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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. 

Some reproductive factors are protective for breast cancer. Reproductive factors associated with a decreased risk of breast cancer risk include whether a woman has had children and whether she has breastfed.

Having children

Convincing

There is compelling and consistent evidence that the factor increases or decreases the risk of breast cancer.

Having had children is associated with a decreased risk of breast cancer.

For each child a woman has had, the risk of breast cancer decreases by about 7%.

When a woman has a full-term pregnancy, changes occur in cells in the breast in preparation for breastfeeding. These changes are thought to make the cells less likely to become cancer cells.

This might explain why women who have had children have a lower risk of breast cancer than women who have not had children.

Evidence classification: Convincing

There is convincing evidence that having children (parity), compared with not having children (nulliparity), is associated with a decreased risk of breast cancer in a dose-response manner. It is estimated that for each child a woman has had, the risk of breast cancer decreases by about 7% (RR 0.93, 95% CI 0.91–0.95).1

Mechanisms

Having children might reduce the risk of breast cancer through changes that occur in breast epithelial cells in preparation for lactation. These changes involve differentiation of epithelial cells, which is thought to make the cells less vulnerable to DNA damage.2

Evidence 

The World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR 2018) report that ‘not bearing children’ is an established risk factor for breast cancer and that the reverse applies, that ‘bearing children reduces the risk of breast.3

A pooled analysis of data from 47 epidemiological studies in 30 countries reported that women with breast cancer had fewer births, on average, than did controls (2.2 vs. 2.6).1 The risk of breast cancer decreased by 7% for each birth (relative risk [RR] 0.93, 95% confidence interval [CI] 0.91–0.95) for each birth.1

A meta-analysis in 2012 found that the risk of breast cancer in women who had not had children compared with women who had children was 1.16 (95% CI 1.04–1.26), and women with 3 or more births had a 0.73 times lower risk of breast cancer than women with no births (odds ratio [OR] 0.73, 95% CI 0.61–0.87).4 A more recent meta-analysis only included studies reporting on the association according to tumour subtype, and found a significant protective effect of having children for luminal breast cancer (oestrogen receptor-positive, ER+ breast cancer).5 

Two more recent cohort studies support the findings of the pooled analysis and meta-analyses.6,7

Read the full Review of the Evidence

References
  1. Collaborative Group on Hormonal Factors in Breast Cancer (2002). Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50 302 women with breast cancer and 96 973 women without the disease. Lancet 360(9328):187–195.
  2. Russo J, Moral R, Balogh GA, et al. (2005). The protective role of pregnancy in breast cancer. Breast Cancer Research 7(3):131–142.
  3. 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.
  4. Nelson HD, Zakher B, Cantor A, et al. (2012). Risk factors for breast cancer for women aged 40 to 49 years: a systematic review and meta-analysis. Annals of Internal Medicine 156(9):635–648.
  5. 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
  6. Dartois L, Fagherazzi G, Baglietto L, et al. (2016). Proportion of premenopausal and postmenopausal breast cancers attributable to known risk factors: estimates from the E3N–EPIC cohort. International Journal of Cancer 138(10):2415–2427.
  7. Ritte R, Tikk K, Lukanova A, et al. (2013). Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort studyBMC Cancer 13(1):584.
Breastfeeding

Probable

The factor is likely to be associated with increased or decreased risk of breast cancer, but the evidence is not as strong as for convincing.

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.

Evidence classification: Probable

Breastfeeding 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. 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
  1. 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.
  2. 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.
  3. Zhou Y, Chen J, Li Q, et al. (2015). Association between breastfeeding and breast cancer risk: evidence from a meta-analysisBreastfeeding Medicine 10:175–182.
  4. 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.
  5. 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.
  6. 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 analysisBreast Cancer Research 19:6.



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