI, 81–99%). There were no anaphylactic reactions, but we found 2 cases with skin necrosis. The application of 1% MBD as a single technique in breast cancer SNB has favorable identification rates and predictive values. It can be used for axillary staging, but nevertheless the technique should be applied with attention to the tumor size and grade to avoid false negative results.
1 June 2021 in Drug Design, Development and Therapy
Introduction: In this research, we used a volumetric absorptive microsampling (VAMS) technique to collect blood samples from the patients. A rapid and simple sample preparation method and LC-MS.MS assay was then developed and validated for the simultaneous analysis of tamoxifen and its three active metabolites. Methods: VAMS extraction was performed in methanol by sonication-assisted extraction method for 25 min after 2 hof VAMS drying. Separation was carried out using Acquity UPLC BEH C18 column (2.1 x 100 mm; 1.7 μm), with a flow rate of 0.2 mL/min, and the mobile phase gradient of formic acid 0.1% and formic acid 0.1% in acetonitrile for 5 min. The multiple reaction monitoring (MRM) values were set at m/z 358.31> 58.27 for N-desmethyltamoxifen, m/z 372.33> 72.28 for tamoxifen, m/z 388.22> 72.28 for 4-hydroxytamoxifen, m/z 374.25> 58.25 for endoxifen, and m/z 260.26> 116.12 for propranolol. Results and Discussion: The lower limit of quantification value (LLOQ) was 2.50 ng/mL for tamoxifen, 2.50 ng/mL for endoxifen, 1.50 ng/mL for 4-hydroxitamoxifen, and 2.00 ng/mL for N-desmethyltamoxifen. Accuracy (%bias) and precision (%CV) were within 20% for LLOQ and 15% for other concentrations. There were no interference responses > 20% of the LLOQ and 5% of the internal standard. The level of ion suppression in all analytes was less than 7%. The preparation system developed in this study successfully extracted more than 90% of analytes from the matrix with precision below 15%. Carryover was shown to be below 6% in all analytes. Stability of analytes in VAMS was demonstrated for up to 30 days, under room temperature storage in a sealed plastic bag with desiccant. This method was successfully applied to analyze tamoxifen and the metabolites level in 30 ER+ breast cancer patients.
22 August 2025 in International Journal of Surgery
Background: Breast cancer treatment-related lymphedema (BCRL) is a chronic progressive morbidity for which a definitive cure has not yet been achieved. Since axillary lymph node dissection (ALND) is the main risk factor, we have studied the pattern of lymphatic drainage and subclinical lymphedema progression with ICG lymphography (ICG-L) after ALND as a part of our strategy to prevent BCRL. Methods: This study was a prospective cohort of breast cancer patients who underwent ALND between October 2022 and August 2024. We prospectively evaluated postoperative lymphatic drainage with ICG-L. Subclinical lymphedema progression to lymphedema was analyzed using the Kaplan–Meier method. Results: Sixty-three patients were analyzed. Five classifications of lymphatic pathways were identified. The most prevalent pattern was arm and chest wall dermal backflow (DB), draining to internal mammary nodes or type III in 54% of cases, followed by arm DB and collateral drainage to clavicular nodes (type II) in 19.1%, and arm DB only (type I) in 14.3% cases. The cumulative incidence of subclinical lymphedema progression to BCRL was 71.7% [95% confidence interval (CI), 47.0–96.4] with a median BCRL incidence of 13.8 months (95% CI, 10.0–17.5). The hazard rate of BCRL reached its peak at 3 and 12 months. Conclusion: The lymphatic drainage pattern of the arm will mainly drain into the internal mammary and clavicular nodes after ALND. A substantial number of subclinical cases progressing to early-stage BCRL can be detected by ICG-L within the first year. This finding could be used to develop strategies for BCRL prevention.
Tamoxifen is a Selective Estrogen-Receptor Modulator (SERM) commonly prescribed for standard of care in estrogen receptor positive (ER+) breast cancer as an adjuvant therapy. Tamoxifen is metabolized by CYP2D6 into its active metabolite, endoxifen, which has been known to play an important role in reducing risk of ER+ breast cancer recurrence. CYP2D6 is a highly polymorphic gene with more than 100 alleles. The phenotype of this gene is categorized into ultrarapid metabolizer (UM), normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM). Certain CYP2D6 polymorphisms may cause reduced activity of this enzyme. Studies have found that reduced CYP2D6 activity in IM and PM patients causes low efficacy of standard tamoxifen therapy. This study aims to observe the distribution of CYP2D6 alleles and its correlation with endoxifen levels in Indonesian ER+ breast cancer patients. 151 patients who have received tamoxifen therapy for at least eight weeks were recruited prospectively. DNA and blood samples were collected with buccal swab and finger-prick methods, respectively. Genotyping was performed using the qPCR method while metabolite level measurement was performed using high performance liquid chromatography tandem mass spectrometry. We found that 40.67% of ER+ breast cancer patients recruited were IM. CYP2D6*10 was the most abundant allele (0.288) in this population, and *10/*36 was the most frequently observed diplotype (0.236). Endoxifen levels between the NM-PM, NM-IM, and IM-PM were statistically significant ( p -value = 6.26 × 10 −5 , 9.12 × 10 −5 , and 4.714 × 10 −3 , respectively), and dose increase of tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline. Given these findings, implementing pharmacogenomic testing of CYP2D6 on ER+ breast cancer women who are about to undergo tamoxifen therapy may be beneficial to increase the likelihood of achieving expected endoxifen levels, thus better treatment efficacy.