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Childbearing and Related Risk Factors
Abstract
A major influence on a woman’s risk of developing breast cancer is the length of her fertile life and her record of childbearing. Increased risk is associated with either having had no children, or else with delay of the first childbirth until after the age of 25. Risk is also increased if a woman shows evidence of prolonged ovarian activity, such as onset of menstruation at a relatively early age (before 12 in Western countries) or delayed onset of menopause (after 49). These are the classic risk indicators. Recent evidence shows that a woman’s breast cancer risk is influenced also by the age at which she has subsequent children after the first, by her total number of children and the length of time for which she breast-feeds her babies [1].
... Height also is reported to be a risk marker for breast cancer and in this respect, height may be a marker of childhood energy intake, as children who experience energy deprivation fail to attain their full potential height. Variations in energy intake in prepubertal children are likely to explain some of the variation internationally in breast cancer incidence (Stoll, 1995a). ...
To examine evidence that specific fibre-associated macronutrients are associated with a decreased breast cancer risk. To review possible mechanisms, the age group when dietary intervention might be most effective and the choice of a suitable dietary supplement.
This review distinguishes specific hormone-metabolic effects of dietary composition from those of body mass and fat distribution, in relation to the age at which they exert major effects on breast cancer risk.
Both obesity and a high-fat/low-fibre diet in Western women may be associated with increased estrogen levels which are widely assumed to increase the risk of developing breast cancer. Both obesity and the Western diet are likely to stimulate insulin resistance, leading to increased levels of bioavailable estrogen. The concomitants of hyperinsulinemia may synergize with estrogen in stimulating progression of pre-neoplastic lesions in the breasts of late pre-menopausal women. Increased intake of fibre-associated macronutrients may reduce insulin resistance in addition to reducing the circulating levels of estrogen.
The effect of dietary intervention on breast cancer risk in Western women may be tested in pre-menopausal women over the age of 40 y, with evidence of atypical hyperplasia in a breast biopsy. The most suitable fibre-associated macronutrient is still problematical but soy protein constituents have been shown to inhibit the growth of rat mammary cancer models and also of human breast cancer cell line in the laboratory.
Aromatase inhibitors have evolved over a period of 20 years to well tolerated agents that can effectively obliterate aromatase activity in postmenopausal women. Breast cancer is the predominant clinical application and here the newer agents have established themselves as the preferred second-line agent after tamoxifen in the treatment of advanced disease. Recent data indicate that they be more efficacious than tamoxifen and, therefore, may replace it as the first-line agent of choice in the near future. On-going clinical trials in the adjuvant setting and prospective prevention studies will elucidate whether these drugs have a yet greater role in breast cancer.
A hospital-based case-control study was conducted over 4 years in Southern France to assess the pattern of established risk factors for breast cancer and to examine its variation according to age at diagnosis. Cases studied (450) were women admitted to the Montpellier Cancer Institute, with histologically confirmed primary breast carcinoma. Controls (576) were patients from a nearby hospital admitted in the early stages of a neurological or mild psychological diseases and from a clinic for general surgery. Any patient with malignant tumours, chronic and cardiovascular diseases were excluded. The total population globally showed the commonly reported pattern for these risk factors. When stratified by age, the reproductive factors occurring early in life (menarche, first full term pregnancy) were shown to be significant risk factors only in the youngest group of patients and do not seem to influence risk in older women, for whom risk factors are those occurring later in life (menopause, obesity). This suggests a complex involvement of the reproductive and sociodemographic features with the various stages of the 'natural history' of breast cancer.
To determine whether there is a short term increase in the risk of breast cancer after a full term birth data from two hospital based, case-control studies in Italy were pooled. Analysis was restricted to women aged under 50 with two or more children (573 women with cancer and 570 controls). A relative risk for breast cancer of 2.66 was seen in women who had given birth during the three years preceding the interview compared with women whose last birth had occurred 10 or more years before, after adjustment for age, age at first birth, and parity. The relative risk slowly decreased for women who had last given birth three to 10 years before. Multivariate analyses confirmed the protective effect of an early age at first birth and the age dependent effect of parity on the risk of breast cancer--that is, a direct relation below age 40 and an inverse one in older women. These data provide epidemiological evidence that a full term birth is followed by a transient increase in the risk of breast cancer, which for some time contrasts with and overcomes the long term protection of pregnancy at an early age. They therefore confirm predictions from animal studies and theoretical models that pregnancy prevents the early stages of breast carcinogenesis but promotes the late stages of the process.
Earlier onset of menarche and tallness in adult women are mainly confirmed as risk markers for breast cancer. Recent disparate case-control studies have reported abdominal-type obesity and higher circulating levels of insulin, testosterone and insulin-like growth factor 1, to be further risk markers for breast cancer. There is evidence that abdominal-type obesity is recognisable in girls even before puberty, and disparate studies have shown it to be correlated with earlier onset of menarche, insulin resistance leading to hyperinsulinaemia, and an abnormal sex steroid profile. The implications are that earlier onset of puberty in a subset of girls can lead to more prolonged exposure of developing breast tissue to an abnormal sex steroid profile and also to a higher circulating level of insulin. It is postulated that these metabolic/endocrine concomitants of abdominal-type obesity could play a role in promoting mammary carcinogenesis at a young age, particularly if genetic predisposition is present.
The causation of breast cancer in certain strains of mice by a virus that can be transmitted vertically, through the milk produced during lactation, has led to the hypothesis that a similar phenomenon could exist in humans. There have been laboratory-based studies in humans suggesting that a virus may be involved in the etiology of female breast cancer although other investigations did not support this hypothesis. Descriptive data and epidemiologic evidence of ecologic nature do not indicate a role of lactation in the causation of human breast cancer, but the hypothesis has not been adequately assessed in analytic epidemiologic studies. A nested case-control study undertaken in Sweden to examine the role of prenatal factors on breast cancer risk in the offspring, allowed the evaluation of the importance of breast-feeding in the causation of this disease. Standardised records concerning women born at the Uppsala University Hospital from 1874 to 1954 were linked with invasive breast cancer incident cases, identified through their unique national registration number in the Swedish Cancer Registry during 1958-1990. For each case with breast cancer, the females born to the first three mothers admitted after the case's mother were selected as potential matching controls. Only controls living in Sweden and free from breast cancer until the time of diagnosis of breast cancer in the corresponding case were eventually included in the study. The analysis was based on 458 cases of breast cancer born in singleton pregnancies and 1,197 singleton age- and birth date-matched controls. Breast-feeding was not a significant or suggestive risk factor for breast cancer in the offspring; compared to women who at discharge were wholly or partly breastfed, women who as newborn were not breastfed had a relative risk of breast cancer of 0.97 with 95% confidence interval 0.44-2.17 (P = 0.95).
Objective - To investigate whether breast feeding is related to subsequent risk of breast cancer. Design - Population based case-control study designed primarily to investigate the relation between oral contraceptives and risk of breast cancer; data obtained from questionnaires administered by interviewers, general practitioner notes, and family planning clinic records. Setting - 11 health regions in Britain. Subjects - Women diagnosed with breast cancer before age 36 living in the defined study areas. One control per case, matched for age, was selected from the list of the case's general practitioner. 755 case-control pairs were interviewed. Main outcome measures - Duration of breast feeding each liveborn infant; timing of return of menses; hormone use; other risk factors for breast cancer. Results - Risk of breast cancer fell with increasing duration of breast feeding (relative risk=0·94 per three months' breast feeding; test for trend p=0·026) and with number of babies breast fed (relative risk=0·86; test for trend, p=0·017). Breast feeding each baby for longer than three months conferred no additional benefit. Breast feeding was more strongly negatively associated with risk of breast cancer than duration of postpartum amenorrhoea (X2 test for trend, p=0·69). Hormonal suppression of lactation was unrelated to risk of breast cancer (relative risk=0·96 per episode of suppressed lactation; test for trend, p=0·72). Conclusions - These results suggest that breast feeding protects against the development of breast cancer in young women.
Among 714 premenopausal and 130 postmenopausal breast cancer cases matched with 8440 controls for age in years and menopausal status, risk indicators for breast cancer were similar, although most associations were stronger in the premenopausal women. Compared with nulliparous women, the relative risk (RR) for those with first birth before age 25 years was 0.7 (95% confidence limits [CL] from 0.5 to 0.9) among premenopausal women, and 0.7 (0.4–1.4) for postmenopausal women. In the premenopausal cases, a history of breast cancer in a sister gave a RR of 3.0 (2.1–4.1) and in a mother 1.9 (1.4–2.5), whereas for the postmenopausal women the RRs were 1.4 (0.6–3.1) and 13 (0.6–2.6), respectively. Fibrocystic breast disease was also a significant predictor of subsequent breast cancer in the premenopausal and postmenopausal women. In relation to women having a single birth, premenopausal women with six or more births had a risk of breast cancer of 0.6 (0.4–1.0), which was present even after adjustment for age at first birth.
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.
Although the importance of the relationship between age and cancer incidence rates is recognized universally, little attention seems to have been paid to the relationship between the physiologic aging process in the breast and breast cancer risk. The natural history of breast cancer was examined in the context of involution of the breast, and it was proposed that the rate and extent of involution might be important determinants of breast cancer risk. It was concluded that additional studies to characterize the process of involution better histopathologically and to examine the associations between the rate and extent of involution and breast cancer risk are warranted.
Several large epidemiological studies in the Nordic countries have failed to confirm an association between age at first birth and breast cancer independent of parity. To assess whether lack of power or heterogeneity between the countries could explain this, a meta-analysis was performed of 8 population-based studies (3 cohort and 5 case-control) of breast cancer and reproductive variables in the Nordic countries, including a total of 5,568 cases. It confirmed that low parity and late age at first birth are significant and independent determinants of breast-cancer risk. Nulliparity was assoclated with a 30% increase in risk compared with parous women, and for every 2 births, the risk was reduced by about 16%. There was a significant trend of increasing risk with increasing age at first birth, women giving first birth after the age of 35 years having a 40% increased risk compared to those with a first birth before the age of 20 years. Tests for heterogeneity between studies were not significant for any of the examined variables. In the absence of bias, this suggests that several individual Nordic studies may have had too little power to detect the weak effect of age at first birth observed in the meta-analysis.
Daily (12-hour) urine collections taken throughout the menstrual cycle were obtained from 30 young women who by genetic analysis
were at risk for familial breast cancer, and from 30 control women carefully matched for age, height, and reproductive history.
Steroids in the urine were extracted by glucuronidase hydrolysis, and the primary glucocorticoid, androgen, and estrogen hormones
and their metabolites were measured by radioimmunoassay. Highly significant differences were observed only in the case of
estrone and estradiol, with the high-risk subjects exhibiting lower values that the controls. This endocrine abnormality in
young women at risk for breast cancer may be a potential discriminant for identifying women at risk for the disease in the
population at large.
A relation between breast augmentation and the subsequent risk of breast cancer has been postulated. Since an estimated 2 million women in the United States alone have received breast implants, even a small increase in the risk of breast cancer could have considerable public health consequences.
We performed a population-based nonconcurrent cohort-linkage study. All women in Alberta, Canada, who underwent cosmetic breast augmentation from 1973 through 1986 were included in the implant cohort (n = 11,676). This cohort was compared with the cohort of all women in Alberta in whom a first primary breast cancer was diagnosed (n = 13,557). The expected number of breast-cancer cases in the implant cohort was estimated by applying age-specific and calendar year--specific incidence rates of breast cancer (obtained from the Alberta Cancer Registry) to the implant cohort. Standardized incidence ratios were calculated by dividing the observed by the expected number of breast-cancer cases in the implant cohort.
Forty-one patients with implants were subsequently found to have breast cancer. The expected number was 86.2. The standardized incidence ratio was thus 47.6 percent, significantly lower than expected (P less than 0.01). The average length of follow-up in the implant cohort was 10.2 years, and the average length of time from breast augmentation to the diagnosis of breast cancer was 7.5 years.
Women who undergo breast augmentation with silicone implants have a lower risk of breast cancer than the general population. This finding suggests that these women are drawn from a population already at low risk and that the implants do not substantially increase the risk.
A case-control study was carried out to assess the risk of breast cancer associated with breast feeding in Japan. The data were obtained in a hospital-based case-control study of 521 women with breast cancer and 521 controls from January 1988 to December 1989. Statistical adjustment for potential confounders as well as a likelihood ratio test for linear trend was done by unconditional logistic regression. Compared with parous women who had never breast-fed, women with a positive history of breast feeding had an odds ratio of breast cancer of 0.62 (95% confidence interval 0.37-1.04). The trend of decreasing risk with increasing average months of breast feeding was statistically significant (chi 2 trend = 4.5, p less than 0.05), while it was was nonsignificant for the number of breast-fed children borne. Among premenopausal women, a significant linear relation with a log-transformed term of average months of breast feeding was noted, regardless of the age of the woman at first full-term pregnancy and parity (chi 2 trend = 5.3, p less than 0.05). The risk was the lowest among premenopausal women who had ever lactated for 7-9 months (adjusted odds ratio = 0.39, 95% confidence interval 0.15-0.97). These findings suggest that lactation has an independent protective effect against breast cancer in Japanese women.
The relationship between socio-economic indicators, body mass, reproductive and menstrual factors and risk of "familial" breast cancer has been analyzed using data from a large case-control study of breast cancer conducted in Italy. A total of 3,037 breast-cancer patients aged 75 years or less admitted to a network of hospitals in the Greater Milan area were interviewed. Controls were 2,569 women aged 75 or less, admitted for acute conditions to the same network of hospitals where cases had been identified. Women were not included as controls if they had been admitted for gynecological, hormonal or neoplastic diseases. A total of 331 cases and 121 controls reported a family history of breast cancer in their first-degree relatives, with a family history tended to be more educated and of higher social class than controls with family history, but these differences were not statistically significant. No relationship emerged with marital status and body-mass index. The estimated multivariate relative risks were, compared with nulliparous women, respectively 0.9, 1.2 and 1.2 for women reporting 1, 2 and 3 or more births. The risk of breast cancer was also greater in women reporting one or more spontaneous abortions: compared with those who did not, the estimated relative risk was 1.9 (95% confidence interval 0.8 to 3.7). Relative to women reporting their first birth below age 25, the estimated relative risks were 1.3 and 0.9 in those reporting it at age 25 to 29 and 30 or more respectively. Likewise, no consistent relationship emerged with lifelong menstrual pattern and menopausal status. These results suggest that menstrual and reproductive factors do not play an important role in the risk of breast cancer in women with a history of the disease in first-degree relatives.
Factors that increase the risk of cancer during adult life may also increase the risk of cancer when they act in utero (eg, ionising radiation and diethylstilboestrol in human beings and chemicals in animals). The existing empirical data seem to be compatible with the hypothesis that increased concentrations of oestrogens in pregnancy increase the probability of future occurrence of breast cancer in daughters.
The role of age at first and at second birth on subsequent breast cancer risk was analyzed using pooled data from 2 hospital-based case-control studies conducted in Italy, for a total of 1,200 biparous cases and 987 controls. Compared with women who gave birth for the first time below age 20, the relative risks were above unity for those with later first birth, even after allowance for age at second birth, although the trend was inconsistent across subsequent strata. A similar direct trend in risk was observed in relation to age at second birth: compared with less than 25 years and after allowance for age at first birth, the point estimates were 1.2, 1.4 and 1.4 for 25-29, 30-34 and greater than or equal to 35 (p for linear trend = 0.04). The results for age at first and at second birth were similar in the 2 studies pooled in this analysis. A significant interaction with age was observed in relation to age at first and at second birth. In younger women (below age 50) a strong and direct association with age at first birth was found, while no apparent protection was conveyed by earlier second birth. Among older women (aged 50 or over), there was no apparent relationship with age at first birth after allowance for age at second, but the role of age at second birth was independent and statistically significant. Thus, our study confirms an independent and significant role of age at second birth in biparous women, after allowance for age at first birth, and indicates that, after reciprocal allowance, the role of first and second birth was not apparently different. The relative risks for both variables were quantitatively moderate, and may be influenced by age or other temporal variables.
The relation between lactation and risk of breast cancer was examined in a cohort of 89,413 parous female US registered nurses aged 30-55 years and free from cancer in 1976 who provided information on total duration of lactation in 1986. Between 1976 and 1986, 1,262 cases of breast cancer occurred during 785,958 person-years of follow-up. There was no independent association between lactation and the risk of breast cancer. After adjustment for age and parity, compared with women who had never lactated, the relative risks (and 95% confidence intervals (CI] were 0.95 (95% CI 0.84-1.08) for women with less than 7 months of lactation, 0.87 (95% CI 0.71-1.08) for 7-11 months, 0.94 (95% CI 0.77-1.14) for 12-23 months, and 0.98 (95% CI 0.76-1.28) for greater than or equal to 24 months (test for trend: z = -0.80, p = 0.42). The association did not differ by age or menopausal status. These results do not confirm reports that relatively short durations of lactation reduce the risk of breast cancer among younger women.
To investigate underlying factors of late menopause and early menarche which are regarded as risk factors for breast cancer, we analyzed the relationships between ages at menarche and menopause, and other environmental and physical factors using the data of a population-based survey conducted in Aichi Prefecture, Japan. The analysis on menopause was based on 3,148 women aged 55 or more and the analysis on menarche was based on 16,392 women aged 40 or more. These subjects were grouped into three groups (early, average and late groups) according to their ages at menopause and menarche. Women with late menopause had larger height, weight and body mass index and included more professional, administrative and office workers, more daily fish & shellfish consumers and more women with colorectal cancer history of the mother and less current smokers. Women with early menarche also had larger height, weight and body mass index and more residence in a metropolitan area and consumed more bread, meats, fish & shellfish, vegetables, fruits, milk and black tea and less rice, miso soup and pickles. In a multiple regression analysis, occupation, weight, daily or occasional drinking and daily intake of fish & shellfish were positively and smoking was inversely associated with late menopause, while residence in a metropolitan area, weight and daily intakes of bread, milk and green-yellow vegetables were positively associated with early menarche. These results suggest the importance of underlying factors of early menarche and late menopause in the etiology and prevention of breast cancer.
Since 1960 a 50% increase has occurred in breast cancer incidence in Denmark. With the present rates one out of fifteen Danish women will develop breast cancer before the age of 75 years. To evaluate the influence of known and suspected epidemiologic factors on the risk of developing breast cancer and on prognosis, a population-based study has been carried out, where cases were identified from the files of the Danish Breast Cancer Cooperative Group (DBCG) and the Danish Cancer Registry. Results are communicated from the case-control part of this study, including 1486 breast cancer cases aged less than 70, diagnosed over a one-year period, and an age-stratified-random sample of 1336 women without breast cancer from the general population. Data on risk factors were collected by self-administered (mailed) questionnaires. Classical risk factors, such as high social status, nulliparity, early menarche and late natural menopause were confirmed, while no association was found between breast cancer and maternal age at first childbirth.
The relations between age at first and last full-term pregnancy and breast cancer risk were investigated after 20 years of follow-up of 63,090 Norwegian women, among whom 1,565 breast cancer cases occurred. An association seen in preliminary analyses between early age at first birth and low risk of breast cancer was removed after adjustment for parity and age at last birth. Age at last birth showed initially no association with breast cancer. After adjustment for parity, however, a significant positive association emerged. The authors' observations suggest that the relation between age when a pregnancy occurs and breast cancer risk may be more complex than previously believed. Despite the overall association between increasing parity and lower risk, the women with many late pregnancies and those with few, widely spaced pregnancies had higher risk than nulliparous women, indicating that both the age when pregnancy occurs and the length of intervals between successive births may modify the protective effect. The findings are consistent with a dual effect of a pregnancy, causing a transient increase followed by a subsequent strong and long-lasting decrease in risk of breast cancer.
The authors report a case-control study of breast cancer based on an analysis of data collected by interview between the years 1957-1965 from women residing in the communities of Buffalo and Kenmore, New York. Prior reproductive factors, including a detailed lactation history, were examined for 453 white females with breast cancer and 1,365 white females without breast cancer who were selected randomly from the population of Buffalo and Kenmore. There is evidence of a negative association between length of nursing and breast cancer risk in premenopausal women which is not seen in the postmenopausal women. This apparent "protective" effect of lactation persists after statistical control for the potential confounding factors of age, parity, age at first pregnancy, age at menarche, and education. Cases are more likely than controls to have reported unsuccessful lactations due to "insufficient milk." The findings of this study, in conjunction with the authors' review of previously published studies that have examined prior lactation as related to breast cancer risk, suggest that there may be an independent negative association between nursing and subsequent breast cancer risk in premenopausal women. Whether this means that breast feeding is protective or that some women who are unsuccessful at lactation are at increased risk for subsequent breast cancer is not clear. A detailed reanalysis of existing data and more careful attention to detailed prior breast function/dysfunction in future studies are recommended.
Age at menopause and type of menopause from hospital records of breast cancer patients were compared with similar information reported by a national probability sample of women. The national sample comprised 3581 women who responded to the 1960-1962 National Health Examination Survey. The cancer series consisted of 3887 patients selected from those reported to the Connecticut Cancer Registry between 1950 and 1959. No substantial bias was identified when the validity of the comparison and the effect of the relatively large number of breast cancer patients whose menopause histories were deficient were evaluated. Overall, surgically induced menopause was associated with a reduction in breast cancer risk to about 60% of that experienced by women having natural menopause induced before age 35, but induction up to age 50 was protective. There was little effect in the 10 years following the surgical procedure, but substantial reduction occurred in all subsequent periods. Among women with menopause induced before age 35, breast cancer risk stayed as low as 1/3 that expected 30 and more years later. Relative risk of breast cancer increased with age at natural menopause. Women with natural menopause at age 55 or older had twice the breast cancer risk experienced by those whose menopause occurred before age 45. The relative risk of breast cancer associated with late natural menopause was greatest after age 70.
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.
Hoel, D. G. (National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709), T. Wakabayashi and M. C. Pike. Secular trends in the distributions of the breast cancer risk factors—menarche, first birth, menopause and weight—in Hiroshima and Nagasaki, Japan. Am J Epidemiol 1983; 118: 78–89.
The results of a mail survey completed by approximately 21,000 female atomic bomb survivors in Hiroshima and Nagasaki in 1970 are studied wtth respect to menarche, first birth, menopause, and weight. These known risk factors for breast cancer can be used to explain some but not all of the differences in Japanese and US breast cancer rates. The results for age at menarche are the most striking, with the presence of a strong secular trend. The average age at menarche in Japan was observed to decrease from 16.4 years for women born In 1902 to 14.4 years for women born in 1942. However, a temporary increase was observed in women whose menarche was expected to occur during the war years of the early 1940s. Differences between US and Japanese women were also observed in age at first birth and nulliparity rates. Age at menopause was similar for the two groups, although US women have a considerably higher rate of surgically induced menopause. Within each birth cohort, It is shown that body weight is negatively correlated with age at menarche and positively correlated with age at menopause.
A biologically based two-stage model for carcinogenesis is presented that relates events occurring at the cellular level to epidemiologic features of breast cancer in females. This model, which accommodates the physiologic responses of breast tissue to menarche, menopause, and pregnancy, predicts age-specific incidence curves that are in close quantitative agreement with those observed in six test populations: Connecticut, Denmark, Finland, Slovenia, Iceland, and Osaka, Japan. According to the model, hormones influence the epidemiology of breast cancer in females by their action on the kinetics of growth of nonneoplastic breast tissue. As a consequence, it is argued that hormones are likely to be unimportant in determining overall risk in populations. The protective effect of an early first birth predicted by the model is in good quantitative agreement with data from a multinational study. Other epidemiologic features of breast cancer are logically explained within the framework of the model. No feature of the epidemiology of breast cancer requires that premenopausal and postmenopausal breast cancer be considered distinct entities from the point of view of pathogenesis.
Age at first full-term pregnancy (FTP) has long been thought to be the major reproductive risk factor in breast cancer but a Norwegian study suggested that age at last FTP might be more important. In Norway "high parity" means 4 or more deliveries. Does this finding hold in an area with a much broader distribution of parity? Data from a case-control study done in 1980-82 in Fortaleza and Recife, two cities in Brazil's impoverished north-east, have been used to explore further the influence of age at last FTP. The cases were 509 women with histologically diagnosed breast cancer who were matched with hospital controls for age and area of residence. The analysis was based on case-control pairs interviewed by the same person. High breast cancer risk was associated with low parity; after adjustment for parity, breast cancer risk was related both to late age at first FTP (odds ratio [OR] 1.21 for each 5 year increase, p = 0.008) and to late age at last FTP (OR 1.24, p = 0.0007). However, multivariate analysis revealed that the effect of age at last FTP dominated that of age at first FTP: once age at last FTP was taken into account the effect of age at first FTP was no longer significant (OR 1.08, p = 0.38) while the association with parity became more striking. These results challenge the view that age at first FTP is the principal reproductive variable related to breast cancer risk. Moreover, they suggest that high parity is protective independent of ages at first and last FTP. Given recent worldwide reductions in fertility rates, breast cancer incidence may be expected to increase. Balancing that may be the willingness of some women to complete their families by, say, age 35 if they were to be told that this might reduce their risk of breast cancer.
The evidence of an association of lactation with a reduction in the risk of breast cancer among women has been limited and inconsistent. The effect of lactation appears to be confined to premenopausal women with a history of long lactation, but most studies of this relation have been limited in statistical power. We conducted a multicenter, population-based, case-control study with a sample large enough for us to describe more precisely the association between lactation and the risk of breast cancer.
Patients less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from lists of licensed drivers if the case subjects were less than 65 years old, and from lists of Medicare beneficiaries if they were 65 through 74 years old. Information on lactation, reproductive history, and family and medical history was obtained by means of telephone interviews. After the exclusion of nulliparous women, 5878 case subjects and 8216 controls remained for analysis.
After adjustment for parity, age at first delivery, and other risk factors for breast cancer, lactation was associated with a slight reduction in the risk of breast cancer among premenopausal women, as compared with the risk among women who were parous but had never lactated (relative risk, 0.78; 95 percent confidence interval, 0.66 to 0.91); the relative risk of breast cancer among postmenopausal women who had lactated, as compared with those who had not, was 1.04 (95 percent confidence interval, 0.95 to 1.14). With an increasing cumulative duration of lactation, there was a decreasing risk of breast cancer among premenopausal women (P for trend < 0.001) but not among postmenopausal, parous women (P for trend = 0.51). A younger age at first lactation was significantly associated with a reduction in the risk of premenopausal breast cancer (P for trend = 0.003). As compared with parous women who did not lactate, the relative risk of breast cancer among women who first lactated at less than 20 years of age and breast-fed their infants for a total of six months was 0.54 (95 percent confidence interval, 0.36 to 0.82).
There is a reduction in the risk of breast cancer among premenopausal women who have lactated. No reduction in the risk of breast cancer occurred among postmenopausal women with a history of lactation.
Two decades ago the relation of certain reproductive characteristics to the risk of breast cancer appeared to be well established. Nulliparity, an early age at menarche, an older age at menopause, and an older age at the first full-term pregnancy were associated with an increased risk, whereas oophorectomy at an early age was known to be protective1. These risk factors are still recognized2. The number of full-term pregnancies, age at the time of full-term pregnancies after the first, and lactation were considered to have little or no independent effect on the incidence of breast cancer once the associations . . .
A self-administered questionnaire was completed by 1,018 women diagnosed with breast cancer during 1988-1989 identified through the British Columbia Cancer Registry and by 1,025 controls selected at random from the Provincial Voters List. Parous premenopausal women who had never nursed (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.9-2.0) or who had lactated for 1 month or less (OR = 1.8, 95% CI 1.3-2.5) had an increased risk of breast cancer adjusted for age and parity, compared with women who had breast-fed 2 months or longer. The risk was particularly elevated (OR = 3.0, 95% CI 1.6-5.4) among women who reported having tried to nurse, but who were unsuccessful. Among women who nursed for at least 2 months, there was an indication of decreasing risk with increasing duration of nursing. Among postmenopausal parous women, no relation between lactation history and breast cancer risk was evident.
Although the importance of the relationship between age and cancer incidence rates is recognized universally, little attention seems to have been paid to the relationship between the physiologic aging process in the breast and breast cancer risk. The natural history of breast cancer was examined in the context of involution of the breast, and it was proposed that the rate and extent of involution might be important determinants of breast cancer risk. It was concluded that additional studies to characterize the process of involution better histopathologically and to examine the associations between the rate and extent of involution and breast cancer risk are warranted.
Cancer Mortality Statistics in the World
- M Kurihara
- K Aoki
- S Tominaga
The trend to greater height and earlier maturation
- M A Preece
- MA Preece
Age at first birth, parity and risk of breast cancer; meta-analysis of 8 studies from the Nordic countries
- M Ewertz
- S W Duffy
- H O Adami
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