Written by: Anna Petherick, Ph.D. | Issue # 109 | 2022
- Developments in the analysis of the vesicles in breast milk have identified constituents that are linked to some breast cancers.
- The analysis of breast milk for the purposes of diagnosing breast cancer risk is especially important because the risk of aggressive breast cancer rises after giving birth.
- To speed research progress, investigators argue for a breast milk repository, where unpasteurized human milk is stored for scientific research.
For many years, researchers have thought about the potential for breast milk samples to help in the diagnosis of breast cancers. The idea is practical in the sense that sampling milk is cheap and non-invasive. There are shortcomings to the idea, of course, most obviously that not all women lactate, and those who do lactate do so for a limited period of time. Moreover, the potential for breast milk to offer clues in the diagnosis of breast cancers hinges on scientists developing a sufficiently deep understanding of its components, and of their variation due to factors other than cancer. But this is where research is developing apace. Of particular note are developments in the study of the vesicle contents of breast milk. Yet for the field to really move forward, some researchers argue that a more systematic means of collecting and assessing breast milk would be hugely helpful [1].
Although using breast milk as a cancer diagnostic may seem like a big step, breast milk samples are already used in the study of disease, and common differences have been established in the milks of women with and without markers of disease. Specifically for metabolic afflictions during pregnancy, such as gestational hypothyroidism and gestational diabetes, researchers have found footprints—associations—of the constituents of mothers’ milk and these medical problems. For example, fewer metabolic and cell-structure proteins have been reported, alongside rising levels of immune proteins, in the colostrum of women with gestational hypothyroidism, a condition where the thyroid gland becomes insufficiently active during pregnancy [2]. These associations serve to make the point that breast milk’s components offer clues as to the state of the maternal body.
There are a few reasons why the analysis of breast milk vesicles might offer potential diagnostics for breast cancers. For various types of cancer, scientists are exploring the idea of using vesicles in body fluids, including saliva, blood and urine, for diagnosis, prognosis and surveillance [3]. But breast milk is especially promising in this regard, as it contains high quantities of these vesicles compared with blood and urine. Moreover, some of the proteins found in breast milk exosomes are known to have oncogenic effects. These include proteins involved in breast involution—the process of remodelling the breast tissue after birth and breastfeeding towards its pre-pregnancy form—that are also linked to metastasis of breast cancers. The proteins in question are matrix metalloproteinase proteins, such as matrix metalloproteinase 2 (MMP-2), MMP-3 and MMP-9.
Such findings go to the heart of why assessing breast cancer risk among women who recently gave birth matters so much. No matter at what age a woman gives birth, having a baby confers a temporarily increased risk of developing breast cancer for a decade after, and indeed for another decade beyond that for women over 35 [4]. During the period half to a full decade after giving birth, the risk of developing metastatic cancer is notably higher [4]. The mechanistic reasons for these elevated risks are frequently linked to processes that happen during postpartum breast involution. Thus, being able to identify in breast milk levels of particular molecules that indicate the degree of elevated risk could select some mothers for more regular check-ups, and lead to much earlier diagnoses—with the potential to save lives. It should be noted that lactating in and of itself reduces the risk of developing breast cancer.
Some research teams claim that the science is mature enough for the use of breast milk in early detection of breast cancers. A review published in May 2022 written by three members of proteomics bioanalytics department at Nestle research in Lausanne, Switzerland, noted that “proteomic tools and methodologies have reached certain maturity” whereby “they are now better suited to discover innovative and robust biofluid biomarkers” [2]. These authors argue that pilot data already supports the hypothesis that specific proteins linked to the early detection and accurate assessment of breast cancer risk can be determined using breast milk samples.
As always, however, more research is needed, and probably a more concerted effort to facilitate it. This is where some form of breast milk repository could be helpful, argue Jeanne Murphy of the U.S. National Cancer Institute, in Bethesda, Maryland, and colleagues [1]. They have in mind a repository similar to the National Children’s Study Vanguard, which is a regional effort. The idea would be to store samples of breast milk from diverse women of different ages, socioeconomic and ethnic groups, at different timepoints in lactation—without processing their milk in such ways as to destroy the chemical components inside, as pasteurization typically does. The authors note that a model project, even though it is for the storage of breast tissue and blood samples rather than milk, is the Komen Tissue Bank. An analogous project to this, storing breast milk samples, would be a long-term investment in the study of “normal” breast milk constituents, and make possible studies using very large numbers of women to assess the performance of breast milk diagnostics.
References
1. Murphy J., Sherman M. E., Browne E. P., Caballero A. I., Punska E. C., Pfeiffer R. M., Yang H, P., Lee M., Yang H., Gierach G. L. & Arcaro K. F. Potential of Breastmilk Analysis to Inform Early Events in Breast Carcinogenesis: Rationale and Considerations. Breast Cancer Res Treat. 157(1): 13–22. doi:10.1007/s10549-016-3796-x (2016)
2. Dayon L., Cominetti O. & Affolter M. Proteomics of Human Biological Fluids for Biomarker Discoveries: Technical Advances and Recent Applications. Expert Rev Proteomics. (In press, 2022)
3. Xu R., Rai A., Chen M., Suwakulsiri W., Greening D. W. & Simpson R.J. Extracellular vesicles in cancer — implications for future improvements in cancer care. Nat Rev Clin Oncol. 15: 617–638. https://doi.org/10.1038/s41571-018-0036-9 (2018)
4. Borges V. F., Lyons T. R., Germain D. & Schedin P. Postpartum Involution and Cancer: An Opportunity for Targeted Breast Cancer Prevention and Treatments? Cancer Res. 80 (9): 1790–1798. https://doi.org/10.1158/0008-5472.CAN-19-3448 (2020)