Breast milk hides the key to detecting breast cancer earlier

A team from the Vall d’Hebron Institute of Oncology (VHIO) has demonstrated for the first time that breast milk of breast cancer patients contains tumor DNA, known as circulating tumor DNA (ctDNA). This ctDNA is susceptible to being detected through liquid biopsy in breast milk and could become a new tool for early diagnosis of breast cancer in the postpartum period. The results of this research, led by Dr. Cristina Saura, head of the Breast Unit of the Vall d’Hebron University Hospital and the VHIO Breast Cancer Group, and Dr. Ana Vivancos, head of the Genomics laboratory of VHIO, have just been published in the magazine Cancer Discovery.

The Breast Unit of the Vall d’Hebron University Hospital has a specific multidisciplinary unit to treat women who are diagnosed with breast cancer during pregnancy or during the postpartum. “During all the years that this unit has been operating,” explains Dr. Saura, “we have observed that patients with breast cancer who are diagnosed during pregnancy or, especially, during the postpartum period have a worse prognosis due to their diagnosis in more advanced stages of the illness”. It is for this reason that new effective early detection methods are needed to detect these tumors.

“The physiological changes that occur in the breast during pregnancy and postpartum make tumors more difficult to detect; We have also observed that biologically, postpartum tumors are more aggressive and women become pregnant at ages when population screening with mammography is not yet done. In Spain, for example, these reviews do not begin until age 50.”

These patients usually have a poor prognosis because the diagnosis is made when the stage of the tumor is already advanced since they are technically more difficult to detect and because, due to age, these women do not enter population screening programs.

Biomedical research, unlike other fields of science, relies on the participation, experience and involvement of patients, either because of their generosity when participating in clinical trials or because they ask scientists questions from a completely different perspective. different.

In this case it was the concern of a patient with breast cancer diagnosed during the pregnancy of her third daughter. She was concerned that she had transmitted the tumor through breast milk to her second daughter during breastfeeding, which had been long and had continued until shortly before her breast cancer diagnosis.

“The patient,” explains Dr. Saura, “brought us a sample of breast milk that she had stored in her freezer. And there, thanks to her, is where our project begins because, although we know that the breast cancer is not transmitted through breast milk, we decided to analyze the sample in search of markers that could help us in the investigation. And, indeed, when analyzing the patient’s breast milk we found DNA with the same mutation that was present in her tumor. “The breast milk had been frozen more than a year before the patient’s cancer diagnosis.”

Liquid biopsy to detect breast cancer

Liquid blood biopsy is used today in patients with metastatic breast cancer for the detection or monitoring of some mutations, but it still has little sensitivity as a tool for early diagnosis or in predicting relapses since a large amount of DNA is needed. circulating tumor too high in the blood to be detected.

In recent years, liquid biopsy has been developed in urine to detect bladder cancer or in saliva for head and neck cancer. “So we think that, due to proximity to the tumor, breast milk could be an alternative source to detect the tumor through liquid biopsy,” says Dr. Ana Vivancos.

The article that the magazine now publishes Cancer Discovery collects the first results of the study. The researchers collected breast milk and blood samples from breast cancer patients diagnosed during pregnancy or postpartum, as well as from healthy women who were in the process of breastfeeding.

“We analyze breast milk and blood samples using two techniques, Next Generation Sequencing (NGS) and Droplet Digital PCR (ddPCR)” explains the Dr. Ana Vivancos. “And we verified that in breast milk there is free circulating DNA of tumor origin. We were able to detect mutations present in the tumor of breast cancer patients in their breast milk sample in 13 of the 15 patients analyzed. While, in the blood samples collected at the same time, ctDNA was only detected in one of them.”

“The breast milk samples of the two patients in whom the mutation was not detected had been collected in the first hours of lactation, they were colostrum,” explains the Dr. Miriam Sansó, lead author and postdoctoral researcher in the Cancer Genomics laboratory during the study, “so we deduced that probably not enough time had passed for the tumor DNA to have been released into the milk. So we decided from then on to take breast milk samples at least two weeks after starting breastfeeding.”

“We have shown for the first time that breast milk obtained from breast cancer patients contains sufficient ctDNA to be detected through liquid biopsy and that this ctDNA can be detected even before the diagnosis of breast cancer can be made by a test.” conventional image” states the Miss Cristina Saura.

Source: Vall d’Hebron Institute of Oncology

“Our next step to give practical use to this discovery was to design a genomic panel based on NGS as a possible method for early diagnosis of breast cancer,” says Dr. Vivancos. Based on public data, the study researchers designed the VHIO-YWBC gene panel which allows detecting the most frequent mutations present in women with breast cancer diagnosed before the age of 45. The panel has “a sensitivity of more than 70%. That is to say, of the samples from our patients analyzed with this panel, 7 out of 10 cases would have been detected with a specificity of 100%.”

“This panel could serve us in the future as a method for early diagnosis of breast cancer in the postpartum” explains Dr. Saura. “In the same way that the heel test is performed on all newborns, we could consider collecting a sample of breast milk from all women after giving birth to perform breast cancer screening.”

One of the cases of high-risk women included in the work further reinforces this idea of ​​using the designed gene panel and the liquid biopsy of breast milk to advance the early diagnosis of breast cancer. She was a healthy woman who, when she became pregnant with her first child at the age of 46, wanted to participate in the study. 18 months after having her child, she was diagnosed with breast cancer thanks to the breast ultrasounds that were performed during the follow-up of the study. “We analyzed the blood and breast milk samples that we had collected in the follow-up at eight and eleven months after delivery and we verified that the mutation that was present in the patient’s tumor was already present in the breast milk of the affected breast. eleven months after delivery, 6 months before the diagnosis made by breast ultrasound. Neither in the blood nor milk samples from the healthy breast did we detect the mutation and, therefore, we could have diagnosed the tumor six months earlier with the use of this technique,” she concludes. Dr. Carolina Ortizresearcher in the VHIO breast cancer group and signatory of the article as first author along with Dr. Saura.

The next step to confirm the usefulness of using breast milk as a new liquid biopsy tool for the early detection of breast cancer in the postpartum is to perform this non-invasive test on thousands of women. Based on the results published today, VHIO will begin a study with the aim of collecting breast milk samples from 5,000 healthy women worldwide who have become pregnant at the age of 40 or older, or of any age who are carriers of mutations. that increase your risk of breast cancer (BRCA1, BRCA2, PALB2, RAD51C/D)

“Our results open the door for the future use of breast milk as a new source of liquid biopsy for the early detection of breast cancer in the postpartum through a non-invasive technique,” ​​says Dr. Cristina Saura. “Before this technique is put into practice, these results must be confirmed in a larger number of patients, but the results published today are encouraging and offer a potential new tool for the early diagnosis of breast cancer in a population.” especially sensitive of young women and mothers. The best way to continue increasing the survival of patients with breast cancer and cure more is to detect it as soon as possible and this is a new strategy that could help us a lot in this regard.”


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