In this prospective cohort study, we did not find any significant association between total dairy consumption and risk of pre- or postmenopausal breast cancer. However, there was a tendency of an inverse association for some dairy products, particularly for premenopausal breast cancer. Total calcium intake was inversely related to breast cancer, whereas no association was seen for fat from milk.
Previous studies on dairy consumption and risk of breast cancer have been inconclusive; overall there does not seem to be a strong association either for total dairy consumption or for specific dairy items [4
]. In the present study, we saw a 50% decreased risk for premenopausal breast cancer among women consuming 25 g of white cheese per day compared to women consuming less than 6 g/day. However, we found no dose–response relationship. In the analysis corrected for measurement errors an increase of 5 g cheese decreased the risk with 24%. Four previous cohort studies [12
] and a pooled analysis of eight cohort studies [10
] did not find any significant association between cheese consumption and breast cancer risk (pre and post), whereas in a study of Seventh-day Adventists there was a positive trend with increasing frequency of cheese consumption [15
]. Also, the results from case–control studies have been conflicting [4
White cheese can be a good source for calcium. The most used white cheeses in Norway typically contain about 800 mg calcium/100 g, and cheese contributes 28% of the calcium intake [27
]. In the present study we saw a negative association between pre- and postmenopausal breast cancer risk and calcium intake. Calcium intake has been inversely related to risk of breast cancer in some prospective studies [12
], although not in all [20
]. In two prospective studies among US women and in a small French study, calcium intake was inversely related to premenopausal breast cancer, but not to postmenopausal breast cancer [21
]. In a Swedish prospective study, pre-diagnostic calcium serum levels were inversely related to premenopausal breast cancer in a dose–response manner, whereas a high level of calcium indicated an increased risk among overweight peri/postmenopausal women [45
]. Further, the Women’s Health Initiative randomized trial did not find any reduced incidence of breast cancer among postmenopausal women who had been given calcium and vitamin D supplementation for 7 years [46
]. The possibility that any beneficial effect of calcium is modified by menopausal status is in accordance with our finding of a somewhat stronger association for premenopausal than for postmenopausal breast cancer.
Calcium may exercise its anticarcinogenic properties through several mechanisms. In experimental studies increased concentration of calcium decreases cell proliferation and induces differentiation of mammary cells [3
]. It may bind and neutralize fatty acids and mutagenic bile acids [6
] and may also decrease fat-induced epithelial hyperproliferation in rodent mammary glands [47
]. Metabolically calcium is closely related to vitamin D, which also has been shown to influence breast carcinogenesis, and it has been hypothesized that some of the anticarcinogenic effect of calcium may be mediated through vitamin D [3
]. For instance, calcium may play an important role in 1,25(OH)2D3 induced apoptosis [48
]. In Norway, dairy products were not fortified with vitamin D at the time of data collection, and the correlation between calcium intake and vitamin D intake in the present cohort was not very strong (Pearson’s r
In our previous analysis of milk consumption and premenopausal breast cancer, we found an inverse association between the combined consumption of milk as a child and as an adult and breast cancer [25
]. No such association was seen in the present study. Also, our previous analysis showed a significant inverse trend between milk consumption as a child and breast cancer incidence restricted to women younger than 40 years at baseline. In the present study, the youngest women were 41 years at baseline. Childhood dairy intake was not associated with development of breast cancer in a 65-year follow-up of the British Boyd Orr cohort [49
], nor was childhood or adolescent consumption of milk or dairy products consistently significantly associated with breast cancer in several studies from North America [21
]. However, indications of a negative association have been reported in two case–control studies [54
Our finding that any weak protective effect of some dairy products and of calcium may be stronger or limited to premenopausal breast cancer is in accordance with previous studies [21
]. The mechanism for this difference is not clear. One hypothesis is that it may be due to the decreased level of insulin growth factors with increasing age, which interact with calcium in promoting growth inhibition in breast cancer cells [5
]. Another suggestion points to calcium’s potential as a regulator in estrogen-driven cell proliferation [56
The strengths of our study are the population-based and prospective design, the large size of the cohort, the complete follow-up with regard to incidence of cancer, death, and emigration, the almost complete histological verification of breast cancer cases, and the opportunity to adjust for all established risk factors for breast cancer. Several questions were asked about dairy consumption and calcium intake was calculated from about 80 semi-quantitative food frequency questions. As dietary data are prone to measurement errors we performed additional analyses correcting the risk estimates for errors by using data from a validation study performed in a subsample of the cohort subjects [28
]. As mentioned, the measurement error corrections did not alter the initial findings much. This may be taken as an indication of robustness toward effects of measurement errors.
Possible limitations of our study should also be considered. We did not have access to repeated exposure measures and to information on calcium supplement use, and most non-dietary exposure variables were self-reported for which we do not know the validity, except for menopausal status and use of HRT [39
We used the linear regression calibration method to adjust for measurement error. This method relies on some assumptions about the structure of possible errors in the reference instrument (the recalls). These errors should be random and independent of both true values and of the errors in the questionnaire. These assumptions may or may not be met in our case. In particular, studies have shown that this last assumption may be doubtful [57
]. This means that our method may not be able to fully correct for measurement error. However, we believe that using this instrument and method is our best option to at least gain some insight into the effects of measurement error in these studies.
In summary, in this prospective, population-based study, we found a non-significant inverse association between calcium consumption and risk of breast cancer. Total dairy, adult and childhood milk consumption was not associated with breast cancer risk, whereas a reduced risk was seen for women with the highest consumption of white cheese. The results seem to be robust against effects of measurement error. To confirm any potential protective effect of calcium and/or specific dairy products, more well-designed prospective studies are needed. The protective potential may be largest for premenopausal breast cancer.