[show abstract][hide abstract] ABSTRACT: While tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results.
In an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case-control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease. We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control.
This exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70 ng.ml), endoxifen may promote recurrence.
[show abstract][hide abstract] ABSTRACT: The EUROCARE study has disclosed large variations of survival across Europe, with the magnitude varying, depending on cancer site. Comparisons of these rates with those from the developing countries are rare, but important in evaluating international cancer care discrepancies. This study aimed to provide up-to-date estimates of cancer survival in a Philippine urban population, and to compare these with those observed in the European countries.
Using the results from the EUROCARE-4 study, the survival estimates of the European patients who were diagnosed in 1995-99 and followed till December 2003 were abstracted. From randomly selected samples drawn from the Manila and Rizal Cancer Registries, 5-year survival was estimated for nine common cancers. Age-adjusted survival estimates were then compared between the Philippine population and Europeans.
In comparison to the European mean, survival estimates for the Philippine residents were lower for most cancers, with differences ranging from 2 to 40% units. Differences with European country-specific estimates were large for cancers of the breast and cervix, where early detection is possible, and for leukaemia, where treatment regimens are costly, highlighting the importance of health care. Smaller discrepancies were observed for stomach, liver and lung cancers, with the 5-year relative survival being similar to the Philippines and to many European countries. A survival advantage was seen though for the Philippine residents for ovarian cancer.
Apart from efforts to prevent cancers, improvements in cancer control and making early diagnosis and treatment more accessible remain major challenges, both in the Philippines and in the European nations.
The European Journal of Public Health 04/2011; 21(2):221-8. · 2.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: The population-based cancer registry in Manila, Philippines, called the Philippine Cancer Society-Manila Cancer Registry, was established in 1983. Cancer registration is pursued by active methods. The registry contributed survival data on a random sample of total incident cancers of breast (500), cervix (500), colon and rectum (300) registered in 1994-1995. Follow-up has been carried out by passive and active methods, with median follow-up ranging between 15-33 months for different cancers. The proportion of histologically verified diagnosis for various cancers ranged between 78-88%; 74-83% of the total submitted cases were included for survival analysis. Complete follow-up at five years was available in 75-82% of cases. Five-year age-standardized relative survival rates was the highest for cancer of the breast (52%) followed by colon (49%), cervix (36%) and rectum (31%). Five-year relative survival by age group did not display any pattern or trend and was fluctuating. A decreasing survival with increasing extent of disease was noted for all cancers.
[show abstract][hide abstract] ABSTRACT: Childhood cancer survival estimates from developing nations are rare.
Using the US SEER and the Manila and Rizal Cancer Registry databases in the Philippines, 5-year survival for childhood leukaemia and lymphoma in 2001-2005 among Asian Americans were compared with both Filipinos and Caucasians in the United States. Estimates for patients in the United States in earlier time periods were compared with that of Philippine residents to estimate delay in achievements of comparable levels of survival.
Childhood leukaemia and lymphoma relative survival was much lower in Filipinos living in the Philippines (32.9 and 47.7%) than in Asian Americans (80.1 and 90.5%) and Caucasians (81.9 and 87%). Achievement of comparable survival rates of Philippine residents lagged behind by 20 to >30 years compared with patients in the United States.
The large differences in survival estimates of US populations and Philippine residents highlight the deficiencies of paediatric cancer care delivery in the Philippines. The long survival lag underlines the need for major improvements in access to diagnostic and treatment facilities.
British Journal of Cancer 06/2010; 103(1):149-54. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Various international comparisons of breast cancer survival have shown discrepancies which may reflect the impact of ethnicity or health care. Using databases from SEER 13 and from the Manila and Rizal Cancer Registries, age adjusted five-year absolute and relative survival estimates were computed and compared between Filipino-American breast cancer patients, Philippine residents and Caucasians in the US. Determinants of survival differences were examined using Cox proportional hazards modelling. Age adjusted five-year relative survival was almost identical in Filipino-Americans (89.1%) and Caucasians (87.7%), but much lower in the Philippine residents (58.4%). Large tumor size, lymph node involvement, distant metastasis, and the large proportion of women not receiving surgery explained a substantial portion of the excess mortality in Philippine residents. The moderate excess risk of Caucasians compared to Filipino-Americans was explained by age differences. Access to, utilization and affordability of cancer care facilities are important for reducing breast cancer deaths in developing countries.
Breast (Edinburgh, Scotland) 04/2010; 19(2):109-14. · 2.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: The database of two population-based cancer registries (Philippine Cancer Society-Manila Cancer Registry and Department of Health-Rizal Cancer Registry) was used to generate age-standardized incidence rates of cancer during 1980-2002. Five-year relative survival rates were obtained for incident cases from 1993 to 2002 using a period analysis method. Overall incidence had increased in both males and females. Among males, lung cancer was the leading cancer and reached a peak in 1988-92. Colorectal and prostate cancers showed rising trends and became more common than liver cancer, with stable incidence over time. Stomach cancer incidence fell steeply. Among females, there was a steady increase in incidence of breast cancer. There was a slight decrease in the incidence of the second common cancer, cervical cancer, and colorectal cancer became equally common. Lung cancer incidence in females also reached a peak by 1998-2002 and then slightly decreased. Oral cavity cancer decreased strongly in the last period. In general, survival rates among Philippine residents were one-third lower than among Filipino-Americans and Whites in the USA especially in cancer sites wherein effective early detection methods may be available such as breast, cervix, colorectal and thyroid cancers. Survival was also lower in Philippine leukemia cases, a disease wherein effective treatment is proven in some types but is quite expensive. Lifestyle factors such as smoking, unhealthy diet, physical inactivity, and human papillomavirus and hepatitis B virus infections were associated with some incidence patterns. Late stage at diagnosis was largely responsible for low survival.
Japanese Journal of Clinical Oncology 04/2010; 40(7):603-12. · 1.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: Few studies have investigated incidence trends in the Philippines.
From the databases of the Manila Cancer Registry, cumulative cancer incidence rates were determined for the five most common cancers for both sexes combined. Using joinpoint analysis, incidence trends for 1983-2002 were estimated.
Among females, increasing trends were found for breast, 5% annual change, lung (0.5%) and colorectal (1.5%) cancers. Decreasing trends were found for cancers of the liver (-1.2%) and cervix (-1.9%). Among males, increasing trends were found for lung cancer (0.5%), whereas liver cancer rates have been decreasing (-1.0%). Colorectal cancer rates fluctuated.
Certain sites showed declining incidence trends, but incidence trends for lifestyle-related cancers continue to rise. The prevention of infection-related cancers should also receive priority, particularly by vaccination programmes.
British Journal of Cancer 04/2010; 102(9):1411-4. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hormone receptor (HR) expression is the most important biomarker and is the cornerstone in the management of breast cancer. Therefore, the accuracy of its testing is critical in treatment decisions.
A total of 160 consecutive patients accrued to an adjuvant hormonal therapy clinical trial between March 2003 and May 2008 were studied. Estrogen receptor (ER) and progesterone receptor (PgR) protein assays of tissues from modified radical mastectomy (MRM) specimens were compared with their previous core needle biopsy (CNB) ER and PgR immunohistochemical assay results.
The tumors of 146 (91.2%) out of the 160 patients with CNB HR-positive disease remained HR positive in MRM specimen assays. Estrogen receptor positivity decreased from 95% in the CNB to 81.9% in MRM specimens and PgR positivity from 93.8% to 86.9%. The overall agreement between CNB and MRM specimens was 81.9% for ER and 85.6% for PgR. The mean Allred scores were significantly higher in CNB than in MRM specimens: ER, 6.6 (SD, 2.02) versus 4.71 (SD, 2.62); PgR, 6.68 (SD, 2.16) versus 5.99 (SD, 2.68); P < .001 and P = .001, respectively.
Core needle biopsy specimens are associated with the identification of more frequent and higher levels of tumoral hormonal receptor proteins than MRM specimens. Delayed fixation of MRM tissues likely accounted for this finding. Optimal selection of patients for hormonal therapies is dependent on tissue management strategies before formal hormonal receptor protein testing procedures.
Clinical Breast Cancer 03/2010; 10(2):154-9. · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous population-based studies showed differences in international and within country colorectal cancer survival estimates, but few investigated the role of prognostic factors. Using a "high resolution approach", we aimed to determine the effect of ethnicity and health care by comparing Filipino-Americans with Philippine residents, who have the same ethnicity, and with Caucasians living in the US, who have the same health care system.
Using databases from the Manila and Rizal Cancer Registries and the United States Surveillance, Epidemiology and End Results, age-adjusted five-year absolute and relative survival estimates were computed and compared between Filipino-American colorectal cancer patients, cancer patients from the Philippines and Caucasian patients. Cox proportional hazards modelling was used to determine factors affecting survival differences.
Much lower 5-year relative survival estimates were obtained for Philippine residents (37%) as compared to those in Filipino-Americans (60.3%) and Caucasians (62.4%). Differences in age, stage and receipt of surgery explained a large proportion of the survival differences between Philippine residents and Filipino-Americans. However, strong excess risk of death for Philippine residents remained after controlling for these and other variables (relative risk, RR, 2.03, 95% confidence interval, 95% CI, 1.83-2.25).
Strong survival disadvantages of Philippine residents compared to Filipino-American patients were disclosed, which most likely reflect differences in access to and utilization of health care. Health education and advocacy, for both patients and health practitioners, should likewise be given priority.
[show abstract][hide abstract] ABSTRACT: Malaysia, Brunei, Singapore, Indonesia, East Timor and the Philippines constitute peninsular and island South-East Asia. For reasons of largely shared ethnicity, with Chinese elements added to the basic Austromalaysian populations, as well as geographical contiguity, they can be usefully grouped together for studies of chronic disease prevalence and underlying risk factors. The fact of problems are shared in common, particularly regarding increasing cancer rates, underlines the necessity for a coordinated approach to research and development of control measures. To provide a knowledge base, the present review of available data for cancer registration, epidemiology and control was conducted. The most prevalent cancer site in males is the lung, followed by the liver, colon or the prostate in the majority of cases, while breast and cervical cancers predominate in most female populations. However, there are interesting differences among the racial groups, particularly regarding the stomach. General tendencies for increase in adenocarcinomas but decrease in squamous cell carcinomas and gastric cancer, point to change in environmental influence over time. Variation in risk factors depends to some extent on the level of economic development but overall the countries of the region face similar challenges in achieving effective cancer control. A major task is persuading the general populace of the efficacy of early detection and clinical treatment.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11 Suppl 2:81-98. · 1.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Population-based cancer survival data, a key indicator for monitoring progress against cancer, are not widely available from countries in Africa, Asia, and Central America. The aim of this study is to describe and discuss cancer survival in these regions.
Survival analysis was done for 341 658 patients diagnosed with various cancers from 1990 to 2001 and followed up to 2003, from 25 population-based cancer registries in 12 countries in sub-Saharan Africa (The Gambia, Uganda), Central America (Costa Rica), and Asia (China, India, Pakistan, Philippines, Saudi Arabia, Singapore, South Korea, Thailand, Turkey). 5-year age-standardised relative survival (ASRS) and observed survival by clinical extent of disease were determined.
For cancers in which prognosis depends on stage at diagnosis, survival was highest in China, South Korea, Singapore, and Turkey and lowest in Uganda and The Gambia. 5-year ASRS ranged from 76-82% for breast cancer, 63-79% for cervical cancer, 71-78% for bladder cancer, and 44-60% for large-bowel cancers in China, Singapore, South Korea, and Turkey. Survival did not exceed 22% for any cancer site in The Gambia; in Uganda, survival did not exceed 13% for any cancer site except breast (46%). Variations in survival correlated with early detection initiatives and level of development of health services.
The wide variation in cancer survival between regions emphasises the need for urgent investments in improving awareness, population-based cancer registration, early detection programmes, health-services infrastructure, and human resources.
Association for International Cancer Research (AICR; St Andrews, UK), Association pour la Recherche sur le Cancer (ARC, Villejuif, France), and the Bill & Melinda Gates Foundation (Seattle, USA).
The lancet oncology 12/2009; 11(2):165-73. · 14.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: In contrast to most other forms of cancer, data from some developing and developed countries show surprisingly similar survival rates for ovarian cancer. We aimed to compare ovarian cancer survival in Philippine residents, Filipino-Americans and Caucasians living in the US, using a high resolution approach, taking potential differences in prognostic factors into account.
Using databases from the SEER 13 and from the Manila and Rizal Cancer Registries, age-adjusted five-year absolute and relative survival estimates were computed using the period analysis method and compared between Filipino-American ovarian cancer patients with cancer patients from the Philippines and Caucasians in the US. Cox proportional hazards modelling was used to determine factors affecting survival differences.
Despite more favorable distribution of age and cancer morphology and similar stage distribution, 5-year absolute and relative survival were lower in Philippine residents (Absolute survival, AS, 44%, Standard Error, SE, 2.9 and Relative survival, RS, 49.7%, SE, 3.7) than in Filipino-Americans (AS, 51.3%, SE, 3.1 and RS, 54.1%, SE, 3.4). After adjustment for these and additional covariates, strong excess risk of death for Philippine residents was found (Relative Risk, RR, 2.45, 95% confidence interval, 95% CI, 1.99-3.01). In contrast, no significant differences were found between Filipino-Americans and Caucasians living in the US.
Multivariate analyses disclosed strong survival disadvantages of Philippine residents compared to Filipino-American patients, for which differences in access to health care might have played an important role. Survival is no worse among Filipino-Americans than among Caucasians living in the US.
[show abstract][hide abstract] ABSTRACT: Few studies have assessed and compared cervical cancer survival between developed and developing countries, or between ethnic groups within a country. Fewer still have addressed how much of the international or interracial survival differences can be attributed to ethnicity or health care. To determine the role of ethnicity and health care, 5-year survival of patients with cervical cancer was compared between patients in the Philippines and Filipino-Americans, who have the same ethnicity, and between Filipino-Americans and Caucasians, who have the same health care system. Cervical cancer databases from the Manila and Rizal Cancer Registries and Surveillance, Epidemiology, and End Results 13 were used. Age-adjusted 5-year survival estimates were computed and compared between the three patient groups. Using Cox proportional hazards modeling, potential determinants of survival differences were examined. Overall 5-year relative survival was similar in Filipino-Americans (68.8%) and Caucasians (66.6%), but was lower for Philippine residents (42.9%). Although late stage at diagnosis explained a large proportion of the survival differences between Philippine residents and Filipino-Americans, excess mortality prevailed after adjustment for stage, age, and morphology in multivariate analysis [relative risk (RR), 2.07; 95% confidence interval (CI), 1.68-2.55]. Excess mortality decreased, but persisted, when treatments were included in the multivariate models (RR, 1.78; 95% CI, 1.41-2.23). A moderate, marginally significant excess mortality was found among Caucasians compared with Filipino-Americans (adjusted RR, 1.22; 95% CI, 1.01-1.47). The differences in cervical cancer survival between patients in the Philippines and in the United States highlight the importance of enhanced health care and access to diagnostic and treatment facilities in the Philippines.
[show abstract][hide abstract] ABSTRACT: Despite the availability of population-based cancer survival data from the developed and developing countries, comparisons remain very few. Such comparisons are important to assess the magnitude of survival discrepancies and to disentangle the impact of ethnic background and health care access on cancer survival. Using the SEER 13 database and databases from the Manila and Rizal Cancer Registries in the Philippines, a 5-year relative survival for 9 common cancers in 1998-2002 of Filipino-American cancer patients were compared with both cancer patients from the Philippines, having the same ethnicity, and Caucasians in the United States, being exposed to a similar societal environment and the same health care system. Survival estimates were much higher for the Filipino-Americans than the Philippine resident population, with particularly large differences (more than 20-30% units) for cancers with good prognosis if diagnosed and treated early (colorectal, breast and cervix), or those with expensive treatment regimens (leukaemias). Filipino-Americans and Caucasians showed very similar survival for all cancer sites except stomach cancer (30.7 vs 23.2%) and leukaemias (37.8 vs 48.4%). The very large differences in the survival estimates of Filipino-Americans and the Philippine resident population highlight the importance of the access to and utilisation of diagnostic and therapeutic facilities in developing countries. Survival differences in stomach cancer and leukaemia between Filipino-Americans and Caucasians in the United States most likely reflect biological factors rather than the differences in access to health care.
British Journal of Cancer 03/2009; 100(5):858-62. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: The value of screening by Clinical Examination of the Breast (CBE) as a means of reducing mortality from breast cancer (BC) is not established. The issue is relevant, as CBE may be a suitable option for countries in economic transition, where incidence rates are on the increase but limited resources do not permit screening by mammography. Our aims were to assess whether mass screening by CBE carried out by trained para-medical personnel is feasible in an urban population of a low-income country, and its efficacy in reducing BC mortality. Our study was designed as a randomised controlled trial of the effect on BC mortality of 5 annual CBE carried out by trained nurses. The target population was women aged 35-64 years, resident in 12 municipalities of the National Capital Region of Manila, Philippines. The units of randomization were the 202 health centres (HC) within the selected municipalities. During 1995 nurses and midwives were recruited and trained in performing CBE. The first round of screening took place in 1996-1997. The intervention however showed a refractory attitude of the population with respect to clinical follow-up and was discontinued after the completion of the first screening round. Cases of breast cancer occurring in the study population during 1996-1999 were identified by the 2 local population-based registries. In the single screening round 151,168 women were interviewed and offered CBE, 92% accepted (138,392), 3,479 were detected positive for a lump and referred for diagnosis. Of these only 1220 women (35%) completed diagnostic follow-up, whereas 42.4% actively refused further investigation even with home visits, and 22.5% were not traced. Of 53 cases that occurred among screen-positive women in the 2 years after CBE only 34 were diagnosed through the intervention. Eighty cases occurred among screen-negative women. The test sensitivity for CBE repeated annually was 53.2%. The actual sensitivity of the programme was 25.6% and positive predictive value 1%. Screen-detected cases were non-significantly less advanced than the others. Previous studies have shown that most breast cancer cases in the Philippines present at advanced stages and have an unfavourable outcome. Although CBE undertaken by health workers seems to offer a cost-effective approach to reducing mortality, the sensitivity of the screening programme in the real context was low. Moreover, in this relatively well-educated population, cultural and logistic barriers to seeking diagnosis and treatment persist and need to be addressed before any screening programme is introduced.
International Journal of Cancer 02/2006; 118(1):149-54. · 6.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: HERDIN Database. A total of 2,156 titles, 427 abstracts and 77 full text articles were appraised. Data from 23 prospective cohort studies were encoded,into the software COCHRANE Review
[show abstract][hide abstract] ABSTRACT: The breast cancer incidence in the Philippines is among the highest in Asia. Age-standardized incidence rates (ASR) in Metro Manila and Rizal Province derived from the Philippine Cancer Society-Manila Cancer Registry and the Department of Health-Rizal Cancer Registry showed increase from 1980 to 2002, and were significantly higher in 7 cities in Metro Manila and significantly lower in 14 cities/municipalities mostly in Rizal Province. The AJCC Clinical Stage did not change from 1993 to 2002 among incident cases, the average distribution being: I= 5%, IIA= 20%, IIB= 18%, IIIA= 9%, IIIB= 10%, IV= 11%, Unknown= 28%. The International Agency for Research on Cancer attempted to run a randomized screening trial in 1995-1997 in the Philippines based on clinical breast examination by trained nurses and midwives. Unfortunately, even after home visits by a team equipped to perform needle biopsy, only 35% of screen-positive cases eventually had a diagnostic test. The estimated prevalence of BRCA mutations among unselected patients in the Philippine General Hospital (PGH) in 1998 was 5.1%, with a prevalence of 4.1% for BRCA2 mutations alone. There is a continuing effort at improving IHC hormone receptor testing at PGH, particularly on early fixation in buffered formalin. It was observed that hormone receptor-positive proportions tended to be higher in core needle biopsy specimens (72%) compared to mastectomy specimens (65%). During the years 1991, 1994 and 1997, 97% of incident cases of early breast cancer underwent modified radical mastectomy, 18% had postoperative radiotherapy, 51% had adjuvant hormone treatment and 47% received adjuvant chemotherapy. Survival of incident cases in 1993 to 2002 was compared to that of Filipino-Americans and Caucasians in the SEER 13 database. The age-adjusted 5-year relative survival, using period analysis, of Metro Manila residents, Filipino-Americans and Caucasians were 58.6%, 89.6% and 88.3% respectively.
Asian Pacific journal of cancer prevention: APJCP 10(1):167-72. · 1.27 Impact Factor