INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Purpose: Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer. Methods: This retrospective study included all patients with stage I–III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore.Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests. Results: A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13–3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16–0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17–0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07–2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11–3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36–0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09–2.44; p = 0.018). Conclusion NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.

PURPOSE: The American Joint Committee on Cancer 8th edition (AJCC8) prognostic stage (PS) was implemented January 1, 2018, but it is complex due to multiple permutations. A North American group proposed a simpler system using the anatomic stage with a risk score system (RSS) of 1 point each for grade 3 tumor and human epithelial growth factor receptor 2 (HER2) and estrogen receptor (ER) negativity. Here we aimed to evaluate this risk score system with our database of Asian breast cancer patients and compare it against the AJCC8 PS. METHODS: Patients diagnosed with breast cancer stage I–IV in 2006–2012 were identified in the SingHealth Joint Breast Cancer Registry. Five-year breast cancer-specific survival (CSS) and overall survival (OS) were calculated for each anatomic stage according to the risk score and compared with the AJCC8 PS. RESULTS: A total of 6,656 patients were analyzed. The median follow-up was 61 (interquartile range, 37–90) months. There was a high receipt of endocrine therapy (84.6% of ER+ patients), chemotherapy (84.3% of node-positive patients), and trastuzumab (86.0% of HER2+ patients). Within each anatomic stage, there were significant differences in survival in all sub-stages except IIIB. On multivariate analysis, the hazard ratio for negative ER was 1.74 (1.48–2.06), for negative HER2 was 1.49 (1.26–1.74), and for grade 3 was 1.84 (1.55–2.19). On multivariate analysis controlled for age, ethnicity, and receipt of chemotherapy, the RSS (Akaike information criterion [AIC] = 10,649.45; Harrell's Concordance Index [C] = 0.85) was not inferior to the AJCC8 PS (AIC = 10,726.65; C = 0.84) for CSS, nor was the RSS (AIC = 14,714.4; C = 0.82) inferior to the AJCC8 PS (AIC = 14,784.69; C = 0.81) for OS. CONCLUSION: The RSS is comparable to the AJCC8 PS for a patient population receiving chemotherapy as well as endocrine- and HER2-targeted therapy and further stratifies stage IV patients.
Asian Continental Ancestry Group ; Biomarkers ; Breast Neoplasms ; Breast ; Drug Therapy ; Estrogens ; Follow-Up Studies ; Humans ; Joints ; Multivariate Analysis ; Trastuzumab

PURPOSE: This study was undertaken to examine the impact of screening and race on breast cancer outcomes in Singapore. METHODS: An institutional database was reviewed, and invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) data were analyzed separately. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were assessed. RESULTS: The study included 6,180 IDC and 1,031 DCIS patients. The median follow-up time was 4.1 years. Among IDC patients, Malay women were the youngest when first diagnosed, and were more likely to present with advanced stage disease. Malay women also had the highest proportion of T3 and T4 tumors at 14.2%, compared with Chinese women at 8.7% and Indian women at 9.6% (p<0.001). Malay women had a higher incidence of node-positive disease at 58.3% compared with Chinese women at 46.4% and Indian women at 54.9% (p<0.001). Malay subjects also had higher-grade tumors; 61.8% had grade 3 tumors compared with 45.8% of Chinese women and 52% of Indian women (p<0.001). Furthermore, tumors in Malay subjects were less endocrine-sensitive and more human epidermal growth factor receptor 2 enriched. Malay women had the lowest 5- and 10-year OS, DFS, and CSS rates (p<0.001). After separating clinically and screen-detected tumors, multivariate analysis showed that race was still significant for outcomes. For screen-detected tumors, the OS hazard ratio (HR) for Malay women compared to Chinese women was 5.78 (95% confidence interval [CI], 2.64–12.64), the DFS HR was 2.18 (95% CI, 1.19–3.99), and the CSS HR was 5.93 (95% CI, 2.15–16.39). For DCIS, there were no statistically significant differences in the tumor size, grade, histology subtypes, or hormone sensitivity. CONCLUSION: Malay race is a poor prognostic factor in both clinically and screen-detected IDC. Special attention should be given to the detection and follow-up of breast cancer in this group.
Asian Continental Ancestry Group ; Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Continental Population Groups ; Disease-Free Survival ; Early Detection of Cancer ; Ethnic Groups ; Female ; Follow-Up Studies ; Humans ; Incidence ; Mass Screening* ; Multivariate Analysis ; Prognosis ; Receptor, Epidermal Growth Factor ; Singapore

INTRODUCTIONMost international clinical practice guidelines for prostate cancer (PCa) are driven by data derived in a Western setting. However, tumour biology and clinical disease progression are likely to differ in the Asian population. We compare the performance of the revised American Joint Committee on Cancer (AJCC) prognostic groups with the commonly used D'Amico Risk Classification and conventional predictors for PCa, in a large cohort of Asian patients.

MATERIALS AND METHODSWe retrospectively reviewed data for 404 consecutive Singaporean patients receiving definitive radiotherapy at our centre between December 1996 and October 2006. The primary outcome was biochemical relapse-free survival (BRFS), defined using the Phoenix definition. The secondary outcome was overall survival (OS). Prognostic risk groups were defined using AJCC 7th edition (AJCC7) and 6th edition (AJCC6). Univariate analysis (UVA) and multivariate analysis (MVA) were performed for the following putative risk factors: age, Gleason score, prognostic grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy and initial PSA value.

RESULTSFor the cohort, median age was 69 years. Median follow-up was 66.3 months. Five-year BRFS rate was 84.3% with 71 biochemical relapses and 5-year OS rate was 89.1% with 54 deaths. The concordance-indices for BRFS prediction were 0.588, 0.550 and 0.567 for AJCC7, AJCC6 and D'Amico respectively. Initial PSA, T-stage and AJCC7 were prognostic for BRFS on UVA. Comparison of AJCC7 vs. D'Amico showed no statistical additional value of either classification system although D'Amico was superior when compared to AJCC6 in predicting BRFS. T-stage ≥3 and D'Amico were significant prognostic factors for BRFS on MVA.

CONCLUSIONIn our local, predominantly Chinese population, neither AJCC6 nor AJCC7 demonstrated a high predictive accuracy for BRFS although AJCC7 has a slightly better predictive ability than AJCC6.

Aged ; Aged, 80 and over ; Asia ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Practice Guidelines as Topic ; Prognosis ; Prostatic Neoplasms ; pathology ; radiotherapy ; Radiotherapy ; methods ; Retrospective Studies ; United States

INTRODUCTIONOur study investigates whether an approximation of breast cancer molecular subtypes using the hormone receptors and HER-2 status prognosticates for disease control after breast conservation therapy (BCT) in node-negative Asian breast cancer patients.

METHODS AND MATERIALSWe retrospectively reviewed 541 women with node-negative breast cancers treated with BCT between 1989 and 2007. Hormone receptors and HER-2 status were obtained from patients' histological report. All patients received radiotherapy. Thirty-six percent and 68% of women received chemotherapy and hormonal treatment respectively.

RESULTSMedian follow-up of patients is 72 months. Five-year local recurrence free survival (LRFS) is 97.2% for the cohort but differs between subtypes: luminal A, 0.8%; luminal B, 1.4%; HER-2, 3.6% and basal-like, 12.7% (P = 0.047). The 5-year distant disease free survival (DDFS) is 96.4% for the cohort but differs between subtypes: luminal A, 98.2%; luminal B, 92.6%; HER-2, 89.5% and basal-like, 91.5% (P = 0.019). The 5-year disease free survival (DFS) is 94.4% for the cohort but differs between subtypes: luminal A, 97.4%; luminal B, 92.7%; HER-2, 86.3% and basal-like, 85.0% (P = 0.007). Univariate analysis with luminal A as baseline revealed an association of the other 3 subtypes with decreased DFS (P = 0.007), Hazard Ratio (HR) of 2.2, 4.4 and 3.3 to Luminal B, HER-2 and basal subtypes, respectively. On multivariate analysis, HER-2 subtype (AHR = 3.3, 95% CI, 1.1 to 9.8, P = 0.036) and basal-like subtype (HR = 3.5, 95% CI, 1.2 to 9.9, P = 0.019) prognosticate adversely for DFS.

CONCLUSIONThe combination of hormone receptors and HER-2 status can be used as surrogates for molecular subtypes in Asian breast cancer patients with node-negative disease to prognosticate LRFS, DFS and DDFS.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; genetics ; pathology ; prevention & control ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Prognosis ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; genetics ; Receptors, Estrogen ; genetics ; Receptors, Progesterone ; genetics ; Retrospective Studies ; Risk Assessment ; Survival Analysis ; Treatment Outcome