RESUMEN
Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2- breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.
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Neoplasias de la Mama , Mutación , Fenotipo , Receptor ErbB-2 , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Pueblo Asiatico/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Análisis por Conglomerados , Estudios de Cohortes , Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Perfilación de la Expresión Génica , Malasia/epidemiología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , TranscriptomaRESUMEN
Seeking health information is an important step for cancer patients to understand their condition and facilitate treatment. It also helps them deal with the unknown and aid in recovery. Therefore, it is vital to understand the factors that drive health information-seeking behavior. This study aims to achieve that objective in a localized context by surveying 421 breast cancer patients in an urban teaching hospital. The patients were presented with a 5-point questionnaire that explored their demography, health status, information-seeking behavior, and literacy level. The prevalence of health information-seeking initiatives reported was 60%. Patients with higher education (OR 3.31; 95% CI (1.39-7.87), p = 0.01), having their own business or were self-employed (OR 4.68; 95% CI (1.03-21.24), p = 0.046), and in a Medium 40 (M40) income level (OR 2.31; 95% CI (1.09-4.88), p = 0.03) and Top 20 (T20) level were more likely to seek health information. The mean e-Health Literacy Score (eHEALS) was 28.01 ± 5.0, with healthcare professionals having the highest level of trust (mean 4.22 ± 0.79) and most useful resource score (mean 4.21 ± 0.78). Even though Google was the most popular online search tool used by respondents, most of them seldom (23.77%) or had never (34.34%) discussed the online information they found with healthcare professionals. In conclusion, it is still best for patients to appraise the sought-after information with experts to avoid misinformation and treatment delay.
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Neoplasias de la Mama , Alfabetización en Salud , Humanos , Femenino , Conducta en la Búsqueda de Información , Neoplasias de la Mama/terapia , Estudios Transversales , Encuestas y Cuestionarios , InternetRESUMEN
BACKGROUND: In recent years, the increase in antibiotics usage locally has led to a worrying emergence of multi-drug resistant organisms (MDRO), with the Malaysian prevalence rate of methicillin-resistant Staphylococcus aureus (MRSA) ranging from 17.2 to 28.1% between 1999 and 2017. A study has shown that 7% of all non-lactational breast abscesses are caused by MRSA. Although aspiration offers less morbidities compared to surgical drainage, about 20% of women infected by MRSA who initially underwent aspiration subsequently require surgical drainage. This study is conducted to determine the link between aetiology, antimicrobial resistance pattern and treatment modalities of breast abscesses. METHODS: Retrospective study of reviewing microbiology specimens of breast abscess patients treated at Universiti Malaya Medical Centre from 2015 to 2020. Data collected from microbiology database and electronic medical records were analysed using SPSS V21. RESULT: A total of 210 specimens from 153 patients were analysed. One-fifth (19.5%) of the specimens isolated were MDRO. Lactational associated infections had the largest proportion of MDR in comparison to non-lactational and secondary infections (38.5%, 21.7%, 25.7%, respectively; p = 0.23). Staphylococcus epidermidis recorded the highest number of MDR (n = 12) followed by S. aureus (n = 8). Adjusted by aetiological groups, the presence of MDRO is linked to failure of single aspirations (p = 0.554) and significantly doubled the risk of undergoing surgical drainage for resolution (p = 0.041). CONCLUSION: MDR in breast abscess should be recognised as an increasing healthcare burden due to a paradigm shift of MDRO and a rise of resistance cases among lactational associated infection that were vulnerable to undergo surgical incision and drainage for resolution.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Femenino , Staphylococcus aureus , Absceso/tratamiento farmacológico , Absceso/cirugía , Estudios Retrospectivos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/epidemiología , Antibacterianos/uso terapéutico , HospitalesRESUMEN
BACKGROUND: There is a paucity of data on the use of intraoperative radiotherapy (IORT) with low-energy X-rays in Malaysian women with early breast cancer. The aim of this study is to evaluate the clinical, cosmetic, and patient-reported outcomes in low- and high-risk early breast cancer patients treated with breast conserving surgery (BCS) and IORT. METHODOLOGY: Patients suitable for BCS who were treated with IORT between January 2016 and June 2019 from three centres were analysed. They were divided into low-risk and high-risk groups based on the risk of recurrence according to the TARGeted Intraoperative radioTherapy (TARGIT) A and B study criteria. Outcomes of interest included local recurrence, wound complications, and radiation toxicity, with a subset analysed for cosmetic and patient-reported outcomes. RESULTS: Within a median follow-up of 31 months, there were 104 and 211 patients in the low- and high-risk groups, respectively. No significant difference was observed in local recurrence rates (low-risk, 1.0% vs. high-risk, 1.4%; p = 1.000). Both cohorts exhibited low frequencies of severe wound complications ranging between 1.4 and 1.9%. No major radiation toxicities were reported in either group. In the subgroup analysis, low-risk patients had significantly better mean scores in the subscales of inframammary fold and scar. Based on the BREAST-Q patient-reported outcomes questionnaire, seven out of nine parameters were scored similarly between both groups with no significant difference. CONCLUSION: This study showed that the use of IORT in both low- and high-risk early breast cancers is efficacious and safe with low recurrence rates and an acceptable toxicity profile.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Estudios ProspectivosRESUMEN
BACKGROUND: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population. METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays. RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks. CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.
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Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Animales , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteína del Grupo de Complementación N de la Anemia de Fanconi/genética , Femenino , Mutación de Línea Germinal , Humanos , Malasia/epidemiología , Masculino , Ratones , Singapur/epidemiologíaRESUMEN
BACKGROUND: The current study aims to evaluate the nipple and skin sensation following nipple-sparing mastectomy (NSM) and identify patient-, surgical-, or treatment-related factors affecting nipple or skin sensation in this cohort. METHODS: Patients who received NSM with postoperative nipple and skin sensation test evaluation at a single institution over the past 10 years were retrospectively retrieved from a prospectively collected breast cancer surgery database. RESULTS: A total of 460 NSM procedures were included in this current study, with the mean age of 48.3 ± 9.1. Three-hundred eighty-three (83.3%) patients had breast reconstructions. One-hundred seventy-four (37.8%) received conventional NSM (C-NSM), 195 (42.4%) endoscopic-assisted NSM (E-NSM), and 91 (19.8%) robotic-assisted NSM (R-NSM) procedures. For nipple sensation assessment, 15 (3.3%) were grade 0, 83 (18.2%) grade I, 229 (49.7%) grade II, and 133 (28.9%) grade III (normal sensation), respectively, with mean grade score of 2.1 ± 0.7. The preserved (grade III) nipple sensation rate was 36.2% (63/174) in the C-NSM group, 26.7% (52/195) in the E-NSM group, and 19.7% (18/91) in the R-NSM group (P = 0.06). The "time since surgery to last evaluation" was significantly longer in the C-NSM group (45.6 ± 34 months) or E-NSM group (44.7 ± 35.8 months) as compared to R-NSM group (31.8 ± 16 months, P < 0.01). In multivariate analysis, peri-areolar incision showed higher grade of nipple sensation (OR: 2.1, P = 0.02) compared to upper outer quadrant incision, and longer follow-up time post-NSM showed significant improvement of nipple or skin sensation (> 60 months vs. ⦠12 months: nipple odds ratio (OR) = 5.75, P < 0.01; skin, OR = 1.97, P < 0.05). CONCLUSION: Our current analysis showed some factors to be related to postoperative nipple or skin sensation, and longer "time after surgery" was associated with significant improvement of nipple and skin sensation in patients who received NSM, regardless of the surgical approaches. SYNOPSIS: Our current analysis showed a significant portion of patients with decrease or loss of nipple or skin sensation after nipple-sparing mastectomy (NSM). Several factors associated with preserved nipple or skin sensation were identified, including age, surgical methods, surgical wound location, and association of time from surgery showing that improvement of partial nipple or skin sensation was evident after a longer follow-up.
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Neoplasias de la Mama , Mamoplastia , Procedimientos Quirúrgicos Robotizados , Humanos , Adulto , Persona de Mediana Edad , Femenino , Mastectomía/efectos adversos , Mastectomía/métodos , Neoplasias de la Mama/cirugía , Estudios Retrospectivos , Pezones/cirugía , Procedimientos Quirúrgicos Robotizados/efectos adversos , Mamoplastia/métodos , SensaciónRESUMEN
OBJECTIVES: This study aimed to investigate the psychological distress and its associated factors among cancer survivors in Malaysia during the COVID-19 pandemic. METHODS: An anonymous Internet-based study was conducted between 23 April and 26 June 2020. During the study period, the country underwent phase 3 and phase 4 of the Movement Control Order (MCO), Conditional Movement Control Order (CMCO), and Recovery Movement Control Order (RMCO). Psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS), which is a 14-item self-assessment scale for measuring distress (total HADS score; HADS-T) with two subscales, namely, anxiety (HADS-A) and depression (HADS-D). Perceived threat of infection was measured based on the health belief model. RESULTS: From a total of 631 responses received, the proportion of participants with anxiety and depression symptoms (above threshold score of 8 on HADS-A and HADS-D) was 29.0 and 20.9%, respectively. Psychological distress (HADS-T > 16) was reported in 22.3% of the respondents. A total of 16.5% had combined anxiety and depression symptoms. The highest HADS-A (6.10; 95% CI 5.64-6.56), HADS-D (5.61; 95% CI 5.14-6.08), and HADS-T (11.71; 95% CI 10.84-12.58) scores were reported among respondents during phase 4 of the MCO. Partial least square-based structural equation modelling (PLS-SEM) revealed that self-perceived health status, perceived susceptibility, and severity of COVID-19 have the greatest effect, leading to higher HADS-A, HADS-D, and HADS-T scores. CONCLUSION: Heightened psychological distress was evident in cancer survivors particularly during the enforcement of the MCO over COVID-19. Providing support to address cancer survivors' psychological and emotional needs during the COVID-19 pandemic is essential.
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COVID-19 , Supervivientes de Cáncer , Neoplasias , Distrés Psicológico , Ansiedad/epidemiología , Depresión/epidemiología , Humanos , Pandemias , SARS-CoV-2 , Estrés Psicológico/epidemiología , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Breast conserving surgeries were previously contraindicated for central breast cancers because of poor cosmetic outcomes of central mastectomy without oncoplastic surgery. Grisotti flap is a breast-conserving surgery incorporating oncoplastic surgery technique for centrally located breast cancers. We present our experience and outcome from Breast Surgery Unit, University Malaya Medical Center. MATERIALS AND METHODS: A prospective analysis of 15 patients with central retroareolar breast cancer operated from 2012 to 2018 in University Malaya Medical Center. We assessed postoperative complications, margins, locoregional recurrence, and survival outcome. All patients received postoperative radiotherapy. Patients were followed-up 1 week, 1 month, 3 monthly for 1 year and 6 monthly for 5 years. RESULTS: Mean age of patients is 62 years. Mean follow-up is 51 months (15-84 months). All tumors were less than 5 cm (1-2.5 cm). Majority of the patients are stage 1 (6 patients/40%) and stage 2 (8 patients/ 53.3%). 2 patients had surgical site infection resolved with antibiotics. One patient had hematoma. None require reoperation. Tumor margins were clear in all patients. No locoregional recurrence. Overall survival is 100%. All are satisfied with their cosmetic outcomes. CONCLUSIONS: Grisotti flap is a volume displacement technique, which provides satisfactory cosmetic outcome for centrally located breast cancer. This evolutionary thinking leads us to changes in existing techniques with the purpose of achieving oncological safety while reaching for better esthetic results. Our 5 years' experience in Asian population showed that this technique is oncologically safe with good cosmetic outcomes and could be used selectively. It provides a good alternative in patients who are otherwise subjected for mastectomy. This relatively simple technique is a worthwhile endeavor and should be offered when feasible.
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Neoplasias de la Mama , Mamoplastia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Mastectomía Segmentaria , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: This study aims to evaluate in vivo skin dose delivered by intraoperative radiotherapy (IORT) and determine the factors associated with an increased risk of radiation-induced skin toxicity. METHODOLOGY: A total of 21 breast cancer patients who underwent breast-conserving surgery and IORT, either as IORT alone or IORT boost plus external beam radiotherapy (EBRT), were recruited in this prospective study. EBT3 film was calibrated in water and used to measure skin dose during IORT at concentric circles of 5 mm and 40 mm away from the applicator. For patients who also had EBRT, the maximum skin dose was estimated using the radiotherapy treatment planning system. Mid-term skin toxicities were evaluated at 3 and 6 months post-IORT. RESULTS: The average skin dose at 5 mm and 40 mm away from the applicator was 3.07 ± 0.82 Gy and 0.99 ± 0.28 Gy, respectively. Patients treated with IORT boost plus EBRT received an additional skin dose of 41.07 ± 1.57 Gy from the EBRT component. At 3 months post-IORT, 86% of patients showed no evidence of skin toxicity. However, the number of patients suffering from skin toxicity increased from 15% to 38% at 6 months post-IORT. We found no association between the IORT alone or with the IORT boost plus EBRT and skin toxicity. Older age was associated with increased risk of skin toxicities. A mathematical model was derived to predict skin dose. CONCLUSION: EBT3 film is a suitable dosimeter for in vivo skin dosimetry in IORT, providing patient-specific skin doses. Both IORT alone and IORT boost techniques resulted in similar skin toxicity rates.
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Neoplasias de la Mama , Traumatismos por Radiación , Anciano , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía Segmentaria , Recurrencia Local de Neoplasia , Estudios ProspectivosRESUMEN
Oncoplastic breast surgery (OBS) improves margin clearance and produces good esthetic outcome in breast cancer treatment. This study evaluates the complications and outcome of OBS in a multiracial patient cohort. Data of 421 patients between 2011 and 2018 were analyzed. The majority were Malays (41.8%), followed by Chinese (39.7%) and Indians (16.8%). Low local complications were noted, with no significant differences in disease-free survival (P = .927) and overall survival (P = .719) between low and high OBS levels. Shared decision-making in offering OBS for Asian women has potential to become a practical option in breast cancer treatment.
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Neoplasias de la Mama , Mamoplastia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia/efectos adversos , Mastectomía Segmentaria , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: Patient-reported outcomes (PROs) in high-income countries (HICs) suggest that physical, emotional, and psychological needs are important in cancer care. To date, there have been few inconsistent descriptions of PROs in low-income and middle-income Asian countries. Using a standard questionnaire developed by the International Consortium for Health Outcomes Measurement (ICHOM), we compared the perceived importance of PROs between patients in Malaysia and those in HICs and between clusters of Malaysian women. METHODS: Breast cancer patients were recruited from three Malaysian hospitals between June and November 2017. We compared the proportion of patients who rated PROs as very important (scored 7-9 on a 9-point Likert scale) between Malaysian patients and data collected from patients in HICs via the ICHOM questionnaire development process, using logistic regression. A two-step cluster analysis explored differences in PROs among Malaysian patients. RESULTS: The most important PROs for both cohorts were survival, overall well-being, and physical functioning. Compared with HIC patients (n = 1177), Malaysian patients (n = 969) were less likely to rate emotional (78% vs 90%), cognitive (76% vs 84%), social (72% vs 81%), and sexual (30% vs 56%) functioning as very important outcomes (P < 0.001). Cluster analysis suggests that older, parous, Malaysian women, who were less likely to have received breast reconstructive surgery, were more likely to rate body image and satisfaction with the breast as very important outcomes. CONCLUSION: Taking into account the differences in PROs by cultural and socioeconomic settings could improve patient expectation of services and refine the assessment of cancer care outcomes.
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Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Medición de Resultados Informados por el Paciente , Calidad de Vida/psicología , Adaptación Psicológica , Adulto , Imagen Corporal/psicología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer/estadística & datos numéricos , Estudios Transversales , Países Desarrollados , Femenino , Humanos , Renta/estadística & datos numéricos , Malasia , Persona de Mediana Edad , Autoimagen , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
Thermal imbalances are very common during surgery. Hypothermia exposes the patient to post-operative shivering, cardiac dysfunction, coagulopathy, bleeding, wound infection, delayed anesthesia recovery, prolonged hospital stay and increased hospitalization cost. There are many factors contributing to intraoperative hypothermia. This is a prospective cohort study conducted through observation and measurement of pediatric surgical patients' temperature. Convenience sampling methods were used in this study. Initial skin temperature and core temperature at 10 min, 30 min,1 h, 2 h, 3 h, 4 h, 5 h, 6 h and at the end of surgery were recorded. Body temperature was monitored from time of transfer to the operating table until recovery and discharge to the respective pediatric ward. The overall incidence of intraoperative hypothermia was still very high at about 46.6% even though active and passive temperature management were carried out during surgery. Patient's age, body weight, duration of surgery, type of surgery, intraoperative blood loss, type of anesthesia and operating room temperature were factors that contributed to intraoperative hypothermia. Hypothermia is common in surgery, especially in major and long duration surgery. Intraoperative hypothermia can be life threatening if it is not handled carefully. Various methods are used before, during and after surgery to maintain a patient's body temperature within the normothermia range. The use of an active warming device like the Bair Hugger® air-forced warming system seems to be a good method for reducing the risk of intraoperative hypothermia and effectively maintaining body temperature for all major and minor surgeries.
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Anestesia/efectos adversos , Hipotermia/etiología , Temperatura Cutánea , Temperatura Corporal , Regulación de la Temperatura Corporal , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Complicaciones Intraoperatorias , Masculino , Monitoreo Intraoperatorio/métodos , Monitoreo Fisiológico , Periodo Posoperatorio , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Reproductive factors are associated with risk of breast cancer, but the association with breast cancer survival is less well known. Previous studies have reported conflicting results on the association between time since last childbirth and breast cancer survival. We determined the association between time since last childbirth (LCB) and survival of women with premenopausal and postmenopausal breast cancers in Malaysia. METHOD: A historical cohort of 986 premenopausal, and 1123 postmenopausal, parous breast cancer patients diagnosed from 2001 to 2012 in University Malaya Medical Centre were included in the analyses. Time since LCB was categorized into quintiles. Multivariable Cox regression was used to determine whether time since LCB was associated with survival following breast cancer, adjusting for demographic, tumor, and treatment characteristics. RESULTS: Premenopausal breast cancer patients with the most recent childbirth (LCB quintile 1) were younger, more likely to present with unfavorable prognostic profiles and had the lowest 5-year overall survival (OS) (66.9; 95% CI 60.2-73.6%), compared to women with longer duration since LCB (quintile 2 thru 5). In univariable analysis, time since LCB was inversely associated with risk of mortality and the hazard ratio for LCB quintile 2, 3, 4, and 5 versus quintile 1 were 0.53 (95% CI 0.36-0.77), 0.49 (95% CI 0.33-0.75), 0.61 (95% CI 0.43-0.85), and 0.64 (95% CI 0.44-0.93), respectively; P trend = 0.016. However, this association was attenuated substantially following adjustment for age at diagnosis and other prognostic factors. Similarly, postmenopausal breast cancer patients with the most recent childbirth were also more likely to present with unfavorable disease profiles. Compared to postmenopausal breast cancer patients in LCB quintile 1, patients in quintile 5 had a higher risk of mortality. This association was not significant following multivariable adjustment. CONCLUSION: Time since LCB is not independently associated with survival in premenopausal or postmenopausal breast cancers. The apparent increase in risks of mortality in premenopausal breast cancer patients with a recent childbirth, and postmenopausal patients with longer duration since LCB, appear to be largely explained by their age at diagnosis.
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Neoplasias de la Mama/mortalidad , Parto , Posmenopausia , Premenopausia , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Malasia/epidemiología , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Historia Reproductiva , Factores de Riesgo , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Factors associated with surgery, adjuvant radiotherapy, and chemotherapy and whether there were missed opportunities for treatment in elderly patients were determined in an Asian setting. METHODS: All 5616 patients, diagnosed with breast cancer in University Malaya Medical Centre from 1999 to 2013 were included. In 945 elderly patients (aged 65 years and above), multivariable logistic regression was performed to identify factors associated with treatment, following adjustment for age, ethnicity, tumor, and other treatment characteristics. The impact of lack of treatment on survival of the elderly was assessed while accounting for comorbidities. RESULTS: One in five elderly patients had comorbidities. Compared to younger patients, the elderly had more favorable tumor characteristics, and received less loco-regional treatment and chemotherapy. Within stage I-IIIa elderly breast cancer patients, 10 % did not receive any surgery. These patients were older, more likely to be Malays, have comorbidities, and bigger tumors. In elderlies with indications for adjuvant radiotherapy, no irradiation (30 %) was associated with increasing age, comorbidity, and the absence of systemic therapy. Hormone therapy was optimal, but only 35 % of elderly women with ER negative tumors received chemotherapy. Compared to elderly women who received adequate treatment, those not receiving surgery (adjusted hazard ratio: 2.30, 95 %CI: 1.10-4.79), or radiotherapy (adjusted hazard ratio: 1.56, 95 %CI: 1.10-2.19), were associated with higher mortality. Less than 25 % of the survival discrepancy between elderly women receiving loco-regional treatment and no treatment were attributed to excess comorbidities in untreated patients. CONCLUSION: While the presence of comorbidities significantly influenced loco-regional treatment decisions in the elderly, it was only able to explain the lower survival rates in untreated patients up to a certain extent, suggesting missed opportunities for treatment.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Comorbilidad , Factores de Edad , Anciano , Neoplasias de la Mama/etnología , Quimioterapia Adyuvante , Femenino , Humanos , Modelos Logísticos , Malasia , Mastectomía Segmentaria , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Tasa de Supervivencia , Carga TumoralRESUMEN
Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers.
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Adenosina Trifosfato/metabolismo , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Reparación del ADN/efectos de los fármacos , Hipoglucemiantes/farmacología , Metformina/farmacología , Células Madre Neoplásicas/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/química , Proteínas Quinasas Activadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Antineoplásicos/metabolismo , Compuestos de Bifenilo , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/metabolismo , Daño del ADN/efectos de los fármacos , Combinación de Medicamentos , Sinergismo Farmacológico , Células Madre Embrionarias/metabolismo , Epirrubicina/metabolismo , Femenino , Fibroblastos/metabolismo , Fluorouracilo/metabolismo , Glucosa/metabolismo , Humanos , Ácido Láctico/metabolismo , Pulmón/citología , Pironas/farmacología , Ribonucleótidos/farmacología , Tiofenos/farmacologíaRESUMEN
BACKGROUND: Breast cancer is the leading cause of cancer deaths in women world-wide. In low and middle income countries, where there are no population-based mammographic screening programmes, late presentation is common, and because of inadequate access to optimal treatment, survival rates are poor. Mammographic screening is well-studied in high-income countries in western populations, and because it has been shown to reduce breast cancer mortality, it has become part of the healthcare systems in such countries. However the performance of mammographic screening in a developing country is largely unknown. This study aims to evaluate the performance of mammographic screening in Malaysia, a middle income country, and to compare the stage and surgical treatment of screen-detected and symptomatic breast cancer. METHODS: A retrospective review of 2510 mammograms performed from Jan to Dec 2010 in a tertiary medical centre is carried out. The three groups identified are the routine (opportunistic) screening group, the targeted (high risk) screening group and the diagnostic group. The performance indicators of each group is calculated, and stage at presentation and treatment between the screening and diagnostic group is analyzed. RESULTS: The cancer detection rate in the opportunistic screening group, targeted screening group, and the symptomatic group is 0.5 %, 1.25 % and 26 % respectively. The proportion of ductal carcinoma in situ is 23.1 % in the two screening groups compared to only 2.5 % in the diagnostic group. Among the opportunistic screening group, the cancer detection rate was 0.2 % in women below 50 years old compared to 0.65 % in women 50 years and above. The performance indicators are within international standards. Early-staged breast cancer (Stage 0-2) were 84.6 % in the screening groups compared to 61.1 % in the diagnostic group. CONCLUSION: From the results, in a setting with resource constraints, targeted screening of high risk individuals will give a higher yield, and if more resources are available, population-based screening of women 50 and above is effective. Opportunistic mammographic screening is feasible and effective in a middle income country with performance indicators within international standards. Waiting until women are symptomatic will lead to more advanced cancers.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Atención a la Salud , Detección Precoz del Cáncer , Recursos en Salud , Mamografía , Tamizaje Masivo , Adulto , Anciano , Biopsia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Malasia/epidemiología , Malasia/etnología , Glándulas Mamarias Humanas/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
BACKGROUND: Depression and anxiety are common psychiatric morbidity among breast cancer patient. There is a lack of study examining the correlation between depression, anxiety and quality of life (QoL) with perceived social support (PSS) among breast cancer patients. This study aims to study the level of depression, anxiety, QoL and PSS among Malaysian breast cancer women over a period of 12 months and their associations at baseline, 6 and 12 months. METHODS: It is a 12 months prospective cohort study. Two hundred and twenty one female patients were included in the study. They were assessed at the time of diagnosis, 6 months and 12 month using Hospital Anxiety and Depression Scale (HADS), Quality-of-Life Questionnaire (QLQ-C30), Version 3.0 of the EORTC Study Group and Multidimensional Scale of Perceived Social Support (MSPSS). The information of age, ethnicity, types of treatment, and staging of cancer were collected. RESULTS: The HADS anxiety and depression subscales scores of the subjects were relatively low. The level of anxiety reduced significantly at 6 and 12 months (Baseline - 6 months, p = 0.002; Baseline - 12 months, p < 0.001). There were no changes in the level of depression over the study period. The global status of QoL and MSPSS scores were relatively high. Correlation between the global status of QoL and MSPSS for the study subjects was positive (Spearman's rho = 0.31-0.36). Global status of QoL and MSPSS scores were negatively correlated with anxiety and depression. CONCLUSION: Malaysian breast cancer women had relatively better QoL with lower level of anxiety and depression. Perceived social support was an important factor for better QoL and low level of psychological distress. It reflects the importance of attention on activities that enhance and maintain the social support system for breast cancer patients.
Asunto(s)
Ansiedad/psicología , Pueblo Asiatico/psicología , Neoplasias de la Mama/psicología , Depresión/psicología , Psicometría/instrumentación , Calidad de Vida/psicología , Apoyo Social , Adulto , Anciano , Estudios de Cohortes , Femenino , Servicios de Salud , Humanos , Malasia , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
PURPOSE: Granular data on breast cancer (BC) are pertinent for surveillance, planning, and monitoring of cancer care delivery. We determined the trends in clinical presentation, management, and survival of women with BC in a multiethnic middle-income Asian setting over 15 years. METHODS: Data of 7,478 Malaysian women newly diagnosed with invasive BC between 2005 and 2019 from three hospital-based cancer registries were included. Trends in demographic, tumor, and treatment characteristics were compared across period 1 (P1): 2005-2009, period 2 (P2): 2010-2014, and period 3 (P3): 2015-2019. Overall survival and net survival were determined. RESULTS: More women in P3 than P1 were older than 60 years at diagnosis. Only a marginal increase in proportion of women with stage I disease was observed (23.7% v 27.2% in P1 and P3, respectively, P = .004). Nonetheless, patients were increasingly presenting with smaller tumors, fewer axillary node involvement, well-differentiated tumors, and hormone receptor expression in recent times. Proportion of women with human epidermal growth factor receptor 2 (HER2)-overexpressed tumors significantly decreased. Among indicated patients, receipt of anticancer therapies was somewhat similar over the calendar periods, except for neoadjuvant chemotherapy and anti-HER2 therapy, where increases in administration were noted. Significant improvements in survival were observed over the 15 years, particularly for HER2-overexpressed BCs. CONCLUSION: Although the improvements in BC survival that we have observed validate ongoing cancer control efforts and treatment advances, study findings suggest that more could be done for earlier detection and improved access to effective therapies in our settings.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico , Persona de Mediana Edad , Anciano , Malasia/epidemiología , AdultoRESUMEN
Triple-negative breast cancers (TNBCs) are a subset of breast cancers that have remained difficult to treat. A proportion of TNBCs arising in non-carriers of BRCA pathogenic variants have genomic features that are similar to BRCA carriers and may also benefit from PARP inhibitor treatment. Using genomic data from 129 TNBC samples from the Malaysian Breast Cancer (MyBrCa) cohort, we developed a gene expression-based machine learning classifier for homologous recombination deficiency (HRD) in TNBCs. The classifier identified samples with HRD mutational signature at an AUROC of 0.93 in MyBrCa validation datasets and 0.84 in TCGA TNBCs. Additionally, the classifier strongly segregated HRD-associated genomic features in TNBCs from TCGA, METABRIC, and ICGC. Thus, our gene expression classifier may identify triple-negative breast cancer patients with homologous recombination deficiency, suggesting an alternative method to identify individuals who may benefit from treatment with PARP inhibitors or platinum chemotherapy.