Affiliations of authors: J. R. Palmer, L. A. Wise, L. Rosenberg, Slone Epidemiology Center, Boston University, Boston, MA; N. J. Horton, Department of Biostatistics, Boston University School of Public Health, Boston; L. L. Adams-Campbell, Howard University Cancer Center, Washington, DC.
Correspondence to: Julie R. Palmer, Sc.D., Slone Epidemiology Center, Boston University, 1010 Commonwealth Ave., Boston, MA 02215 (e-mail: jpalmer{at}slone.bu.edu).
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
SUBJECTS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
An attempt was made to obtain medical records for all 349 participants who reported incident breast cancer on the 1997 and 1999 questionnaires. Records were obtained for 167 (48%) potential case subjects. The primary reason for not obtaining records was nonconsent, with many participants citing concerns about privacy and confidentiality. A diagnosis of breast cancer was confirmed for all 167 reviewed case subjects, with 136 case subjects classified as having invasive breast cancers and 31 as having carcinoma in situ. These results suggest that a self-report of breast cancer by Black Womens Health Study participants is acceptably accurate. Therefore, all first occurrences of breast cancer reported on the 1997 and 1999 questionnaires were included in the present analysis, for a total of 349 case subjects.
Data were obtained on the outcome of each pregnancy and the participants age at each full-term pregnancy. The number of years since the last pregnancy was calculated from the participants age at most recent full-term pregnancy and age at each follow-up. Thus, it was possible to classify each participant as to number of births, years since last birth, and age at first birth at the beginning of follow-up and at the end of each of the 4 years of follow-up.
Statistical Analysis
All analyses were carried out separately among women younger than 45 years and women 45 years or older at the beginning of each follow-up period. Age-stratified Cox regression models were used to derive incidence rate ratios (IRRs) for breast cancer in relation to three childbearing variablesparity, age at first birth, and years since last birth (8). Multivariable age-stratified Cox proportional hazards regression models controlled for family history of breast cancer, age at menarche, duration of oral contraceptive use, years of education, and body mass index (in kilograms per square meter) and included all three of the childbearing variables. Departures from the proportional hazards assumption were tested by a likelihood ratio test comparing models with and without age by covariate interaction terms. No statistically significant violations of this assumption were found. IRRs for nulliparity relative to one birth were estimated in models in which the reference category was women of the median age at first birth (age 2024) and the median time since last birth (59 years for women younger than 45 years and 25 years for women 45 years or older). All 95% confidence intervals (CIs) are two-sided. SAS statistical software (version 8.02; SAS Institute, Inc., Cary, NC) was used to perform the analyses.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
We next examined whether late age at first birth was associated with an increased risk of breast cancer before age 45. For women whose first birth was at age 30 years or older, the multivariable IRR was 2.5 (95% CI = 1.1 to 5.8) relative to women whose first birth was at an age younger than 20 years (Table 3). A less consistent association was observed for breast cancer diagnosed at age 45 years or older: the IRR for women whose first birth was at age 2529 years was 1.5 (95% CI = 0.9 to 2.2), but the IRR for women whose first birth was at age 30 years or older was 0.7 (95% CI = 0.4 to 1.4).
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Studies of white women (4,9) have suggested that multiparity modestly decreases the risk of breast cancer in older women. Janerich and Hoff (10) hypothesized that full-term pregnancy may increase the risk of breast cancer at younger ages, and a number of studies of white women (1115) have provided data supporting the hypothesis. Using large datasets, Lambe et al. (6) and Liu et al. (5) demonstrated that there is a small transient increase in risk of breast cancer associated with each full-term birth, followed by a reduction in risk many years later. The increase is greatest for the first birth, but subsequent births also appear to be associated with a small transient increase in risk. Lambe et al. (6) and others (10,13) have speculated that full-term pregnancy may have several effects that could influence the risk of breast cancer. The most striking effect, demonstrated by Russo et al. (16) in rat experiments, may be the terminal differentiation of lobular mammary cells that occurs at completion of a full-term pregnancy, which would leave mammary cells less susceptible to malignant transformation. Therefore, women whose first birth occurs at a young age may ultimately have a reduced risk of breast cancer because they have had a shorter period, i.e., the time between onset of menarche and first birth, during which breast cells are at risk of transformation. This line of reasoning would also explain why nulliparous women have a higher risk of breast cancer than parous women at older ages. In addition, the increased hormone levels that occur in each full-term pregnancy may promote the growth of cells that have already undergone malignant transformation. In this case, there would be some period of increased risk associated with each full-term pregnancy. With the passage of time, the increased risk would dissipate and a reduced risk would be observed, resulting from the differentiation of additional breast cells with each pregnancy. Liu et al. (5) estimated that the small increased risk of breast cancer associated with each pregnancy reaches its highest level at approximately 5 years after the birth and disappears approximately 15 years later.
Our finding of an increased risk of breast cancer associated with increased parity among women younger than age 45 years is consistent with the hypothesized transient increase in breast cancer risk after each pregnancy (5,6), which could be caused by the additional hormone exposure during the pregnancy. Given this finding, one might have expected to observe an association between time since last birth and breast cancer risk. Among women aged 45 years or older, we observed a relative risk of 2.0 for those with the shortest interval since last birth. However, this estimate was made on the basis of only five case subjects and was not statistically significant. After controlling for the number of births and age at first birth, there was no apparent association between time since last birth and breast cancer risk among the younger women. One possible explanation for the lack of association is the small sample size; a much larger sample would be required to demonstrate the small effect of time since last birth. From the Swedish Fertility Register, with over 30 000 breast cancer case subjects available for study, Liu et al. (5) documented a small increase in the risk of breast cancer for each of the first few years after a birth, with adjustment for age at delivery in 1-year increments. Other studies, with considerably smaller numbers of white women, have produced mixed results: some observed an increased risk for shorter interval since last birth (1719) and a few found no association (15,20,21).
In our study, late age at first birth was associated with an increased risk of breast cancer before age 45 years, but there was little evidence of such an association among older women. Age at first birth is considered an established risk factor for breast cancer (22), although the magnitude of the association is unclear, with population-based and more recent studies showing weak associations (4,9,23,24).
Most previous work on childbearing in relation to breast cancer risk has been based on data from white women. Moreover, only two studies (25,26) have reported the relation of these factors to breast cancer risk in African-American women separately for younger and older women. Mayberry (25) analyzed data on 490 African-American breast cancer case subjects and their matched controls from the Cancer and Steroid Hormone Study. Although increased parity was associated with a reduced risk of breast cancer both among women younger than 40 years and among those aged 4054 years, the association was statistically significant only among the older women. Age at first birth was not associated with risk of breast cancer among the younger women and was weakly positively associated with that among the older women. Brinton et al. (26) analyzed data on 281 case subjects and their matched controls from a more recent multicenter casecontrol study. Among women younger than 40 years, those with two or more births had a somewhat higher risk than primiparous women, but the increase was not statistically significant. Among women aged 4054 years, higher parity was not associated with a reduced risk relative to primiparity. Age at first birth was strongly associated with increased risk among younger women (i.e., those younger than 40 years) but not among older women, in accordance with Mayberrys findings (25) and with the findings of the present study.
Because our data are from a prospective cohort study with a low loss to follow-up, it is likely that information provided on the number and timing of births was unbiased with regard to subsequent development of breast cancer. Data were obtained by self-administered, self-coded questionnaires, and some participants did appear to confuse pregnancy with full-term birth and vice versa. Thus, approximately 2% of participants were excluded from analysis because of missing data on the key pregnancy variables or conflicting information on those variables. Nevertheless, there were probably other women who were misclassified with regard to the timing and, perhaps, the number of their births. Such nondifferential misclassification of pregnancy variables would have resulted in underestimation of incidence rate ratios.
The Black Womens Health Study cohort under-represents African-American women from the lowest socioeconomic strata. Indeed, 97% of the Black Womens Health Study participants had graduated from high school, whereas approximately 83% of African-American women of the same ages have done so (27). In general, less educated women have more children and have them at an earlier age than do more educated women. The parity and ages at first birth of the Black Womens Health Study participants are thus not representative of all African-American women. However, we consider that the etiologic results are most likely generalizable to all African-American women because there is no reason to believe that the underlying biology would differ across socioeconomic strata.
In summary, our study is the first, to our knowledge, to demonstrate a dual association of parity with breast cancer risk in African-American women. The findings provide an explanation, at least in part, for the relatively high incidence of breast cancer in young African-American women. In the future, with the occurrence of more breast cancers in the Black Womens Health Study participants, it may be possible to compare age-specific incidence rates in this cohort with rates in a comparable cohort of white women and examine whether differences in incidence are attenuated by adjustment for parity and age at first birth.
![]() |
NOTES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1 Ries LA, Kosary CL, Hankey BF, Miller BA, Edwards BK, editors. SEER cancer statistics review, 19731995. Bethesda (MD): National Cancer Institute; 1998.
2 Pathak DR, Osuch JR, He J. Breast carcinoma etiology: current knowledge and new insights into the effects of reproductive and hormonal risk factors in black and white populations. Cancer 2000;88:12308.[CrossRef][Medline]
3 National Center for Health Statistics. Health, United States, 1998 with socioeconomic status and health chartbook. Hyattsville (MD): 1998. p. 1725.
4 Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993;15:3647.[Medline]
5 Liu Q, Wuu J, Lambe M, Hsieh SF, Ekbom A, Hsieh CC. Transient increase in breast cancer risk after giving birth: postpartum period with the highest risk. Cancer Causes Control 2002;13:299305.[CrossRef][Medline]
6 Lambe M, Hsieh CC, Trichopoulos D, Ekbom A, Pavia M, Adami HO. Transient increase in breast cancer risk after giving birth. N Engl J Med 1994;331:59.
7 Rosenberg L, Adams-Campbell L, Palmer JP. The Black Womens Health Study: a follow-up study for causes and prevention of illness. J Am Med Womens Assoc 1995;50:568.[Medline]
8 Cox DR. Regression model and life tables (with discussion). J R Stat Soc (B) 1972;34:187220.
9 Layde PM, Webster LA, Baughman AL, Wingo PA, Rubin GL, Ory HW, et al. The independent associations of parity, age at full term pregnancy, and duration of breastfeeding with the risk of breast cancer. J Clin Epidemiol 1989;42:96373.[Medline]
10 Janerich DT, Hoff MB. Evidence for a crossover in breast cancer risk factors. Am J Epidemiol 1982;116:73742.[Medline]
11 Trichopoulos D, Hsieh CC, MacMahon B, Lin T, Lowe CR, Mirra AP, et al. Age at any birth and breast cancer risk. Int J Cancer 1983;31:7014.[Medline]
12 Lubin JH, Burns PE, Blot WJ, Lees AW, May C, Morris LE, et al. Risk factors for breast cancer in women in northern Alberta, Canada, as related to age at diagnosis. J Natl Cancer Inst 1982;68:2117.[Medline]
13 Pathak DR, Speizer FE, Willett WC, Rosner B, Lipnick RJ. Parity and breast cancer risk: possible side effect on age at diagnosis. Int J Cancer 1986;37:215.[Medline]
14 Negri E, La Vecchia C, Bruzzi P, Dardamoni G, Decarli A, Palli D, et al. Risk factors for breast cancer: pooled results from three Italian case-control studies. Am J Epidemiol 1988;128:120715.[Abstract]
15 Vatten LJ, Kvinnsland S. Pregnancy-related factors and risk of breast cancer in a prospective study of 29,981 Norwegian women. Eur J Cancer 1992; 28A:114853.
16 Russo J, Tay LK, Russo IH. Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Res Treat 1982;2:573.[Medline]
17 Williams EM, Jones L, Vessey MP, McPherson K. Short term increase in risk of breast cancer associated with full term pregnancy. BMJ 1990;300:5789.[Medline]
18 Bruzzi P, Negri E, La Vecchia C, Decarli A, Palli D, Parazzini F, et al. Short term increase in risk of breast cancer after full term pregnancy. BMJ 1988;297:10968.[Medline]
19 Kalache A, Maguire A, Thompson SG. Age at last full-term pregnancy and risk of breast cancer. Lancet 1993;341:336.[CrossRef][Medline]
20 Cummings P, Weiss NS, McKnight B, Stanford JL. Estimating the risk of breast cancer in relation to the interval since last term pregnancy. Epidemiology 1997;8:48894.[CrossRef][Medline]
21 Adami HO, Bergstrom R, Lund F, Meirik O. Absence of association between reproductive variables and the risk of breast cancer in young women in Sweden and Norway. Br J Cancer 1990;62:1226.[Medline]
22 MacMahon B, Cole P, Lin TM, Lowe CR, Mirra AP, Ravnihar B, et al. Age at first birth and breast cancer risk. Bull World Health Organ 1970;43:20921.[Medline]
23 Ewertz M, Duffy SW, Adami HO, Kvale G, Lund E, Meirik O, et al. Age at first birth, parity and risk of breast cancer: a meta-analysis of 8 studies from the Nordic countries. Int J Cancer 1990;46:597603.[Medline]
24 Chie WC, Hsieh CC, Newcomb PA, Longnecker MP, Mittendorf R, Greenberg ER, et al. Age at any full term pregnancy and breast cancer risk. Am J Epidemiol 2000;151:71522.[Abstract]
25 Mayberry RM. Age-specific patterns of association between breast cancer and risk factors in black women, ages 20 to 39 and 40 to 54. Ann Epidemiol 1994;4:20513.[Medline]
26 Brinton LA, Benichou J, Gammon MD, Brogan DR, Coates R, Schoenberg JB. Ethnicity and variation in breast cancer incidence. Int J Cancer 1997;73:34955.[CrossRef][Medline]
27 Educational attainment in the United States. Current population reports. Series P-20, No. 513. U.S. Department of Commerce, Washington, D.C. 1998.
Manuscript received September 24, 2002; revised January 8, 2003; accepted January 17, 2003.
This article has been cited by other articles in HighWire Press-hosted journals:
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |