Results from this large, population-based prospective study suggest that the association between green tea consumption and breast cancer risk differed by onset age and menopausal status. Unlike black tea22
, very few studies have examined green tea drinking and breast cancer risk. All four previous case-control studies, including one conducted among Asian Americans37
and three conducted among Chinese women24,25,38
, found a significantly reduced risk of breast cancer associated with green-tea drinking. On the other hand, three cohort studies all conducted in Japan39,40
did not find a significant association with green tea drinking, with an overall RR of 0.85 (95% CI: 0.66–1.09). A recent nested case-control study conducted in Singapore also did not find an association41
. Thus, the results from previous studies on green tea and breast cancer risk have been inconsistent.
Our observations of differing associations between green-tea drinking and breast cancer by menopausal status and age of onset may provide one possible explanation for the inconsistencies reported in previous studies. It is possible that overall RRs associated with tea consumption derived from cohort studies may be influenced by the proportion of postmenopausal women at baseline as well as factors related to age of onset, such as average age tea drinking began, average age at baseline, and length of follow-up years. For example, in the pooled analysis of two cohort studies conducted in Japan, the combined RR was 0.84 (95% CI: 0.57–1.24)(≥5 cups daily vs. <1 cup daily)40
. Cohort 1 was substantially older at baseline and more postmenopausal than Cohort 240
. The RR (95%CI) was 1.17 (0.67–2.05) for the Cohort 1 whereas the corresponding RR (95%CI) was 0.61 (0.36–1.06) for the Cohort 2. In addition, two Japanese studies of breast cancer recurrence may also provide some indirect support. The first Japanese study42
found that an increased green tea consumption was associated with fewer axillary lymph node metastases among premenopausal stage I and II breast cancer patients. In the first and the second Japanese survival cohorts42,43
, green tea drinking was also associated with decreased recurrence of stage I and II breast cancer. These findings indicate that instead of totally eliminating cancer initiation, green tea may primarily delay cancer progression. Therefore, it will be very interesting to examine whether green tea drinking may delay or prevent breast cancer recurrence in further studies.
Another interesting observation is that previous case-control studies are more likely to find an inverse association or a stronger inverse association than cohort studies22
. Although the difference could be due to recall bias in case-control studies, recall bias on tea drinking habits is considered to be less serious than dietary factors. Also, in a case-control setting, every eligible case from all age groups in the target population is recruited in a very short period of time. Thus, follow-up time is not relevant in the estimation of overall OR in the case-control study. In this regard, the association estimates from case-control and cohort design could be different. The Shanghai Breast Cancer Study (SBCS) is a large-scale population-based case-control study conducted in urban Shanghai where the SWHS is being conducted. We also found in the SBCS that drinking green tea was weakly, but significantly, related to a reduced breast cancer risk 24
We found log-log survival curves for green tea drinkers and non-drinkers cross over around menopausal age. The exact mechanism is still unclear and the following is one possible interpretation. Among premenopausal women, estrogens are converted from androgens mainly via aromatase in ovary although they are also through aromatase in fat tissues in a small amount; whereas among postmenopausal women this process is predominantly dependent on aromatase distributed in fat tissues. As a result, levels of estrogen are much higher in premenopausal women than postmenopausal women. It is conceivable that tea drinking may be more potent among premenopausal women in decreasing estrogen levels compared to that among postmenopausal women. As a result, a larger reduction in risk associated with drinking tea would be expected among premenopausal women than among postmenopausal women. In the current study, age of breast cancer onset was significantly later for breast cancer patients who drank green tea than for those who did not, among premenopausal women who began drinking tea and were diagnosed with breast cancer before menopause, and among postmenopausal women who both began drinking tea and were diagnosed with breast cancer after menopause. On the other hand, we found that among postmenopausal breast cancer patients, green tea drinkers who started before menopause had comparable age of onset to the nondrinkers. One possible explanation for the findings is that, for breast cancer patients who drank green tea before menopause, the effect of green tea drinking may be primarily through delaying the onset from before menopause to after menopause. In other words, some of the breast cancer patients diagnosed after menopause would have had breast cancer before menopause if they had not been drinking green tea before menopause. This may explain why green tea drinking was associated with an increased risk of postmenopausal breast cancer for those who started tea drinking before menopause (Data not shown). However, the detailed mechanisms remain unclear. We are conducting further biomarker studies to explore other possible explanations.
Other than polyphenols, many other tea components, such as caffeine, may also possess chemopreventive effects. However, very few women in our study population drank coffee regularly whereas tea contains much lower caffeine than coffee6,26,27
Our study has several strengths. These include a population-based prospective design, large sample size, and high rates for baseline participation and follow-up, which minimize potential differential recall bias or selection bias inherent to many case-control studies. We have also specifically designed a questionnaire to capture the amount of tea consumption and lifetime duration patterns. The dose-response relationship between urinary excretion of epigallocatechin and amount of consumed tea leaves indicates tea consumption information is valid. In addition, the study population has a unique exposure pattern; 98.2% of tea drinkers are green tea drinkers and thus black tea drinkers were excluded from the analysis. We adjusted for many potential confounding factors. However, we cannot totally exclude the possibility that some unknown residual confounding may still remain.
Future studies are necessary to confirm our finding. Our hypothesis, if confirmed, may help in the understanding of the mechanism for tea and other chemopreventive agents when they only delay the onset of cancer.