About ten years ago, scientists showed not only that there is a breast microbiome but also that there is a link between breast cancer and disturbances in this microbial community (1,2). Since then, Katherine Cook, a cancer biologist at Wake Forest School of Medicine, has explored strategies for altering the breast microbiome to make it more resistant to cancer. In 2018, her team showed that dietary choices restructure the gut and the breast microbiomes in distinct ways (3). 

Now, in a recent Cell Reports Medicine  study, they have shown that the commonly prescribed breast cancer medication tamoxifen also modifies the breast microbiome in mice and monkeys and that those bacterial changes may limit tumor growth (4).

“The breast tissue has its own microbiome, and it is flexible,” said Cook. “We could manipulate it further for breast cancer prevention.”

Tamoxifen, which has relatively low toxicity for a cancer drug, blocks estrogen receptors that promote tumor growth. Although doctors use it to treat breast cancer, they also prescribe it as a breast cancer preventative, especially for postmenopausal women (5).

“The breast tissue has its own microbiome, and it is flexible.”
– Katherine Cook, Wake Forest School of Medicine

To understand how this particular use of tamoxifen might affect the breast microbiome, Cook and her team gave the drug to female monkeys without ovaries. When they took samples of the monkeys’ breast tissue and checked for bacterial DNA, the scientists found that tamoxifen changed the relative abundance of the various bacteria living in the tissue. Among other shifts, tamoxifen-treated breasts had more bacteria in the genus Lactobacillus, which includes food-fermenting species that people commonly consume as probiotics.

Cook knew from her previous work that diet can also alter the breast microbiome, so she decided to see if a healthy diet would enhance the effects of tamoxifen. They fed some mice a Mediterranean-style diet rich in olive and fish oils, and another group of mice ate a Western diet heavy on animal fat. The researchers treated all of the mice with tamoxifen. The drug caused a more pronounced shift in the bacteria collected from the mammary glands of the first group of mice, which ate the healthier diet.

To see if these microbiome shifts correlated with better outcomes for people, Cook’s team collected and analyzed tumor samples from patients who were taking aromatase inhibitors or Faslodex, both of which, like tamoxifen, deprive breast cancer cells of estrogen. They found that bacteria like Lactobacillus  were more common in patients with reduced tumor growth. 

Still, Cook wanted to move beyond associations. “As we increased Lactobacillus within the mammary gland tissues, would this reduce tumor formation?” she asked.

To find out, Cook’s team injected Lactobacillus and Bifidobacteria, another common probiotic, directly into the nipples of mice with breast tumors. Like people, mice with more beneficial bacteria had lower levels of tumor proliferation biomarkers. Analyzing the molecules in the mice’s mammary glands revealed that the probiotics changed how tumor cells produced energy, depriving the cancer of its preferred fuel source.

Finally, Cook’s team dosed tumor cells in vitro  with a tamoxifen metabolite and trehalose, a bacterial metabolite, to see if one of them was responsible for the changes they were seeing. As it turned out, both harmed the cancer cells.

Moving forward, Saori Furuta, a cancer biologist at Case Western Reserve University who was not involved in the study, hopes that Cook will investigate other bacterial metabolites as well. “What are those metabolites,” wondered Furuta, “those special, miracle metabolites that could be used for maybe cancer treatment or cancer prevention?”

Cook plans to explore this question, but she also wants to figure out what active steps women can take on their own to build healthier breast microbiomes. “We would never want to inject bacteria into humans,” she said. “We want to understand ways we can manipulate and change the human breast microbiome, [potentially] through diet.”

References

1. Urbaniak, C. et al.  Microbiota of human breast tissue. Appl Environ Microbiol  80, 3007-3014 (2014).
2. Xuan, C. et al.  Microbial dysbiosis is associated with human breast cancer. PLoS One  9, e83744 (2014).
3. Shively, C.A. et al.  Consumption of Mediterranean versus Western Diet leads to distinct mammary gland microbiome populations. Cell Rep  25, 47-56.e3 (2018).
4. Arnone, A.A. et al.  Endocrine-targeting therapies shift the breast microbiome to reduce estrogen receptor-a breast cancer risk. Cell Rep Med  6, 101880 (2025).
5. Howell, A. & Howell, S.J. Tamoxifen evolution. Br J Cancer  128, 421-425 (2023).