Breast cancer remains the most commonly diagnosed non-skin cancer in both Caucasian and African American (AA) women in the US (1, 2). Meat consumption in the US has been rising (3), but the impact on breast cancer is inconclusive (4–13), although the evidence is largely based on data from Caucasian women. Nevertheless, due to strong evidence linking red and processed meats to other cancers such as colorectal cancer (14–17), the World Cancer Research Fund and American Institute for Cancer Research recommends limiting red meat intake to less than 500 g/week (18 oz) with very little if any to be processed (14).

Although the overall incidence of breast cancer is higher in Caucasian women, AA women are more likely to be diagnosed at younger ages and present with tumors with more aggressive characteristics, with high grade, lack of expression of estrogen receptor (ER), and basal-like phenotypes (2, 18–20). Despite these disparities, a recent review (21) that summarized the evidence on food, nutrition, and physical activity and breast cancer risk in AA women found no studies on any foods of animal origin and breast cancer risk in AA women. In parallel, there are clear racial differences in red meat and poultry consumption patterns with NHANES data showing higher mean consumption of red meat and poultry in AA compared to Caucasian women (22). The relevance of red meat and poultry consumption to carcinogenesis involves cooking meat at high temperatures and the exposure to heterocyclic amines (HCAs), nitrosamines, saturated fat, and heme iron (14, 23–25).

Most epidemiological evidence supports a positive association between degrees of meat doneness and risk of human cancers (24). A greater proportion of AA also report grilling or barbequing hamburgers and beefsteak than Caucasians in the US based on data adapted from FDA/USDA Consumer Food Safety Surveys (26), which elevates the need to investigate the relationship between meat and breast cancer in a large sample of AA women. We evaluated the role of red meat and poultry intake and breast cancer risk in the Women’s Circle of Health Study, a case-control study based in New Jersey (NJ) and New York (NY). This is one of the first studies to examine this association in AA women, and the first study to report findings stratified by race.

The distribution of demographic and socio-economic characteristics as well as potential risk factors for breast cancer in the entire study population, stratified by race is summarized in Table 1. Overall, Caucasian women tended to have higher education and were less likely to be obese than AA women. As compared to AA and Caucasian controls, both AA and Caucasian cases were more likely to have ever used HRT, have a history of benign breast disease, and family history of breast cancer. Consistent with the literature, a higher percentage of AA cases were diagnosed at stage 2 or higher and with ER negative tumors. Unprocessed red meat intake was higher in Caucasian than in AA women while the opposite was true for processed meat and poultry consumption.

Tables 2 and 3 show associations between meat consumption and breast cancer risk among Caucasian women, also stratified by menopausal status and ER status. Among Caucasian women overall, consuming processed meat appeared to increase breast cancer risk, when comparing the highest quartile to the lowest (OR=1.48; 95% CI: 1.07–2.04). Similar associations were noted for unprocessed red meat (OR=1.40; 95% CI: 1.01–1.94) and poultry consumption (OR=1.42; 95% CI: 1.01–1.99), although a significant linear trend was only noted for poultry intake (p trend=0.04). Associations with consumption of processed meat were stronger among postmenopausal Caucasian women (OR=1.74; 95% CI: 1.06–2.87) while among premenopausal women, risk was significantly increased with higher unprocessed red meat (OR=1.66; 95% CI: 1.05–2.64) and poultry intakes (OR=2.33; 95% CI: 1.44–3.77). However, significant heterogeneity in odds ratios across menopausal status was only observed for associations with poultry intake (p for heterogeneity=0.03).

When stratifying by ER status among Caucasian women (Table 3), there were no marked differences in risk associated with consumption of red meat although a significant association was observed for increased risk of ER positive tumors (OR=1.51; 95% CI: 1.02–2.24), with a significant linear trend (p=0.03). The magnitude of associations with processed meat were stronger for ER negative tumors (OR=1.89; 95% CI: 1.00–3.57), while consuming unprocessed red meat in the highest quartile increased risk of ER positive tumors (OR=1.64; 95% CI: 1.10– 2.43), but numbers in these cells were relatively small and tests for heterogeneity of odds ratios across the two ER groups were not significant. Although there were no associations between poultry intake and ER positive breast cancer, higher consumption was significantly associated with risk of ER negative tumors (OR=2.55; 95% CI: 1.29–5.03, p trend=0.01), with a statistically significant p for heterogeneity (p=0.02). In case-only analyses, the increased risk of ER negative tumors associated with poultry intake in the highest quartile remained (OR=2.22; 95% CI: 1.07– 4.61).

Similar analyses for AA women are shown in Tables 4 and 5. In contrast to results observed in Caucasian women, there was no clear evidence of an association between red meat, poultry, and breast cancer risk in AA women overall or when stratified by menopausal status. When evaluating by ER status (Table 5) or in case-only analyses in AA women, there were no significant associations observed except for a borderline increase in risk of ER positive tumors associated with consuming processed meat (OR for quartile 4 vs. 1=1.36; 95% CI: 0.94–1.97) and a significant linear trend (p trend=0.04). None of the tests for heterogeneity of odds ratios were statistically significant.

Overall tests for heterogeneity to assess difference in odds ratios by race resulted in p values of 0.11 for total red meat, 0.39 for processed meat, 0.08 for unprocessed red meat, and 0.27 for poultry (data not shown). Mutual adjustment of processed meat, unprocessed red meat, and poultry did not meaningfully change odds ratios (data not shown). Adjusting for fruit and vegetable intake did not alter any of the associations observed or direction of OR, with the only notable change being an attenuation of OR for processed meat in Caucasian postmenopausal women (OR=1.54; 95% CI: 0.94–2.53), and for total red meat among all Caucasian women (OR=1.29; 95% CI: 0.93–1.81). None of the results from sensitivity analyses altered study conclusions.

In this case-control study involving a large sample of AA and Caucasian women, a positive association between intake of processed and unprocessed red meat, poultry and breast cancer risk was limited to Caucasian women. To our knowledge, this is the first investigation of these foods and breast cancer risk in a study of both AA and Caucasian women with evaluation by menopause as well as ER status. Consumption of processed meat in the highest quartile appeared to be more strongly associated with postmenopausal breast cancer while unprocessed red meat and poultry were strongly associated with premenopausal breast cancer in Caucasian women, but odds ratios across menopausal status were significantly different only for poultry intake. Similarly, poultry consumption appeared particularly harmful for ER negative tumors among Caucasian women. Red meat intake in both processed and unprocessed forms increased breast cancer risk in Caucasian women regardless of hormone receptor status, albeit not all risk estimates reached statistical significance. Among AA women, there was no strong evidence relating red meat and poultry intake to breast cancer risk except for a significant positive linear trend between consuming processed meat and ER positive tumors.

Results from past studies that have investigated the impact of red and processed meats on breast cancer risk are inconsistent and have largely involved only Caucasian women. No significant association between consumption of total meat, red meat and breast cancer risk was observed in the Pooling Project (9) or in the EPIC cohort (10) for red and processed meat. In contrast, increased breast cancer risks associated with consumption of processed meat (6, 11, 12), red meat (11, 12, 32), or total red meat combining both processed and unprocessed meat (5) have been observed, similar to findings in Caucasian women in our study. Among AA women, the null findings are consistent with the only other study on this topic, the Black Women’s Health Study (33), which also found no association between any meat type and breast cancer risk in AA women even when stratified by menopausal and hormone receptor status. However, in our study, a significant linear trend was observed for consumption of processed meat and ER positive tumors among AA women, but the odds ratios were not significantly different by hormone receptor status.

Racial differences in the association between diet and cancer risk have been observed for other cancer sites. For example, a high fat/meat/potatoes pattern appeared to increase risk of rectal cancer only in Caucasians and not in AA despite the pattern being observed in both race groups (34). A fruit-vegetable pattern was significantly associated with reduced colon cancer risk only in Caucasians in the North Carolina Colon Cancer Study (35). In our study, the overall test for heterogeneity by race was borderline significant only for fresh red meat intake (p=0.08) despite stronger associations in Caucasian women for red meat and poultry consumption. Hence, further evaluation by menopausal and hormone receptor status was conducted.

It has been postulated that similar to risk factors such as adiposity, diet in early life may have a different impact on breast cancer risk than diet in later ages; thus indicating potential modification of risks by menopausal status (36). A meta-analysis (37) of 10 studies that investigated the impact of red meat consumption and breast cancer risk focusing on premenopausal women observed a summary relative risk of 1.24 (95% CI: 1.08–1.42). In our study, although risk estimates for processed meat were stronger in postmenopausal Caucasian women, in general, associations for total red meat were similar in pre and postmenopausal Caucasian women, which was also confirmed by tests of heterogeneity. This is consistent with findings from the UK Women’s Cohort Study (12) that reported highest risk for highest red meat eaters (processed and unprocessed) in both pre- and postmenopausal groups, with stronger estimates in postmenopausal women, in addition to a Canadian study reporting an elevated breast cancer risk among postmenopausal women with consumption of total meat and processed meat (38).

Further research has been proposed to also investigate the association between consumption of red meat and breast cancer specifically stratified by hormone receptor status (4, 39). Previous studies that evaluated all red meat intake and breast cancer risk stratified by receptor status have observed stronger associations for hormone receptor positive tumors than for hormone receptor negative tumors (36, 40). In our study, although total red meat was associated with increased risk of ER positive tumors among Caucasian women, processed meat appeared to be more strongly related to increased risk of ER negative tumors. However, tests for heterogeneity of odds ratios suggested no significant difference in the associations by hormone receptor status. Recent results from the Shanghai Breast Cancer Study reported elevated breast cancer risk for all types of meat regardless of hormone receptor status (5). These findings could indicate presence of both estrogenic and non-estrogenic pathways involving meat and carcinogenesis.

There are several potential mechanisms for the role of red meat in the carcinogenesis process. Nitrites that are used to preserve processed meats undergo chemical reactions endogenously to form nitrosamines, also a mutagen and probable carcinogen (14, 41). Cooking red meat at high temperatures (charring, grilling, frying) lead to the production of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons, which are mutagens and suspected carcinogens (14, 42). HCA content of cooked meat has shown to directly relate to increases in cooking temperature (24). A 4.6-fold increased risk of breast cancer was observed among postmenopausal women who consistently ate well-done red meat in the Iowa Women’s Health Study (43). Results from the Nashville Breast Health Study also showed stronger risk for high intake of well-done red meat in both pre and postmenopausal women (44). A past report (45) from the Behavioral Risk Factor Surveillance System observed a much higher percentage of Caucasian respondents reporting consumption of ‘pink’ hamburgers compared to AA respondents in both NY (24.3% vs. 6.8%) and NJ (26.2% vs. 8.6%), which could indicate increased susceptibility of carcinogens for AA women. However, there is also some evidence that the impact of well-done meat on breast cancer risk could be modified by certain polymorphisms in the NAT1, NAT2, GSTM1, GSTT1, and SULT1A1 genes that encode enzymes involved in HCA activation or detoxification (46). In fact, a case-control study (47) nested in an Iowa cohort of postmenopausal women observed a 3.4-fold greater breast cancer risk among women who consumed well- or very well done meat compared to consuming meat that was rare or medium, and who carried a null GSTM1 or GSTT1 genotype. Interestingly, Caucasians appear to have a much higher frequency of a null GSTM1 or GSTT1 gene than AA (48). Hence, it is possible that there are potential racial differences in gene-environment interactions resulting in differences in the way animal foods and other potential carcinogens are metabolized and their consequential impact on breast tissue.

Other plausible mechanisms include potential estrogenic effects of HCAs shown in animal studies, thus resulting in possible stimulation of ER and PR gene expression (49, 50).

Furthermore, heme iron present in red meat and responsible for its dark red color could have a catalytic effect on endogenous formation of nitrosamines (23), and has been shown to promote estrogen-induced tumors (51). Exposure to meat-derived mutagens has also been observed to be significantly correlated with DNA adducts in breast tissue, potentially leading to unrepaired DNA damage and carcinogenesis (52). A cross-sectional analysis found mean plasma concentrations of sex hormone-binding globulin (SHBG) to be lower with higher intakes of total and fresh red meat (53). Lower SHBG levels correspond with increased bioavailability of estradiol (54, 55). Finally, there is evidence linking exogenous hormone treatment of beef cattle to increased risk of estrogen-related illnesses even with low levels of exposure in the long term (56).

In our study, there was also a positive association between poultry consumption and breast cancer risk in Caucasian women, with over 2-fold greater risk among premenopausal Caucasian women and among women with ER negative tumors, most commonly seen among premenopausal women (18). Past evidence relating poultry intake and breast cancer risk is inconclusive (5, 8, 9, 14, 44, 52). A recent cross-sectional study reported that intake of chicken, high-fat dairy products, and animal fat may be important determinants of oxidative stress in women with breast cancer (57), and increased breast cancer risk with high poultry consumption was also reported in the Shanghai Breast Cancer Study (5). The null findings in AA women related to poultry consumption are consistent with results from the Black Women’s Health Study (33).

Biological mechanisms for the role of white meat in the cancer process involve HCAs (24) and the potential influence of fat in the meat supplemented by meal preparation methods such as frying. Adjusting for fat did not have a major impact on study results. We also repeated analyses adjusting for red meat, but the findings for poultry intake remained unchanged. The largest proportion (∼ 70%) of mean dietary intake of total HCAs in the US appears to be comprised of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), with AA consuming more than Caucasians, which has been attributed to higher intake of chicken and pan-fried meats (26). High PhIP concentrations in well done chicken and beef have also been shown in other studies (24, 25, 58, 59). However, results from the Nashville Breast Health Study on chicken consumption and breast cancer risk were null, and even when poultry consumption was high, there was no correlation between cooking poultry at high temperatures and formation of DNA adducts in breast tissue (44, 52). The null findings in AA women in our study, despite higher poultry intake levels warrants further investigation into potential racial differences in biological pathways involving PhIP metabolism. Nevertheless, findings may have occurred due to chance and need replication in view of potential biases described herein.

Limitations of this study include lack of information on meat doneness levels that precluded assessment of risks associated with different cooking methods. This study could have been affected by inherent limitations of the case-control study design such as recall and selection bias. For instance, cases could have changed their dietary habits as a result of the cancer diagnosis, and report recent behavior instead of recalling behavior prior to diagnosis. To evaluate the extent of this bias, we evaluated behavioral change after diagnosis (data not shown). A greater proportion of both AA and Caucasian cases reported that they had decreased meat intake and chicken intake since diagnosis than controls. However, this only suggests that we may be underestimating the association with meat and poultry consumption.

To further assess if there were racial differences in recall, we also compared the proportion of AA and Caucasian cases and controls who had increased or decreased meat and chicken intake since the reference date. Although a higher proportion of cases in both races had decreased meat intake and chicken intake since diagnosis as compared to controls, the differences in proportions were similar in AA and Caucasian women. Self-reported dietary data have also been used to assess racial differences in nutrition by other studies (60, 61). The low response rates, especially among controls in our study could result in potential selection bias, but response rates as low as 50% are not uncommon in population studies (62). Finally, to evaluate selection bias resulting from possible differences by source of controls, we repeated analyses after excluding AA community controls, but results did not change.

The major strength of this study is the large sample of AA women that allowed subgroup analyses to further evaluate associations by menopausal status and hormone receptor status in each race. Extensive collection of all major and potential risk factors as well as in-person interviews to collect detailed dietary data enabled accounting for potential confounding to a large extent.

This study supports an association between processed and unprocessed red meat, poultry meat consumption and increased breast cancer risk in Caucasian women. Although heterogeneity tests across race, menopausal status, and hormone receptor status sub-groups confirmed differences only for poultry intake, magnitude of associations appeared stronger in certain sub-groups, which may be obscured if studies do not stratify but only adjust for these factors. As this is one of the first studies to examine red meat and poultry consumption and breast cancer risk in AA women, further research is needed to make more definitive conclusions in this minority population while taking into account cultural preferences for cooking methods and meat doneness levels.