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Background: Gail and others developed a model (GAIL) using age-at-menarche, age-at-birth of first live child, number of previous benign breast biopsy examinations, and number of first-degree-relatives with breast cancer as well as baseline age-specific breast cancer risks for predicting the 5-year risk of invasive breast cancer for Caucasian women. However, the validity of the model for projecting risk in South-East Asian women is uncertain. We evaluated GAIL and attempted to improve its performance for Singapore women of Chinese, Malay and Indian origins., Methods: Data from the Singapore Breast Screening Programme (SBSP) are used. Motivated by lower breast cancer incidence in many Asian countries, we utilised race-specific invasive breast cancer and other cause mortality rates for Singapore women to produce GAIL-SBSP. By using risk factor information from a nested case-control study within SBSP, alternative models incorporating fewer then additional risk factors were determined. Their accuracy was assessed by comparing the expected cases (E) with the observed (O) by the ratio (E/O) and 95% confidence interval (CI) and the respective concordance statistics estimated., Results: From 28,883 women, GAIL-SBSP predicted 241.83 cases during the 5-year follow-up while 241 were reported (E/O=1.00, CI=0.88 to 1.14). Except for women who had two or more first-degree-relatives with breast cancer, satisfactory prediction was present in almost all risk categories. This agreement was reflected in Chinese and Malay, but not in Indian women. We also found that a simplified model (S-GAIL-SBSP) including only age-at-menarche, age-at-birth of first live child and number of first-degree-relatives performed similarly with associated concordance statistics of 0.5997. Taking account of body mass index and parity did not improve the calibration of S-GAIL-SBSP., Conclusions: GAIL can be refined by using national race-specific invasive breast cancer rates and mortality rates for causes other than breast cancer. A revised model containing only three variables (S-GAIL-SBSP) provides a simpler approach for projecting absolute risk of invasive breast cancer in South-East Asia women. Nevertheless its role in counseling the individual women regarding their risk of breast cancer remains problematical and needs to be validated in independent data.

Introduction: Double-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone. These are thought to reflect accelerated tumour growth at micrometastatic sites mediated by angiogenesis after primary tumour removal as well as tumor dormancy. Similar data are not available for Asian populations. We sought to investigate whether differences exist in the pattern of mortality hazard function between Western breast cancer patients and their Asian counterparts in Singapore, which may suggest underlying differences in tumor biology between the two populations., Methods: We performed a retrospective cohort study of female unilateral breast cancer patients diagnosed in Singapore between October 1994 and June 1999. Data regarding patient demographics, tumour characteristics and death were available. Overall survival curves were calculated using the Kaplan-Meier method. The hazard rate was calculated as the conditional probability of dying in a time interval, given that the patient was alive at the beginning of the interval. The life table method was used to calculate the yearly hazard rates., Results: In the 2,105 women identified, 956 patients (45.4%) had mastectomy alone. Demographic characteristics were as follows: 86.5% were Chinese, 45.2% were postmenopausal, 38.9% were hormone receptor positive, 54.6% were node negative and 44.1% had high histological grade. We observed a double-peaked mortality hazard pattern, with a first peak in mortality achieving its maximum between years 2 and 4 after mastectomy, and a second large peak in mortality during year 9. Analyses by subgroups revealed a similar pattern regardless of T stage, or node or menopausal status. This pattern was also noted in high-grade tumors but not in those that were well to moderately differentiated. The double-peaked pattern observed in Singaporean women was quantitatively and qualitatively similar to those reported in Western series., Conclusion: Our study confirms the existence of a double-peaked process in Asian patients, and it gives further support to the tumour dormancy hypothesis after mastectomy.

Our study reports on the interval cancers arising in the subsequent 3 years in women screened as part of the Singapore Breast Cancer Screening Programme that commenced in 1994. Women, the majority of Chinese ethnicity, were either invited or not invited by random allocation to be screened. All women, other than those identified with breast cancer at screening, whether invited or not, were followed for 3 years, and information on all breast cancers arising in this period was obtained through the national registry. In particular, the cancers arising from those women who were deemed free of the disease at screening were noted. The mammographs taken at screening of those women who developed such an interval cancer were rereviewed by 3 radiologists. In the 28,099 women who were screened and deemed free of disease, 59 interval cancers were reported with annual rates of 2.1, 10.6 and 10.8 per 10,000 women-years in the succeeding 3-year periods. In 39,425 women who were invited but declined screening, the rates were 17.0, 15.5 and 11.7, while the corresponding rates from 97,294 women not invited were 12.8, 13.3 and 13.0. Whereas the annual incidence at 1 year in women who have been screened is much lower than those in the 2 groups who were not screened, it is of a similar magnitude by 2 years. This suggests that locally an optimal screening interval may be close to 1 year. The rereview of the mammograms of those 59 women with interval cancers suggested that the maximum possible number of these that might have been detected at screening was 10 (17%)., (Copyright 2002 Wiley-Liss, Inc.)

This study investigates seasonality in the diagnosis of 3219 female breast carcinoma cases reported between 1995-8 in Singapore. There is little evidence of marked seasonal variation. Angular regression suggested that observed differences in peak diagnosis with respect to menopausal status, tumour size, ER and PR status may be chance., (Copyright 2001 Cancer Research Campaign http://www.bjcancer.com.)

Purpose: The objective of this study was to determine whether the thermal dose delivered during hyperthermia treatments and other thermal factors correlate with outcome after combined radiation and hyperthermia of breast carcinoma recurrences. Data were from the combined hyperthermia and radiation treatment arms of four Phase III trials, which when pooled together, demonstrated a positive effect of hyperthermia., Methods and Materials: Four Phase III trials addressing the question of whether hyperthermia could improve the local response of superficial recurrent breast cancer to radiation therapy were combined into a single analysis. Thermal dosimetry data were collected from 120 of the 148 breast cancer recurrence patients who received hyperthermia. The data were analyzed for correlations between thermal parameters as well as important clinical parameters and outcome (complete response rate, local disease free survival, time to local failure, and overall survival)., Results: Five thermal parameters were tested, all associated with the low regions of the measured temperature distributions. Max(TDmin) and Sum(TDmin) were associated with complete response where TDmin is the minimum thermal dose measured by any of the tumor temperature sensors during a treatment: Max(TDmin) is the maximum of TDmin over a series of treatments. Using a categorical relationship with a cutoff of 10 min for Sum(TDmin), the complete response rate was 77% for Sum(TDmin) > 10 min and 43% for Sum(TDmin) < or = 10 min (p = 0.022, adjusted for study center and significant clinical factors). The overall complete response rate for hyperthermia and radiation was 61% compared to 41% for radiation alone. Either Max(TDmin) or Sum(TDmin) were also associated with local disease free survival, time to local failure and overall survival., Conclusions: An earlier report of this trial demonstrated a significant benefit when hyperthermia was added to radiation in the treatment of breast cancer recurrences. The analysis of thermal factors demonstrates that parameters representative of the low end of the measured temperature distributions are associated with initial complete response rate, local disease-free survival, time to local failure and overall survival.

An analysis of 351 HT treatment sessions administered to 101 patients receiving radiotherapy and hyperthermia (RT + HT) who were entered into Phase III concurrent randomized trials for recurrent (BrR) and intact (BrI) breast tumours is presented. A complete response (CR) was recorded in 50 of 84 (59.5%) fields in the case of recurrent breast patients and in 10 of 17 (59%) fields in the case of the intact breast patients. In comparison, 15 of 60 (25%) patients entered into BrR who received RT alone and 8 of 12 (66.7%) patients receiving RT alone entered into BrI trial achieved CR. A set of thermal parameters is defined and evaluated on a treatment by treatment basis. Patient and tumour characteristics influential on CR are identified and thermal parameters which have additional prognostic value are investigated. Multivariate logistic analysis of the non-thermal data showed that maximum depth of tumour, presence or history of disease outside the treated area and RT regimen were most influential on CR. Tumour volume (cm3) (OR = 0.996, 95% CI = 0.993-1.004, p = 0.08) was not a strong prognostic covariate; tumour area and linear dimensions were even less significant (p = 0.41). The cumulative minimum thermal isoeffect dose (equivalent minutes at 43 degrees C) accrued over the 1st, 1st and 2nd, and 1st, 2nd and 3rd treatment sessions was the only thermal parameter to exhibit an association with CR consistently, Other thermal parameters found to contribute to the predictive models were MINTIME > 42 degrees C calculated for the first treatment session and %sensors > 43 degrees C (peak) calculated for the 2nd treatment session.

The aim of this was to derive population-based norms for women completing the EORTC QLQ-C30 version 1 which is designed for use with patients who have cancer. The study was conducted using two different questionnaires: one designed for use in female patients with breast cancer, the other for those with gynaecological cancers, but both including the EORTC QLQ-C30. The women were drawn from the Danish Central Population Register without knowledge of their health status and divided at random between the two questionnaires. All procedures for collecting data were identical. The response rate for those receiving the gynaecological cancer (GS) questionnaire was 49% and it was 71% for the breast cancer (BS) questionnaire. Detailed comparison between the two samples revealed several EORTC QLQ-C30 items showing a clear difference in distribution of scores between them. Because of this and the possible bias due to the relative low age-related response rate in GS, only the results from the BS are used for constructing norms. The norms cover all 30 single items on the EORTC QLQ-C30 and the nine derived scales, for women in four 10-year age groups commencing at 30 years and for those aged 70-75. Clear trends in, for example, declining ability to undertake strenuous activity are illustrated and quantified. Levels of certain symptoms, such as pain, are surprisingly high although it is recognized that the population sampled will contain a proportion of women with active disease including cancer. We recommend the use of these norms both as an aid to the clinical assessment of an individual patient, and to assist in the interpretation of clinical trial and longitudinal quality of life data. As a secondary result, we note that a population-based sample will have a lower response rate to a questionnaire with more questions, especially if many of these extra questions are on sexual issues.

Geographical variation in the standardized years of potential life lost ratio (SYPLR) in women aged 20-74 dying from breast cancer has been mapped by local authority district in England and Wales and compared with the variation as described by the standardized mortality ratio (SMR). The geographical distribution of areas of low and high SMRs is similar to that observed some 15 years earlier, showing an increase from north to south. In contrast, the pattern of SYPLRs shows a less obvious trend. Years of life lost because of breast cancer mortality were particularly high in eight of the 401 county districts (SYPLR 1.22-1.48) and particularly low in nine (0.60-0.86). Mapping SYPLRs for breast cancer gives a different pattern from mapping SMRs, and one which is possibly more appropriate for targeting resources in circumstances in which death at younger age will have major social consequences. Care is required in interpreting maps indicating high and low rates in the presence of multiple comparisons. However, the range of values observed is suggestive of the need to investigate districts with contrasting values of SYPLR with respect to the inter-relationships between sociodemographic characteristics, duration of symptoms, clinical presentation and treatment efficacy.

Purpose: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed., Methods and Materials: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials., Results: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses., Conclusion: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that hyperthermia appears to have an important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hyperthermia are warranted.

A total of 291 consecutive patients with early breast cancer who did not receive any supraclavicular prophylactic irradiation of the ipsilateral fossa have been followed for a minimum of 5 years. Isolated relapse in that site occurred in 4.5% of patients and was controlled by radical radiotherapy with a post-relapse 5-year survival of 33%. Relapse with co-existing distant metastases occurred in a further 7% and no patient survived to 3 years. Supraclavicular fossa irradiation contributes to morbidity, does not improve survival and should be abandoned in favour of delayed treatment for proven recurrence.

We have analysed the data of biopsy, tumour size, size, side and axillary lymph node status in a group of 866 patients presenting with breast cancer in Southampton from September 1975 to August 1981 and a group of 1424 women presenting with benign disease in the same period. The whole group showed a seasonal variation, with a peak presentation in June. The pre-menopausal age group account for almost all of this seasonality. The cause of the variation is not established and requires further investigation. The control group of benign breast disease cases did not show a seasonal variation.