Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women

The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45-0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12-2.38) and 1.35 (95% CI 1.02-1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60-1.04), 0.69 (95% CI 0.54-0.88), 0.66 (95% CI 0.51-0.85) and 0.64 (95% CI 0.48-0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer.     

A case-control study of breast cancer in Tianjin, China.

In a population-based case-control study of breast cancer in Tianjin, China, involving 300 cases and 300 population controls interviewed during 1985-1986, a number of strong risk factors were identified. Although average age at menarche was late by Western standards in this developing country (14.4 years), it was clearly related to risk. Women with their first menstrual period at age 12 years or earlier had 80% greater risk than women who started at age 17 years or later. Age at first full-term pregnancy was also strongly related to risk, with women whose first birth after age 30 years having 3.2 times the risk of women whose first birth was under age 20 years. Other established breast cancer risk factors in Western populations (family history of breast cancer, a history of benign breast disease, and use of oral contraceptives late in reproductive life) were also risk factors in this population. Parity and duration of lactation were both strongly protective against breast cancer development in univariate analyses. These two variables were highly correlated with each other and with age at first full-term pregnancy. Although the effects of each variable dissipated somewhat in multivariate analysis, our data strongly suggest that both parity and lactation independently contribute to breast cancer risk.     

Lactation, lactation suppression hormones and breast cancer

One hundred and fifty-four parous women with pathologically confirmed newly diagnosed breast cancer in National Taiwan University Hospital were selected as the case group. Three hundred and eighty-six parous inpatient controls were individually matched for each case by age and date of admission. Information was collected from questionnaire interview and medical record. Effects of lactation and lactation suppression hormone were assessed with conditional logistic regression analysis. In univariate analysis, lactation had a weak protective effect, after adjusting for educational level, body mass index, family history of breast cancer, reproductive factors, oral contraceptive and lactation suppression hormone use, the weak negative associations changed to weak positive ones. The use of lactation suppression hormone was consistently associated with a higher breast cancer risk. The major confounders between lactation and breast cancer risk were parity and age at first full-term birth. Lower breast cancer risks were found in high parity - long lactation, and in younger ages at first full-term birth - long lactation groups. The differences among different lactation lengths within each parity and age at first full-term birth category were small. The protective effects disappeared after adjusting for other potential confounders. The results of this study questions the independent protective effect of lactation in a population having both a variable duration of lactation and rapid socioeconomic change. The role of lactation suppression hormones needs further study.     

Reproductive factors associated with mammographic density: a Korean co-twin control study

To determine the mechanism by which menstrual and reproductive factors are associated with the risk of breast cancer, we examined the relationships between mammographic density and known menstrual and reproductive risk factors for breast cancer. A co-twin control study was conducted with 122 pairs of monozygotic Korean female twins selected from the Healthy Twin study. Mammographic density was measured from digital mammograms using a computer-assisted method. Information on selected menstrual and reproductive factors was collected through a self-administered questionnaire. Within-pair differences for each mammographic measure were regressed against within-pair differences for each menstrual and reproductive risk factor with an adjustment for body mass index and other menstrual and reproductive factors. The percent dense area was inversely associated with the age at the first full-term childbirth (FFTB) and the number of live births, although the associations were marginally significant with an adjustment for BMI and other reproductive factors. The non-dense area was positively associated with the age at the FFTB and the number of live births. The absolute dense area was positively associated with the duration of breast feeding. The age at menarche was not associated with any component of the mammographic measures. This finding suggests that mammographic density can mediate the protective effect of greater parity against breast cancer, at least in part while age at menarche, age at the FFTB, and breast feeding do not exert their effects through mammographic density.     

Reproductive factors related to the risk of colorectal cancer by subsite: a case-control analysis

The authors hypothesized that reproductive factors of colorectal cancer, which are probably mediated by endogenous hormones, would differ according to colonic subsite. Information on reproductive factors was obtained from 372 female colorectal cancer cases (113 proximal colon, 126 distal colon, 133 rectum) and 31,061 cancer-free controls at the Aichi Cancer Center Hospital, Japan, between 1988 and 1995. Multiple logistic analysis showed that late age at interview, family history of colorectal cancer among first-degree relatives, menstrual regularity, late age at menopause, late age at first pregnancy and late age at first full-term pregnancy were significantly associated with the risk of colorectal cancer. None of the risk factors were significantly dissociated between colon and rectal cancer. In polytomous logistic regression analysis, particularly noteworthy was the fact that the odds ratios for age at menarche (P-value for heterogeneity of odds ratios = 0.010), age at first pregnancy (P = 0.016) and age at first full-term pregnancy (P = 0.028) were significantly higher for distal than for proximal colon cancer. This study supports the hypotheses that there might be an association between reproductive factors and risk of colon cancer, and that the carcinogenesis of colon cancer, by subsite, might show aetiologic distinctions.     

Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden

In southern Sweden during the 1960s, women began to use oral contraceptives (OCs) extensively at a young age. This case-control study investigates the relationship between the use of OCs and breast cancer development in women in southern Sweden diagnosed in the early 1980s. The risk for breast cancer after OC use among premenopausal women was modeled, after adjustment was made for age, age at menarche, and age at first full-term pregnancy or parity. Both the duration of OC use before 25 years of age and commencement of OC use at a young age were associated with a significant increase in the risk of breast cancer as well as a significant trend. The duration of OC use before the first full-term pregnancy was associated with an increased risk of breast cancer, but it did not show a significant trend. The total duration of OC use was weakly, but not significantly, associated with breast cancer development. The odds ratio for women starting OC use before 20 years of age was 5.8 [95% confidence interval (CI), 2.6-12.8]; for women using OCs for greater than 5 years before age 25, it was 5.3 (95% CI, 2.1-13.2); and for women using OCs for greater than or equal to 8 years before first full-term pregnancy, it was 2.0 (95% CI, 0.8-4.7). In multivariate analyses including the different measurements of OC use, only starting age of OC use was significantly associated with breast cancer. The exposure-response relationship between duration of OC use and risk of breast cancer depended on the age at first use of OCs. Given a fixed duration of OC use, the risk increased with younger starting age of OC use. The findings point to the importance of the early reproductive years as risk determinants for breast cancer after OC use.     

Reproductive factors and breast cancer in New Zealand

A national population-based case-control study was used to assess the influence on breast cancer risk of reproductive factors and the possibility of an interaction with age at diagnosis. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. There was a declining risk of breast cancer with increasing age at menarche (p = 0.06), the strongest effect being seen in women aged less than 40. Parous women had a 27% lower risk of breast cancer than nulliparous women, a reduced risk being evident in all but the youngest age group. A falling risk of breast cancer with rising parity was clear only in women diagnosed when aged at least 45 years. Breast cancer risk tended to fall amongst parous women with increasing duration of breastfeeding (p = 0.14); the association was most apparent in the youngest women, while those over 40 years at diagnosis showed no clear negative trend. There was no association of breast cancer risk with age at first full-term pregnancy, time since last full-term pregnancy, abortion (spontaneous or induced), abortion before first full-term pregnancy, or ability to conceive, and there was no trend in risk with age at natural menopause. Women in the highest category of body mass index at age 20 had the lowest risk of breast cancer in the age group studied. When each reproductive factor was formally tested for effect modification by age at diagnosis, the interaction term in logistic models approached statistical significance only for parity (p = 0.07). Int. J. Cancer 76:182–188, 1998.© 1998 Wiley-Liss, Inc.     

The international variation in breast cancer rates: An epidemiological assessment

Part of the international differences in breast cancer incidence rates can be explained by geographic variation in reproductive and other breast cancer risk factors. Age at menarche and age at onset of regular ovulatory menstrual cycles are two such factors; both vary across populations directly according to breast cancer risk, and both are acknowledged as breast cancer risk factors. Consideration of the body of evidence on these factors, as well as that on age at menopause, suggests that the cumulative frequency of ovulatory menstrual cycles is a critical determinant of breast cancer risk. Although age at first term pregnancy explains the majority of the protective effect of parity on breast cancer risk, two recent studies have demonstrated a small residual protective effect of increasing number of births. It appears that pregnancy hasparadoxical effects on breast cancer risk in terms of hormone production and metabolism. The initial effect is an increased risk associated with first trimester estrogen exposure. However, the hormonal consequences of completing the pregnancy counteract this negative effect of early pregnancy. The effect of body weight, a breast cancer risk factor for postmenopausal women, can be explained in terms of increased extraglandular conversion of androstenedione to estrone. Further evidence supporting a pathogenic role of estrogens in the development of breast cancer comes from international studies of endogenous hormones in populations with differing risks of breast cancer. These risk factors have been incorporated into a mathematical model which is based on the concept that breast tissue ages according to hormonal (primarily estrogen) exposure; this model closely predicts the incidence rates throughout the world.     

The international variation in breast cancer rates: An epidemiological assessment

Part of the international differences in breast cancer incidence rates can be explained by geographic variation in reproductive and other breast cancer risk factors. Age at menarche and age at onset of regular ovulatory menstrual cycles are two such factors; both vary across populations directly according to breast cancer risk, and both are acknowledged as breast cancer risk factors. Consideration of the body of evidence on these factors, as well as that on age at menopause, suggests that the cumulative frequency of ovulatory menstrual cycles is a critical determinant of breast cancer risk. Although age at first term pregnancy explains the majority of the protective effect of parity on breast cancer risk, two recent studies have demonstrated a small residual protective effect of increasing number of births. It appears that pregnancy hasparadoxical effects on breast cancer risk in terms of hormone production and metabolism. The initial effect is an increased risk associated with first trimester estrogen exposure. However, the hormonal consequences of completing the pregnancy counteract this negative effect of early pregnancy. The effect of body weight, a breast cancer risk factor for postmenopausal women, can be explained in terms of increased extraglandular conversion of androstenedione to estrone. Further evidence supporting a pathogenic role of estrogens in the development of breast cancer comes from international studies of endogenous hormones in populations with differing risks of breast cancer. These risk factors have been incorporated into a mathematical model which is based on the concept that breast tissue ages according to hormonal (primarily estrogen) exposure; this model closely predicts the incidence rates throughout the world.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women: a case-control study

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR = 0.45, 95% CI = 0.30-0.66; OR = 0.34, 95% CI = 0.22-0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR = 0.36, 95% CI = 0.14-0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

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.     

Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.

We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR=0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.     

Role and impact of menstrual and reproductive factors on breast cancer risk in Japan.

The aim of this study was to clarify the role and impact of menstrual and reproductive factors in relation to breast cancer and its hormone receptor-defined subtype, overall and separately among premenopausal and postmenopausal women in a low-risk population, using data from the Japan Public Health Center-based Prospective study. A total of 55 537 women aged 40-69 years completed a self-administered questionnaire, which included items about menstrual and reproductive history. During 1990-2002, 441 newly diagnosed cases of breast cancer were identified. Early age at menarche for premenopausal women, late age at natural menopause, nulliparity and low parity for both premenopausal and postmenopausal women, and late age at first birth for postmenopausal women were significantly associated with an increased risk of breast cancer. No overall significant associations were seen between the use of exogenous female hormones or breast feeding and breast cancer risk. Age at menarche and age at natural menopause were somewhat more closely associated with the risk of progesterone receptor-negative than positive breast cancer although no difference was observed for estrogen receptor status. Risks associated with parity, number of births and age at first birth did not significantly differ by hormone receptor-defined breast cancer. Our findings suggest that menstrual and reproductive factors may play an important role in the development of breast cancer among low-risk populations, similarly as they do in Western populations, and that risk factors might differ by hormone receptor status.     

Risk of breast cancer in relation to reproductive factors in Denmark

The effect of reproductive factors on breast cancer risk was evaluated in a population-based case-control study, including 1,486 breast cancer cases diagnosed over a one-year period in Denmark. They were identified from the files of the nationwide trial of the Danish Breast Cancer Co-operative group and the Danish Cancer Registry. The control group was an age-stratified random sample of 1,336 women from the general population. Data on risk factors were collected by self-administered (mailed) questionnaires. Significantly increased relative risks (RR) were associated with never being pregnant (RR = 1.47), an early terminated first pregnancy (RR = 1.43), and having a natural menopause after the age of 54 (RR = 1.67). Trends of decreasing risk were observed by increasing parity and age at menarche. These findings were independent of age at first full-term pregnancy which overall was not related to breast cancer risk, though a weak association appeared in women less than 50 years at diagnosis. The study confirmed that pregnancies must continue to term to offer protection against breast cancer.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR=0.45, 95% CI=0.30–0.66; OR=0.34, 95% CI=0.22–0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR=0.36, 95% CI=0.14–0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Reproductive history and risk of second primary breast cancer: the WECARE study.

BACKGROUND: Women with an initial breast cancer diagnosis are at elevated risk of developing subsequent cancer in the contralateral breast. Studies of reproductive factors and contralateral breast cancer (CBC) have provided inconsistent results. METHODS: We employed a case-control study nested within five population-based cancer registries in the United States and Denmark to examine associations between reproductive history and CBC risk. Cases were women with asynchronous CBC who had their first primary invasive breast cancer before age 55 years. Two controls, who had only one primary breast cancer diagnosis, were individually matched to each case on age and year of diagnosis, race, and registry. A total of 694 case-control triplets and 11 case-control pairs were enrolled. Information regarding possible CBC risk factors was obtained via telephone interviews. Multivariable conditional logistic regression was used to estimate rate ratios (RR) and 95% confidence intervals (95% CI) associated with risk factors of interest. RESULTS: Increasing number of full-term pregnancies (FTP) was inversely associated with CBC risk (P trend, 0.001). Women who reported menarche before age 13 years had an increased risk of CBC (RR, 1.26; 95% CI, 1.01-1.58). Age at first FTP, breastfeeding history, and age at menopause were not significantly associated with CBC risk. CONCLUSIONS: These results suggest age at menarche and parity, which are established risk factors for first primary breast cancer, are associated with CBC, whereas other reproductive risk factors associated with first primary breast cancer, such as age at first FTP, are less important factors in the development of CBC.     

Incidence of thyroid cancer in women in relation to known or suspected risk factors for breast cancer

There is evidence to suggest that breast and thyroid tumors occur together in the same woman more often than would be expected by chance. This study investigates the possibility that various known risk factors for breast cancer also influence the risk of thyroid cancer in women. Female residents of western Washington, in whom papillary, follicular, or mixed thyroid cancer had been diagnosed between 1974 and 1979 (N = 182), were interviewed regarding their medical and reproductive histories. For comparison, a random sample of 389 women from the same population were interviewed. Women who had a history of breast cancer were almost 3 times (95% confidence interval, 0.78-7.9) more likely to develop thyroid cancer than women with no such history. However, a history of breast cancer in a woman's mother did not increase her risk of thyroid cancer. Neither nulliparity, infertility, late age at first full-term pregnancy, early age at menarche, nor a history of abortion or miscarriage before first full-term pregnancy appeared to influence the occurrence of thyroid cancer. Increased weight was associated with an increased risk of thyroid cancer; relative to women who weighed 52 kg or less, those who weighed 60 kg or more had a 2.5-fold elevation in risk. These findings suggest that while cancers of the breast and thyroid are epidemiologically similar in a few ways, there are important differences in a number of their risk factors.     

Oral contraceptives and breast cancer risk in Taiwan,a country of low incidence of breast cancer and low use of oral contraceptives

One hundred and seventy four (81% of all) pathologically confirmed new incident cases of female breast cancer identified from a medical center in Taipei from February, 1993 to June, 1994 were selected as the case group. Four hundred and fifty three inpatient controls who were without obstetric-gynecological, breast, or malignant diseases were individually matched for each case by age and date of admission. Information was obtained through direct interview and review of medical records. Conditional logistic regression was used to estimate the effects of each risk factor. After adjusting for education level, body mass index, age at menarche and first full-term pregnancy, parity, menopausal status and age at menopause, lifetime lactation, use of lactation inhibition hormones, and family history of breast cancer, breast cancer risk significantly elevated in use of OC before 25 years old and before 1971. In stratified analysis, significantly higher risk were found in OC use before 25 years old and in duration of use less than one year among post-menopausal subjects. Our results support the notion that OC use in early life for younger women and in early calendar years increase breast cancer risk. Int. J. Cancer 77:219–223, 1998.© 1998 Wiley-Liss, Inc.     

A cohort study of reproductive factors and family history of breast cancer in southern Sweden

Background. Studies have been contradictory regarding the hypothesis that reproductive risk factors of breast cancer as parity and age at first full-term pregnancy (AFFP) operate differently in women with and without a family history of breast cancer. Methods. The overall tumour incidence and breast cancer incidence related to fertility factors were followed in a population based cohort of 29,508 women aged 25–65 when interviewed between 1990 and 1992 in south Sweden. At the end of the follow up in December 1999, the cohort constituted 226,611 person years. The risk of breast cancer in relation to reproductive factors were studied in women with at least one first degree relative with breast cancer and compared with women without a family history. Findings. A total of 1145 malignant tumours were seen and 1166.6 were expected (SIR = 0.98, 95% CI = 0.93–1.04). Slightly more breast cancer cases were seen 434 than expected 387.69 (SIR = 1.12, 95% CI = 1.02–1.23). A family history of breast cancer among a first degree relative was present in 1615 women. Forty-five breast cancers were seen among these women while 24.27 was expectecd (SIR = 1.85, 95% CI = 1.35–2.48). Nulliparous women with a family history of breast cancer had a higher risk of breast cancer, SIR = 1.76, 95% CI = 0.64–3.82, compared with nulliparous women without a family history, SIR = 1.13, 95% CI 0.99–1.29. Similarly women with parity 1–2 with a family history had a higher SIR = 1.81, 95% CI = 1.16–2.69 compared with women without a family history having 1–2 children, SIR = 1.13, 95% CI = 0.99–1.29. In women with 3 children those with a family history continued to have a high SIR = 1.98, 95% CI = 1.11–3.27 compared with women without a family history SIR = 0.90, 95% CI = 0.73–1.09. An early full-term pregnancy was protective in both groups. A higher risk than nulliparous women were seen after age 25 in the family history group and after age 30 in the sporadic cancer group. Interpretation. Women with a first degree family history of breast cancer do not experience the same protection from a high number of pregnancies as women without a family history. However, an early first full-term pregnancy seems to offer a substantial protection in the family history group if undertaken before age 20. This suggest that reproductive factors tend to operate differently in the two groups of women.     

Reproductive factors in hereditary breast cancer

Background: An early age at menarche, a short menstrual cycle length, and a high age at first full term pregnancy or nulliparity are known risk factors for breast cancer. These risk factors have previously been reported to differ between breast cancer patients with and without a family history of breast cancer and also between breast cancer patients and controls. Methods: Self-administered questionnaires were filled out by 95 women belonging to 24 families with known BRCA1 mutations, 16 women belonging to nine families with known BRCA2 mutations, and 95 women belonging to 65 families with hereditary breast cancer where no BRCA1 or BRCA2 mutations could be detected. Thirty-nine women were BRCA1 mutation carriers and 56 women were BRCA1 negative, 11 women were BRCA2 carriers and five BRCA2 negative. All women were born between 1905 and 1979. Results: Age at menarche, physiological menstrual cycle length at age 30 or at current age in younger women (when not using oral contraceptives), age at first full term pregnancy, and nulliparity did not significantly differ between BRCA1 mutation carriers and BRCA1 negative women. Too few women were BRCA2 negative to serve as a control group. BRCA2 mutation carriers were therefore compared with BRCA1 negative and BRCA2 negative women. None of the above reproductive factors did significantly differ between BRCA2 mutation carriers and from BRCA1 and BRCA2 families. Women from non-BRCA1/BRCA2 hereditary breast cancer families had a higher age at menarche, but this was no longer significant after adjustment for other factors in a multivariate model. Conclusion: Our results suggest that reproductive risk factors of breast cancer are not related to BRCA1 or BRCA2 carrier status. There was also no indication that these factors differ in carriers of unknown susceptibility genes compared with non-carriers from BRCA1 and BRCA2 families.