Research opens the door to early detection of breast cancer through breast milk

A study detects, for the first time, tumor DNA in breast milk of patients with breast cancer and proposes liquid biopsy of this fluid as a tool for early diagnosis of the disease.

Some time ago, a woman with breast cancer gave her doctor, oncologist Cristina Saura, samples of breast milk that she had frozen 18 months before her diagnosis. The tumor was detected when she was pregnant with her third child, and the woman feared that she had transmitted the disease through her breast milk to her second daughter, whom she breastfed until shortly before she became ill. Saura and her team knew that the tumor is not transmitted through breastfeeding, but the patient’s concern led them to “turn on a light bulb,” explains the oncologist: perhaps in that milk sample there were already signs of the cancer that would help the research.

And they found something: in that frozen food many months before the cancer diagnosis, there was already tumor DNA that betrayed the presence of cancer in the organism. In a subsequent study involving fifteen patients and published in the journal Cancer Discovery, Saura and his team at the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona confirmed the presence of fragments of tumor DNA in breast milk. The research opens the door to using the analysis of this fluid as a tool to diagnose breast cancer early in the postpartum period.

The technique of liquid biopsy has shaken up cancer research. This diagnostic approach consists of searching the body’s fluids, especially blood, for signs or traces of a tumor before it shows its face, such as pieces of DNA released by cancer cells into the bloodstream. In this way, a type of blood test (much less invasive than a traditional biopsy) can detect the presence of even invisible tumors. Liquid blood biopsy has already been tested for colon or breast cancer, but also cerebrospinal fluid biopsy for brain tumors, urine biopsy for bladder neoplasms or saliva biopsy for oral cancer. Breast milk is the new body fluid in close contact with a tumor that is now showing its potential in the early diagnosis of the disease at a particularly complex stage, such as the postpartum period.

Research opens the door to early detection of breast cancer through breast milk

The finding lands in a field, that of gestation and lactation, where all the variables play against each other. Starting with incidence. Breast cancer is the most common cancer detected in these stages: “Breast tumors diagnosed in the postpartum period or during pregnancy represent up to 55% of the tumors diagnosed under the age of 45,” warns Saura. And the forecast is that “cases will increase in the coming years,” warn the researchers in the study, bearing in mind that aging increases the risk of this ailment and that there is a tendency to delay pregnancy in developed countries. In addition to the fact that the incidence is on the rise, in these contexts, this disease tends to have a complex diagnosis and, sometimes, a more unfavorable prognosis.

Following the request from Saura’s patient, the Vall d’Hebron researchers began a study and analyzed samples of breast milk and blood from fifteen women with breast cancer and a dozen healthy volunteers. “In women who have breast cancer diagnosed in pregnancy or breastfeeding we found circulating tumor DNA in breast milk. In 13 of the 15 patients, the [milk] samples were positive,” explains Saura, who is head of the Breast Unit at Vall d’Hebron Hospital and head of VHIO’s Breast Cancer Group. In the other two, the samples collected were colostrum (the first milk) and the researchers suspect that the tests were negative because the tumor DNA did not have time to come into contact with this fluid. “For the DNA to be released from the cells, several days have to pass. We believe that [with colostrum] not enough milk has been produced to carry tumor DNA,” the oncologist says. The frequencies of the variants detected in the colostrum, in fact, were “almost seven times lower compared to those collected after 14 days of lactation and considered mature samples,” the study states. No traces of the tumor were found in the milk analysis of healthy volunteers.

The researchers also found that the sensitivity of the breast milk tests was higher than that of the blood samples, which were almost all negative. “It was expected,” Saura qualifies, because, in breast cancer, to find tumor DNA in a liquid blood biopsy, a high disease burden is needed (for example, when there is metastasis). “With a localized tumor, the amount of tumor DNA in the blood is always low. In milk, on the other hand, we are already able to detect tumor DNA,” explains the physician.

Towards an early diagnostic test

With the study, the scientists demonstrated, for the first time, that the breast milk of breast cancer patients has enough tumor DNA to detect it through a liquid biopsy, even before the diagnosis can be made with conventional imaging tests. Saura points out that the results of the study open the door to developing an early diagnostic test in the postpartum period in women who decide to breastfeed, but admits that this finding is still the first step.

Teresa is one of the study participants and her case, like that of that first patient who triggered the research, illustrates the potential of this screening technique: she was healthy when she became pregnant, but she was 46 years old and, because of the risk factor of age, wanted to participate in the study. “At 18 months [after the child was born], at one of the trial controls [a follow-up breast ultrasound], they detected the tumor and I put myself in their hands. Because it was detected at an early stage, chemotherapy was not necessary. I had surgery and radiation therapy,” explains the 50-year-old woman on the other end of the phone. However, in the analysis of breast milk samples taken as part of the trial 11 months after delivery (half a year before the breast ultrasound diagnosis), fragments of tumor DNA were already visible. This means that, with this technique, the diagnosis could have been made six months earlier, according to the authors of the study.

The research is still underway and, in order to realize the potential of their findings, Saura and his team have also developed a panel of genes with the most frequent mutations present in women with cancer diagnosed before the age of 45. As with the heel prick test in infants to detect congenital metabolic disorders, this panel, which will be used to analyze breast milk samples, could also function as a method of early diagnosis in the postpartum period, the researchers predict. “The third step, for this to be translated into a useful test for early diagnosis, is to demonstrate it, and we will carry out a study that will include 5,000 healthy women at risk of breast cancer [over 40 years of age and/or with a genetic predisposition] who will have a blood sample taken, as well as a milk sample from each breast, will undergo an ultrasound scan and will be followed up for two years,” Saura points out.

Joan Albanell, head of the Oncology Department at the Hospital del Mar in Barcelona, describes this research, in which he did not participate, as “innovative”: “At the clinical level, the impact is yet to be determined, but it is a conceptual advance,” he agrees. The doctor emphasizes that, according to this study, breast milk “is a more reliable source for detecting circulating tumor DNA” and opens the door to the possibility that, with liquid biopsy, “the diagnosis can be brought forward”. But Albanell is cautious about the timing: “To see if this can be transferred to systematic screening of patients, multicenter studies are needed to validate the value and efficiency of the technique.

Saura insists that, “if everything goes well, there will be a new tool for the early detection of breast cancer in the postpartum period”. In practice, he specifies, this could mean an improvement in prognosis and survival because it will be possible to “detect tumors when they are localized”, at earlier stages.