It is estimated that around a quarter of breast cancers could potentially be prevented through lifestyle and other changes. Modifiable risk factors are factors that we can change to reduce our risk for breast cancer, for example keeping to a healthy body weight, reducing alcohol consumption and regular physical activity.
Read more below to find out which factors you can change to reduce your risk of breast cancer, and what you can do.
Lifestyle factors
Lifestyle factors are behaviours that are part of everyday life that are associated with increased or decreased risk of breast cancer.
Modifiable lifestyle factors associated with risk of breast cancer include overweight and obesity, physical activity and alcohol consumption.
Read more below to find out changes you can make to reduce your risk of breast cancer, and what you can do.
Overweight and obesity
After menopause
Being overweight or obese is associated with an increased risk of breast cancer for women who have experienced menopause (postmenopausal women).
Body fatness can be measured in several ways including:
- body mass index (BMI);
- waist circumference.
Both measures are associated with increased risk of breast cancer among women after menopause.
For each 5-unit increase in BMI after menopause, the risk of breast cancer increases by about 12%.
For each 10 cm increase in waist circumference, the risk of postmenopausal breast cancer increases by about 6%.
It is estimated that 8% of postmenopausal breast cancers each year in Australia are attributable to overweight or obesity.
The way in which body fat increases or decreases the risk of breast cancer is not fully understood. The most likely explanation is that higher body fatness after menopause influences the levels of circulating hormones in the body, including oestrogen, which can affect the risk of breast cancer.
Before menopause
In contrast to the effect of higher BMI in women after menopause, having a higher BMI before menopause is associated with a decreased risk of premenopausal breast cancer.
For each 5-unit increase in BMI the risk of premenopausal breast cancer is decreased by about 7%.
The link between body fatness and premenopausal breast cancer is complex and not well understood.
* Body mass index (BMI) is a measure of body fat based on your weight in relation to your height, and applies to most adult men and women aged 20 and over.
Commonly accepted BMI ranges are underweight: under 18.5 kg/m2, normal weight: 18.5 to 25 kg/m2, overweight: 25 to 30 kg/m2, obese: over 30 kg/m2.
- Cancer Australia Position Statement – Lifestyle risk factors and the primary prevention of cancer
- Healthy Weight Guide – Australian Government Department of Health
- Australia’s Physical Activity and Sedentary Behaviour Guidelines – Australian Government Department of Health
Summary of the evidence
Evidence classifications:
- Convincing (adult body fatness marked by BMI, waist circumference and waist‒hip ratio and increased risk of postmenopausal breast cancer)1
- Probable (body fatness before the menopause and decreased risk of premenopausal breast cancer)1
There is convincing evidence that being overweight or obese is associated with an increased risk of breast cancer in postmenopausal women. Being overweight or obese before the menopause is probably associated with a decreased risk of premenopausal breast cancer.
Body fatness can be measured in several ways including:
- Body mass index (BMI);
The increased risk of postmenopausal breast cancer associated with BMI in adulthood is estimated as RR 1.12 (95% CI 1.09–1.15) (per 5 kg/m2).
The decreased risk of premenopausal breast cancer is estimated as RR 0.93 (95% CI 0.90–0.97) per 5 kg/m2 during the premenopausal period. 1
- Waist circumference.
Waist circumference was associated with an increased risk for postmenopausal breast cancer (RR per 10 cm increase = 1.06, 95% CI 1.01–1.12; based on studies adjusted for BMI).1
Despite BMI being associated with a decreased risk of premenopausal breast cancer, waist circumference was associated with an increased risk of premenopausal breast cancer (RR per 10 cm increase = 1.14, 95% CI 1.04–1.26; based on studies adjusted for BMI).1
Mechanisms
The mechanisms by which differences in body fat and fat distribution affect breast cancer are complex, particularly during early life and young adulthood, but are likely to involve the effects of adipose tissue on circulating sex hormone levels.2 Obesity in premenopausal women probably reduces ovarian progesterone production.1 Obesity in postmenopausal women increases the production of oestradiol.1 Both hormones are associated with breast cancer. In addition, studies are increasingly implicating obesity as associated with a low-grade chronic inflammatory state and the activation of inflammatory cascades is one process that may predispose to carcinogenesis.1
Evidence
WCRF/AICR (2018) summarised a vast literature in relation to measures of body fatness across the life-course and risk of premenopausal and postmenopausal breast cancer (see above).1 The International Agency for Research on Cancer (IARC) concluded in 2016 that ‘the absence of excess body fatness decreases the risk of cancer of the breast in postmenopausal women’, citing an approximately increased risk of 1.1 per 5 kg/m2 BMI.2,3
The conclusions of IARC (2016) and WCRF/AIRC (2018) are supported by more recently published analyses. For example, a recent meta-analysis of data from seven prospective cohort studies also found a significantly increased risk of postmenopausal breast cancer associated with higher BMI (hazard ratio [HR] per 1 standard deviation (SD) increase = 1.15, 95% confidence interval [CI] 1.03–1.27).4 A pooled analysis of Australian cohort studies reported an increased risk of postmenopausal breast cancer associated with increasing waist circumference (relative risk [RR] per 1 SD increase = 1.06, 95% CI 1.01–1.12).5
Several cohort studies have shown that the association between body fatness and postmenopausal breast cancer risk may only occur, or may be greater, in women who do not use menopausal hormone therapy (MHT).1,4,6,7 However, another cohort study did not find an effect of MHT use on the relationship between BMI and postmenopausal breast cancer risk.8
In a large, multicentre pooled analysis of premenopausal women aged 18–54 years, BMI at all ages during the premenopausal period was negatively associated with risk of breast cancer, with a dose-response relationship (RR per 5 kg/m2 0.77, 95% CI 0.73–0.80).9 The effect was greater for younger age groups. It is estimated that 8% of postmenopausal breast cancers each year in Australia are attributable to overweight or obesity.10
It is estimated that 8% of postmenopausal breast cancers each year in Australia are attributable to overweight or obesity.10
Read the full Review of the Evidence
References
- 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.
- Lauby-Secretan B, Scoccianti C, Loomis D, et al. (2016). Body Fatness and Cancer – Viewpoint of the IARC Working Group. New England Journal of Medicine 375(8);794–8
- International Agency for Research on Cancer (2016). IARC handbooks volume 16: questions and answers, IARC, Lyon, https://www.iarc.who.int/wp-content/uploads/2018/11/QAHandbook16.pdf.
- Freisling HM, Arnold M, Soerjomataram I, et al. (2017). Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. British Journal of Cancer 116(11):1486–1497.
- Harding JL, Shaw JE, Anstey KJ, et al. (2015) Comparison of anthropometric measures as predictors of cancer incidence: A pooled collaborative analysis of 11 Australian cohorts. International Journal of Cancer 137 (7):1699–708
- Horn-Ross PL, Canchola AJ, Bernstein L, et al. (2016). Lifetime body size and estrogen-receptor-positive breast cancer risk in the California Teachers Study cohort. Breast Cancer Research 18(1):132.
- Collaborative Group on Hormonal Factors in breast cancer (1996). Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 347(9017):1713–1727
- Neuhouser ML, Aragaki AK, Prentice RL, et al. (2015). Overweight, obesity, and postmenopausal invasive breast cancer risk: a secondary analysis of the Women’s Health Initiative randomized clinical trials. JAMA Oncology 1(5):611–621.
- Premenopausal Breast Cancer Collaborative Group (2018). Association of body mass index and age with subsequent breast cancer risk in premenopausal women. JAMA Oncology e181771.
- Kendall BJ, Wilson LF, Olsen CM, et al. (2015) Cancers in Australia in 2010 attributable to overweight and obesity. Australian and New Zealand Journal of Public Health 39 (5):452–457
Weight gain
Postmenopausal women
Gaining weight as an adult is associated with an increased risk of postmenopausal breast cancer.
The risk of postmenopausal breast cancer increases by about 6% for each 5 kg increase in a woman’s weight. This corresponds to approximately a 12% and 26% increased risk for 10 kg and 20 kg weight gain, respectively.
The way that weight gain affects breast cancer risk is likely to involve hormones. Weight gain means that the body is storing more fat, which can affect levels of circulating hormones.
In postmenopausal women, weight gain increases the levels of circulating oestrogen. This can affect the risk of some types of breast cancer.
Premenopausal women
There is no conclusive evidence that weight gain in premenopausal women is associated with increased risk of breast cancer. Only a small number of studies have been done and the evidence was inconclusive.
- Cancer Australia Position Statement – Lifestyle risk factors and the primary prevention of cancer
- Australian Dietary Guidelines
Summary of the evidence
Evidence classifications:
- Convincing (postmenopausal breast cancer)
- Inconclusive (premenopausal breast cancer)
There is convincing evidence that adult weight gain is associated with an increased risk of postmenopausal breast cancer. The increase in risk is estimated as 6% for each 5 kg increase in weight (RR 1.06, 95% CI 1.05–1.08).1
The evidence for an association between adult weight gain and risk of premenopausal breast cancer is inconclusive. There are only a small number of studies examining this association.
Mechanisms
Long-term weight gain in adults is associated with increased storage of body fat. This may increase the risk of breast cancer in postmenopausal women by reducing levels of serum hormone binding protein, which results in higher levels of circulating oestrogen.2
Evidence
The International Agency for Research on Cancer (IARC) concluded that there was sufficient evidence for a cancer-preventive effect of avoidance of weight gain for postmenopausal breast cancer;3 and the World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) concluded that there was convincing evidence that greater weight gain in adulthood is a cause of postmenopausal breast cancer.1 A dose-response analysis provided a relative risk per 5 kg increase in weight of 1.06 (95% confidence interval [CI] 1.05–1.08).1
WCRF/AICR reported that the increased risk associated with weight gain was significant only for oestrogen receptor positive, progesterone-receptor positive (ER+PR+ ) breast cancer, and not ER+PR- or ER-PR- disease. Contrary to the IARC review, risk was not affected by use of menopausal hormone therapy (MHT).1
For premenopausal breast cancer, IARC concluded that the available evidence suggested a lack of a cancer-preventive effect of avoidance of weight gain.3 WCRF/AICR considered the evidence for an association between adult weight gain and premenopausal breast cancer to be limited, and no conclusion was made.1
Findings from two more recent cohort studies are consistent with the findings of the WCRF/AICR.4,5
Read the full Review of the Evidence
References
- 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.
- Endogenous Hormones Breast Cancer Collaborative Group (2003). Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Journal of the National Cancer Institute 95(6):1218–1226.
- International Agency for Research on Cancer (2002). Weight control and physical activity, IARC Handbooks of Cancer Prevention, vol 6, IARC, Lyon.
- Neuhouser ML, Aragaki AK, Prentice RL, et al. (2015). Overweight, obesity, and postmenopausal invasive breast cancer risk: a secondary analysis of the Women’s Health Initiative randomized clinical trials. JAMA Oncology 1(5):611–621.
- Nitta J, Nojima M, Ohnishi H, et al. (2016). Weight gain and alcohol drinking associations with breast cancer risk in Japanese postmenopausal women: results from the Japan Collaborative Cohort (JACC) Study. Asian Pacific Journal of Cancer Prevention 17(3):1437–1443.
Alcohol
Drinking alcohol on a daily basis is associated with an increased risk of breast cancer in postmenopausal women. Drinking alcohol is probably associated with an increased risk of breast cancer in premenopausal women also.
Women who drink one standard glass of alcohol each day have a 7% higher risk of breast cancer than women who never drink alcohol. The risk of breast cancer increases as the number of drinks regularly consumed increases.
It is estimated that nearly 6% of breast cancer cases each year in Australia are due to alcohol consumption.
There does not appear to be a ‘safe’ level of regular alcohol consumption for risk of breast cancer, according to the evidence.
Alcohol may increase risk for breast cancer in a number of ways, including helping cancer-causing molecules to enter cells or damaging cell DNA. Alcohol is also thought to increase levels of the hormone oestrogen, which can influence breast cancer risk.
- Cancer Australia Position Statement - Lifestyle risk factors and the primary prevention of cancer
- Standard Drink Guide - National Health and Medical Research Council (NHMRC)
Summary of the evidence
Evidence classification:
There is convincing evidence that alcohol consumption is associated with an increased risk of breast cancer, particularly in postmenopausal women. The risk of breast cancer among women who regularly drink alcohol compared to women who never drink alcohol is estimated by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR 2018) to increase by 7% for every 10 grams increase in daily alcohol consumption (RR 1.07, 95% CI 1.05–1.09).1 This corresponds to an increase in risk of breast cancer by 15% for 2 drinks per day and 31% for 4 drinks per day. (One ‘standard’ drink contains approximately 10 grams of alcohol).
Mechanisms
Several mechanisms have been proposed for how alcohol may increase breast cancer risk. Alcohol is a lipid solvent and can help carcinogens to enter cells. Alcohol can also increase the level of free-radical oxygen species, which can lead to DNA damage in cells. Genetic differences in ethanol metabolism can affect breast cancer risk. Alcohol consumption has also been associated with higher circulating oestrogen concentrations which can influence risk of breast cancer.1
Evidence
The International Agency for Research on Cancer (2012) concluded that there is ‘sufficient evidence’ that ‘alcohol consumption causes cancer of the breast’.2
The findings of World Cancer Research Fund International/American Institute for Cancer Research (2018)1 were based on evidence from 62 studies, 23 of which were included in dose–response meta-analyses. A relative risk (RR) for every 10 g/day increase in alcohol consumption of 1.05 (95% confidence interval [CI] 1.02–1.08) was reported for premenopausal breast cancer and of 1.09 (95% CI 1.07–1.12) for postmenopausal breast cancer.1 There is no threshold for consumption with an increased risk of breast cancer observed even at low levels of daily alcohol consumption.1,3,4 A pooled analysis of prospective cohort studies has indicated a positive association between oestrogen receptor-positive (ER+) and alcohol consumption, but not oestrogen receptor-negative (ER-) breast cancers,5 as observed in analyses by WCRF/AICR (2018).
It is estimated that about 5.8% of breast cancer cases each year in Australia are due to alcohol consumption.6
Read the full Review of the Evidence
References
- 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.
- International Agency for Research on Cancer (2012). Personal habits and indoor combustions, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, volume 100E, IARC Working Group on the Evaluation of Carcinogenic Risk to Humans, Lyon, http://monographs.iarc.fr/ENG/Monographs/vol100E/mono100E.pdf.
- Bagnardi V, Rota M, Botteri E, et al (2013). Light alcohol drinking and cancer: a meta-analysis. Annals Oncology 24: 301–308.
- Seitz HK, Pelucchi C, Bagnardi V, et al. (2012). Epidemiology and pathophysiology of alcohol and breast cancer: Update 2012. Alcohol and Alcoholism 47(3): 204–212
- Jayasekara H, MacInnis RJ, Room R, et al. (2016). Long-term alcohol consumption and breast, upper aero-digestive tract and colorectal cancer risk: a systematic review and meta-analysis. Alcohol and Alcoholism 51(3): 315–330.
- Pandeva N. Wilson LF. Webb PM et al (2015) Cancers in Australia in 2010 attributable to the consumption of alcohol. Australian and New Zealand Journal of Public Health 39 (5): 408–13
Physical activity
Physical activity is associated with a decreased risk of breast cancer.
Women who do large amounts of physical activity, including vigorous, occupational, recreational, walking and household activity, probably have an approximately 13% lower risk of postmenopausal breast cancer than women who do the lowest amounts of physical activity.
Women who do large amounts of vigorous physical activity such as running or cycling probably have around 17% lower risk of premenopausal breast cancer and around 10% lower risk of postmenopausal breast cancer than women who do low levels of vigorous physical activity.
It is estimated that nearly 8% of postmenopausal breast cancers in Australia each year are attributable to a lack of physical activity.
There are several ways in which physical activity could lower the risk of breast cancer. One is through lowering hormone levels, such as oestrogen, in the body. Other ways include effects on levels of metabolic hormones and on the immune system.
- Cancer Australia Position Statement – Lifestyle risk factors and the primary prevention of cancer
- Building more movement into your daily life – Australian Government Department of Health
Summary of the evidence
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
- 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.
- International Agency for Research on Cancer (2002). Weight control and physical activity, IARC Handbooks of Cancer Prevention, Vol 6, IARC, Lyon.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Johnsson A, Broberg P, Johnsso A, et al. (2017). Occupational sedentariness and breast cancer risk. Acta Oncologica 56(1):75–80
- 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
Medical history and medications
Factors in a woman’s medical history can be associated with an increased or decreased risk of breast cancer.
Modifiable medical factors associated with risk of breast cancer include menopausal hormonal therapy and the oral contraceptive pill.
Read more below to find out changes you can make to reduce your risk of breast cancer, and what you can do.
Menopausal hormonal therapy (combined oestrogen-progestogen)
Using menopausal hormone therapy (MHT) that contains both oestrogen and progestogen is associated with an increased risk of breast cancer.
Women who are currently using combined oestrogen-progestogen MHT, also referred to as combined hormone replacement therapy or combined HRT, have about 1.7 times the risk of breast cancer as women who have never used it. The risk of breast cancer increases the longer a woman uses combined MHT, and decreases after treatment is stopped.
It is estimated that 3.2% of breast cancers each year in Australia are attributable to the use of MHT that contains the hormones oestrogen and progestogen.
Some women take MHT around the time of menopause to help manage the symptoms of menopause, such as hot flushes. The use of MHT may also have other benefits including reduction in osteoporosis and fracture risk and colorectal cancer.
The way in which combined oestrogen-progestogen MHT increases the risk of breast cancer is likely to be through hormonal pathways. It increases a woman’s lifetime exposure to oestrogen and progestogen. Longer exposure to oestrogen and progestogen promote the growth of breast cancer cells.
Summary of the evidence
Evidence classification: Convincing
There is convincing evidence that menopausal hormone therapy (MHT) that contains combined oestrogen-progestogen is associated with an increased risk of breast cancer.
Current users of combined oestrogen-progestogen MHT are estimated to be 1.72 (95% CI 1.55–1.92) times the risk in women who have never used combined MHT.1 The risk in current users increases with increasing duration of use. Cohort studies have consistently shown that risk decreases after stopping use of combined MHT.
Mechanisms
Combined MHT, also referred to as hormone replacement therapy or HRT, involves the co-administration of an oestrogen and a progestogen to perimenopausal or menopausal women to mitigate the effects of diminishing oestrogen and progesterone at menopause.
Use of combined MHT may influence breast cancer risk through hormonal-mediated pathways. It increases a woman’s lifetime exposure to oestrogen and progestogen.2
Evidence
The International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence that combined MHT causes cancer of the breast.1,3 It noted evidence for an increasing risk with increasing duration of use among current users.
The World Cancer Research Fund International/American Institute for Cancer Research lists combined MHT as an established cause of breast cancer, and stated that ‘hormone therapy (also known as hormone replacement therapy) containing oestrogen with or without progesterone increases the risk of breast cancer, and the risk is greater with combined oestrogen plus progesterone preparations’.4
Two large meta-analyses published since the evaluation by IARC have reported an approximately 1.3 times increased risk of breast cancer forever versus never use of combined MHT.1,5 For current users compared with never users the relative risk was 1.72 (95% confidence interval [CI] 1.55–1.92).1 This association was seen only for oestrogen-receptor-positive, progesterone-receptor-positive (ER+PR+) breast cancer, and not for ER-PR- breast cancer.1
Some recent cohort studies have reported higher relative risks for current users versus never users of combined MHT.6,7
Long-term follow-up of the Women’s Health Initiative (WHI) randomised controlled trial has shown an increased risk of breast cancer in current users of combined MHT.8,9 The risk remained elevated after use of MHT stopped, up to a median of 13.2 years.8 However, numerous cohort studies have found that the increased risk did not persist after stopping use.
The increased risk of breast cancer among current users of combined MHT is greater with longer duration of use – this was noted in meta-analyses cited by the IARC and in several cohort studies.
With regard to formulations of MHT, one cohort study7 reported similarly elevated risks for both continuous (every day) and sequential (cyclic) MHT use, whereas two other cohort studies10,11 suggested that the risk associated with continuous regimes was higher.
It is estimated that 3.2% of breast cancers each year in Australia are attributable to the use of MHT that contains the hormones oestrogen and progestogen. 12
Read the full Review of the Evidence
References
- Munsell MF, Sprague BL, Berry DA, et al. (2014). Body mass index and breast cancer risk according to postmenopausal estrogen–progestin use and hormone receptor status. Epidemiologic Reviews 36:114–136.
- International Agency for Research on Cancer (2012). Pharmaceuticals, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, volume 100A, IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Lyon.
- International Agency for Research on Cancer (2007). Combined estrogen–progestogen contraceptives and combined estrogen–progestogen menopausal therapy, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, volume 92, IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Lyon.
- 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.
- Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, et al. (2013). Risk factors of breast cancer: a systematic review and meta-analysis. Asia Pacific Journal of Public Health 25(5):368–387.
- Jones ME, Schoemaker MJ, Wright L, et al. (2016). Menopausal hormone therapy and breast cancer: what is the true size of the increased risk? British Journal of Cancer 115:607–615.
- Román M, Sakshaug S, Graff-Iversen S, et al. (2015). Postmenopausal hormone therapy and the risk of breast cancer in Norway. International Journal of Cancer 138:584–593.
- Manson JE, Chlebowski RT, Stefanick ML, et al. (2013). Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA: The Journal of the American Medical Association 310(13):1353–1368.
- Chlebowski RT, Rohan TE, Manson JE, et al. (2015). Breast cancer after use of estrogen plus progestin and estrogen alone analyses of data from 2 Women’s Health Initiative randomized clinical trials. JAMA Oncology 1:296–305.
- Bakken K, Fournier A, Lund E, et al. (2011). Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer 128(1):144–156.
- Porch JV, Lee IM, Cook NR, et al. (2002). Estrogen-progestin replacement therapy and breast cancer risk: the Women’s Health Study (United States). Cancer Causes & Control 13(9):847–854.
- Whiteman DC, Webb PM, Green AC, et al. (2015). Cancers in Australia in 2010 attributable to modifiable factors: summary and conclusions. Australian and New Zealand Journal of Public Health 39 (5):477–84
Oral contraceptive pill (combined oestrogen-progestogen)
Taking ‘combined’ oral contraceptives (that contain both oestrogen and progestogen) is associated with a small increased risk of breast cancer while a woman is currently using it. Oral contraceptives are also known as birth-control pills or ‘the Pill’.
The risk of breast cancer in women who are currently using the ‘combined’ oral contraceptive pill increases by about 7% for every 5 years of use. The risk goes down again when a woman stops using it.
It is estimated that 0.7% of breast cancers each year in Australia are attributable to the use of oral contraception that contains the hormones oestrogen and progestogen.
However, combined oral contraceptives are associated with a decreased risk of endometrial and ovarian cancer, which may persist for decades after stopping use.1,2
The way in which combined oral contraceptives increase the risk of breast cancer is likely to be through hormonal pathways. Oestrogen and progestogen affect the growth of some types of breast cancer.
Summary of the evidence
Evidence classification: Convincing
There is convincing evidence that current use of the combined oestrogen-progestogen oral contraceptive pill is associated with an increased risk of breast cancer.
The risk of breast cancer among current users of combined oral contraceptives is estimated to increase by 7% for every 5 years of use (RR 1.07, 95% CI 1.03–1.11).3 The increased risk decreases when use of the oral contraceptive ceases.
Mechanisms
Combined hormonal oral contraceptives contain an oestrogen and a progestogen. Their main contraceptive action is through preventing ovulation. Combined oral contraceptives are available in many combinations of the oestrogen and progestogen components, dosages and modes of delivery.
Oestrogens and progestogens may influence breast cancer risk through hormone-receptor-mediated pathways or through hormone-induced DNA damage.4,5
Evidence
The International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence in humans for the carcinogenicity of combined oestrogen–progestogen oral contraceptives for cancer of the breast.5 Evidence considered by IARC included a large pooled analysis of data from more than 150,000 women who participated in 54 epidemiologic studies.6 The relative risk (RR) of breast cancer among women who were currently using the oral contraceptive pill compared with women who had never used oral contraceptives was 1.24 (95% confidence interval [CI]1.15–1.33); and for recent users, 1–4 years after stopping it, the relative risk was 1.16 (95% CI 1.08–1.23).6 There was no increased risk 10 years after use of the combined oral contraceptive had stopped.6
A recent meta-analysis7 and cohort study8 support IARC findings that the incidence of breast cancer is higher in recent users of combined oral contraceptives (less than 5 years since use stopped) than in the general population, and this risk declines with time after stopping use.
In addition, a dose-response meta-analysis suggested an increased risk for every 5 years of use of 7% (RR 1.07, 95% CI 1.03–1.11).3
Several other cohort studies have reported an increased risk of breast cancer associated with use of oral contraceptives. One found that current use of triphasic preparations containing levonorgestrel as the progestin was associated with a higher risk than use of other formulations.9
It is estimated that 0.7% of breast cancers each year in Australia are attributable to the use of oral contraception that contains the hormones oestrogen and progestogen.10
Read the full Review of the Evidence
References
- Collaborative group on Epidemiological Studies on Endometrial Cancer (2015). Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncology 16 (9):1061–1070
- Havrilesky LJ, Moorman PG, Lowery WJ, et al. (2013). Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis. Obstetrics and Gynecology 122 (1):139–47
- Zhu H, Lei X, Feng J & Wang Y (2012). Oral contraceptive use and risk of breast cancer: a meta-analysis of prospective cohort studies. European Journal of Contraception & Reproductive Health Care 17(6):402–414.
- Pike MC, Spicer DV, Dahmoush L et al. (1993). Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiologic Reviews 15(1):17–35.
- International Agency for Research on Cancer (2012). Pharmaceuticals, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, volume 100A, IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Lyon.
- Collaborative Group on Hormonal Factors in Breast Cancer (1996). Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 347:1713–1727.
- Iversen L, Sivasubramaniam S, Lee AJ, et al. (2017). Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study. American Journal of Obstetrics & Gynecology 216(6):580.
- Gierisch JM, Coeytaux RR, Urrutia RP, et al. (2013). Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiology, Biomarkers & Prevention 22(11):1931–1943.
- Hunter DJ , Colditz GA, Hankinson SE, et al. (2010). Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiology, Biomarkers & Prevention 19:2496–2502.
- Whiteman DC, Webb PM, Green AC, et al. (2015). Cancers in Australia in 2010 attributable to modifiable factors: summary and conclusions. Australian and New Zealand Journal of Public Health 39 (5):477–84
Reproductive factors
Reproductive factors can have an important effect on a woman’s risk for breast cancer by influencing her hormone levels, which, over a woman’s lifetime, can be associated with increased or decreased risk of breast cancer.
Modifiable reproductive factors associated with risk of breast cancer include whether a woman has breastfed children.
Read more below to find out changes you can make to reduce your risk of breast cancer, and what you can do.
Breastfeeding
Breastfeeding is probably associated with a decreased risk of breast cancer.
The longer a woman breastfeeds, the lower her risk of breast cancer. The risk of breast cancer decreases by about 2% for every 5 months that a woman breastfeeds. This is equivalent to a 5% decrease in risk of breast cancer for a lifetime total of 12 months of breastfeeding.
When a woman is lactating (producing milk) and breastfeeding, the level of the hormone oestrogen in her body is lower. Oestrogen promotes the growth of some types of breast cancer. A period of breastfeeding reduces the amount of oestrogen that a woman is exposed to during her lifetime. This might be one of the ways in which breastfeeding protects against breast cancer.
Another possibility is that breastfeeding changes the cells in the breast in ways that make them more resistant to cancer. In addition, cells are lost from the lining of the breast ducts during breastfeeding, which might eliminate cells that have already accumulated DNA damage and that could lead to cancer in the future.
Summary of the evidence
Evidence classification: Probable
Breasfeeding is probably associated with a small decreased risk of breast cancer.1
There is evidence of a dose-response relationship, that is, the longer the duration of breastfeeding, the larger the protective effect. Breastfeeding probably decreases the risk of breast cancer1, with evidence of a dose-response relationship present. The risk of breast cancer has been estimated to decrease by 2% for every 5 months that a woman breastfeeds (RR 0.98, 95% CI 0.97–0.99).1 This is equivalent to a 5% decrease in risk of breast cancer for a cumulative total of 12 months and 9% decrease in risk of breast cancer for a cumulative total of 24 months of breastfeeding.
Mechanisms
Several mechanisms have been suggested for the way in which breastfeeding might influence breast cancer risk. The most plausible is the effect of lactation-induced amenorrhea in reducing a woman’s lifetime exposure to oestrogen.2 Lactation may also cause epigenetic changes that affect the risk of cancer. Exfoliation of breast tissue during lactation may reduce breast cancer risk by eliminating cells with DNA damage.1,2
Evidence
The WCRF/AICR concluded that ‘lactation probably protects against breast cancer’.2 This was based on analysis of 13 prospective cohort studies, which showed a small but significant dose–response effect. The risk of breast cancer was estimated to be decreased by 2% per 5-month duration of breastfeeding (relative risk [RR] 0.98, 95% confidence interval [CI] 0.97–0.99).
Several of the recent meta-analyses included in the analysis by WCRF/AICR3-5 reported a protective effect of ever breastfeeding compared with never breastfeeding.3-5 A greater protective effect of longer duration of breastfeeding was also found in two of these meta-analyses.3,6 For example, the decreased risk among women who breastfed for the longest versus shortest duration was estimated to be 0.47 (95% CI 0.37–0.60).3 Preliminary evidence indicates that the protective effect may be significant only for certain types of breast cancer, including triple negative subtypes.1,4-6
Read the full Review of the Evidence
References
- 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.
- World Cancer Research Fund International/American Institute for Cancer Research (2018). Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity, and cancer: a global perspective. London, UK.
- Zhou Y, Chen J, Li Q, et al. (2015). Association between breastfeeding and breast cancer risk: evidence from a meta-analysis. Breastfeeding Medicine 10:175–182.
- Islami F, Liu Y, Zhou J, et al. (2015). Breastfeeding and breast cancer risk by receptor status: a systematic review and meta-analysis. Annals of Oncology 26:2398–2407.
- Lambertini M, Santoro L, Del Mastro L, et al. (2016). Reproductive behaviors and risk of developing breast cancer according to tumor subtype: a systematic review and meta-analysis of epidemiological studies. Cancer Treatment Reviews 49:65–76.
- Ma H, Ursin G, Xu X, et al. (2017). Reproductive factors and the risk of triple-negative breast cancer in white women and African–American women: a pooled analysis. Breast Cancer Research 19:6.