Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer.

PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes. METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase. RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%. CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

BACKGROUND: For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. METHODS: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. RESULTS: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. CONCLUSIONS: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.

Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer.

BACKGROUND: In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described. METHODS: In 270 Filipino and Vietnamese premenopausal patients participating in a clinical trial assessing the impact of the timing in the menstrual cycle of adjuvant surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar spine and femoral neck before this treatment, and at 6, 12, and 24 months after surgical and tamoxifen therapies. RESULTS: In women with a pretreatment BMD assessment and at least 1 other subsequent BMD assessment, no significant change in femoral neck BMD was observed over the 2-year period (-0.006 g/cm2 , -0.8%, P = .19), whereas in the lumbar spine, BMD fell by 0.045 g/cm2 (4.7%) in the first 12 months (P < .0001) and then began to stabilize. CONCLUSIONS: Surgically induced menopause with tamoxifen treatment is associated with loss of BMD at a rate that lessens over 2 years in the lumbar spine and no significant change of BMD in the femoral neck.

Cancer survival differences between European countries and an urban population from the Philippines.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Recent trends and patterns in breast cancer incidence among Eastern and Southeastern Asian women.

BACKGROUND: Incidence of breast cancer is rising in Asian countries, and breast cancer is the most common cancer among Asian women. However, there are few recent descriptive reports on the epidemiology of breast cancer among Eastern and Southeastern Asian populations. METHODS: We examined incidence trends for invasive breast cancer in women aged ≥20 years from 15 registries in Eastern (China, Japan, the Republic of Korea, Taiwan) and Southeastern Asia (the Philippines, Singapore, Thailand) for the period 1993-2002 mainly using data from Cancer Incidence in Five Continents, Volumes VIII and IX. We compared trends in annual incidence rates and age-specific incidence curves over a 10-year period. We also compared the incidence rates of Asian-Americans with the rates of their Asian counterparts. RESULTS: Breast cancer incidence rates increased gradually over time in all study populations. Rates were relatively high in Southeastern Asia and became progressively lower along a south-to-north gradient, with a fourfold geographic variation within the study populations. Age-specific incidence curves showed patterns that gradually changed according to incidence rates. Breast cancer incidence among Asian women living in the United States was 1.5-4 times higher than the corresponding incidence rate in the women's respective countries of origin. CONCLUSION: Breast cancer incidence is expected to continue to increase for the next 10 years in Asia and may approach rates reported among Asian-Americans. The number and mean age of breast cancer cases is expected to increase as the female Asian population ages, the prevalence of certain risk factors changes (early menarche, late menopause, low parity, late age at first live birth, and low prevalence of breastfeeding), and as Asian countries introduce mass screening programs.

Cancer epidemiology and control in peninsular and island South-East Asia - past, present and future.

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.

Cancer incidence and survival in Metro Manila and Rizal province, Philippines.

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.

Inter-country and ethnic variation in colorectal cancer survival: comparisons between a Philippine population, Filipino-Americans and Caucasians.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Breast cancer survival in different country settings: comparisons between a Filipino resident population, Filipino-Americans and Caucasians.

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.

Ovarian cancer survival population differences: a "high resolution study" comparing Philippine residents, and Filipino-Americans and Caucasians living in the US.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Ethnicity and health care in cervical cancer survival: comparisons between a Filipino resident population, Filipino-Americans, and Caucasians.

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.

Epidemiology and clinicopathology of breast cancer in metro Manila and Rizal Province, Philippines.

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.

Proposal for a cooperative study on population-based cancer survival in selected registries in East Asia.

Reliable population-based cancer survival data are essential for assessment of the effectiveness of cancer screening programs, distribution of cancer therapy and prevalent cancer cases. International comparisons are useful to allow societies, mass media and health authorities to gain a real appreciation of the cancer problem in their own country and provide an impetus to improve registration and cancer control planning. Since directly comparable survival data among East Asian countries are presently very limited, a comparative study on population-based cancer survival involving China, Indonesia, Japan, Korea, the Philippines and Taiwan, with Nepal as an observer, was proposed. At the 1st Working Group meeting in Tokyo on March 18th, 2009, it was decided to publish the present Commentary as a step towards realization of truly comparable cancer survival statistics in the region. Included are general information and quality of data of cancer registration at each participating registry and five-year relative survival rates of cancer of the stomach, colo-rectum, liver, lung, breast and cervix.