Older first-time mothers may have an increased risk of developing breast cancer because of the impact of pregnancy on breast cells, according to a new study reported last night.
Researchers from Imperial College, London, reported a complex relationship between genetic mutations, pregnancy and breast cancer risk and their findings provide important clues as to what happens when breast cells turn cancerous.
The research, published in the latest edition of Nature Communications, may also explain why women who have their first child later in life could have a higher long-term risk of breast cancer compared to those who have babies earlier.
Lead study author Dr Biancastella Cereser, from Imperial’s Department of Surgery and Cancer, said: “In recent decades, women have begun having children later because of societal changes and personal preferences. Previous research has found that this is associated with a heightened breast cancer risk.
“Our own research delves into the genetic mysteries that govern this risk. We found that the human breast, like other organs, accumulates mutations with age – but also that pregnancy has an additional effect meaning that older first-time mothers might have a higher chance of developing harmful changes in their breast cells compared to other women.”
Several studies have reported that first-time mothers under the age of 24 have about a 20-35% lower risk of developing breast cancer in the long-term than women who do not have any children. However, the risk of breast cancer progressively increases for mothers who have their first child after the age of 24 – with a 5% increase in risk for every five years.
For this study, the team examined healthy breast cells from 29 women: first-time mothers under 25 years; first-time mothers between 35 and 55; and women, aged 24-53, with no children. None had a history of previous use of hormonal contraception and none had inherited mutations in BRCA1 or BRCA2 genes.
When they sequenced the entire genomes of their frozen healthy breast tissues, they found the healthy breast accumulates mutations with age, at rate of about 15 mutations a year in the epithelium tissue. Most of these have no negative effect and were not in genes known to be associated with cancer.
The researchers looked at clonal patches, which occur when a mutated cell shares its mutation with its daughter cells. They found breast tissue from first-time mothers aged between 35-55 years had significantly more, and larger, clonal patches.
“Nobody has looked at the entire genome of the healthy breast before, let alone differentiating into groups of women who had given birth at different ages, as well as women who did not have any children,” said Dr Cereser.
“I hope this study could be used as a resource for researchers looking at the genetics of healthy tissue in general, aside from the breast, and of course other breast cancer researchers, who could use the dataset of mutations we found as a reference.”
Dr Cereser believes as women age their breast cells naturally accumulate mutations.
While these may not be sufficient on their own to cause, pregnancy could induce a rapid expansion of breast cells, in preparation for breast feeding, according to the researcher. If cells harbouring driver mutations replicate and expand, these could have a competitive advantage over neighbouring non-mutated cells, potentially leading to a runaway effect, and ultimately creating a cancerous tumour.
However, Dr Cereser says further research needs to be carried out.
Cereser B, Yiu A, Tabassum N et al. The mutational landscape of the adult healthy parous and nulliparous human breast. Nature Communications 6 September 2023
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