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Does abrupt weaning increase the risk of breast cancer?

Does abrupt weaning increase the risk of breast cancer?

In 2019, Basree et al. published a scientific study in which they studied whether abrupt weaning caused histological and molecular changes in the mammary gland (1) with the aim of understanding possible mechanisms of cancer protection in extended breastfeeding. This study assumes that breastfeeding generally decreases the risk of breast cancer, but it has been observed that the duration of breastfeeding has an impact on the risk of developing some types of cancer, such as triple negative breast cancer (TNBC), which is also an aggressive type of cancer with high mortality. In an observational study published in 2018 (2), they found that women with high parity (more than 3 pregnancies) and who did not breastfeed or breastfed for less than 12 months had an increased risk of TNBC. In contrast, women who breastfed for more than 24 months during their lifetime did not have an increased risk of TNBC.

In this context, Basree et al. conducted a study in female mice comparing the mammary tissues of mice with short (7-day) lactation and abrupt weaning with full lactation mice and gradual weaning. In the study, they observed that the mammary glands of mice which experienced an abrupt involution had denser stroma, an altered collagen composition, increased inflammation and proliferation, and increased oestrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. All these parameters are associated with increased risk of cancer. In addition, at 4 months postpartum those who underwent abrupt breast involution developed ductal hyperplasia and squamous metaplasia, which can be interpreted as precursor lesions of breast cancer. 

Although these results may sound alarming, they should be interpreted with caution and do not mean that abrupt weaning in general can increase the risk of cancer:  

  • The study has been performed in female mice and the results may not be extrapolated to women. 
  • The study has used FVN/N strain mice which, despite being widely used in animal models for breast cancer research, have been reported to develop spontaneous mammary lesions and tumours accompanied by pituitary gland abnormalities and those have a major impact on the human breast cancer model (3) and therefore may not be a valid or ideal model to perform this study.  
  • The study defines abrupt weaning as the breastfeeding that is not initiated after birth or is abruptly discontinued soon after initiation, causing the breast tissue to undergo a forced and abrupt remodelling. Therefore, the abrupt weaning defined involves either not initiating breastfeeding after the birth of the infant or interrupting it soon after birth during the postpartum period, but the results cannot be extrapolated to other stages of breastfeeding, such as weaning at 6 or 12 months. 
  • This same study included breast tissue samples from women who had undergone breast reduction and donated the removed tissue. These women had given birth previously and the study compared those who had breastfed less than 6 months vs. more than 6 months. But due to the limited number of samples available, they considered the total number of lactation months for all pregnancies (cumulative number of months). Parity and lactation time in these women was taken into account when performing the analyses. It should be noted that the number of pregnancies is the most influential factor in the development of breast cancer. But the authors found a limited number of samples available and a highly variable parity among women. Therefore, the results are not comparable with abrupt weaning. 
  • The aim of the study is to understand why longer duration of breastfeeding may decrease the risk of certain types of breast cancer and does not aim to study the impact of weaning per se

 

In conclusion, this study does not provide evidence that non-progressive weaning increases the risk of cancer. It does provide evidence that the duration of breastfeeding has an impact at molecular and histological level on the mammary gland and that abrupt weaning at the onset of breastfeeding or non-initiation of breastfeeding may modify this pattern.

 

References: 

  1. Basree MM, Shinde N, Koivisto C, Cuitino M, Kladney R, Zhang J, et al. Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer. Breast cancer Res [Internet]. 2019;21(1):80.
  2. John EM, Hines LM, Phipps AI, Koo J, Longacre TA, Ingles SA, et al. Reproductive history, breast-feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) Study. Int J Cancer [Internet]. 2018;142(11):2273–85.
  3. Raafat A, Strizzi L, Lashin K, Ginsburg E, McCurdy D, Salomon D, et al. Effects of Age and Parity on Mammary Gland Lesions and Progenitor Cells in the FVB/N-RC Mice. PLoS One [Internet]. 2012;7(8):1–8.
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