Mee-Hoong See

Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer.

Background:Peripheral blood-derived inflammation-based scores such as the neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.Methods:Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR.Results:Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6–82.1%) in quintile 1, 79.4% (95% CI: 74.4–83.7%) in quintile 2, 72.1% (95% CI: 66.3–77.3%) in quintile 3, 65.6% (95% CI: 59.8–70.8%) in quintile 4 and 51.1% (95% CI: 43.3–58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08–1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9–59.2%) vs 77.0% (95% CI: 70.9–82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04–1.52).Conclusions:Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.

Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells

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.

The Will Rogers phenomenon in the staging of breast cancer – Does it matter?

INTRODUCTION Changes in the American Joint Commission on Cancer staging for breast cancer occurred when the 5th Edition was updated to the 6th Edition. OBJECTIVE To investigate how these changes affected stage and survival. METHODS 3127 cases of breast cancer were restaged. RESULTS Late stages increased from 27.7% to 38.1%. The five-year survival improved in Stage 2 (82.9-86.1%) and Stage 3 (50.6-59%). DISCUSSION Stage shift leads to an erroneous impression that women are presenting with later stages and stage-specific survival is improving. CONCLUSION Standardizing cancer staging is important when reporting stage and survival in different time periods.

Trends in presentation, management and survival of patients with de novo metastatic breast cancer in a Southeast Asian setting

Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient’s demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996–2000, 2001–2005 and 2006–2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996–2000, 7% in 2001–2005, and 9% in 2006–2010. Patients in 2006–2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%–28·2%), 28·8% (95% CI: 23·4%–34·2%), and 33·6% (95% CI: 28·8%–38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study.

Determinants of choice of surgery in Asian patients with early breast cancer in a middle income country

BACKGROUND Breast-conserving surgery (BCS) plus radiotherapy is equivalent to modified radical mastectomy (MRM) in terms of outcome. However there is wide variation in mastectomy rates dependent both on tumour and patient characteristics. OBJECTIVE This study aimed to assess the determinants of surgery choice in Asian patients with early breast cancer in a middle-income country. MATERIALS AND METHODS 184 patients with early breast cancer treated between Jan 2008 and Dec 2010 were recruited to complete a questionnaire. Chi-square test was used to analyze the association between surgery choice and demographic and tumour factors, surgeon recommendation, family member and partner opinions, fear of recurrence, avoidance of second surgery, fear of disfigurement, interference with sex life, fear of radiation and loss of femininity. RESULTS 85 (46%) had BCS while 99 (54%) had mastectomy. Age >60, Chinese ethnicity, lower education level, and larger tumour size were significantly associated with mastectomy. Surgeon recommendation was important in surgery choice. Although both groups did not place much importance on interference with sex life, 14.1% of the BCS group felt it was very important compared to 5.1% in the mastectomy group and this was statistically significant. There was no statistical difference between the two groups in terms of the other factors. When analyzed by ethnicity, significantly more Malay and Indian women considered partner and family member opinions very important and were more concerned about loss of femininity compared to Chinese women. There were no statistical differences between the three ethnic groups in terms of the other factors. CONCLUSIONS When counseling on surgical options, the surgeon has to take into account the ethnicity, social background and education level, age and reliance on partner and family members. Decision-making is usually a collective effort rather than just between the patient and surgeon, and involving the whole family into the process early is important.

Advanced Stage at Presentation Remains a Major Factor Contributing to Breast Cancer Survival Disparity between Public and Private Hospitals in a Middle-Income Country

Background: Survival disparities in cancer are known to occur between public and private hospitals. We compared breast cancer presentation, treatment and survival between a public academic hospital and a private hospital in a middle-income country. Methods: The demographics, clinical characteristics, treatment and overall survival (OS) of 2767 patients with invasive breast carcinoma diagnosed between 2001 and 2011 in the public hospital were compared with 1199 patients from the private hospital. Results: Compared to patients in the private hospital, patients from the public hospital were older at presentation, and had more advanced cancer stages. They were also more likely to receive mastectomy and chemotherapy but less radiotherapy. The five-year OS in public patients was significantly lower than in private patients (71.6% vs. 86.8%). This difference was largely attributed to discrepancies in stage at diagnosis and, although to a much smaller extent, to demographic differences and treatment disparities. Even following adjustment for these factors, patients in the public hospital remained at increased risk of mortality compared to their counterparts in the private hospital (Hazard Ratio: 1.59; 95% Confidence Interval: 1.36–1.85). Conclusion: Late stage at diagnosis appears to be a major contributing factor explaining the breast cancer survival disparity between public and private patients in this middle-income setting.

Patient-reported outcome measures among breast cancer survivors: A cross-sectional comparison between Malaysia and high income countries

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.

Breast-conserving surgery versus mastectomy in young women with breast cancer in Asian settings: Breast-conserving surgery versus mastectomy in young Asian women

Mastectomy rates among women with early breast cancer in Asia have traditionally been high. This study assessed trends in the surgical management of young women with early‐stage breast cancer in Asian settings. Survival in women treated with breast‐conserving surgery (BCS; lumpectomy with adjuvant radiotherapy) and those undergoing mastectomy was compared.

Risk of Treatment Related Death and Febrile Neutropaenia with First Line Palliative Chemotherapy for De Novo Metastatic Breast Cancer in Clinical Practice in a Middle Resource Country

BACKGROUND The risk of febrile neutropaenia (FN) and treatment related death (TRD) with first line palliative chemotherapy for de novo metastatic breast cancer (MBC) remains unknown outside of a clinical trial setting despite its widespread usage. This study aimed to determine rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). MATERIALS AND METHODS Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature >38.5° or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test. RESULTS Between 1st January 2002 and 31st December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319). CONCLUSIONS In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.

Central pedicle reduction mammoplasty: a reliable technique.

Reduction mammoplasty is one of the most frequently performed procedures in plastic surgery for macromastia or gigantomastia. Recently it is also evolved for oncoplastic breast cancer surgery due to equivalent in terms of outcome for breast conserving surgery with radiotherapy versus mastectomy. Various techniques and modification has been made to achieve long lasting and aesthetically good result with minimal morbidity. Central (posterior) reduction mammoplasty is known for its versatile pedicle due to its good blood supply and innervation for maintaining of nipple sensation with unremarkably long term complication and proven in preservation of breastfeeding function. It is one of the good and reliable options to correct breast hypertrophy and ptosis. Various modifications were introduced by different authors to improve the technique and reduce scar formation which will give more satisfaction to patients.