Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Spatial structure of broad-area vertical-cavity regenerative amplifiers.

We investigate the spatial structure of broad-area vertical-cavity regenerative amplifiers injected with a homogeneous beam. The emerging patterns have a predominantly sixfold rotational symmetry, verifying the recent prediction of formation of hexagons. The length scale is controllable by means of detuning and follows the prediction for tilted waves.

Spatial distribution of the intensity noise of a vertical-cavity surface-emitting semiconductor laser.

We studied anticorrelated quantum fluctuations between the TEM(00) and the TEM(01) transverse modes of a vertical-cavity surface-emitting semiconductor laser by measuring the transverse spatial distribution of the laser beam intensity noise. Our experimental results are found to be in good agreement with the predictions of a phenomenological model that accounts for quantum correlations between transverse modes in a light beam.

Shape and representational status in children's early naming.

Why are ontological distinctions commonly ignored in ordinary language use? For example, why is a toy bear called a 'bear'? Jones and Smith argue that shape is central to the semantic representations of both children and adults (Jones, S.S., Smith, L.B., 1993. The place of perception in children's concepts. Cognitive Development 8, 113-139). In contrast, Soja et al. suggest that children do not rely on shape per se, but rather name representations, which are often indexed by shape (Soja, N.N., Carey, S., Spelke, E.S. 1992. Perception, ontology, and word meaning. Cognition 45, 101-107). Two studies were designed to test the latter hypothesis. Forty-seven children (2 years 5 months-3 years 11 months) and 32 adults participated. Each saw a series of line-drawings roughly shaped like various namable objects (e.g. a man). For half the participants, each line-drawing was described as depicting a shape that was created intentionally (e.g. someone painted a picture). For the remaining participants, each drawing was described as depicting a shape that was created accidentally (e.g. someone spilled some paint). Participants were simply asked to name each picture. We hypothesized that subjects would use shape as the basis of naming primarily when the shapes were intentional (and thus plausibly representations). The findings supported the predictions, for both children and adults. These results suggest that, although shape does play an important role in children's early naming, other factors are also important, including the mental state of the picture's creator (intentional vs. not). Thus, the data suggest that from an early age, children's picture naming incorporates their theory of mind.

[C-erbB-2, PCNA and histomorphologic factors in breast carcinoma after oral contraceptive use]. / C-erbB-2, PCNA und histomorphologische Faktoren beim Mammakarzinom nach Einnahme oraler Kontrazeptiva.

The influence of oral contraceptives (OC) on histomorphological and molecular biological prognostic factors was studied in 471 breast cancer patients. Differences in histological tumor type, histological grade, tumor size, lymph node status, hormonal receptor status, PCNA expression and c-erbB-2 protein overexpression were investigated in relation to the duration of OC use (< 5 years/ > or = 5 years) and the time since last use. A total of 297 (63%) patients had used oral contraceptives at some time in their life; 186 patients (39.5%) had used OC's for 5 years or more. There were no significant differences in the tumor characteristics investigated with respect to OC use in general. Neither long-term use at some time in their life nor long-term use until breast cancer diagnosis had an effect on histomorphological and molecular biological factors. Thus, steroid hormones contained in OC's had no direct effect on prognostic factors in breast cancer.

Colour term knowledge in two-year-olds: evidence for early competence.

It is commonly believed that colour terms are acquired unusually slowly. However, several recent studies suggest that preschoolers have more colour term knowledge than previously believed. In two studies, we investigated the colour term knowledge of 49 two-year-olds and the influence of schooling on their colour term acquisition. Both studies revealed considerable knowledge in such young children. A longitudinal comparison of children with and without school experience in Study 2 indicated that the higher performance of the school group could not be accounted for by differences predating that group's experience. In reviewing the evidence from the children's performance, we conclude that contemporary children's early and frequent experience with colour terms may account for this cohort's improved performance over previous generations of children.

[Gestational trophoblastic tumors--a report of experiences]. / Gestationsbedingte Trophoblasttumoren--Ein Erfahrungsbericht.

The paper reports on clinical experiences of treatment of 58 patients with Gestational Trophoblastic Tumors (GTT), collected between 1978 and 1991. According to the Bagshawe-Score, 29 patients were at low-risk, 10 patients were assigned to the high-risk category. Among 29 metastatic cases, 5 patients had brain metastasis. In 33 patients, treatment started from the time of diagnosis. In 25 cases, treatment was initiated at other hospitals and patients were referred only after various unsatisfactory treatment measures. Low-risk patients were mainly subjected to methotrexate and folinic acid. Patients at medium-risk received a sequential chemotherapy. In high-risk patients we preferred the CHA-MOCA- or the EMA/CO-regimen. Treatment was successful in 91.4% of patients including all cases of low- and medium-risk. Five patients with brain metastases received systemic chemotherapy combined with intrathecal application of methotrexate and radiotherapy. Three of them could be cured. Patients taken from other hospitals more often underwent primary hysterectomies prior to systemic chemotherapy (40% versus 3%) and more often developed drug resistant tumors due to inadequate primary treatment. Five patients (8.6%) died from their disease, but only one of them received primary treatment in our department. Thus, the outcome (1/33 compared to 4/25) was significantly better for patients treated primarily at specialized centers.

Prognostic value of proliferating cell nuclear antigen and c-erbB-2 compared with conventional histopathological factors in breast cancer.

Expression of proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein has been assessed in 471 women with breast cancer to evaluate their prognostic value as compared to conventional histopathological factors. In univariate analysis, high PCNA expression (> or = 20%) predicted a significantly worse survival in lymph-node-negative tumors (univariate P = 0.031). However, the effect disappeared in multivariate analysis and the histological grade remained the only independent factor for this group. Despite its close correlation to histological grade (P < 0.001), PCNA expression discriminated subsets with different survival within the heterogeneous group of moderately differentiated tumors (univariate P = 0.073, multivariate P = 0.075). PCNA expression was not found to be a significant prognostic factor in lymph-node-positive tumors, thus it was of limited value for breast cancer patients as a whole. c-erbB-2 protein overexpression was associated with a worse survival (univariate P = 0.019, multivariate P = 0.057) for the entire group of patients. The effect was mainly attributed to the significance of c-erbB-2 as an independent factor in lymph-node-positive (up to three nodes, multivariate P = 0.04; four or more nodes: multivariate P = 0.017) and large tumors (> 2 cm: multivariate P = 0.002). c-erbB-2 was without significance in lymph-node-negative patients. Though both factors might amplify the prognostic information for distinct patient subsets they do not achieve the strong prognostic value of conventional histopathological features in breast cancer.

[Does previous exposure to oral contraceptives modify survival in breast cancer?]. / Beeinflusst die vorangegangene Einnahme oraler Kontrazeptiva das Uberleben beim Mammakarzinom?

The influence of a positive history of oral contraceptive (OC) use on survival of breast cancer was studied in 471 patients. 297 (63%) of them were ever users of OCs and 202 (43%) were long-term users (> or = 49 months). The median follow-up amounted to 56 (6-96) months. Except for a significantly higher frequency of poorly differentiated tumours in OC users (p = 0.01) there was no difference in the distribution of histopathological features between OC users and non-users. Nevertheless, compared to non-users OC user showed a significantly increased 5-year-survival (p = 0.017). This effect was strongly correlated with duration of use (p = 0.004) and time since last use (p = 0.02). The influence of OC use achieved significance after a duration of use of four or more years or in case of OC use at the time of diagnosis. The positive effect persisted in multivariate analyses and was mainly attributed to long-term OC users with tumours of a generally expected poor prognosis.

Children's use of context in interpreting "big" and "little".

In order to use the words "big" and little" appropriately, adults use 3 kinds of contexts: normative (the size of the object is compared to a stored mental representation), perceptual (the object is compared to another physically present object of the same kind), and functional (the object is judged with regard to its intended use). In 3 experiments, we examined how flexibly children switch from one context to another. 2-4-year-olds judged a series of everyday objects as "big" or "little". To answer correctly, children had to judge each object twice, once in a normative context and once in a perceptual or functional context. Results showed that switching from one context to another was not inherently difficult, even for 2-year-olds. However, the direction of switch was important: children throughout the age range tested switched easily from a normative context but made errors when asked to switch to a normative context. We suggest that the normative context differs from the perceptual and functional contexts in that it is unmarked, and that unmarked contexts are accessible only when no other context has been recently experienced. When context is marked more explicitly, children shift flexibly among different meanings.

Oral contraceptive use and the prognosis of breast cancer.

In 471 breast cancer patients the influence of a positive history of oral contraceptive (OC) use on survival was investigated. 297 (63%) patients used OCs during any period of their life and 92 (20%) used them still at the time of diagnosis. Sixty months after diagnosis OC users had a significantly increased overall survival (p = 0.037). Survival rates amounted to 79.5% and 70.3% for OC users and non-users, respectively. The effect persisted after adjustment for other prognostic factors and was mainly attributed to women who had taken OCs four years or longer (p = 0.025). Comparing the survival after a 56 months median follow-up dependent on duration of OC use (never, 1-48 months, > or = 49 months) in subgroups of prognostic factors, the most significant influence on survival was observed among long-term users with tumors more than 2 cm in diameter (p = 0.005), with axillary node-positive tumors (1-3 nodes, p = 0.055/ > or = 4 nodes, p = 0.019), and with tumors of low estrogen receptor (p = 0.015) or progesterone receptor content (p = 0.04). The difference in survival between OC users and non-users cannot be explained by the distribution of prognostic factors investigated (histological type, histological grade, tumor size, lymph node involvement, hormonal receptor content). OC users had an even higher percentage of poorly differentiated tumors (p = 0.003). These results suggest an effect of OC use on tumor biology during the preclinical phase of the disease.

C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk.

The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.

Comparison of recalled and validated oral contraceptive histories.

From a case-control study of the relation between oral contraceptives and breast cancer carried out in East Germany during 1982-1986, the authors obtained information on oral contraceptive use through interviews of study subjects and from the records of prescribing gynecologists. The degree of agreement regarding information from these two sources was assessed for 234 breast cancer cases and 524 controls who had ever used oral contraceptives. Agreement between information obtained from medical records and that from interviews on total duration of use, number of episodes of use, and time since first and last use was reasonably good, and levels of agreement did not differ appreciably between cases and controls. Lower levels of agreement were observed for individual brand names and the duration of use of specific brands. Attempts should be made to obtain information on specific brands from medical records when investigating the effects of individual preparations.

PIP: Researchers used the results of interview data on oral contraceptive (OC) use in both breast cancer cases and hospital controls to compare the accuracy of their recall with data from gynecologic records. The 234 breast cancer cases were patients at the Central Institute of Cancer Research in Berlin, the German Democratic Republic. The 524 age=matched controls were patients in the ear, nose, and throat; eye; orthopedic; and skin wards at Klinikum Berlin-Buch, the district hospital. All the data were collected between November 1982 and June 1986. Interviewers used a calendar and samples of OC brands to help the women recall periods of use and brand names used. The availability of gynecologists' records was significantly associated with use of medical care, including cervical smears, duration of OC use, and the time since last OC use (p .01). When the interval since first and last OC use within 12 months, the agreement between patients and gynecologists was essentially the same for both cases and controls (first OC use, 72.4% vs. 67.8%; weighted kappa = .81 vs. .79; p .001) (last OC use, 80.4% vs. 68.7%, weighted kappa = .86 vs. .89; p .001). The highest percentages of agreement on ever use of OCs occurred with the most recently introduced brand name (Minisiston, 98.7% for cases and 99% for controls) and phasic OCs (Deposiston, 97.9% and 96.4%, respectively; Sequenz-Ovosiston, 92.7% and 89.9%, respectively). These findings showed that use of a calendar and brand samples results in rather accurate recall of overall OC use. They also indicated that having breast cancer does not affect recall of OC use. This study's investigators suggested that in studies examining the effects of individual substances or doses, researchers should try to obtain data from medical records.

Accuracy of recall of use of an intrauterine device.

Within a case-control study of the relationship between oral contraceptives and breast cancer, information on other contraceptive practices, including use of an intrauterine device (IUD) was obtained through interviews of study subjects and from the records of gynaecologists. Information from these two sources was compared for 239 women who had ever used an IUD. The results showed that agreement on total duration, number of IUD episodes, and time since first and time since last IUD use was excellent. As approximately 75% of IUDs used were unknown, agreement on brands could not be investigated. Studies investigating the effects of individual types of IUDs should use physician records as an additional source of information.

PIP: Researchers analyzed interview and physician records' data on 45 women with breast cancer (cases) admitted to the Central Institute of Cancer Research in Berlin, East Germany between November 1982-June 1986 and born in 1983 or later and 194 women (controls) admitted to the Klinikum Berlin-Buch also in East Germany for conditions other than breast cancer to compare recall accuracy in women who had ever used an IUD. These women were drawn from case control study of the relationship between breast cancer and oral contraceptive use was part of the WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Agreement between patient recall and physician records was exceptional for duration of IUD use (p.001), number of IUD episodes (kappa=0.79), time since 1st IUD and time since last IUD use (p.001). Agreement rates did not differ between cases and controls. 75% of the women could not name the IUD brand used so the researcher could not examine agreement of brand name. Thus, other than brand name, this study showed that validity of information on IUD use obtained from interviews is significant. In fact, it also pointed out that case control studies probably yield sound relative risk estimates.

Nonexperimental evaluation of the effectiveness of a screening program for lung cancer.

The effectiveness of screening to control lung cancer was examined in the German Democratic Republic by analyzing data from a cancer registry and incidence and mortality rates for lung cancer relative to different screening policies, and by two case-control studies. Mortality from lung cancer did not appear to be affected by the screening programs studied. The high cost of mass screening, combined with uncertainty about the benefits of early treatment of lung cancer, outweigh the vague advantages of such screening.

Treatment results of the thioether lipid ilmofosine in patients with malignant tumours.

In a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies.