Background The effect of pregnancy on the risk of breast canceris not clear. We tested the hypothesis that the risk of breastcancer increases transiently after pregnancy but then fallsto a level below that of age-matched nulliparous women.
Methods We conducted a case-control study of a nationwide cohortin Sweden, using a computerized record linkage between the CancerRegistry and the Fertility Registry. The study subjects werewomen born from 1925 through 1960 who were resident citizensof Sweden at the time of the 1960 census. A total of 12,666patients with breast cancer were compared with 62,121 age-matchedcontrol subjects. We used conditional logistic regression toestimate odds ratios for the development of breast cancer atdifferent ages, according to maternal age at first delivery(in uniparous as compared with nulliparous women) and age atsecond delivery (in biparous as compared with uniparous women).
Results Uniparous women were at higher risk of breast cancerthan nulliparous women for up to 15 years after childbirth andat lower risk thereafter. The excess risk was most pronouncedamong women who were older at the time of their first delivery(odds ratio 5 years after delivery among women 35 years oldat first delivery, 1.26; 95 percent confidence interval, 1.10to 1.44). Women who had two pregnancies had a less strikingincrease in risk.
Conclusions Pregnancy has a dual effect on the risk of breastcancer: it transiently increases the risk after childbirth butreduces the risk in later years. In women with two pregnancies,the short-term adverse effect is masked by the long-term protectionimparted by the first pregnancy. A plausible biologic interpretationis that pregnancy increases the short-term risk of breast cancerby stimulating the growth of cells that have undergone the earlystages of malignant transformation but that it confers long-termprotection by inducing the differentiation of normal mammarystem cells that have the potential for neoplastic change.
Source Information
From the Department of Social Medicine (M.L.) and the Cancer Epidemiology Unit (M.L., A.E., H.-O.A.), University Hospital, Uppsala, Sweden; the Department of Epidemiology, Harvard School of Public Health, Boston (C.H., D.T., A.E., M.P., H.-O.A.); and the Cattedra di Igiene, Facolta di Medicina di Catanzaro, Universita di Reggio Calabria, Catanzaro, Italy (M.P.).
Address reprint requests to Dr. Lambe at the Department of Social Medicine, University Hospital, S-751 85 Uppsala, Sweden.
Lord, S. J., Bernstein, L., Johnson, K. A., Malone, K. E., McDonald, J. A., Marchbanks, P. A., Simon, M. S., Strom, B. L., Press, M. F., Folger, S. G., Burkman, R. T., Deapen, D., Spirtas, R., Ursin, G.
(2008). Breast Cancer Risk and Hormone Receptor Status in Older Women by Parity, Age of First Birth, and Breastfeeding: A Case-Control Study. Cancer Epidemiol. Biomarkers Prev.
17: 1723-1730
[Abstract][Full Text]
Britt, K., Ashworth, A., Smalley, M.
(2007). Pregnancy and the risk of breast cancer. Endocr Relat Cancer
14: 907-933
[Abstract][Full Text]
Shakhar, K., Valdimarsdottir, H. B., Bovbjerg, D. H.
(2007). Heightened Risk of Breast Cancer Following Pregnancy: Could Lasting Systemic Immune Alterations Contribute?. Cancer Epidemiol. Biomarkers Prev.
16: 1082-1086
[Abstract][Full Text]
Largent, J. A., Capanu, M., Bernstein, L., Langholz, B., Mellemkjaer, L., Malone, K. E., Begg, C. B., Haile, R. W., Lynch, C. F., Anton-Culver, H., Wolitzer, A., Bernstein, J. L.
(2007). Reproductive History and Risk of Second Primary Breast Cancer: The WECARE Study. Cancer Epidemiol. Biomarkers Prev.
16: 906-911
[Abstract][Full Text]
Ferretti, G., Felici, A., Cognetti, F.
(2007). Pregnancy Levels of Estrogen and Progesterone: The Double-Edged Sword. Cancer Epidemiol. Biomarkers Prev.
16: 634-634
[Full Text]
Gupta, P. B., Proia, D., Cingoz, O., Weremowicz, J., Naber, S. P., Weinberg, R. A., Kuperwasser, C.
(2007). Systemic Stromal Effects of Estrogen Promote the Growth of Estrogen Receptor-Negative Cancers. Cancer Res.
67: 2062-2071
[Abstract][Full Text]
Barlow, W. E., White, E., Ballard-Barbash, R., Vacek, P. M., Titus-Ernstoff, L., Carney, P. A., Tice, J. A., Buist, D. S. M., Geller, B. M., Rosenberg, R., Yankaskas, B. C., Kerlikowske, K.
(2006). Prospective breast cancer risk prediction model for women undergoing screening mammography.. JNCI J Natl Cancer Inst
98: 1204-1214
[Abstract][Full Text]
Andrieu, N., Goldgar, D. E., Easton, D. F., Rookus, M., Brohet, R., Antoniou, A. C., Peock, S., Evans, G., Eccles, D., Douglas, F., EMBRACE, , Nogues, C., Gauthier-Villars, M., Chompret, A., GENEPSO, , Van Leeuwen, F. E., Kluijt, I., GEO-HEBON, , Benitez, J., Arver, B., Olah, E., IBCCS Collaborators Group, , Chang-Claude, J.
(2006). Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS).. JNCI J Natl Cancer Inst
98: 535-544
[Abstract][Full Text]
Gago-Dominguez, M., Castelao, J. E., Pike, M. C., Sevanian, A., Haile, R. W.
(2005). Role of Lipid Peroxidation in the Epidemiology and Prevention of Breast Cancer. Cancer Epidemiol. Biomarkers Prev.
14: 2829-2839
[Abstract][Full Text]
Cnattingius, S., Torrang, A., Ekbom, A., Granath, F., Petersson, G., Lambe, M.
(2005). Pregnancy Characteristics and Maternal Risk of Breast Cancer. JAMA
294: 2474-2480
[Abstract][Full Text]
Hill, D. A., Gilbert, E., Dores, G. M., Gospodarowicz, M., van Leeuwen, F. E., Holowaty, E., Glimelius, B., Andersson, M., Wiklund, T., Lynch, C. F., van't Veer, M., Storm, H., Pukkala, E., Stovall, M., Curtis, R. E., Allan, J. M., Boice, J. D., Travis, L. B.
(2005). Breast cancer risk following radiotherapy for Hodgkin lymphoma: modification by other risk factors. Blood
106: 3358-3365
[Abstract][Full Text]
Truong, T., Orsi, L., Dubourdieu, D., Rougier, Y., Hemon, D., Guenel, P.
(2005). Role of Goiter and of Menstrual and Reproductive Factors in Thyroid Cancer: A Population-based Case-Control Study in New Caledonia (South Pacific), a Very High Incidence Area. Am J Epidemiol
161: 1056-1065
[Abstract][Full Text]
Chavez-MacGregor, M., Elias, S. G., Onland-Moret, N. C., van der Schouw, Y. T., Van Gils, C. H., Monninkhof, E., Grobbee, D. E., Peeters, P. H.M.
(2005). Postmenopausal Breast Cancer Risk and Cumulative Number of Menstrual Cycles. Cancer Epidemiol. Biomarkers Prev.
14: 799-804
[Abstract][Full Text]
Hall, I. J., Moorman, P. G., Millikan, R. C., Newman, B.
(2005). Comparative Analysis of Breast Cancer Risk Factors among African-American Women and White Women. Am J Epidemiol
161: 40-51
[Abstract][Full Text]
Dano, H., Jacobsen, R., Hansen, K. D., Petersen, J. K., Lynge, E.
(2004). Use of census data for construction of fertility history for Danish women. Scand J Public Health
32: 435-441
[Abstract]
Brinton, L. A., Scoccia, B., Moghissi, K. S., Westhoff, C. L., Althuis, M. D., Mabie, J. E., Lamb, E. J.
(2004). Breast cancer risk associated with ovulation-stimulating drugs. Hum Reprod
19: 2005-2013
[Abstract][Full Text]
Phillips, K.-A., Milne, R. L., Friedlander, M. L., Jenkins, M. A., McCredie, M. R.E., Giles, G. G., Hopper, J. L.
(2004). Prognosis of Premenopausal Breast Cancer and Childbirth Prior to Diagnosis. JCO
22: 699-705
[Abstract][Full Text]
Foulkes, W D
(2004). BRCA1 functions as a breast stem cell regulator. J. Med. Genet.
41: 1-5
[Abstract][Full Text]
Siegelmann-Danieli, N., Tamir, A., Zohar, H., Papa, M. Z., Chetver, L. L., Gallimidi, Z., Stein, M. E., Kuten, A.
(2003). Breast Cancer in Women With Recent Exposure to Fertility Medications is Associated With Poor Prognostic Features. Ann. Surg. Oncol.
10: 1031-1038
[Abstract][Full Text]
Rookus, M. A.
(2003). RESPONSE: Re: Potential for Bias in Studies on Efficacy of Prophylactic Surgery for BRCA1 and BRCA2 Mutation Carriers. JNCI J Natl Cancer Inst
95: 1344-1344
[Full Text]
Palmer, J. R., Wise, L. A., Horton, N. J., Adams-Campbell, L. L., Rosenberg, L.
(2003). Dual Effect of Parity on Breast Cancer Risk in African-American Women. JNCI J Natl Cancer Inst
95: 478-483
[Abstract][Full Text]
Lillberg, K., Verkasalo, P. K., Kaprio, J., Teppo, L., Helenius, H., Koskenvuo, M.
(2003). Stressful Life Events and Risk of Breast Cancer in 10,808 Women: A Cohort Study. Am J Epidemiol
157: 415-423
[Abstract][Full Text]
Mann, R. J., Keri, R. A., Nilson, J. H.
(2003). Consequences of Elevated Luteinizing Hormone on Diverse Physiological Systems: Use of the LH{beta}CTP Transgenic Mouse as a Model of Ovarian Hyperstimulation-induced Pathophysiology. Recent Prog Horm Res
58: 343-375
[Abstract][Full Text]
Woo, J. C., Yu, T., Hurd, T. C.
(2003). Breast Cancer in Pregnancy: A Literature Review. Arch Surg
138: 91-98
[Abstract][Full Text]
Milliken, E. L., Ameduri, R. K., Landis, M. D., Behrooz, A., Abdul-Karim, F. W., Keri, R. A.
(2002). Ovarian Hyperstimulation by LH Leads to Mammary Gland Hyperplasia and Cancer Predisposition in Transgenic Mice. Endocrinology
143: 3671-3680
[Abstract][Full Text]
Peck, J. D., Hulka, B. S., Poole, C., Savitz, D. A., Baird, D., Richardson, B. E.
(2002). Steroid Hormone Levels during Pregnancy and Incidence of Maternal Breast Cancer. Cancer Epidemiol. Biomarkers Prev.
11: 361-368
[Abstract][Full Text]
Stevens, A., Nelson, J. L.
(2002). Maternal and Fetal Microchimerism: Implications for Human Diseases. NeoReviews
3: e11-19
[Full Text]
Wohlfahrt, J., Andersen, P. K., Mouridsen, H. T., Melbye, M.
(2001). Risk of Late-stage Breast Cancer after a Childbirth. Am J Epidemiol
153: 1079-1084
[Abstract][Full Text]
Potter, J., Ship, A. N., Love, R. R., Burstein, H. J., Winer, E. P.
(2001). Survivors of Breast Cancer. NEJM
344: 309-310
[Full Text]
Melbye, M., Wohlfahrt, J., Lei, U., Pedersen, B. N., Mouridsen, H. T., Lambe, M., Michels, K. B.
(2000). {alpha}-Fetoprotein Levels in Maternal Serum During Pregnancy and Maternal Breast Cancer Incidence. JNCI J Natl Cancer Inst
92: 1001-1005
[Abstract][Full Text]
Gertig, D. M., Stillman, I. E., Byrne, C., Spiegelman, D., Schnitt, S. J., Connolly, J. L., Colditz, G. A., Hunter, D. J.
(1999). Association of Age and Reproductive Factors with Benign Breast Tissue Composition. Cancer Epidemiol. Biomarkers Prev.
8: 873-879
[Abstract][Full Text]
Egan, K. M., Quinn, J. L., Gragoudas, E. S.
(1999). Childbearing History Associated With Improved Survival in Choroidal Melanoma. Arch Ophthalmol
117: 939-942
[Abstract][Full Text]
Kroman, N., Wohlfahrt, J., Andersen, K. W., Mouridsen, H. T, Westergaard, T., Melbye, M.
(1997). Time since childbirth and prognosis in primary breast cancer: population based study. BMJ
315: 851-855
[Abstract][Full Text]
Melbye, M., Wohlfahrt, J., Olsen, J. H., Frisch, M., Westergaard, T., Helweg-Larsen, K., Andersen, P. K.
(1997). Induced Abortion and the Risk of Breast Cancer. NEJM
336: 81-85
[Abstract][Full Text]
Rajan, J. V., Wang, M., Marquis, S. T., Chodosh, L. A.
(1996). Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. Proc. Natl. Acad. Sci. USA
93: 13078-13083
[Abstract][Full Text]
Colditz, G. A.
(1996). Postmenopausal Estrogens and Breast Cancer. Reproductive Sciences
3: 50-56
Thompson, W. D., Lambe, M., Hsieh, C.-c.
(1995). The Risk of Breast Cancer after Giving Birth. NEJM
332: 63-64
[Full Text]
Stampfer, M, Grodstein, F, Spiers, D, Posthuma, W F M, Westendorp, R G J, Vandenbroucke, J P
(1994). Cardioprotective effect of hormone replacement therapy Is not due to a selection bias. BMJ
309: 808b-809
[Full Text]