RE: "BREASTFEEDING AND REDUCED RISK OF BREAST CANCER IN AN ICELANDIC COHORT STUDY"

David B. Thomas, Karin A. Rosenblatt and Roberta M. Ray

Fred Hutchinson Cancer Research Center Seattle, WA 98109

In the abstract of their paper, "Breastfeeding and Reduced Risk of Breast Cancer in an Icelandic Cohort Study," Tryggvadóttir et al. (1Go) stated that their study was the first cohort study to indicate a negative association between breastfeeding and breast cancer. In fact, it is the second such study. Approximately 1 year ago, we published results from a cohort study carried out in Shanghai, China (2Go). Although our study and the Icelandic study both provided evidence for a protective effect of lactation against breast cancer, our study showed a reduced risk only among women who had lactated for more than 3 years, as compared with Tryggvadóttir et al.'s report of a reduced risk even in women who had lactated for just a few weeks. Given this difference, we would like to point out a possible source of bias that could have resulted in spuriously low relative risk estimates in women who had lactated for a short time in Iceland.

As the authors noted in their Discussion (1Go), women who did not breastfeed may have had medical problems that might have been related to an increased risk of breast cancer. In fact, their own data suggest that this was true. Based on the numbers of cases and controls shown in their table 2 (1Go, p. 39), the crude relative risk of breast cancer in women who had lactated for 1–4 weeks was 0.39 in comparison with women who had never lactated. It is unlikely that breastfeeding for less than 1 month would reduce risk of breast cancer by over 60 percent. It therefore seems both unwise and statistically dubious to have combined into a single reference group the women who lactated for 1–4 weeks and the women who did not breastfeed at all. If one assumed that the women who lactated for 1–4 weeks were not at unusual risk of breast cancer and used them as the reference group, the odds ratios shown in table 2 would be increased by approximately 25 percent (varying from 24 percent to 34 percent, by our crude calculations), and all estimates but the one for women who breastfed for more than 105 weeks (2 years) would probably have 95 percent confidence intervals that included 1.0. This would make the results of Tryggvadóttir et al.'s study fairly compatible with our own. It would also render the results compatible with those of two other cohort studies (3Go, 4Go) that did not show evidence for a protective effect of lactation but included few women with prolonged breastfeeding. The authors stated that their results were strongest for women under age 40 years (1Go). Our study contained too few women under 40 who had lactated for a prolonged time to allow us to estimate risk in relation to breastfeeding in this group separately. However, we did show that risk related to long-term breastfeeding was reduced among women who had gone through menopause (2Go). Given the above concern and the fact that statistical tests for interactions between breastfeeding and age were not statistically significant in the Iceland data, we do not believe that there is strong evidence for restriction of any effect of breastfeeding to young women.


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TABLE 2. Effect of lifetime duration of breastfeeding on risk of breast cancer among parous women, according to age at diagnosis, in comparison with women who had lactated for 1–4 weeks,* Iceland, 1979–1995

 
In summary, the preponderance of the evidence from all cohort studies, including the Iceland study, suggests that breastfeeding for up to 2 or 3 years does not provide protection against breast cancer but that more prolonged lactation might.

REFERENCES

  1. Tryggvadóttir L, Tulinius H, Eyfjord JE, et al. Breastfeeding and reduced risk of breast cancer in an Icelandic cohort study. Am J Epidemiol 2001;154:37–42.[Abstract/Free Full Text]
  2. Rosenblatt KA, Gao DL, Ray RM, et al. Re: "History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature." (Letter). J Natl Cancer Inst 2000;92:942.[Free Full Text]
  3. Kvale G, Heuch I. Lactation and cancer risk: is there a relation specific to breast cancer? J Epidemiol Community Health 1987;42:30–7.[Abstract]
  4. Michels KB, Willett WC, Rosner BA, et al. Prospective assessment of breastfeeding and breast cancer incidence among 89,887 women. Lancet 1996;347:431–6.[ISI][Medline]

 

THE AUTHORS REPLY

Laufey Tryggvadóttir, Trausti Sigurvinsson, Hrafn Tulinius and Jórunn E. Eyfjord

Epidemiological Unit Icelandic Cancer Society Skogarhlid 8 Reykjavik, Iceland
Icelandic Cancer Registry Icelandic Cancer Society Skogarhlid 8 Reykjavik, Iceland
Molecular and Cell Biology Laboratory Icelandic Cancer Society Skogarhlid 8 Reykjavik, Iceland

We thank Thomas et al. (1Go) for their comments on our study (2Go). By a strange coincidence, their report on the third cohort study ever to assess the relation between breastfeeding and breast cancer was published only a month after the text of our paper was completed. This explains our failure to refer to the study by Rosenblatt et al. (3Go). We finished writing our text in May 2000 (the article was submitted to the American Journal of Epidemiology in July 2000), and in June 2000 Rosenblatt et al. published their preliminary results (3Go). We appreciate this opportunity to acknowledge that their study was indeed the first cohort study to indicate a negative association between breastfeeding and breast cancer, and ours was the second.

We do not agree with Thomas et al. that the small group of parous women who had never breastfed should have been excluded from the reference category, even though this is certainly a matter of concern. We based our decision not to exclude this group on the following. First, the exclusion of the 24 cases and 66 controls who had never lactated had little effect on results in the analysis with duration of breastfeeding entered as a continuous variable. This can be seen when one compares the present table 1 (below) with the published table 3 from our paper (2Go, p. 39). Second, even though we did point out in the Discussion that selection bias could explain the increased risk in the group of parous women who had never lactated, the possibility remains that the increased risk is real. That would be so if any lactation, even of very short duration, were protective in comparison with totally suppressing the physiologic function of breasts that are prepared for breastfeeding.


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TABLE 1. Multivariate analysis* of breast cancer risk among parous women with increasing duration of breastfeeding (per 6 months), by age at diagnosis, after exclusion of women who had never lactated, Iceland, 1979–1995

 
When duration of breastfeeding is entered as a categorical variable and is not grouped by age at diagnosis (see the present table 2), the exclusion of women who have never lactated has the effect postulated by Thomas et al. (1Go). Here, the inverse association between lactation and breast cancer is not statistically significant for durations under 2 years. However, as is also shown in the present table 2, when the analysis is restricted to women diagnosed at less than 40 years of age, the association is statistically significant, even for relatively short durations of lactation.

In summary, removing the group in question from the comparison category does not have much impact on the results when the exposure variable is entered as a continuous variable, whereas when duration of lactation is categorized, the lowering of risk associated with durations of less than 2 years is not statistically significant in the overall study group. However, in a separate analysis of women diagnosed before age 40 years, the inverse association suggesting a protective effect of breastfeeding is statistically significant, even for short durations.

Therefore, we reiterate our former conclusion that, based on our data, the inverse association between lactation and breast cancer risk appears to be stronger in women diagnosed before age 40 than in women diagnosed at ages over 39 years. The separate analyses of the younger group indicated this, even though the interaction term between duration of breastfeeding and age at diagnosis was only close to statistical significance (p = 0.08) (2Go). We are not stating that the effect is restricted to the younger group but rather that the effect in this group is stronger and easier to detect.

REFERENCES

  1. Thomas DB, Rosenblatt KA, Ray RM. Re: "Breastfeeding and reduced risk of breast cancer in an Icelandic cohort study." (Letter). Am J Epidemiol 2001;154:975–6.[Free Full Text]
  2. Tryggvadóttir L, Tulinius H, Eyfjord JE, et al. Breastfeeding and reduced risk of breast cancer in an Icelandic cohort study. Am J Epidemiol 2001;154:37–42.[Abstract/Free Full Text]
  3. Rosenblatt KA, Li Gao D, Ray RM, et al. Re: "History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature." (Letter). J Natl Cancer Inst 2000;92:942.[Free Full Text]