Early-stage breast cancer detection in breast milk

Researchers at VHIO, led by Dr. Cristina Saura, head of the VHIO Breast Most cancers Group and the Breast Unit at Vall d’Hebron College Hospital, and Dr. Ana Vivancos, head of VHIO’s Genomics laboratory, has proven for the primary time that breast milk from breast most cancers sufferers comprises tumor DNA, generally known as circulating tumor DNA (ctDNA).

This ctDNA will be detected by means of liquid biopsy in breast milk and will grow to be a brand new device for early prognosis of breast most cancers within the postpartum interval. The outcomes of this analysis have simply been revealed within the journal Cancer Discovery.

The Vall d’Hebron College Hospital Breast Unit has a selected multidisciplinary unit to deal with girls identified with breast most cancers throughout being pregnant or in the course of the postpartum interval. “Throughout all of the years that this unit has been working,” explains Dr. Saura, “we’ve noticed that breast most cancers sufferers who’re identified throughout being pregnant or, particularly, in the course of the postpartum interval, have a worse prognosis as a result of they’re identified at extra superior phases of the illness.” Because of this new and efficient early detection strategies are wanted to detect these tumors.

“The physiological adjustments that happen within the breast throughout being pregnant and postpartum make tumors harder to detect; we’ve additionally noticed that biologically, postpartum tumors are extra aggressive, and ladies grow to be pregnant at ages when inhabitants screening with mammography is just not but carried out. In Spain, for instance, these check-ups don’t begin till they attain the age of fifty.”

A venture that started due to a affected person’s issues

Biomedical analysis, in contrast to different fields of science, depends on the participation, expertise, and involvement of sufferers both due to their generosity in collaborating in medical trials or as a result of they ask scientists questions from a very completely different perspective.

On this case it was the issues of a breast most cancers affected person identified whereas pregnant together with her third daughter. She was involved that she had handed the tumor by means of her breast milk to her second daughter throughout breastfeeding, which had been lengthy and had lasted till shortly earlier than her breast most cancers prognosis.

“The affected person” explains Dr. Saura “introduced us a pattern of breast milk that she had saved in her freezer. So, due to her, that is the place our venture began, as a result of though we all know that breast most cancers is just not transmitted by means of breast milk, we determined to investigate the pattern in quest of markers that would assist us in our analysis. And certainly, once we analyzed the affected person’s breast milk, we discovered DNA with the identical mutation that was current in her tumor. The breast milk had been frozen greater than a 12 months earlier than the affected person’s most cancers prognosis.”

Liquid biopsy in breast most cancers

Liquid blood biopsy is at the moment utilized in sufferers with metastatic breast most cancers for the detection or monitoring of sure mutations, however it nonetheless has low sensitivity as a device for early prognosis or predicting relapse because it requires a really excessive quantity of circulating tumor DNA within the blood to be detected.

In recent times, liquid biopsy has been developed to display screen urine for bladder most cancers or saliva for head and neck most cancers. “So we thought that, due to its proximity to the tumor, breast milk may very well be an alternate supply for detecting the tumor by liquid biopsy,” says Dr. Ana Vivancos.

The article outlines the primary outcomes of the examine. The researchers collected breast milk and blood samples from breast most cancers sufferers identified throughout being pregnant or postpartum, in addition to from wholesome girls who had been breastfeeding.

“We analyzed the breast milk and blood samples utilizing two methods, Subsequent Era Sequencing (NGS) and Droplet Digital PCR (ddPCR),” explains Dr. Ana Vivancos. “And we discovered that there was free circulating DNA of tumor origin within the breast milk. We had been in a position to detect mutations which had been current within the tumors of sufferers with breast most cancers within the samples of breast milk of 13 of the 15 sufferers analyzed. Whereas, within the blood samples collected on the identical time, ctDNA was solely detected in certainly one of them.”

“The breast milk samples of the 2 sufferers in whom the mutation was not detected had been collected throughout the first hours of lactation and had been colostrum”, explains Dr. Miriam Sansó, lead writer and postdoctoral researcher within the Most cancers Genomics laboratory in the course of the examine, “so we deduced that in all probability not sufficient time had handed for the tumor DNA to have been launched into the milk. So we’ve since determined to take breast milk samples not less than two weeks after initiating breastfeeding.”

“We now have proven for the primary time that breast milk obtained from breast most cancers sufferers comprises adequate ctDNA to be detected by liquid biopsy and that this ctDNA will be detected even earlier than breast most cancers will be identified utilizing standard imaging,” states Dr. Cristina Saura.

“Our subsequent step in making this discovery virtually helpful was to design an NGS-based genomic panel as a potential methodology of early prognosis in breast most cancers,” says Dr. Vivancos. Primarily based on publicly obtainable information, the researchers designed the VHIO-YWBC gene panel to detect essentially the most frequent mutations current in girls with breast most cancers identified earlier than the age of 45.

The panel has “a sensitivity of greater than 70%. Because of this, of the samples from our sufferers examined with this panel, 7 out of 10 instances would have been detected with a specificity of 100%.”

“This panel may very well be used sooner or later as a way for the early prognosis of breast most cancers within the postpartum interval,” explains Dr. Saura. “In the identical means {that a} heel prick is carried out on all newborns, amassing a breast milk pattern from all girls after beginning for breast most cancers screening is also thought-about.”

“We analyzed the blood and breast milk samples that we had collected within the follow-up at eight and eleven months postpartum and located the instances of high-risk girls included within the examine additional reinforces this concept of utilizing the designed gene panel and liquid breast milk biopsy to advance the early prognosis of breast most cancers. This was a wholesome lady who wished to take part within the examine when she turned pregnant together with her first little one on the age of 46.”

“18 months after giving beginning to her son, she was identified with breast most cancers on account of breast ultrasound scans as a part of the follow-up. The mutation within the affected person’s tumor was already current within the breast milk of the affected breast at eleven months postpartum, 6 months earlier than the breast ultrasound prognosis. We didn’t detect the mutation within the blood or the milk samples from the wholesome breast and due to this fact may have identified the tumor six months earlier with using this method,” concludes Dr. Carolina Ortiz, researcher within the breast most cancers group at VHIO and lead uthor of the article, along with Dr. Saura.

The subsequent step in confirming the usefulness of utilizing breast milk as a brand new liquid biopsy device for the early detection of breast most cancers within the postpartum interval is to carry out this non-invasive take a look at on hundreds of ladies. Primarily based on the outcomes revealed at this time, we’re initiating a examine to gather breast milk samples from 5,000 wholesome girls worldwide who turned pregnant at 40 years of age or older, or at any age who carry mutations that improve their threat of breast most cancers (BRCA1, BRCA2, PALB2, RAD51C/D).

“Our outcomes open the door to the long run use of breast milk as a brand new supply of liquid biopsy for the early detection of breast most cancers within the postpartum interval utilizing a non-invasive method,” affirms Dr. Cristina Saura.

“Earlier than this method will be put into observe, these outcomes must be confirmed in a bigger variety of sufferers, however the outcomes revealed so far are encouraging and provide a possible new device for the early prognosis of breast cancer in a very delicate inhabitants of younger girls and moms. One of the simplest ways to proceed to extend the survival and remedy of breast cancer patients is to detect it as early as potential and this can be a new technique that would tremendously assist us on this regard.”

Offered by
Vall d’Hebron Institute of Oncology