The effect of different formalin concentrations on the nociceptive response in the formalin test was examined in mice. Subcutaneous formalin injection induces 2 distinct periods of high licking activity: an early phase lasting the first 5 min, and a late phase lasting 20-30 min after the injection. Formalin concentrations of 0.02-0.2% induced only the early phase, while concentrations of 1% or more induced both the early phase and the late phase. The ability of the test to show the antinociceptive effect of morphine and acetylsalicylic acid was similar for high and low formalin concentrations. For both these analgesics, a lower dose was needed to induce antinociception in the late phase than in the early phase using the same formalin concentration. Indomethacin had no effect in the early phase. In the late phase indomethacin induced antinociception when 1% formalin was used, while no significant effect was observed using 5% formalin. Clear histological changes in the paw were demonstrated after formalin concentrations that induced both phases. Lower formalin concentrations induced only very small changes. Using a low formalin concentration (0.2%), repeated testing using the same paw could be performed at intervals of 1 week without any significant change in the response. It was concluded that the formalin concentration should be kept as low as possible to minimize the suffering of the animal. Formalin concentrations of 0.05-0.2% are recommended for studying the early phase. Formalin concentrations of 1% or higher have to be used when studying the nociceptive response in the late phase.

The hypothesis that birth weight is positively associated with adult risk of breast cancer implies that factors related to intrauterine growth may be important for the development of this malignancy. Using stored birth records from the two main hospitals in Trondheim and Bergen, Norway, we collected information on birth weight, birth length and placenta weight among 373 women who developed breast cancer. From the same archives, we selected as controls 1150 women of identical age as the cases without a history of breast cancer. Information on age at first birth and parity were collected from the Central Person Registry in Norway. Based on conditional logistic regression analysis, breast cancer risk was positively associated with birth weight and with birth length (P for trend=0.02). Birth weights in the highest quartile (3730 g or more) were associated with 40% higher risk (odds ratio, 1.4, 95% confidence interval, 1.1 -1.9) of breast cancer compared to birth weights in the lowest quartile (less than 3090 g). For birth length, the odds ratio for women who were 51.5 cm or more (highest quartile) was 1.3 (95% confidence interval, 1.0 -1.8) compared to being less than 50 cm (lowest quartile) at birth. Adjustment for age at first birth and parity did not change these estimates. Placenta weight was not associated with breast cancer risk. This study provides strong evidence that intrauterine factors may influence future risk of breast cancer. A common feature of such factors would be their ability to stimulate foetal growth and, simultaneously, to influence intrauterine development of the mammary gland.

The present study consists of 1,238 women with unilateral breast cancer treated with modified radical mastectomy living in the geographic area of Haukeland Hospital. Their weight and height had been measured years before presentation of the disease. Age-adjusted Quetelet's index (weight/height2) showed that obese women had a 49% higher risk of dying from breast cancer than lean ones. The relative risk decreased slightly when adjusted for tumour diameter, lymph node status, and mean nuclear area of the tumour cells. The prognostic effect of Quetelet's index was examined according to the estrogen and/or progesterone receptor status of the tumour. In patients with a hormone receptor positive tumour, obese women had a risk that was more than three times higher than lean ones. In patients with hormone receptor negative tumour, the effect of obesity was reversed, lean patients having a risk that was more than six times higher than obese ones, even after adjustment for lymph node status, tumour diameter, and mean nuclear area. Quetelet's index, while being a prognostic variable in its own right, thus acts differently in patients with hormone receptor positive and negative tumours.

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Breast cancer patients who are obese have a higher risk of lymph node metastases and a poorer prognosis than those who are slim. It has been claimed that estrogens derived from fat are important for these associations. If estrogens are important, these relationships must be stronger in the hormone receptor-positive than in the hormone receptor-negative groups. Body mass index (BMI) was used as a measure of obesity. The second, third, and fourth quintiles of BMI were treated as one group and termed 'medium'. Patients in the fifth quintile were termed 'obese' and those in the first quintile 'slim'. The number of women with unilateral disease treated with modified radical mastectomy and included in the study was 1211. Of all patients included, obese patients had a 1.53 higher risk of lymph node metastases compared to slim patients (p=0.02). In the PgR-negative group, obesity gave a 3.08 times higher risk of lymph node metastases (p=0.03). The risk of dying of breast cancer tended to be higher in obese than in slim patients when all patients in the study were compared (relative risk=1.38, p=0.06). BMI did not show a statistically significant relationship with prognosis if only hormone receptor status was considered. However, if lymph node status and hormone receptor status were taken together, the association was strong and reversed in the lymph node-positive group with ER-negative tumours. The adjusted relative risk was 0.33, showing that slim patients had a 3.03 (1.0/0.33) times higher risk of dying of breast cancer compared to obese patients (p=0.002). These results indicate that non-hormonal mechanisms could be important.

BackgroundBirth size, and particularly birth length, is positively associated with breast cancer risk in adulthood. The objective of this study was to examine whether birth size is associated with survival among breast cancer patients.MethodsInformation on birth size (weight, length and ponderal index (kg/length (m3)) was collected from birth archives for 331 breast cancer patients who were diagnosed at two university hospitals in Norway (Bergen and Trondheim). The patients were followed from the time of diagnosis until death from breast cancer, death from another cause, or to the end of follow-up, and birth size was related to survival, using Cox regression analysis.ResultsBreast cancer patients with birth length ≥ 52 cm had nearly twice the risk of dying (hazard ratio, 1.92, 95% confidence interval, 1.09-3.41) from breast cancer compared to women with birth length less than 48 cm, after adjustment for place of birth and year of diagnosis.Similar analyses related to birth weight and ponderal index showed no clear association with breast cancer survival.ConclusionsPoorer outcome of breast cancer patients with high birth length may reflect effects of factors that stimulate longitudinal growth and simultaneously increase the risk of metastases and fatal outcome. It is possible that the insulin-like growth factor (IGF) system is involved in the underlying mechanisms.

Hormonal mechanisms have been offered as an explanation for the higher frequency of large tumours, lymph node metastases and poorer prognosis in obese breast cancer patients than in lean ones. If hormonal mechanisms are important for these relations, they should probably act more strongly in patients with hormonal receptor positive tumours than in those with negative ones. We have examined if the relations between premorbid body weight or Quetelet's index (weight/height2) and tumour diameter are modified by estrogen receptor alpha (ER) and progesteron receptor (PgR) status. The analyses were based on 1,241 women with unilateral disease treated with modified radical mastectomy living in the geografic area of Haukeland Hospital. Their body weight and height have been measured as a mean 12.5 years before presentation of the disease. Body weight and Quetelet's index have been adjusted for age. The relations were studied using linear regression analyses adjusting the effect of body weight with height and mean nuclear area of the tumour cells and adjusting the effect of Quetelet's index for mean nuclear area. The main findings showed that patients with high body weight or Quetelet's index presented more often with PgR positive tumours than lean ones. Quetelet's index was also positively related to ER. These relations were present in patients older than 50 years of age (older). Patients with large tumours (>2.0 cm) had significantly higher body weight and Quetelet's index than those with small ones. These differences were significantly present in older patients and in patients with PgR negative and ER negative-PgR negative tumours. Linear regression analyses confirmed that tumour diameter increases with body weight and Quetelet's index. These relations were present in both lymph node groups and in older patients. Stratification according to hormonal receptor status showed these relations to be significant in patients with ER negative, with PgR negative and those with ER negative-PgR negative tumours only. Taking age and hormonal receptor status into consideration simultaneously, both body weight and Quetelet's index were significantly related to tumour diameter in older patients with hormone receptor negative tumours. In conclusion body size was positively related to hormone receptor status and to diameter of the primary tumour. The relation to tumour diameter was present in older patients with hormone receptor negative tumours. Although hormonal mechanisms able to act on the tumour can not be excluded, mechanisms acting independent of hormonal receptors must be considered. Different mechanisms related to body fat cytokines are discussed.

Aims-To consider the prognostic role of oestrogen receptor and progesterone receptor status in relation to the age at surgery, length of follow up and lymph node status.Methods-The study population comprised 977 patients with histologically confirmed breast carcinoma, with a median follow up of nine years. The actuarial life table method was used to test for survival differences. The Cox proportional hazard model was used to test for interaction effects between each hormone receptor and age, lymph node status and length of follow up. As the analysis involved multiple subgroups, significance was set at the 1% level (p < 0.01). Results-When the patients were subdivided into groups according to lymph node status and age, progesterone and oestrogen receptor status predicted prognosis in middle aged (46-60 years) patients with lymph node positive breast cancer. Their prognostic effect in this subgroup, however, was restricted to the first five years after surgery. Progesterone receptor status was the strongest predictor of outcome. Few reports have focused on the effect of oestrogen and progesterone receptor status in relation to age. Shek et al'6 showed a weak effect for oestrogen receptor status in patients aged 45 years or less, whereas the strongest effect was found in those between 45 and 54 years of age. We have shown that oestrogen, progesterone and androgen receptor status are more important in predicting five year survival in patients aged 60 years or less than in those over 60.'7 The association with age became even stronger after consideration of lymph node status and tumour diameter. As this study included 269 patients only, it did not permit further subdivision according to age. By excluding the need for androgen receptor status in the present study we could increase the study population to 977 and follow up to about nine years. ConclusionBased on these considerations we hypothesise that the prognostic importance of oestrogen and progesterone receptor status should be examined in middle aged patients separately, taking lymph node status and length of follow up into consideration. Identification of interactions between these variables would allow these well established prognostic markers to be used more precisely in patients with breast cancer. MethodsThe study population comprised 977 patients with unilateral breast cancer treated by modified radical mastectomy with axillary dissection. All types of histologically confirmed infil-920 on 12 May 2018 by guest. Protected by copyright.