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diseases. Additionally, we know from epidemiological studies that high socioeconomic status correlates with a higher incidence of these inflammatory diseases,2 probably owing to lower antigen exposure. In the study by Sears and colleagues, children were significantly more likely to be breastfed than formula-fed if they were born to parents of higher socioeconomic status. This factor is probably important in the discussion of why breastfed children have a higher incidence of asthma later in life, since one could speculate that antigen exposure is lower in this group. Furthermore, children born into a higher socioeconomic class probably have better access to health-care facilities, resulting in their being prescribed more antibiotics. Prescription of antibiotics in the first year of life is associated with a higher incidence of asthma.3 Sears and colleagues speculate that breastfeeding, which is associated with a Bifidobacterium/Lactobacillus-dominant intestinal flora, might reduce the effect of bacteria and endotoxins on the immune system. However, experimental and clinical studies suggest that such an intestinal flora is associated with reduced incidence of atopy.4 In summary, the higher incidence of asthma in the breastfed group in this population could be associated with lower antigen exposure and increased antibiotic consumption in the higher socioeconomic class. Therefore, it would be interesting to study the differences in antigen exposure and the use of antibiotics in the different socioeconomic classes. Reduced early antigen exposures and alterations in intestinal flora are said to be important environmental factors associated with the steady rise in the incidence of allergic and autoimmune diseases in developed countries.
Jaap Jan Boelens
Leiden University Medical Center, Department of Paediatrics: J6-Q-208, PO Box 9600, 2300 RC Leiden, Netherlands (e-mail: Boelensjj@yahoo.com) 1 Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360: 90107. Stewert AW, Mitchel EA, Pearce N, Strachan DP, Weilandon SK. The relationship of per capita gross national product to the prevalence of symptoms of asthma and other atopic diseases in children (ISAAC). Int J Epidemiol 2001; 30: 17379. Droste JHJ, Wieringa MH, Weyler JJ, Nelen VJ, Vermeire PA, Van Bever HP. Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease? Clin Exp Allergy 2000; 30: 154753. Bjorksten B, Sepp E, Julge K, Voor T,

Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001; 108: 51620.

Authors reply
SirThe duration of breastfeeding was recorded by interviewers when these 1037 children were first recruited into the longitudinal study at age 3 years. At age 9 years, we reviewed books maintained through the New Zealand Plunket Nurse Program in which infants were assessed through regular home and clinic visits through the first year. These recorded the introduction of cows milk and complementary feeding, allowing us to analyse the effects of exclusive breastfeeding among the 815 children seen at age 9 years. These were briefly reported in our paper, but more detail is provided below. These analyses confirm more atopy and asthma among breastfed children compared with those not breastfed, but some of the trends are not significant because of smaller numbers. There is no evidence in our study that exclusive breastfeeding, even to 24 weeks, provided protection against atopy and asthma, compared with those not breastfed. We selected a 4-week cutpoint because preliminary analyses in 70 children who discontinued breastfeeding before 4 weeks yielded outcomes very similar to those not breastfed at all, and different to those breastfed for longer than 4 weeks. If we compare outcomes in children breastfed for any duration with those never breastfed, as Renaud Becquet and colleagues request, and as shown in the table below, the findings are essentially unchanged. Exposure to cows milk formula in the maternity hospital was almost universal in the 1970s. If exposure A increases risk and exposure B decreases risk, then an admixture of A and B would reduce the effect of either exposure. We have identified an increased risk of atopy and asthma
Never breastfed Cat allergy at 13 years House dust mite allergy at 13 Any atopy at 13 Cat allergy at 21 House dust mite allergy at 21 Any atopy at 21 Asthma ever by 9 Asthma current at 9
*p<005. p<001.

in association with exposure to breast milk, and so addition of cows milk would reduce the effect of that exposure rather than increase it as the correspondents suggest. We do not state that breastfeeding is contraindicated, and indeed have advocated continuation of breastfeeding for its many benefits. Our study simply removes protection against atopy and asthma from the list of reasons why breastfeeding is beneficial to children, and confirms the findings of another cohort study.1 There is increasing support for the hygiene hypothesis as an explanation for the increase in asthma and allergies in recent decades.2 If increased breastfeeding reduced childhood infections because of better immune protection, deviation of cytokine responses from Th1 dominance to Th2 dominance could explain the increase in allergy and consequently in allergic asthma. Before formula feeding became popular, childhood infection rates were higher than at present, and this might have reduced asthma prevalence rates. Breastfeeding has increased in recent years, but the risk of infections has not, and so a relation between increased breastfeeding and increased allergy seems possible via the hygiene hypothesis. The relation between breastfeeding and atopy or asthma is unlikely to be a direct causal one, because there was no dose-response effect with respect to duration of breastfeeding (see table 3 in the original paper) or duration of exclusive breastfeeding (see current table).
*M R Sears, D R Taylor, J M Greene, R Poulton, G P Herbison
*Firestone Institute for Respiratory Health, St Josephs Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada (MRS); Department of Medicine, McMaster University, Hamilton, Ontario, Canada (JMG); and Departments of Medicine (RP), Preventive and Social Medicine (DRT), and Dunedin Multidisciplinary Health and Development Research Unit (GPH), University of Otago, Dunedin, New Zealand (e-mail: searsm@mcmaster.ca)

Breastfed exclusively 4 weeks 12 weeks 51/289 (177%) 98/289 (339%)* 28/177 (158%)* 58/177 (328%)

24 weeks 10/53 (189%)* 16/53 (302%)

38/389 (98%) 105/389 (270%) 154/389 (396%) 113/464 (244%) 242/464 (522%) 287/464 (619%) 32/457 (70%) 24/457 (53%)

151/289 (523%) 89/177 (503%)* 25/53 (472%) 97/306 (317%)* 54/192 (281%) 13/56 (232%) 190/306(621%) 114/192 (594%) 34/56 (607%) 218/306 (712%) 135/192 (703%)* 40/56 (714%) 40/338 (118%)* 21/212 (99%) 8/67 (119%) 36/338 (107%) 17/212 (80%) 5/67 (75%)

Prevalence of atopy and asthma in children exclusively breastfed for different durations, compared with those never breastfed

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CORRESPONDENCE

Wright AL, Holberg CJ, Taussig LM, Martinez FD. Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood. Thorax 2001; 56: 19297. Von Mutius E. Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence. Eur Respir J 2001; 18: 87281.

Number of cases Months of breastfeeding (median) Never (0) 6 (3) 718 (12) 1930 (24) 3154 (37) 55 (70) Relative risk per 12 months 98 273 391 151 69 7 ..

Relative risk (95% CI)* 1 (reference) 099 (079125) 095 (076120) 094 (071123) 089 (062128) 050 (021123) 095 (087103)

*Based on Poisson regression analysis, adjusted for age (5-year groups), birth cohort (5-year groups), urban/ rural residence, parity (1, 2, . . .6, 7+), and age at first birth (19, 2024, 2529, 3034, 35 years).

Breast cancer and breastfeeding

SirIn referring to the worldwide epidemiological data on breast cancer and breastfeeding, the Collaborative Group on Hormonal Factors in Breast Cancer (July 20, p 187)1 list the ten studies that are not included in the combined analysis. We were surprised to notice that the first report from a cohort study, published by our group 14 years ago,2 was not referred to. Our cohort included women in three counties in Norway, born in 18861928 and living mostly in rural areas, largely reflecting breastfeeding habits different from those seen later. The mean total period of breastfeeding in parous women was 166 months (SD 160 months). Our original follow-up included diagnoses recorded at the Cancer Registry of Norway in 196180. We have now done statistical analyses covering the complete period 196198. Among 46 503 parous women with information on breastfeeding and age at first birth, 2184 cases of breast cancer occurred. Since associations between breast cancer and breastfeeding can depend on age at diagnosis,3 our analysis was subdivided according to attained age. Relative risk estimates in the middle age interval 5069 years (989 cases; table) showed a moderate inverse relation. For women younger than 50 years (199 cases), the relative risk estimate per 12 months of breastfeeding was 106 (95% CI 085131) and for women 70 years of age or older (996 cases), the estimate was 104 (097112). Our estimate represents a reduction in relative risk of 54% for every 12 months of breastfeeding in the past among women aged 5069 years, which is consistent with the overall 43% reduction seen in the collaborative study.1 For women younger than 50 years, our risk estimate did not represent an inverse relation, but confidence limits were wide. By contrast, the confidence limits for women 70 years of age or older could be compatible with a protective effect of breastfeeding,

Relative risk of breast cancer according to total duration of breastfeeding among parous women aged 5069 years

which has mostly disappeared some time after the lactation period.4 Another possibility is that prolonged breastfeeding simply delays the occurrence of breast cancer in younger women.3 Few age-specific results were given in the collaborative study,1 although relative risk estimates were similar for women younger than 50 years and 50 years or older. With a mean age at diagnosis of 501 years, the age distribution cannot be fully representative of an ordinary population of breast cancer patients. Whether the data indicate an attenuation of the protective effect of breastfeeding in older women would still be interesting to know. This information could have major implications for the estimated reduction in cumulative breast cancer incidence,1 which might be achieved by adopting other breastfeeding patterns in developed countries.
*Ivar Heuch, Bjarne K Jacobsen, Gunnar Kvle
*Department of Mathematics, University of Bergen, N-5008 Bergen, Norway (IH); Institute of Community Medicine, University of Troms, Troms, Norway (BKJ); and Center for International Health, University of Bergen, Bergen, Norway (GK) (e-mail: heuch@mi.uib.no) 1 Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50 302 women with breast cancer and 96 973 women without the disease. Lancet 2002; 360: 18795. Kvle G, Heuch I. Lactation and cancer risk: is there a relation specific to breast cancer? J Epidemiol Community Health 1988; 42: 3037. Lipworth L, Bailey LR, Trichopoulos D. History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature. J Natl Cancer Inst 2000; 92: 30212. Tryggvadottir L, Tulinius H, Eyfjord JE, Sigurvinsson T. Breastfeeding and reduced risk of breast cancer in an Icelandic cohort study. Am J Epidemiol 2001; 154: 3742.

SirThe meta-analysis by the Collaborative Group on Hormonal Factors in Breast Cancer1 represents assessment of the effect of breastfeeding on breast cancer incidence to the best

level of evidence achievable. However, this evidence alone is not sufficient to guide clinical practice. Breast cancer is not only of great public health significance, it is also a disease that affects an organ with powerful symbolic and emotional connotations related to feminity, sexuality, and maternity.2 Breastfeeding has important personal and cultural meanings. Women should have the right to decide if, when, and for how long they will breastfeed their children. This principle of autonomy requires adequate information. This article provides relevant scientific data on the association between breastfeeding and reduced breast cancer risk, which should be provided to all women. However, it does not follow that women must breastfeed, and the beneficial effect should be presented cautiously. Every physician involved in breast cancer management has faced women who wonder whether they are to blame for their breast cancer because they did not breastfeed,3 or women who say I dont understand, I have three children and breastfed all of them. The message in this paper should not be oversimplified to suggest total protection; the use of a phrase such as risk reduction or risk mitigation might better convey the papers main finding, in a similar manner to the cautious wording suggested by the US Food and Drug Administration (FDA) for tamoxifen.4 This approach is particularly important for women at increased risk, who may derive less benefit from breastfeeding; indeed, the meta-analysis found a smaller effect for women with a mother or a sister with breast cancer. From the same perspective, the striking effect suggested by stating that breast cancer would be reduced by more than half, while accurate, is a misleading way to present the data to women considering whether or not to breastfeed. An alternative way to present results would be to note that among 1000 women who breastfeed their children, 937 will have no benefit in terms of breast cancer risk reduction because they would never have

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