Pooled analysis of 3 European case-control studies of epithelial ovarian cancer: III. Oral contraceptive use

The relationship between use of oral contraceptives (OCs) and other contraceptive methods and the risk of ovarian cancer was examined in a combined analysis of 3 hospital-based case-control studies conducted in Italy, the United Kingdom, and Greece, for a total of 971 ovarian cancer cases and 2,258 controls under age 65. Compared with never-users, the combined multivariate relative risk (RR) for ever-users was 0.6 (95% confidence interval, CI = 0.4-0.8) and the estimates were consistent in the 3 datasets. The protection was also similar across strata of age and parity. Considering various measures of OC use, available in the Italian and British datasets only, the protection conveyed on ovarian cancer risk increased with the duration of use and persisted in the medium-long period: the RR in women reporting their last OC use greater than or equal to 15 years prior to diagnosis was 0.5 (95% CI = 0.2-1.0). The risks in ever-users were appreciably lower in those women who reported their first OC use before 25 years of age (RR = 0.3 for first use before age 25, 0.8 for first use at age 25-34 and 0.7 at 35 years or after). Such findings emerged similarly from Italian and British data. This combined analysis, besides offering further quantitative estimates of the protective effects of OCs on ovarian cancer risk in European populations, provides useful insights into the time pattern of the relationship between OC use and ovarian carcinogenesis, suggesting that the protection persists for 15 years or more after cessation of use and may be larger for use at younger age.     

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. © 1995 Wiley-Liss, Inc.     

Oral contraceptive use and risk of breast cancer in older women (New Zealand)

the effect of oral contraceptive (OC) use at older ages on the risk of breast cancer was examined in a national population-based case-control study conducted in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer, and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk (RR) of breast cancer for women aged 45 to 54 years at diagnosis who had ever used OCs was 1.0 (95 percent confidence interval [CI]=0.77–1.3). There was no significant increase in risk of breast cancer among recent users of OCs of any age. Analyses according to age at first and last use among women aged 40 years and older at diagnosis showed no group with an elevated risk of breast cancer. Women who had used OCs for 10 years or longer after age 40 had an apparent increase in risk (RR=2.7, CI=0.97–7.5), but the trend in risk with duration of use was not significant. These findings suggest that OC use in older women does not affect their risk of breast cancer appreciably, but it is not possible to rule out a modest increase in risk with such use.This research was supported by grants from the Medical Research Council of New Zealand and from the Special Programme of Research, Development, and Research Training in Human Reproduction, World Health Organization.     

Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh-day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow-up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12-2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00-1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71-2.85).     

No Increase in Breast Cancer Risk in Japanese Women Taking Oral Contraceptives: a Case-Control Study Investigating Reproductive,Menstrual and Familial Risk Factors for Breast Cancer

Background: Low-dose oral contraceptives (OC) were approved by the Japanese Ministry of Health, Laborand Welfare in 1999, yet despite their contraceptive and non-contraceptive health benefits, only 5% of the targetpopulation use them. Fear of increased cancer risk, particularly breast cancer, is one reason for this. Due tolow OC uptake and low screening participation, a paucity of data is available on the risk of OC use and breastcancer in Japanese women. The present study investigated OC use and breast cancer risk, as well as menstrual,reproductive and family factors. Materials and Methods: This was a clinic-based case-control study of womenaged 20-69yrs who had undergone breast screening between January 2007 and December 2013 in central Tokyo.In all, 28.8% of the participants had experience with OC use. Cases were 155 women with a pathologicallyconfirmed diagnosis of breast cancer. Controls were the remaining 12,333 women. Results: Increased age was asignificant risk factor for breast cancer (p<0.001). A lower risk was found in premenopausal women presentlytaking OC compared to never users (OR 0.45; 95% CI 0.22-0.90) after adjusting for age, parity and breastfeeding, and a family history of breast cancer. Conclusions: Increased age rather than OC use had a greatereffect on breast cancer risk. This risk may be decreased in premenopausal women with OC use, but furtherlong-term prospective studies are necessary.     

Hormone replacement therapy and breast cancer in former users of oral contraceptives--The Norwegian Women and Cancer study

Combined estrogen-progestin menopausal therapy (HRT) and combined estrogen-progestin contraceptives (OC) both increase breast cancer risk during current use and a few years after. We investigated risk of breast cancer in women who were users of HRT dependant on former history of OC use in a large, national population-based cohort study, the Norwegian Women and Cancer study (NOWAC). Exposure information was collected through postal questionnaires. Based on follow-up of 30,118 postmenopausal women by linkage to national registers of cancer, deaths, and emigration we revealed 540 incident breast cancer cases between 1996 and 2004. Compared to never users of either drugs current use of HRT gave a significant (p = 0.002) higher risk of breast cancer in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for estrogen only and combinations with progestin added in ever users of OCs. The increased risk of breast cancer in current HRT users with a history of former OC use could have potential great impact on postmenopausal breast cancer risk as the proportion of postmenopausal women with former OC use will continue to increase.     

Oral contraceptives and breast cancer in northern Italy. Final report from a case-control study.

To assess the relation between oral contraceptive (OC) use and breast cancer, we analysed data from a case-control study conducted in Northern Italy between 1983 and 1991 on 2,309 cases below age 60 and 1,928 controls admitted to hospital for acute diseases unrelated to OC use and to any of the known or potential risk factors for breast cancer. OC use was reported by 16% of cases and 14% of controls. The multivariate relative risk (RR) for ever vs never use of combination OC was 1.2 (95% confidence interval (CI) 1.0-1.4). However, there was no trend in risk with duration. The RR was elevated for very short use, but declined to 0.8 (95% CI = 0.5-1.0) for five or more years'' use. No noteworthy relationship was found for other major measures of OC use, although RR estimates were above unity for women who had stopped use less than 5 years before (RR = 1.5, 95% CI = 1.1-2.0), started use less than 10 years before (RR = 1.3, 95% CI = 1.0-1.9), started when 25 or more years old (RR = 1.4, 95% CI = 1.1-1.7), or after first birth (RR = 1.2, 95% CI = 1.0-1.5). No interaction was observed between OC use and family history of breast cancer, parity and age at first birth. A separate analysis of 373 cases and 456 control below age 40 showed no association with ever use (RR = 0.9, 95% CI = 0.6-1.2).     

A case-control study of oral contraceptive use and breast cancer

Among 989 cases of breast cancer and 9,890 controls selected from a cohort of married, female registered nurses aged 30-55 years, the relative risk (RR) of breast cancer for women who had ever used oral contraceptives (OC) compared with those who had never used them was 1.0, with 95% confidence limits 0.9-1.2. Among OC users, there was no consistent pattern of excess risk with increasing duration; in fact, the few women who had used OC longest (greater than 10 yr) had a slightly lower risk than never-users. Moreover, there was no association between OC use and breast cancer among women with a positive history of breast cancer in the mother or sister or with OC use before their first pregnancy. The only subgroup of women among whom any adverse effect was apparent was current OC users aged 50-55 years (two onsets expected vs. seven observed). This finding is consistent with earlier reports of an increased risk of breast cancer among older OC users; however, it is also likely to reflect, at least to some extent, the play of chance, since at ages 45-49 and in each younger age group fewer cases than expected were observed among current OC users.     

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n=6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n=9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR]=1.1, 95 percent confidence interval [CI]=10–1.2). Total duration of usealso was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI=0.9–1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR=2.0, CI=1.1–3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m²) less than 20.4, RR=1.7, CI=1.1–2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.Authors are with the University of Wisconsin Comprehensive Cancer Center, Madison, WI, USA (Dr Newcomb, Ms Trentham Dietz); NIEHS Epidemiology Branch, Research Triangle Park, NC (Dr Longnecker); Fred Hutchinson Cancer Research Center, Seattle, WA (Dr Surer); Department of Obstetrics and Gynecology, Pritzker School of Medicine, The University of Chicago, Chicago, IL (Dr Mittendorf); Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH (Dr Baron); Boston University, School of Public Health, Boston, MA (Dr Clapp); Department of Epidemiology and Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Harvard Medical School and Department of Medicine, Brigham and Women's Hospital, Boston, MA (Dr Willett). Address correspondence to: Dr Polly A. Newcomb, University of Wisconsin-Madison Comprehensive Cancer Center, 1300 University Ave., #4780, Madison, WI 53706, USA. Supported by Public Health Service (National Cancer Institute) grants R01 CA 47147 and R01 CA 47305.     

A prospective study of oral contraceptive use and risk of breast cancer (Nurses' Health Study, United States)

Results of previous epidemiologic studies have provided reassurance that there is little, if any, increase in risk of breast cancer with oral contraceptive (OC) use in general. However, in several studies, an increased risk of breast cancer has been observed in two subgroups, young women who used OCs for extended durations and in women who used OCs prior to a first-term pregnancy. We evaluated these relationships using data from the ongoing Nurses' Health Study cohort (United States). We documented 3,383 cases of breast cancer from 1976 to 1992 among 1.6 million person-years of follow-up. We observed no overall relationship between duration of OC use and breast cancer risk, even among women who reported using OCs for 10 or more years (multivariate relative risk [RR]=1.11, 95 percent confidence interval [CI]=0.94-1.32). Among women less than 45 years of age, the multivariate RR for using OCs for 10 or more years was 1.07 (CI=0.70-1.65) compared with never-users. The risk associated with five or more years of OC use prior to a first full-term pregnancy compared with never-use was 0.96 (CI=0.65-1.43). Among women less than 45 years of age, we observed no evidence of an increased risk with OC use before a first full-term pregnancy (use for five or more years: RR=0.57, CI=0.24-1.31). Because of the age distribution of our cohort, we were unable to evaluate these relationships among women less than 40 years of age. Our study provides considerable evidence that long-term past OC use, either overall or prior to a first full-term pregnancy, does not result in any appreciable increase in breast cancer risk in women over 40 years of age.     

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.     

Influence of oral contraceptives on the prognosis of breast cancer in young women

The possible effect of oral contraceptive (OC) use on the prognosis of established breast cancer was investigated in 154 young women aged 35 and younger. No significant differences were found between the study group of 59 OC users, and the control group of 95 nonusers in age, parity and gravidity, family history of breast cancer, benign breast disease, morphology, or surgical therapy. No appreciable differences were found between OC users and nonusers in extent of disease at presentation (P = 0.78), histologic features of tumor (P = 0.83), or axillary node involvement (P = 0.88). No significant or even suggestive differences were found between users and nonusers in disease-free interval (P = 0.41), metastatic period (P = 0.66), or survival (P = 0.54), respectively, either alone or when adjusted for extent of node involvement, duration of OC use, or other risk factors. In this study no evidence was found that the use of OC has any harmful or beneficial effect on evolution and survival of breast cancer.     

Oral contraceptives as related to cancer and benign lesions of the breast.

We conducted a case-control study to search for any relationship between use of oral contraceptives and development of breast cancer or benign breast disease. Women less than 50 years old with these diseases were matched with 2 controls by age, race, religion, and hospital. Home interviews elicited information on oral contraceptive use and other host and environmental factors. The study population comprised 1,770 women, including 452 with breast cancer and 446 with benign breast disease. The relative risk of developing cancer or benign disease was measured by matched set and summary chi-square analyses. Although the relative risk of developing breast cancer among "ever-users" of oral contraceptives was 1.1, the risk among women using oral contraceptives for 2-4 years was 1.9 (significantly increased). This risk estimate reached 2.5 for the 2- to 4-year users if they were still taking oral contraceptives when entered into study. Moreover, prior biopsy for benign breast disease increased the cancer risk among long-term users by as much as 11-fold. The relative risk of breast cancer did not vary by age, interval since first use, earliest year of use, or interval since last use. These results could be interpreted to indicate that oral contraceptives did not induce breast cancer but may have accelerated the growth rate of preexisting breast cancer. The relative risk of developing benign breast disease among ever-users of oral contraceptives was 0.8 (significantly reduced); it decreased with longer duration of use until it reached 0.2 for women who took these hormones 8 years or more. The relative risk of benign breast was not affected by earliest year of use or interval since last use. We concluded that oral contraceptives reduced the incidence of benign breast disease, but that use of steroid hormones is ill-advised for women with already established benign breast disease.     

Early oral contraceptive use and premenopausal breast cancer--a review of studies performed in southern Sweden.

In southern Sweden, extensive oral contraceptive use (OC use) among young women was a reality during the 1960s, thus making our region especially suited for studies investigating the hypothesis that early OC use is associated with the development of premenopausal breast cancer after a possible latency time between the exposure and the disease. The results of this study revealed that the risk of developing premenopausal breast cancer in women, who during the 1960s used the pill as teenagers, is five times greater than nonusers. The risk for early users is further modified by the duration of use at an early age, implying a dose-response relationship. Later use of OCs is not associated with an increased risk for the disease. Women with breast cancer, who at an early age have used the pill, have larger breast tumors, lower estrogen receptor concentrations of their primary tumor, and a worse prognosis compared with later and nonusers with breast cancer. The incidence of breast cancer in Sweden rapidly increased in women 25 to 40 years of age between 1970 and 1984. Conventional risk factors or a change in diagnostic activities of breast cancer cannot explain the increase in incidence which could be due to the OC exposure. Studies on the risk with modern OCs must wait another 20 years because of a too short latency time.     

Use of oral contraceptives and risk of breast cancer in young women

Many studies have shown that oral contraceptive (OC) use increases a young woman's risk of breast cancer, although some studies suggest that the risk may be limited to recent use. The objective of this study was to determine what particular aspects of OC use could be important for breast cancer development at an early age in the cohort of women who had the opportunity to use OCs all of their reproductive life. The cases were first diagnosed with breast cancer at age 40 or younger between 1983 and 1988, and identified by the Los Angeles County Cancer Surveillance Program. Control subjects were individually matched to participating cases on birth date (within 36 months), race (white), parity (nulliparous versus parous), and neighborhood of residence. Detailed OC histories were obtained during in-person interviews with subjects. In general the risk estimates were small, and not statistically significant. Compared to no use, having used OCs for 12 years or more was associated with a modest non-significant elevated breast cancer risk with an odds ratio (OR) of 1.4 (95% confidence interval (CI)=0.8–2.4). Long-term (12 years or more) users of high-dose estrogen pills had a non-significant 60% higher breast cancer risk than never users (CI=0.9–3.2). Early use was associated with slightly higher ORs among young women (age 35), and among parous women. Recent use was associated with somewhat higher ORs among parous women and women above age 36. Analyses by stage, body weight, and family history yielded similar results. This study is consistent with a modest effect of early OC use on breast cancer risk in young women.     

Age at first birth and the risk of epithelial ovarian cancer

The relationships between age at first birth, parity, and the risk of ovarian cancer were evaluated in a case-control study of 272 women with histologically confirmed epithelial ovarian cancer and 544 age-matched controls with a spectrum of acute conditions unrelated to any of the established or potential risk factors for ovarian cancer. Late age at first birth was associated with increased risk: Compared to women who first had a child before the age of 22 years, the relative risks (RR) for those who first gave birth at ages 22-24, 25-27, and 28 or more were 2.7, 3.2, and 4.0, respectively. Nulliparous women showed increased RR (3.9) comparable to the RR among women who first bore a child at age 25 or more, regardless of the number of births. The elevated risk associated with later age at first birth was not accounted for by low parity. The risk of ovarian cancer, as expected, increased with decreasing parity: RR estimates for women having 5 or more, 3 or 4, and 1 or 2 children and for nulliparae were 1.0, 1.7, 1.9, and 2.6, respectively. However, the inverse association between parity and ovarian cancer could be accounted for largely by the importance of age at first birth, because when adjustment was made for that variable, the RR for 3 or 4 and 1 or 2 children decreased to 1.3 and 1.2, respectively. Thus the results of the present study show a strong independent effect of age at first birth on the risk of epithelial ovarian cancer, whereas the association with parity can be explained largely or totally in terms of a high correlation between total parity and age at first birth. The pattern of ovarian cancer risk that emerges from this study, therefore, is similar to the epidemiology of breast cancer. General evidence on this issue from various other studies, however, is rather controversial, and similar analysis of other data-sets would be useful.     

Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study

The incidence of breast cancer among Japanese women, a traditionally low-risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38,159 Japanese women, aged 40-79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow-up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P=0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P=0.05), the association being very apparent among menopausal women (trend P=0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72-6.21) and 3.33 (1.07-10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women.     

Oral contraceptive use and mammographic patterns.

High-risk mammographic patterns represent an increased risk of contracting breast cancer and may be used as a surrogate endpoint for the disease. We examined the relationship between oral contraceptive (OC) use and mammographic patterns among 3218 Norwegian women, aged 40-56 years. Information on ever OC use, duration, and age of first OC use and other epidemiological data were obtained through questionnaires. The mammograms were categorized into five groups. Patterns I-III were combined into a low-risk group and patterns IV and V into a high-risk group. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression and adjusted for age, menopausal status, parity, age at first birth, and body mass index. Women who reported ever having used OCs were 20% more likely (OR 1.27, 95% CI 1.0-1.6) to have high-risk mammographic patterns compared with those reporting never having used OCs. There was no dose response between different measures of OC use and high-risk patterns. Among nulliparous women, ever OC users were four times more likely (OR 4.65, 95% CI 2.1-10.3) to have high-risk patterns compared with never users. Our findings suggest that, especially among nulliparous women, ever OC use may exert its effect on breast cancer risk through changes in breast tissue, which can be observed on a mammogram.     

Oral contraceptive use and the risk of ovarian cancer: An Italian case-control study

The association between oral contraceptive (OC) use and the risk of ovarian cancer was analysed in a case-control study, conducted between 1985 and 1989 on 505 epithelial ovarian cancer cases under 60 years of age, and 1375 controls in hospitals for a spectrum of acute conditions, not gynaecological, hormonal or neoplastic, apparently unrelated to OC use. 41 (8.1%) women with epithelial ovarian cancer and 192 (14.0%) controls reported OC use. The multivariate relative risk (RR) for ever use was 0.7 (95% confidence interval (CI) = 0.5–1.0). The risk decreased with duration of use: compared with never users the multivariate RRs were 0.9 and 0.5 respectively for less than 2 years and 2 years or more users (X²₁ trend = 6.17, P = 0.01). The risk of ovarian cancer decreased with recency and latency of use: the estimated RR were 0.5 and 0.9 in women reporting last OC use less than 10 or 10 years or more from the diagnosis of the disease, and 0.6 and 0.8 in those reporting first OC use less than 10 or 15 or more years before. The protective effect of OC was consistent in separate strata of selected covariates, including parity and other major known or suspected risk factors for ovarian cancer. There was some indication that the protection declines with advancing age, but the risk estimates were similar in premenopause and postmenopause.     

A prospective study of the independent effects of parity and age at first birth on breast cancer incidence in England and Wales

The independent effects of parity and age at first birth on breast cancer incidence are investigated in a 1% sample of women aged 16 to 59 from the 1971 Census of England and Wales. Over the period 1971-81, 1,003 breast cancer cases occurred in the cohort of 113,263 women who were either married, widowed or divorced at the time of Census. Age at first birth was positively related to breast cancer risk, women giving birth to their first child after 35 years being at greater risk than nulliparous women. This effect remained, after adjustment for number of live-born children. Breast cancer risk showed a statistically significant decline with increasing parity even after adjustment for age at first birth. These results are consistent with other published evidence which suggests that other births subsequent to the first have an independent effect on breast cancer risk.