Dietary Lignan Intake and Breast Cancer Risk

By Donald J. Brown, ND, Director, Natural Product Research Consultants, Seattle, WA. Dr. Brown is a consultant to the supplement industry. He reports no financial relationships relevant to this field of study.

This article originally appeared in the August 2012 issue of Integrative Medicine Alert.

Synopsis: In this case-control study, dietary lignan intake was inversely associated with risk of breast cancer in both premenopausal and postmenopausal women. Also noted were more favorable prognostic characteristics associated with lignan intake, especially in premenopausal women.

Source: McCann SE, et al. Dietary intakes of total and specific lignans are associated with clinical breast tumor characteristics. J Nutr 2012;142:91-98.

To evaluate the relationship between dietary lignan intake and breast cancer as well as tumor characteristics, the researchers investigated dietary intakes of total and specific lignans in 683 women with breast cancer and 611 healthy women enrolled in the Data Bank and BioRespository (DBBR) at Roswell Park Cancer Institute (RPCI) in Buffalo, NY. The total population of premenopausal women was 214 with breast cancer (mean age 44.6 years) and 202 controls (mean age 44.4 years). In the group of postmenopausal women, there were 469 with breast cancer (mean age 63.7 years) and 409 controls (mean age 62.1 years). Clinicopathologic data were obtained from the RPCI breast cancer database. The data were linked with epidemiologic data from the DBBR and included tumor stage and grade, estrogen receptor (ER) and progesterone receptor (PR) status, and HER2 protein expression. Daily intakes of total lignans and found individual lignans (matairesinol, lariciresinol, pinoresinol, and secoisolariciresinol) were obtained from a food frequency questionnaire that was part of the DBBR. Odds ratio [OR] and 95% confidence interval [CI] for associations between daily intakes of total and specific lignans with clinicopathologic characteristics compared to women without breast cancer were estimated.

Women in the highest compared to the lowest tertile of total lignan intakes had approximately 40-50% lower odds of having breast cancer. Higher total lignan intakes also were associated with significantly reduced odds of having an invasive tumor, especially among premenopausal women (OR 0.48 [95% CI 0.26-0.86] for premenopausal women and OR 0.70 [95% CI 0.47-1.06] for postmenopausal women).

The reductions in risk of breast cancer and invasive cancer were linked primarily to higher intakes of lariciresinol and pinoresinol in premenopausal women and of lariciresinol and matairesinol in postmenopausal women. For premenopausal women, there was a borderline significant 50% reduction in odds of having either stage I or II breast cancer but no association with higher stages. The association was strongest for the lignans lariciresinol and pinoresinol. In postmenopausal women, there was a significant 50% reduction only in stage I cancers that was associated with increased intake of matairesinol. Higher total lignan and matairesinol intakes were associated with lower risk of grade 3 tumors, primarily among premenopausal women.

Higher total lignan intakes were strongly inversely correlated with risk of ER- breast cancer among premenopausal women (OR 0.16 [95% CI 0.03-0.44]) independent of the specific lignan. Among postmenopausal women there was an inverse correlation related to ER+ breast cancer that was predominantly associated with lariciresinol and matairesinol intakes. Higher intakes of total lignans were associated with both negative and positive HER2 status in premenopausal women, with the estimates much stronger for HER2+ (OR 0.21 [95% CI 0.05-0.87]) than HER2- (OR 0.56 [95% CI 0.30-1.05]). There was no association between total lignan intakes and HER2 status in postmenopausal women, but there was a lower risk of HER2+ tumors in those consuming higher amounts of matairesinol (OR 0.36 [95% CI 0.14-0.89]). Among premenopausal women, those in the highest tertile of total lignan intake had greatly reduced odds of having triple negative tumors compared to those in the lowest tertile (ER-, PR-, HER2-; OR 0.16 [95% CI 0.04-0.62]). This reduction was primarily associated with lariciresinol and pinoresinol.

Commentary

The results of this ambitious study expand on previous epidemiological studies that have found an inverse correlation between dietary lignan intake and breast cancer risk (please note brief review below) by adding more detailed data on reduced risk of specific types of cancer as well as prognosis. Lignans are naturally occurring diphenolic compounds that are classified as phytoestrogens.1 Commonly found in whole grains, seeds, nuts, legumes, fruit, and vegetables, the highest concentrations are currently found in flaxseed powder extracts standardized to secoisolariciresinal and a 7-hydroxymatairesinol (HMR) powder extracted from the knot wood of Norwegian Spruce.1,2 The researchers report in the Discussion section of the paper that the primary sources of total lignans in the study population were apricots, broccoli, berries, coffee, and red wine. The primary sources of matairesinol intakes were onions, oranges, "salty snacks," peaches, and coffee. The primary sources of lariciresinol were broccoli, winter squash, berries, apricots, and coffee. Interestingly, they did not include flaxseed or tea in the list of foods or beverages.

Dietary lignans are converted by gut microflora to the mammalian lignans enterolactone (ENL) and enterodiol (END). Matairesinol and HMR are directly converted to ENL while pinoresinol, lariciresinol, and secoisolariciresinal are first converted END, which then partially converts to ENL.1 One study found that sesame seeds, a rich source of matairesinol, more efficiently raised ENL levels when compared to flaxseed.3

Several, but not all, epidemiological studies have reported reduced risks of breast cancer associated with either increased intake of dietary lignans and/or higher blood levels of ENL.4 A case-control study of premenopausal women found that overall breast cancer risk was inversely correlated with plasma ENL.5 Another found an inverse correlation between breast cancer risk and plasma ENL in both premenopausal and postmenopausal women.6 Two additional studies found that increased plasma ENL was associated with a significant decrease in risk of ER- breast cancer in premenopausal7 and postmenopausal women.8 Finally, in a large case-control study, higher dietary lignan intake and serum levels of ENL and END were associated with a significantly reduced risk of ER- and PR+ breast cancer in postmenopausal women.9

As pointed out by the authors of this new study, ER- tumors are more common among younger women and have a poorer prognosis because of fewer treatment options.10 While less common, triple negative breast cancer also has a poor prognosis due to lack of effective treatments. The identification of simple modifiable lifestyle changes such as increased lignan intake could potentially reduce the occurrence of less favorable tumor types, and perhaps have a considerable impact toward reducing the burden of the disease in both premenopausal and postmenopausal women.

References

1. Aldercreutz H. Lignans and human health. Critical Rev Clin Lab Sci 2007;44:483-425.

2. Horn-Ross PL, et al. Sources of phytoestrogen exposure among non-Asian women in California, USA. Cancer Causes Control 2000;11:299-302.

3. Coulman KD, et al. Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed. Nutr Cancer 2005;52:156–165.

4. Velentzis LS, et al. Lignans and breast cancer risk in pre- and postmenopausal women: Meta-analyses of observational studies. Br J Cancer 2009;100:1492-1498.

5. Piller R, et al. Plasma enterolactone and genistein and the risk of premenopausal breast cancer. Eur J Cancer Prev 2006;15:225-232.

6. Pietinen P, et al. Serum enterolactone and risk of breast cancer: A case-control study in Eastern Finland. Cancer Epidemiol Biomarkers Prev 2001;10:339-344.

7. McCann SE, et al. Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status. Breast Cancer Res Treat 2006;99:309-311.

8. Olsen A, et al. Plasma enterolactone and breast cancer incidence by estrogen receptor status. Cancer Epidemiol Biomarkers Prev 2004;13:2084-2089.

9. Touilland MS, et al. Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J Natl Cancer Inst 2007;99:475-486.

10. Anderson WF, et al. Incidence of breast cancer in the United States: Current and future trends. J Natl Cancer Inst 2011;103:1397-402.