Protective factors

Evidence classifications:

• Probable (physical activity and postmenopausal breast cancer)

• Probable (vigorous physical activity and postmenopausal and premenopausal breast cancer)

• Suggestive (physical activity and premenopausal breast cancer)

Highest versus lowest levels of physical activity (including vigorous, occupational, recreational, walking and household activity) are probably associated with a 13% decreased risk of postmenopausal breast cancer (relative risk [RR] 0.87, 95% confidence interval [CI] 0.79–0.96).¹

Highest versus lowest levels of vigorous physical activity are probably associated with a 17% (RR 0.83, 95% CI 0.73–0.95) and 10% (RR 0.90, 95% CI 0.85–0.95) lower risk of premenopausal and postmenopausal breast cancer, respectively.¹ Physical activity may be associated with a decreased risk of premenopausal breast cancer, but there is currently a limited amount of evidence, although generally consistent in direction of effect.

Mechanisms

Physical activity is any movement of the body produced by skeletal muscle that requires energy expenditure.² Different types of activity are commonly equated through metabolic equivalents (METs); one MET is considered to represent resting energy expenditure, moderate-vigorous activity is any activity of 3–5.9 METs and vigorous activity ≥6 METs.

Physical activity could reduce the risk of breast cancer through several mechanisms. For example, physical activity lowers the levels of biologically available oestrogen, progesterone and androgens.^3,4 It can also change the levels of metabolic hormones and adipokines (cytokines secreted by adipose tissue), and affect oxidative stress and immune function.⁵

Evidence 

Based on studies published up to 2001, the International Agency for Research on Cancer concluded that there was ‘sufficient evidence’ that physical activity was protective for breast cancer.²

Dose-response analyses were considered not possible by the World Cancer Research Fund/American Institute for Cancer Research (WCFR/AICR) due to the variety of measures used to collect data on physical activity, hence the judgements and risk estimates were determined for highest versus lowest levels of exposure¹. WCRF/AIRC¹ reviewed more than 40 cohort studies and meta-analyses published up to 2014, and a meta-analysis of 31 prospective studies.⁶  

Occupational physical activity, recreational physical activity, walking and household activity had a protective effect against breast cancer in the studies reviewed by the WCFR/AICR.

Additional meta-analyses, with considerable overlap between included studies with each other and the analyses by WCRF/AICR, have also shown that physical activity decreases the risk of breast cancer.^7-9 One of these found a significant dose–response relationship between physical activity and risk of breast cancer.⁸ One meta-analysis indicated a protective effect of physical activity only in women who had not used menopausal hormone therapy.⁹

The evidence was too limited for any analyses or conclusions regarding sedentary behavior by WCRF/AICR.¹ A recent cohort study in Sweden showed a significantly increased risk of breast cancer associated with sedentary occupations in women younger than 55 years.¹⁰

It is estimated that about 7.8% of postmenopausal breast cancers in Australia each year are attributable to a lack of physical activity.¹¹

Read the full Review of the Evidence

References

1. World Cancer Research Fund/American Institute for Cancer Research (2018). Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and breast cancer. London, UK.
2. International Agency for Research on Cancer (2002). Weight control and physical activity, IARC Handbooks of Cancer Prevention, Vol 6, IARC, Lyon.
3. McTiernan A, Tworoger SS, Rajan KB, et al. (2004). Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiology, Biomarkers & Prevention 13(7):1099–1105. 
4. Mitsuzono R & Ube M (2006). Effects of endurance training on blood lipid profiles in adolescent female distance runners. Kurume Medical Journal 53(1–2):29–35.
5. de Boer MC, Wörner EA, Verlaan D & van Leeuwen PAM (2017). The mechanisms and effects of physical activity on breast cancer. Clinical Breast Cancer 17(4):272–278.
6. Wu Y, Zhang D, Kang S (2013). Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Research and Treatment 137(3):869–882.
7. Neilson HK, Farris MS, Stone CR, et al. (2017). Moderate–vigorous recreational physical activity and breast cancer risk, stratified by menopause status: a systematic review and meta-analysis. Menopause 24(3):322–344.
8. Kyu HH, Alexander LT, Mumford JE, et al. (2016). Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study. British Medical Journal 354: i3857.
9. Pizot C, Boniol M, Mullie P, et al. (2016). Physical activity, hormone replacement therapy and breast cancer risk: a meta-analysis of prospective studies. European Journal of Cancer 52:138–154.
10. Johnsson A, Broberg P, Johnsso A, et al. (2017). Occupational sedentariness and breast cancer risk. Acta Oncologica 56(1):75–80
11. Olsen CM, Wilson LF, Nagle CM, et al. (2015) Cancers in Australia in 2010 attributable to insufficient physical activity. Australian and New Zealand Journal of Public Health 39 (5):458–463

Mechanisms

Dairy products are foods made from the milk of mammals such as cows, sheep and goats. They include milk, butter, cheese, yoghurt and ice-cream.

The mechanism for any association between intake of dairy foods and breast cancer risk may be via the calcium that occurs in these foods.¹ Calcium plays a role in regulating cell proliferation, cell differentiation and programmed cell death (apoptosis). For yoghurt, probiotics and the effect of fermentation might also play a role.¹

Evidence 

The World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) has classified the evidence for an association of intake of dairy products with reduced risk of premenopausal breast cancer as ‘limited – suggestive’.² The WCRF/AICR has classified the evidence for an association with risk of postmenopausal breast cancer as ‘limited – no conclusion’.²

Meta-analyses undertaken in the WCRF/AICR review found a dose-response association between dairy product intake and reduced risk of breast cancer overall (relative risk [RR] per 200 g/day 0.96, 95% confidence interval [CI] 0.94–0.99) and reduced risk of premenopausal breast cancer (RR per 200 g/day 0.95, 95% CI 0.92–0.99), but not postmenopausal breast cancer (RR per 200 g/day 0.97 (95% CI 0.93–1.01).³ No dose-response association was found for intake of total milk or whole milk and risk of breast cancer.

The WCRF/AICR cited a pooled analysis⁴ of eight cohort studies which examined fluid and solid dairy intake separately and which found no associations between dairy intake and breast cancer risk. 

Two recent meta-analyses^1,5 have reported findings that are consistent with those of the WCRF/AICR. One found a borderline significant association for high versus low consumption of skim milk and yoghurt, but not total milk or whole milk, and reduced risk of breast cancer.⁵ The other found that high and modest dairy consumption (>600 and 400–600 g/day, respectively) was associated with reduced risk of breast cancer compared with low dairy consumption (<400 g/day).¹

Read the full Review of the Evidence

References

1. Zang J, Shen M, Du S, et al. (2015). The association between dairy intake and breast cancer in western and Asian populations: a systematic review and meta-analysis. Journal of Breast Cancer 18(4):313–322.
2. World Cancer Research Fund/American Institute for Cancer Research (2018). Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and breast cancer. London, UK.
3. World Cancer Research Fund (2017). Continuous Update Project Systematic Literature Review: The associations between food, nutrition and physical activity and the risk of breast cancer. London, UK.
4. Missmer SA, Smith-Warner SA, Spiegelman D, et al. (2002). Meat and dairy consumption and breast cancer: a pooled analysis of cohort studies. International Journal of Epidemiology 31: 78–85
5. Wu J, Zeng R, Huang J, et al. (2016). Dietary protein sources and incidence of breast cancer: a dose–response meta-analysis of prospective studies. Nutrients 8(11)

The evidence for any association between intake of calcium supplements and risk of breast cancer is inconclusive. No association was found in two meta-analyses, based on a very limited amount of evidence.^1, 3

Mechanisms

Calcium is an essential mineral in the diet and is found in many foods. Foods high in calcium include dairy products, dark green vegetables, some fortified soy products and fish with edible bones. Calcium may also be taken as a supplement, sometimes with vitamin D supplements.

Calcium plays a role in regulating cell proliferation, cell differentiation and programmed cell death (apoptosis). Evidence from animal studies suggests that calcium has anti-proliferative and pro-differentiation actions in breast cells that might reduce the risk of cancer.¹

Evidence 

Methodological limitations to the evidence include inconsistent measurement of dietary calcium intake using questionnaires. There are also many potential confounders, such as age, reproductive factors, body mass index and alcohol consumption.^1, 3

The World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) has classified the evidence for an association between diets high in calcium and reduced risk of both premenopausal and postmenopausal breast cancer as ‘limited – suggestive’.²

Dose–response meta-analyses undertaken in the WCRF/AICR systematic literature review [SLR] found an association between calcium intake in food and lower risk of both premenopausal (relative risk [RR] per 200 g/day 0.96, 95% confidence interval [CI] 0.94–0.99; six studies with no heterogeneity) and postmenopausal breast cancer (RR per 200 g/day 0.95, 95% CI 0.92–0.99; seven studies, no heterogeneity), but not breast cancer risk overall.³ A meta-analysis of six randomised controlled trials (not primarily designed to assess cancer risk) did not find an association between taking calcium supplements and risk of breast cancer.³ Cohort studies, with one exception, also reported no association between use of calcium supplements and risk of breast cancer.³ Total calcium intake, from food and supplements, was not associated with breast cancer risk in the cohort studies in the SLR, except in one study that found a decreased premenopausal breast cancer risk associated with highest compared with lowest total calcium intake.³

A recent meta-analysis of 11 prospective cohort studies (with considerable overlap with the SLR) also reported that a high versus a low intake of dietary calcium but not total or supplementary calcium was associated with a reduced risk of breast cancer.¹

Read the full Review of the Evidence

References

1. Hidayat K, Chen GC, Zhang R, et al. (2016). Calcium intake and breast cancer risk: meta-analysis of prospective cohort studies. British Journal of Nutrition 116(1):158–166. 
2. World Cancer Research Fund/American Institute for Cancer Research (2018). Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and breast cancer. London, UK.
3. World Cancer Research Fund (2017). Continuous Update Project Systematic Literature Review: The associations between food, nutrition and physical activity and the risk of breast cancer. London, UK.

The evidence is suggestive of an association between intake of non-starchy vegetables and decreased risk of oestrogen receptor negative (ER-) breast cancer.

A dose-response analysis by the World Cancer Research Fund International / American Institute for Cancer Research (WCRF/AICR) of data from three prospective studies showed that increased intake of non-starchy vegetables is associated with a decreased risk of ER- breast cancer. The stronger association for decreased risk of ER- breast cancer has also been found in a recent cohort study with long-term follow up.

Mechanisms

‘Vegetables’ refers to edible parts of plants such as edible leaves, roots, tubers, bulbs, stems and stalks, flowers, and grains used as vegetables (e.g. sweetcorn). Nuts, seeds and most grains are not classified as vegetables. Vegetables can be either starchy or non-starchy. Starchy vegetables, such as potatoes, have higher carbohydrate content. Non-starchy vegetables include green leafy vegetables, carrots, broccoli and onions.

Vegetables contain vitamins (C and E), minerals, fibre and other bioactive compounds. Bioactive compounds might have a more detectable effect on ER- cancers than on oestrogen receptor-positive (ER+) cancers, where the larger effect of oestrogens might obscure any effect from vegetables.¹

One possible mechanism is a reduction in the level of epidermal growth factor receptor by phytochemicals in vegetables.¹

Evidence 

The WCRF/AICR classified the evidence for an association between the intake of non-starchy vegetables and ER- breast cancer as ‘limited – suggestive’ for premenopausal and postmenopausal breast cancer.¹

Meta-analyses by the WCRF/AICR found a dose–response relationship for the association of intake of non-starchy vegetables with decreased risk of ER- breast cancer (relative risk [RR] 0.79, 95% confidence interval [CI] 0.63–0.98).² A pooled analysis of data from 20 cohort studies also found that vegetable intake was associated with a decreased risk (in a dose-response relationship) of ER– breast cancer, but not ER+ breast cancer.³ There was a dose-response relationship for ER- breast cancer.

A report on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort showed a decreased risk of breast cancer for the highest versus lowest intakes of vegetables (hazard ratio [HR] 0.87, 95% CI 0.80-0.94).⁴

Long-term follow-up of the Nurses’ Health Study I and II has also shown an association between high versus low intakes of vegetables and decreased risk of breast cancer (>4.5 versus ≤1.5 servings/day of vegetables; HR 0.91, 95% CI 0.84–1.00).⁵ Associations were stronger for ER- breast cancer and for cruciferous and green leafy vegetables and yellow and orange vegetables.

Read the full Review of the Evidence

References

1. World Cancer Research Fund/American Institute for Cancer Research (2018). Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and breast cancer. London, UK.
2. World Cancer Research Fund (2017). Continuous Update Project Systematic Literature Review: The associations between food, nutrition and physical activity and the risk of breast cancer. London, UK.
3. Jung S, Spiegelman D, Baglietto L, et al. (2013). Fruit and vegetable intake and risk of breast cancer by hormone receptor status. Journal of the National Cancer Institute 105(3):219–236.
4. Emaus MJ, Peeters PH, Bakker MF, et a. (2016). Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort. American Journal of Clinical Nutrition 2103(1):168–177.
5. Farvid MS, Chen WY, Rosner BA, et al. (2018) Fruit and vegetable consumption and breast cancer incidence: Repeated measures over 30 years of follow-up. International Journal of Cancer Jul 6. DOI: 10.1002/ijc.31653

Evidence classification: Suggestive

The evidence is suggestive of an association between intake of foods high in carotenoids and decreased risk of breast cancer. However there are some limitations to the evidence.

Findings have been inconsistent across the range of carotenoids and across studies. This may be partly due to differences in measurement of exposure. The decreased risk is seen predominantly for oestrogen receptor-negative (ER-) breast cancer.

Mechanisms

Carotenoids are pigments (yellow, orange and red) that occur naturally in many fruits and vegetables such as carrots, sweet potatoes and tomatoes. Around 40–50 different carotenoids occur in the human diet, including alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin and lycopene⁴.

Metabolism of carotenoids may affect the risk of breast cancer through effects on cell growth, differentiation and apoptosis.¹ Carotenoids also have antioxidant properties, which might protect against DNA damage.¹ Alteration of gene expression by carotenoids is another possible mechanism for effects on breast cancer risk.²

The level of circulating carotenoids may be a better measure of carotenoid exposure than dietary intake because of measurement error in studies estimating carotenoid intake, differences in bioavailability of carotenoids from different foods, and individual differences in absorption and metabolism.¹

Evidence 

The World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) judged the evidence to be ‘Limited-suggestive’ of an association between circulating carotenoids and decreased risk of breast cancer.¹

Meta-analyses showed that circulating beta-carotene, circulating total carotenoids and circulating lutein are associated with a decreased risk of breast cancer (relative risk [RR] per 50 μg/dL 0.78, 95% confidence interval [CI] 0.66–0.92; RR per 100 μg/dL 0.82, 95% CI 0.71–0.96; RR per 25 μg/dL 0.72, 95% CI 0.55–0.93; respectively).³ No associations were seen for circulating alpha-carotene, beta-cryptoxanthin or lycopene, or dietary beta-carotene. Associations between carotenoids and decreased breast cancer risk was stronger for ER- breast cancers, although the findings varied by type of carotenoid.^1,3

Long-term follow-up of the Nurses’ Health Study I and II cohorts showed that higher intakes versus lower intakes of vegetables rich in alpha-carotene and beta-carotene were associated with a decreased risk of breast cancer (≥3 servings/week versus <2 servings/month HR 0.91, 95% CI 0.84–0.98 and >1 servings/day versus ≤2 servings/week HR 0.87, 95% CI 0.80–0.94; respectively). The associations were stronger, and an association existed for lutein, for ER- breast cancer.⁴

Two nested case-control studies have shown an association of plasma levels of alpha-carotene and beta-carotene and decreased risk of ER- breast cancer,⁵ and plasma alpha-carotene and decreased risk of postmenopausal breast cancer.⁶

Read the full Review of the Evidence

References

1. World Cancer Research Fund/American Institute for Cancer Research (2018). Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and breast cancer. London, UK.
2. Gong X, Smith JR, Swanson HM et al. (2018). Carotenoid lutein selectively inhibits breast cancer cell growth and potentiates the effect of chemotherapeutic agents through ROS-mediated mechanisms. Molecules 23:905.
3. World Cancer Research Fund (2017). Continuous Update Project Systematic Literature Review: The associations between food, nutrition and physical activity and the risk of breast cancer. London, UK.
4. Farvid MS, Chen WY, Rosner BA, et al. (2018) Fruit and vegetable consumption and breast cancer incidence: Repeated measures over 30 years of follow-up. International Journal of Cancer Jul 6. DOI: 10.1002/ijc.31653
5. Bakker MF, Peeters PH, Klaasen VM, et al. (2016). Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort. American Journal of Clinical Nutrition 103(2):454–464.
6. Wang Y, Gapstur SM, Gaudet MM, et al. (2015). Plasma carotenoids and breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer Causes & Control 26(9):1233–1244.