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Aims: Because of a lack of recent data from New Zealand older men, we examined dietary supplement use in this demographic., Methods: We surveyed men aged $gt;40 years who were participating in a trial of calcium supplementation on bone and cardiovascular outcomes., Results: Forty-seven percent reported using at least one supplement and 30% of users took more than two different supplements. Amongst users, median monthly expenditure on these products was NZ$20 (interquartile range: $10-$45). The most common supplements used were vitamins or minerals (49%), followed by nutritional oils (22%) (including fish oils, 13%) and glucosamine/chondroitin preparations (13%). Supplements were mainly taken for reasons of non-specific prophylaxis or health maintenance (58% of reasons), although 21% of reasons cited treatment or symptom alleviation for a medical condition. Daily requirements for vitamins A, D and E were exceeded, from supplement intake alone, by 12%, 10% and 40% of supplement users respectively., Conclusions: Many older New Zealand men spend substantial amounts of money on dietary supplements despite uncertain health benefits. Health professionals should remain alert to supplement use by their patients, including males.

Fracture risk calculators estimate the absolute risk of osteoporotic fractures. We investigated the performance of the FRAX and Garvan Institute fracture risk calculators in healthy, older, New Zealand, postmenopausal women with normal bone mineral density (BMD) for their age. Fractures were ascertained in women initially enrolled in a 5-year trial of calcium supplements and followed on average for 8.8 years. Baseline data (1422 women, mean age 74 years, mean femoral neck BMD T-score -1.3) were used to estimate fracture risk during follow-up using the FRAX and Garvan calculators. The FRAX-New Zealand tool was used both with and without baseline BMD. The discrimination of the calculators was assessed using the area under the curve (AUC) of receiver operating characteristic curves. The calibration was assessed by comparing estimated risk of fracture with fracture incidence across a range of estimated fracture risks and clinical factors. For each fracture subtype, the calculators had comparable moderate predictive discriminative ability (AUC range: hip fracture 0.67-0.70; osteoporotic fracture 0.62-0.64; any fracture 0.60-0.63) that was similar to that of models using only age and BMD. The Garvan calculator was well calibrated for osteoporotic fractures but overestimated hip fractures. FRAX with BMD underestimated osteoporotic and hip fractures. FRAX without BMD underestimated osteoporotic and overestimated hip fractures. In summary, none of the calculators provided better discrimination than models based on age and BMD, and their discriminative ability was only moderate, which may limit their clinical utility. The calibration varied, suggesting that the calculators should be validated in local cohorts before clinical use., (Copyright © 2011 American Society for Bone and Mineral Research.)

Factors involved with calcium metabolism, such as serum calcium and phosphate and calcium intake, have been associated with vascular disease in different populations. We investigated whether this association is mediated via increased vascular calcification by assessing relationships between these factors and abdominal aortic calcification (AAC) and coronary artery calcification (CAC). A total of 1471 healthy postmenopausal women participated in a 5-year randomized, placebo-controlled trial of calcium 1 g/day, and 323 healthy middle-aged and older men participated in a 2-year randomized, placebo-controlled trial of calcium 600 or 1200 mg/day. AAC was assessed on vertebral morphometric images at baseline and follow-up. Based on computed tomography, 163 men had CAC assessed, on average, 1.5 years after study completion. In elderly women, AAC was positively related to serum calcium (p < .001), phosphate (p = .04), and the calcium-phosphate product (p = .003), but changes in AAC over time and incidence of cardiovascular events were not related to these variables. In middle-aged men, AAC and CAC were not consistently related to these variables. Neither dietary calcium intake nor calcium supplementation was associated with changes in the prevalence of AAC over time, and calcium supplementation also was not related to CAC scores in men. After adjusting for age, AAC was not associated with low bone mineral density (BMD) at baseline, changes in BMD over time, or fracture incidence. CAC also was not related to baseline BMD. In summary, serum calcium and phosphate are associated with AAC in older women, but dietary calcium intake and calcium supplementation were not associated with changes in AAC over 2 to 5 years., (Copyright © 2010 American Society for Bone and Mineral Research.)

Abdominal aortic calcification (AAC) measured on spine X-rays is an established risk factor for cardiovascular disease. We investigated whether AAC assessed using vertebral morphometry and a recently developed scoring system (AAC-8) is reliable and associated with cardiovascular risk factors or events. A total of 1471 healthy postmenopausal women and 323 healthy middle-aged and older men participated in 5 and 2 year trials of calcium supplements, respectively. AAC-8 was assessed on vertebral morphometry images at baseline and follow-up. In addition, 163 men also had coronary artery calcification measured using computed tomography. Cardiovascular events during the trials were independently adjudicated. We found strong inter- and intrameasurer agreement for AAC-8 (kappa > 0.87). The prevalence of AAC increased with age (p < .01) in women and in men. AAC was associated with many established cardiovascular risk factors, with serum calcium in women (p = .002) and with higher coronary calcium scores in men (p = .03). Estimated 5 year cardiovascular risk increased with increasing AAC-8 score (p < .001) in women and in men. The presence of AAC independently predicted myocardial infarction (MI) in women [hazards ratio (HR) = 2.30, p = .007] and men (HR = 5.32, p = .04), even after adjustment for estimated cardiovascular risk in women. In women, AAC independently predicted cardiovascular events (MI, stroke, or sudden death) (HR = 1.74, p = .007), and changes in AAC-8 score over time were associated with MI and cardiovascular events, even after adjustment for estimated cardiovascular risk. In summary, scoring AAC on vertebral morphometric scans is a reproducible method of assessing cardiovascular risk that independently predicts incident MI and cardiovascular events, even after taking into account traditional cardiovascular risk factors., (Copyright 2010 American Society for Bone and Mineral Research.)

Background: Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies. However, some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [25(OH)D]., Objective: We sought to determine the effect of vitamin D status on health outcomes., Design: Healthy community-dwelling women (n = 1471) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation. 25(OH)D was measured at baseline in all women. Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline., Results: Fifty percent of women had a seasonally adjusted 25(OH)D concentration <50 nmol/L. These women were significantly older, heavier, and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration > or =50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration <50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities. Women with a seasonally adjusted 25(OH)D concentration <50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome, including fracture, falls, bone density, or grip strength or any nonskeletal outcomes, including death, myocardial infarction, cancer, heart failure, diabetes, or adverse changes in blood pressure, weight, body composition, cholesterol, or glucose., Conclusions: Vitamin D insufficiency is more common in older, frailer women. Community-dwelling older women with a seasonally adjusted 25(OH)D concentration <50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities. Randomized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes. This trial was registered at www.anzctr.org.au as ACTRN 012605000242628.

Objective: To determine the association, if any, between male-pattern hair loss (baldness) and serum 25-hydroxyvitamin D (25-OHD) levels., Design and Participants: A cross-sectional study of 296 healthy middle-aged and older men., Main Outcome Measures: Degree of baldness was independently assessed by two researchers using the Hamilton-Norwood scale and serum 25-OHD was measured in all men., Results: Classification of the degree of baldness by the two researchers showed a high level of agreement (kappa = 0.93). Forty-eight per cent of men had no hair loss or mild frontotemporal recession, 15% had predominant vertex loss, and 37% had significant scalp and vertex loss. After data were adjusted for potential confounding factors - including age, month of 25-OHD measurement, exercise levels, use of sunscreen, skin type and frequency of outdoor hat wearing - no significant differences in 25-OHD levels between these groups was detected (P = 0.60)., Conclusions: The degree of baldness does not appear to influence serum 25-OHD levels. The high prevalence of baldness in older men does not explain sex differences in 25-OHD levels. Other novel hypotheses are required to help determine whether baldness serves any physiological purpose.

Background: The effect of season on vitamin D status is often overlooked in studies of optimal vitamin D concentrations and in clinical practice., Objectives: We aimed to determine the effects of seasonal variation of 25-hydroxyvitamin D [25(OH)D] on a previously selected minimum concentration for vitamin D sufficiency (50 nmol/L) and to determine whether fat mass modifies these effects., Design: A cross-sectional study evaluated 1606 healthy postmenopausal women and 378 older men from Auckland, New Zealand, who were undergoing single measurements of 25(OH)D., Results: Concentrations of <50 nmol 25(OH)D/L were seen in 49% (range: 23%-74%) of women and 9% (range: 0%-26%) of men when measured, but 73% of women and 39% of men were predicted to have trough 25(OH)D concentrations < 50 nmol/L, according to the demonstrated seasonal variation. The predicted duration of 25(OH)D concentrations < 50 nmol/L was 250 d/y in women and 165 d/y in men., Conclusion: Seasonal variation significantly affects the diagnosis of vitamin D sufficiency, which requires seasonally adjusted thresholds individualized for different locations. Clinicians should consider the month of sampling and the amount of body fat when interpreting 25(OH)D measurements.

Objective: 25-hydroxyvitamin D (25OHD) levels are inversely related to body weight, and have been reported to decline with age and be lower in women than men. We hypothesized that these findings might be explained by effects of these variables on vitamin D binding protein (DBP) levels. We set out to determine the relationships between DBP and gender, 25OHD, body weight and body composition., Design: Cross-sectional analysis., Patients: One hundred healthy, middle-aged and older, community-dwelling men and women., Measurements: All participants were measured for 25OHD, DBP, body weight, bone mineral density and body composition., Results: Women had higher mean DBP levels than men but lower total 25OHD levels [DBP: women, mean (SD) 339 (36) mg/l, men 307 (71) mg/l, P = 0.005; 25OHD: women 67 (23) nmol/l, men 91 (39) nmol/l, P < 0.001]. In women, there were significant positive relationships between DBP and albumin (r = 0.33) and 25OHD (r = 0.34) whereas in men there were no significant relationships between DBP and any measured variables. There was no significant relationship between DBP and age, body weight, body mass index, fat mass or percentage fat in men or women., Conclusion: We found no evidence to support the hypothesis that DBP levels are related to age, or adiposity. The changes in 25OHD levels with age, gender, or fat mass are not due to underlying relationships between DBP and these variables. This suggests that the relationships consistently observed between 25OHD and body composition and gender are of biological origin and not due to adaptation to changes in transport proteins.

Introduction: Previously we reported seasonal variation in 25-hydroxyvitamin D (25OHD) levels in postmenopausal women living in a subtropical climate. Because studies have suggested that there are gender differences in 25OHD levels, we sought to determine (1) the levels and determinants of 25OHD in men drawn from the same community, (2) whether seasonal variation of 25OHD occurs in men at this latitude (37 degrees S), and (3) whether these findings were comparable to those we previously observed in postmenopausal women., Methods: Cross-sectional study of 378 healthy, middle-aged and older community-dwelling men in Auckland, New Zealand., Results: The mean 25OHD (SD) level was 85 (31) nmol/l. We found significant seasonal variation in 25OHD levels (peak in autumn 103 nmol/l, nadir in spring 59 nmol/l). Vitamin D insufficiency (25OHD <50 nmol/l) was uncommon (prevalence in summer 0-17%, in winter 0-20%). The major determinants of 25OHD were month of blood sampling, fat percentage, physical activity, and serum albumin. Men had higher levels of 25OHD throughout the year than women did, a finding that persisted after adjusting for potential confounding factors. In men and women the determinants of 25OHD were similar., Conclusion: There is significant seasonal variation in 25OHD levels in men living in a subtropical climate. In contrast to postmenopausal women, men have low rates of suboptimal vitamin D status, even in winter. Routine vitamin D supplementation for this population of men is not warranted.

Studies performed in the Northern Hemisphere and in areas distant from the equator have demonstrated significant seasonal variation in 25-hydroxyvitamin D (25OHD) levels. Whether such variation occurs in a subtropical area such as Australasia is not clear. We performed a cross-sectional study of 1,606 healthy, postmenopausal women recruited over a 33-month period. The study had three goals: to determine the normal levels of 25OHD in healthy postmenopausal women living in Auckland, New Zealand; to determine whether seasonal variation of 25OHD occurs at this latitude; to assess the relationship between 25OHD, biochemical indices, anthropometric variables and bone mineral density (BMD). We found significant seasonal variation in 25OHD levels, with the change in monthly ultraviolet dose from summer to winter being followed 6-8 weeks later by a corresponding change in 25OHD levels. Vitamin D insufficiency (25OHD <50 nmol/l) was common. During summer, 28-58% of participants had suboptimal vitamin D status, while in winter, the frequency increased to 56-74%. 25OHD levels correlated with participants' age (r=-0.15), weight (r=-0.11), body mass index (r=-0.13), fat mass (r=-0.14), percentage body fat (r=-0.16), physical activity (r=0.10) and the month of blood sampling (all P<0.0001). Collectively, age, fat mass, physical activity, and month of sampling explained 21% of the variance in 25OHD. No significant relationships were noted between 25OHD and BMD at any site. Other variables that showed significant monthly variation were glucose (P=0.002), serum phosphate, alkaline phosphatase, and albumin (all P<0.0001). There was no monthly variation in BMD at the lumbar spine or proximal femur. In conclusion, there is significant seasonal variation in 25OHD levels, even in a subtropical climate. Furthermore, despite generous amounts of sunlight, considerable numbers of women have suboptimal vitamin D status, even in summer. Our findings support the suggestion that vitamin D supplementation should become standard practice in this population of women, particularly during winter.

Background: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) appear to influence the growth of breast cancer cells in vitro, and epidemiological studies suggest higher serum IGF-I levels increase the risk of breast cancer. IGF-I and IGFBP-3 have therefore been measured in women with advanced breast cancer to determine if changes in serum levels predict the response to treatment by chemotherapy., Methods: Serum IGF-I and IGFBP-3 levels were measured in 14 patients before and after 1 week of chemotherapy. Changes in serum levels were compared with duration of survival., Results: Mean basal serum levels of IGF-I and IGFBP-3 were not significantly different between patients with advanced breast cancer and controls or women with early breast cancer. Serum IGFBP-3 fell significantly 1 week after initiation of chemotherapy. Patient survival was not significantly related to baseline IGF-I or IGFBP-3 levels, but when the fall in serum levels 1 week after starting treatment was expressed either as absolute change or as a percentage of baseline, those individuals with a decrease in IGFBP-3 greater than the median had significantly poorer survival (median survival 5.5 months vs 18 months). These results were independent of other prognostic variables such as previous disease-free survival, and were also unaffected by the change in serum albumin with treatment. The fall in IGF-I and IGFBP-3 with chemotherapy mainly occurred in those with hepatic metastases, but prediction of survival was explained solely by the extent of the fall in IGFBP-3., Conclusions: This preliminary study has shown that serum IGFBP-3 falls significantly following initiation of chemotherapy and the extent of reduction significantly predicts the response to treatment.

Background: There is evidence that insulin-like growth factors play a role in the development of breast cancer. Antiestrogens reduce circulating levels of IGF-I, but the influence of other breast cancer treatments, including surgery, is unknown and is investigated in this study., Methods: Circulating serum concentrations of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured before and after breast surgery in 31 patients with breast cancer and 12 controls with benign breast lesions. Serum albumin was measured as a marker of the nonspecific metabolic effect of surgery., Results: Serum IGF-I, IGF-II, IGFBP-3, and albumin fell 24 hours after surgery for breast cancer but largely normalized again over the next 7 days. The fall in IGF-I and IGFBP-3 was not significant when the change in serum albumin was used as a covariate, suggesting a nonspecific effect of surgery. However, the reduction in IGF-II remained significant when adjusted for albumin and was greater after lumpectomy of malignant tumors (-8 +/- 2%) compared with benign disease (2 +/- 2%, P = .001). The fall in IGF-II was significantly related to the size of the removed tumor., Conclusions: Breast cancer may directly influence the serum concentration of IGF-II, possibly by direct tumor production.

Background: The insulin-like growth factors IGF-I and IGF-II and their major binding protein IGFBP-3 influence the growth of breast cancer cells in vitro. Some benign non-breast tumours appear to be associated with increased serum IGFBP-3 levels which would tend to reduce bioactive-free IGF concentrations. The present study investigates whether this pattern also occurs in neoplastic breast disease., Methods: Serum IGF-I, IGF-II and IGFBP-3 were measured by specific radioassay in 12 women with benign breast disease, 31 patients with breast cancer and in age-matched controls., Results: The mean (+/-SD) serum IGFBP-3 concentration was higher in benign breast disease (3.6+/-0.7 mg/L) than in controls (2.7+/-0.6 mg/L) or in breast cancer patients (2.7+/-0.5 mg/L) (P = 0.001). Serum IGF-I and IGF-II levels were not significantly different among the groups. However, the index of free unbound IGF measured as the molar ratio of IGF-I plus IGF-II divided by IGFBP-3 was significantly lower in benign breast disease than in the other subjects., Conclusions: Either the production or clearance of IGFBP-3 is altered in benign breast disease so that there is less free IGF available to cells. This may serve to protect against malignant transformation in patients with benign breast disorders.

Hormones such as melatonin whose serum concentrations vary seasonally have been previously implicated in the growth of breast cancer. The present study was undertaken to identify possible seasonal variation in a range of mammotrophic hormones which could exert a chronobiologic influence in women with breast tumours. Fifteen premenopausal women with a history of previous breast cancer (BC subjects) and 10 control women underwent 2-hourly serum sampling for 24 h at both summer and winter solstice for measurement of melatonin, growth hormone (GH), insulin-like growth factor-I (IGF-I), cortisol, prolactin and thyrotrophin (TSH). Hormone secretion at the different seasons was compared by measuring the area under the 24 h serum hormone concentration x time curves and by time series analysis of summer-to-winter differences in hormone concentration. Control women had significantly higher GH and IGF-I levels in summer compared to winter and significantly higher cortisol secretion in winter than summer. In contrast, BC women had no significant seasonal difference in IGF-I concentrations and had a reversal of the normal seasonal pattern of melatonin secretion, although seasonal changes in GH production were similar to controls. Prolactin and TSH showed no significant summer/winter variation in either group. Thus, seasonal variations in hormone secretion seen in normal women were, with exception of GH, absent or reversed in women with a previous history of breast cancer. As a result these individuals may be exposed to an asynchronous hormonal stimulus which could influence tumour growth. These changes could reflect a constitutional abnormality in BC women or may have been induced by the previous breast tumour.

The effect of concurrent or subsequent pregnancy or lactation has been studied in women with breast cancer to determine if these variables influence prognosis. Information was collected from 382 women potentially capable of bearing children, aged less than 45 years, in the Auckland Breast Cancer Study Group data file, a consecutive series of women diagnosed with breast cancer from 1976 to 1985, with a median follow-up of 10.2 years. The prevalence of both pregnancy at diagnosis and lactation at diagnosis was 2.6%. The incidence of pregnancy subsequent to diagnosis was 3.9%. Women pregnant at the time of breast cancer diagnosis had significantly more advanced disease than non-pregnant patients, and there was a similar trend for women lactating at diagnosis. Overall survival in these women was poor compared with the non-pregnant and non-lactating groups; only 2 of 10 pregnant patients and 0 of 10 lactating patients survived more than 12 years. The adverse outcome for women lactating at diagnosis of their breast cancer persisted despite allowance for nodal status, tumour size and age. However, survival was similar between pregnant and non-pregnant patients when these variables were taken into account. No significant differences in survival were found between those women who had pregnancies subsequent to diagnosis of breast cancer and breast cancer patients who did not become pregnant.

Aims: To assess the effect of prognostic factors on overall survival from node negative breast cancer., Methods: Information was collected on 1138 node negative breast cancer patients in the Auckland region, diagnosed between 1976 and 1985. Prognostic variables investigated included oestrogen (ER) and progesterone (PR) receptor status, tumour grade, tumour size, body mass index, lactation history and parity. The effects of these variables on overall survival were assessed separately in pre and postmenopausal groups., Results: Over a median follow up time of 10.2 years, improved survival was seen in premenopausal women with PR+ status (p = 0.0007), ER+ status (p = 0.03), positive lactational history (p = 0.03) and low tumour grade (p = 0.04). In postmenopausal women, only ER+ status (p = 0.01) and PR+ status (p = 0.02) were associated with improved survival. Multivariate analysis suggested that positive PR status combined with tumour size provided the best prognostic discrimination in premenopausal women, whereas ER status was the dominant prognostic variable in postmenopausal patients., Conclusions: For premenopausal node negative women, progesterone receptor status, considered either alone, or together with tumour size, provides the best prognostic prediction of survival. By comparison, oestrogen receptor status is the most important predictor of overall survival in postmenopausal women.

Measurement of insulin-like growth factor II (IGF-II) in human serum is complicated by the presence of IGF binding proteins and usually involves cumbersome extraction procedures followed by radioimmunoassay. We have utilized an extraction process developed for measuring insulin-like growth factor II in ovine serum using Sephacryl HR100, and have applied this to the extraction of human samples followed by radioimmunoassay for human IGF-II. The assay yielded 98% recovery of unlabelled IGF-II, parallelism between dilutions of eluate and the standard curve, complete removal of binding proteins and near-complete removal of IGF-I, and intra- and interassay coefficients of variation of 5% and 9%, respectively. The normal range for serum IGF-II in women was 490-1056 micrograms/L, and IGF-II levels were positively correlated with serum concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) but not with IGF-I levels. Mean serum concentrations of IGF-II were reduced below normal in a number of hypopituitary patients and children with short stature and IGF-II concentrations in these subjects correlated positively with IGF-I and IGFBP-3. In acromegalic patients IGF-II levels were usually normal and were negatively correlated with IGF-I concentrations. From our experience with the above results the present assay appears particularly suitable for clinical measurements and research projects where high sample throughput is required.

Aim: A descriptive study of the treatment of breast cancer in Auckland between the years 1976 to 1985., Methods: A database was constructed utilising information from all new breast cancer cases recorded in the Auckland region from September 1976 to September 1985. Details of treatment were obtained at the time of diagnosis and the database was updated every 9 months. Patient survival was measured and changes in the pattern of treatment were assessed., Results: After a median follow up of 9 years 41% of patients were alive without evidence of breast cancer, 9% were alive with recurrence and 50% had died, 38% having died of breast cancer. Survival of node positive patients at 5 years of follow up who received adjuvant tamoxifen or adjuvant chemotherapy was 57 (SE 4)% and 63 (4)% respectively. The proportion of less than mastectomy surgical procedures increased over the study period, and local recurrence in these patients was reduced by postoperative radiotherapy., Conclusions: Between 1976 and 1985 there was an increasing rate of conservative surgery for breast cancer in Auckland. Overall survival of patients was comparable to that reported in international studies, with increasing use of adjuvant endocrine therapy but a decline in adjuvant chemotherapy over the duration of the study.

The relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7 alpha-hydroxy DHA (7 alpha DHA), and tumour oestrogen receptor (ER) and progesterone receptor (PR) status were examined in pre, peri-, and postmenopausal women with breast cancer. Androgenic steroids and their metabolites decreased with age in women with breast cancer. In perimenopausal women there was a significant association of PR positive tumours and high androgen levels, whereas in postmenopausal women high androgen levels were associated with ER negative tumours. Survival was significantly related to plasma DHA level and tumour steroid receptor status. Thus, adrenal androgen levels below the group mean were associated with significantly decreased survival in women with postmenopausal receptor-positive tumours, and the association was particularly apparent in those who were axillary node negative. Since the number of patients studied was small these results should be regarded as provisional in nature. Nonetheless, the identification of this subgroup of node negative breast cancer women with reduced survival may be important when considering node negative patients for adjuvant therapy.

Aims: To determine the efficacy and extent of screening mammography for detection of contralateral breast cancer in a cohort of women with previous unilateral mammary carcinoma, and to assess the effect of endocrine therapy on the risk of developing cancer in the contralateral breast., Methods: Women with previous breast cancer eligible for mammography were identified from the Auckland breast cancer data file and the extent and outcome of mammographic screening determined by questionnaire and survey of mammography reports. The extent of adjuvant hormonal therapy and development of contralateral breast cancer was ascertained from the ABCDF records., Results: Of 703 eligible subjects, 59% had undergone screening mammography with a cancer detection rate of 17 per 1000 mammograms and a benign to malignant ratio was 1.7 to 1. Contralateral breast cancer developed in 2.9% of 1980 women with previous unilateral mammary tumours who did not receive endocrine therapy with 1.1% of 374 women who were given adjuvant hormonal treatment (p = 0.04)., Conclusions: The efficacy of mammography in those screened was comparable to major overseas screening programs, but the proportion of women undergoing mammography in this high risk group was relatively low suggesting a need for greater promotion of mammography in Auckland. The use of adjuvant endocrine therapy significantly reduced the rate of development of contralateral breast tumours supporting the current development of formal trials of chemoprevention of breast cancer in women at high risk groups of the disorder.

Aims: to assess the effect of age at diagnosis and ethnicity on overall survival from breast cancer., Methods: information was collected from 2706 breast cancer patients in the Auckland region, diagnosed between 1976 and 1985. Age at diagnosis was categorised into four groups: < 35 years, 35-49 years, 50-74 years and 75 years or older. Ethnicity was self reported in three categories: European, Maori and Pacific Island Polynesian. Independent effects were assessed by controlling for extent of disease, specifically metastases at presentation, nodal status and size of tumour., Results: age and ethnic group were both significantly related to overall survival in univariate analyses. In multivariate analysis, age had an independent effect on survival mainly due to a significant survival difference between women aged less than 35 years and those aged 35 to 49 years (p < 0.0001; RR = 2.02). Survival was not significantly different between other age groups when adjustments were made for extent of disease. There was no significant effect of ethnicity on survival in the reduced dataset used for the multivariate analysis. Separate analyses suggested that ethnic differences in the extent of disease at diagnosis may be the cause of the apparent initial effect of ethnicity on survival., Conclusions: women < 35 years at diagnosis have a significantly poorer prognosis than women aged 35-49 years. Other differences between age groups were not significant when stage of disease was taken into account. Ethnicity was not an independent factor influencing survival after controlling for extent of disease but numbers in the Maori and Pacific Island groups were too small to conclusively evaluate any effect of ethnic group on prognosis.

Data on all new breast cancer cases in the Auckland area during the nine years September 1976 to September 1985 were used to obtain epidemiological information on breast cancer in the Auckland region. Breast tumours were found in 2706 women (300 per year), yielding a lifetime risk of breast cancer of one in 15. No significant difference in breast cancer incidence was detected between European, Maori and Pacific Island Polynesian women. Confidence limits for incidence were wide in the later groups. Fifty-one percent of women presented with intermediate sized (2-5 cm) tumours, and most (66%) were node negative. Eleven percent had evidence of metastatic disease at presentation. When the relationships between race, tumour size, nodal status and metastases were examined, Pacific Island women more frequently presented with large tumours and metastases, whereas Maori women were more frequently node positive. Eighty-five percent of tumours were invasive ductal carcinomas, 55% grade II, 35% grade III, and 10% grade I. Sixty-seven percent of tumours were oestrogen receptor positive (ER+ve) and ER status was significantly related to age; the proportion of ER+ve tumours was greater in older women. Fifty-seven percent of tumours were progesterone receptor positive (PR+ve), and PR distribution was bimodal with age. These data from the Auckland region are similar to breast cancer figures from other western countries, with some ethnic differences in tumour size and frequency of metastatic disease at presentation.

There are conflicting reports of seasonal changes in steroid hormone receptor levels in breast cancer tissue. Estrogen receptor and progesterone (PR) receptor levels from 1132 tumors were thus grouped according to month of initial tumor detection or month of tissue sampling/surgery. There was a significant circannual variation in the mean monthly PR receptor concentration in patients grouped according to month of tissue sampling/surgery with peak PR levels in April (late summer-early autumn) and nadir values in August and September (late winter-early spring). There was no significant cyclic variation in estrogen receptor values. A significant annual variation in tumor PR concentration was also seen when receptor levels from individual tumors were grouped according to month of initial tumor detection, with peak PR levels found in January and February. The time interval between tumor detection and biopsy/surgery was 3.3 +/- 5.3 months (mean +/- SD) which was close to the interval between the peak PR concentration expressed by month of tumor detection compared with month of tissue sampling for receptor assay. There was also a significant seasonal variation in the month of initial tumor detection, with peak detection occurring in December (summer). The close synchrony between month of maximum tumor detection and month of peak PR concentration suggests that seasonal changes in detection of breast cancer may in part relate to seasonal changes in hormone responsiveness within tumor tissue.

1675 breast cancer patients in the Auckland regional area have been divided into two major groups according to delay in diagnosis greater or less than six weeks. Overall there is no difference in survival although the variables tumour size, skin attachment, and nipple retraction are more common in the group with longer delay, and grade III tumours in those with short delay. Three important prognostic variables (the presence of tumour steroid receptors, positive axillary nodes, and distant metastases at diagnosis) are equally distributed and have a similar effect on survival within the two delay groups. However, in a subgroup of women with negative axillary nodes, short delay is associated with poorer survival, independent of tumour size. More tumours with grade III histology and a negative progesterone receptor status are found in this subgroup. Thus, short delay may constitute a new prognostic variable of some importance when in association with negative axillary nodes.

The rate of initial detection of breast tumours varies during the year in a seasonal fashion, more tumours being discovered in late spring/early summer than at other times of the year. This phenomenon is particularly pronounced in young women (less than 50 years) with progesterone receptor positive tumours. The present study investigates whether season of tumour detection influences the predictive capacity of several recognised prognostic and risk factors in patients with breast cancer. Axillary nodal status, tumour progesterone receptor status, and season of tumour detection significantly influenced survival in both older (greater than 50 yrs) and younger (less than 50 yrs) patients. Parity, lactational history, body mass index, tumour oestrogen receptor status, and patient age also influenced survival, but these effects were significant only in age groups less than 50 or greater than 50 yrs. Season of detection of tumour did not effect the prognostic significance of axillary nodal status. However, the effect of oestrogen receptor status on survival was more significant in patients who detected their tumours in the spring/summer compared with winter (odds ratio 0.52 and 0.73 respectively). Negative progesterone receptor status was associated with significant poorer survival only in patients with tumours found in the winter. There was a significant survival disadvantage for nulliparous compared with parous women with breast cancer who were greater than or equal to 50 years at diagnosis, and for women who had never lactated compared with those who had lactated, but this disadvantage was restricted to those who found their tumours in the summer. An increased body mass index (greater than or equal to 28) was associated with decreased survival, but this was significant only for those detecting tumours in winter. The increased incidence of detection of breast cancer in spring/summer may reflect cyclic influences on tumour growth. Such influences may be hormonal in nature and may underlie the effect of season of tumour detection on the prognostic influence of lactation, parity, body mass index, and oestrogen and progesterone receptor status in patients with breast cancer.

The relationship between obesity and breast cancer has been investigated in 1281 Auckland breast cancer patients. Using a definition of obesity as a Body Mass Index (BMI) of greater than or equal to 28 kg/m2, 179 (14%) breast cancer patients were classified as obese. The heights, weights, and BMI of 822 breast cancer patients aged 35-64 compared to 518 randomly selected Auckland women of similar age showed no significant difference. Within the breast cancer patients, there was no variation in nodal status or estrogen and progesterone receptor status between obese and non-obese women. However, tumours greater than 5 cm occurred significantly more often in obese patients. Time to recurrence was reduced in obese women with tumours less than or equal to 5 cm, no tumour in the axillary nodes, positive estrogen or progesterone receptor, and without metastases at the time of presentation of the disease. Although obesity has not been shown to influence breast cancer incidence, an effect on tumour recurrence is seen in patients with less advanced disease. This is similar to other reports which suggest that obesity is a weak but positive risk factor for recurrence.

A significant circannual variation of the month in which patients detect the first sign or symptom of tumour has been defined in 1413 patients with breast cancer. The months of highest detection were in the late spring-early summer, and lowest detection was in late autumn-early winter. Analysis of subgroups indicates that this cyclic trend was most significant in younger women with small or moderate-sized tumours containing steroid hormone receptors, particularly progesterone receptors. It seems likely that this variation is related to the effect of cyclic hormonal changes on tumour growth, possibly mediated through the pineal.

Cytosol oestrogen receptor (ER) and progesterone receptor (PR) levels were measured in tumours from three patients with breast cancer during pregnancy and from three patients developing breast cancer while lactating. All lactating patients were ER-positive and two were PR-positive, whereas pregnant patients were uniformly ER-negative and PR-negative. Pregnant patients had a significantly shorter disease-free survival compared with matched nonpregnant women with breast cancer. Of five patients developing metastatic disease, one from the lactating group had a complete remission with chemotherapy and one had static disease with endocrine treatment, whereas all others had progressive disease despite a variety of treatments. Although numbers are too small to permit generalisation, these provisional data suggest that patients presenting with breast cancer during pregnancy may have mainly receptor-negative tumours, a short disease-free interval, and may be relatively resistant to treatment of metastatic disease. By comparison, patients with breast tumours during lactation have receptor-positive disease and metastases may respond to systemic therapy.

Estrogen receptor status, tumor histology, and the interval between the development of tumors were assessed in 99 patients with bilateral breast cancer. Tumors were first grouped into those simultaneously detected in both breasts or within 12 months of each other (synchronous bilateral breast cancer, of which there were 64) and second, those detected within more than 12 months of each other (asynchronous bilateral breast cancer, of which there were 35). Nineteen percent of all tumors were lobular carcinomas. Overall, the rate of receptor discordance between the two tumors was not significantly different from that previously reported between biopsies of primary tumor and metastases in patients with unilateral breast cancer. Synchronous receptor-positive tumors occurred significantly more frequently than expected, suggesting that the development of the two tumors was influenced by a common mechanism. In patients with asynchronous bilateral breast cancer there was a significantly longer interval between tumors if both were receptor-positive compared with concordant receptor-negative tumors and tumors with discordant receptor status. There was a significant discordance in the receptor status of asynchronous tumors when the histology also differed, indicating that the tumors in this group were likely to be separate primary tumors.

Plasma concentrations of dehydroepiandrosterone (DHA), DHA-sulphate (DHAS) and 7 alpha hydroxy-DHA (7 alpha OHDHA) were measured and compared with tumor estrogen receptor (ER) status in 33 postmenopausal patients with breast cancer. Although the plasma concentrations of DHA, DHAS and 7 alpha OHDHA were not different between the ER-positive (ER+) and ER-negative (ER-) patient groups, the ratios of 7 alpha OHDHA/DHAS and of DHA/DHAS were significantly higher (P less than 0.001 and P less than 0.001 respectively) in the ER- group. Nine women (normal or with benign breast disease) of similar age and menopausal status had values for plasma 7 alpha OHDHA/DHAS and DHA/DHAS between those of ER+ and ER- patient groups. The measurement of these steroid ratios in the plasma of breast cancer patients thus provides an indirect estimate of ER status. Since DHA and 7 alpha OHDHA are major metabolites of precursor DHAS in mammary tumor tissues, changes in their relative quantities in plasma may reflect the influence of receptor-mediated events on mammary steroid metabolism. Alternatively, the relative increase in tumor metabolism of androgens inferred from high 7 alpha OHDHA/DHAS and DHA/DHAS ratios in the ER- group may disrupt the hormonal microenvironment of the estrogen receptor. These events may, in turn, predispose toward ER status and a poor response to endocrine therapy.

Estrogen receptor (ER) and progesterone receptor (PR) levels have been measured in 374 tumors from patients with primary breast cancer and compared with axillary nodal status and other patient variables to determine their relationship to prognosis. Nodal status reliably predicted disease-free interval and overall survival, and both ER and PR status predicted overall survival both individually and within node-positive and node-negative subgroups. PR but not ER status was also able to predict disease-free survival both overall and in the node-positive subgroup. When the two receptor measurements were used in combination, a group of receptor-negative, (ER- and PR-negative), node-negative patients were identified with a significantly worse survival than that for an ER- and PR-positive group of node-positive patients. It is apparent that receptor status provides useful prognostic information in patients with early breast cancer and that ER and PR assays used in combination identify a subgroup of node-negative patients with poor prognosis who are likely to benefit from adjuvant therapy following mastectomy.

Between September 1976 and May 1980, 135 patients with operable breast cancer and positive axillary nodes received l-phenylalanine mustard, adjunct to surgery, 0.15 mg/kg for five days, six weekly, and were randomised prospectively to levamisole 150 mg for three days, two weekly, or a placebo. Treatment was continued for two years or until evidence of treatment failure, whichever was the sooner. At 4 1/2 years, for all patients, there was no significant difference between the two groups (P = 0.09), but in a subgroup of women less than or equal to 50 with 1-3 positive nodes, levamisole had a negative effect (P = 0.05). Although an analysis of the same age group, independent of the nodal status, did not reach significance, there was a trend in favor of placebo (P = 0.08) which was also apparent in premenopausal women (P = 0.15). In postmenopausal patients, however, and in those with more advanced disease with four or more positive nodes, although the results also failed to reach significance the trend in these subgroups favored levamisole. The results of this study suggest that levamisole has no place in the primary therapy of breast cancer in younger women and those with more favorable disease. The value of this agent in older patients and those with more advanced primary disease, remains unproven, but the favorable trends are in accord with a number of other studies with levamisole in metastatic breast and resectable lung cancer. Retrospective analysis confined to those women who received 75% or more of the total dose of l-phenylalanine mustard showed no evidence for a dose-responsive effect of adjuvant chemotherapy on the described pattern of results.

The season of recurrence of tumour was investigated by follow-up of 1324 patients with breast cancer and compared with the season of initial tumour detection. Unlike primary tumours, where an increased incidence of detection has previously been observed in late spring and early summer, there was no significant seasonal variation in the time of recurrence. However, women with oestrogen receptor positive or progesterone receptor negative primary tumours recurred significantly more frequently in the same season that their primary cancer was initially detected. Overall there was an increased frequency of recurrence one year from diagnosis. Women less than age 50 who initially found their tumour in winter or autumn had a significantly shorter disease-free interval before recurrence than those first detecting their tumour in summer or spring. This relationship was independent of nodal status and tumour size. Tumours initially detected in winter or autumn thus appeared to follow a more aggressive growth profile. This study indicates that the season of first detection of a breast cancer relates significantly to aspects of the future biologic behaviour of the tumour.