Maternal age and birth rank of women with breast cancer.

Data from a large international case-control study of breast cancer suggested that women born to young mothers had a 25% lower risk of breast cancer. The association was not secondary to a tendency for these women themselves to have had children at early ages. The data provided no indication of a meaningful association between breast cancer risk and birth rank. Confounding was controlled by stratification according to a summary confounder score.

The development of radiotherapy in Slovenia.

The historical data on the development of radiotherapy in Slovenia are presented from its first use in this county in 1902 until the present. The Institute of Oncology in Ljubljana was established in 1938 with the intention of providing a sound development of radium and roentgen cancer treatment. After World War II, the development of radiotherapy was dynamic, which is evident from the data on new radiation sources in external beam therapy (accelerators, telecobalt units), in brachytherapy (various sealed radioisotopes) as well as in the introduction of therapy with unsealed radioisotopes. In 1947, a Chair of Oncology and Radiotherapy was instituted at the Medical Faculty of the University of Ljubljana (with the seat at the Institute of Oncology). In 1955, radiotherapy and oncology were officially recognized as a separate branches of medicine requiring special obligatory postgraduate residency training. Within the Medical Society of Slovenia, the Section for Radiotherapy was established in 1987. The following year, the Section for Radiotherapy of Slovenia became a member of the European Society for Therapeutic Radiology and Oncology. Considering the size of population of Slovenia (nearly 2 million), it was reasonable that by this time radiotherapy became almost completely concentrated in one central institution, the Institute of Oncology, whose core and cohesive activity were represented in the multidisciplinary cancer treatment approach.

Computation of cancer incidence rates for defined small geographical areas--matching of numerator and denominator.

The authors present the problem of validity of numerator and pertinence of denominator for small geographical areas on sample of average annual crude incidence rates of stomach cancer in Slovenia during the period 1968--1974. At census in 1971 this country counted 1 727 137 of population. According to the residence of the patients the rates have been calculated for 60 municipalities, and besides for 29 so called "epidemiological regions", defined by their geographical and ethnic characteristics. Although in both instances great differences in incidence rates have been found, only a few areal units exhibited a significantly lower or higher rate from the national average. Specially areas with small population base "disappeared" in the average, although the value of the rate for them was rather low or high. A formula is presented by which at given rate for total country it is possible to determine the minimal size of population which still could provide estimation of statistically significant lower rate. Thus, for areas with small population a period of observation through many years is required in order to obtain the necessary minimal population base. The question is pointed out, whether this approach is reasonable as to the epidemiological interest, considering that some factors related to cancer may change during the long period of time. On the other hand, when merging small areas into larger ones, attention must be paid that these are not too heterogeneous as to their cancer incidence rate, geographical, ethnic, socio-economic and life-style features.

A case-control study of breast cancer in relation to oral contraceptive use in Slovenia.

With the aim to investigate a possible association between oral contraceptive (OC) use and breast cancer occurrence, 534 women aged 24--54 years with newly diagnosed breast cancer and 1989 individually matched hospital controls were interviewed during 1980--1983. The overall risk for ever-users vs. never-users estimated by logistic regression and adjusted for several possible confounding factors was 1.62 (p less than 0.05). The analysis of potential biases indicated that this risk may be overestimated, especially because the controls might not be fully representative of the basic population. The risk was increasing with total duration of OC use, reaching the highest value by more than 7 years of use. As to the latency, the risk was the highest for women starting pill use 4--8 years before diagnosis, thus suggesting that OCs might act as promoters rather than initiators of tumor growth. There was no substantial difference in risk between women starting pill use before 25 years of age and those starting it later. The number of users before first term pregnancy was too small to warrant relative risk estimation. Interaction (significant) was found between OC use and family history of breast cancer; there was no such evidence in other subgroups of women being at baseline breast cancer risk. There were no significant differences in the distribution of cases and controls classified by individual OC formulations used. The increased relative risk for users was concentrated in early stages of breast cancer, most likely owing to detection bias. Considering the indicated biases, the results of the study may not be quite conclusive as to the adverse effect of OCs on the breast, but they call for further investigation of this problem.

Breast-cancer risk and oral contraceptive use in Slovenian women aged 25 to 54.

Results of a previous case-control study in Slovenia showed a significantly elevated risk of breast cancer for ever-OC users aged 25 to 54 years. A further study was conducted in 1988-1990 in the whole of Slovenia, employing more rigorous epidemiological methodology. Cases were 624 women with breast cancer, aged 25 to 54 years, diagnosed at the Institute of Oncology in Ljubljana and other Slovenian hospitals. Controls were 624 women identified through the Population Registry, randomly selected and matched with cases by date of birth and commune of residence. Data were collected by personal interview, using coloured photographs of packages of all OC on the Slovenian market since 1964. A calendar of reproductive life events was constructed with participants to improve estimation of exposure. The adjusted odds ratio (OR) for ever-users was 1.09. There was no increase in risk with total duration of use, interval since first use, age at starting OC, according to use before or after first delivery and time between menarche and age at first use. Increased risk (OR = 2.92) was found for OC users at the time of diagnosis and for those stopping them less than 6 months before (current users). The risk was not increased for those who stopped OC more than 6 months before diagnosis. The results of this study are consistent with most studies showing no overall effect of OC in women aged till 55 years ever using them. Increased risk of breast cancer in current OC users suggests a possible promoting effect of the pill in susceptible women, and indicates the need for careful breast surveillance of these women while they are using OC and in the period immediately following cessation.

Some international differences in treatment and survival in breast cancer.

In a recent study, 5-year survival rates for breast cancer patients in Boston (Massachusetts), Glamorgan (Wales), Slovenia (Yugoslavia) and Tokyo (Japan) were 57.3%, 49.5%, 41.9% and 74.9%, respectively. In this report, data are presented on the types of treatment used in the four areas and on the relationship of differences in treatment practices to the differences in survival rates. Generally, surgically treated patients who also had radiotherapy had lower survival rates than patients in the same area who had similar operations without radiotherapy. In each area, the survival rate was higher for patients who had radical mastectomy than for those who had simple mastectomy. The Japanese patients had the highest survival rate within nearly every treatment and extent-treatment category. Thus, the high survival rate of these patients was not explained by the variables considered. Survival differences between Boston, Glamorgan and Slovenia were largely explained by differences in extent of disease and type of treatment. As the nature of the treatment--survival trends was consistent with the interpretation that treatment tended to be selected according to apparent prognosis, the degree to which treatment customs were determinants of the differences in survival rate among the three areas is uncertain.

Lactation and cancer of the breast. A summary of an international study.

An international collaborative study has been carried out to test the hypothesis that prolonged lactation protects women against cancer of the breast. While pregnancy itself seemed to confer some protection against breast cancer in all areas studied, no consistent differences in duration of lactation were found between breast cancer patients and unaffected women, once the fact that breast cancer patients have fewer pregnancies had been allowed for. Even in areas where some women had lactated for a total of 5 years or more, such women occurred proportionately no less frequently among breast cancer patients than among unaffected women. In the light of this and other recent evidence, it is unlikely that lactation has any protective effect against breast cancer in women, and other explanations must be sought for the remarkable international differences in the frequency of this disease.

Age at first birth and breast cancer risk.

An international collaborative study of breast cancer and reproductive experience has been carried out in 7 areas of the world. In all areas studied, a striking relation between age at first birth and breast cancer risk was observed. It is estimated that women having their first child when aged under 18 years have only about one-third the breast cancer risk of those whose first birth is delayed until the age of 35 years or more. Births after the first, even if they occur at an early age, have no, or very little, protective effect. The reduced risk of breast cancer in women having their first child at an early age explains the previously observed inverse relationship between total parity and breast cancer risk, since women having their first birth early tend to become ultimately of high parity. The association with age at first birth requires different kinds of etiological hypotheses from those that have been invoked in the past to explain the association between breast cancer risk and reproductive experience.

Age at menarche, urine estrogens and breast cancer risk.

In 511 nulliparous women aged 15-19 years and 347 aged 30-39, an analysis has been undertaken of the relationship of urine concentrations of the three principal estrogens to age, age at menarche and Quetelet's index of adiposity. The analysis was undertaken by means of multiple regression, controlling for each of the 12 centers from which the data originated, as well as for the other study variables. In the younger women, age was strongly and positively related to concentrations of E1 and E2 and less so to E3. In the age group 30-39, follicular phase specimens showed positive relationships with age for all three fractions but luteal specimens did not. Age at menarche showed inverse relationships to levels of E1 and E2 which were significant in the younger but not in the older age group. The associations of estrogens with Quetelet's index were weak and not statistically significant. The data suggest that women whose menarche occurs early not only have a longer duration of exposure to estrogens during years which are probably important in the initiation of breast cancer but, in addition, their exposures are at a higher level during those years and probably at later ages also. These observations support the hypothesis that the mechanism of the association of early menarche with breast cancer risk is via the association of both with estrogen stimulus.

Age at menarche, probability of ovulation and breast cancer risk.

An analysis is undertaken of the frequency of ovulation in 17 groups of women aged 15 to 19 who had been the subjects of other studies. A urine specimen of at least 8 h accumulation had been provided on the 20th or 21st day of a menstrual cycle by 681 women. Analysis is restricted to 431 specimens which had been collected between 11 and 3 days prior to the onset of the subsequent menstrual period. A pregnanediol concentration of less than 1 mg per litre in such a specimen was taken as evidence that the cycle was anovular. The probability of a cycle being anovular was inversely and significantly related to the number of years since menarche, and, with years since menarche held constant, was positively but not significantly associated with age at menarche. This observation indicates that women with early menarche do not have a longer duration of exposure to anovular cycles than do those whose menarche is delayed, and that variation in the duration of exposure to post-menarcheal anovular cycles does not explain the association of breast cancer risk with early age at menarche. The 17 groups of women were classified into four categories according to ethnic origin and breast cancer incidence in the populations from which they derived. Anovular cycles were not more common in the high-risk groups; indeed, the two centers in the lowest risk category had the highest proportion of anovular cycles.

Age at any birth and breast cancer risk.

In an effort to assess the relative importance of age at first birth, age at subsequent births, and total parity to the occurrence of breast cancer, reproductive data from 4,225 women with breast cancer and 12,307 hospitalized women without breast cancer were analyzed by a multiple logistic regression model. Age at first birth was confirmed to be the most important reproductive risk indicator; it was associated with a 3.5% increase of relative risk for every year of increase in age at first birth (the 95% confidence interval of this estimate was 2.3 to 4.7% increase per year). However, age at any birth after the first was also an independent and statistically significant risk indicator; it was associated with a 0.9% increase of relative risk for every year of increase in age at any (and every) birth (the 95% confidence interval of this estimate was 0.4 to 1.5% increase per year). There is evidence that the age of approximately 35 years represents for every birth a critical point; before this age any full-term pregnancy confers some degree of protection; after this age any full-term pregnancy appears to be associated with increase in breast cancer risk. The effect of parity is determined by the age of occurrence of the component pregnancies. While most pregnancies occur under the age of 35, the distribution varies from population to population, and this may account for the differences between populations in whether or not a protective effect is seen for births after the first, and if it is seen, its extent.