Breast cancer breakthrough could stop disease from returning in patients

Woman examining her breast for cancer

Scientists believe they have come up with a way of preventing breast cancer returning

Even in the earliest stages of breast cancer, cells can migrate to bone marrow and lie dormant and safe from chemotherapy, causing future relapse. A breakthrough could prevent breast cancer returning after scientists discovered how the disease hides from treatment in the bones.

This explains why breast cancer survivors can relapse up to ten or 15 years later and US scientists may have found ways to prevent this.

They identified a molecular key that breast cancer cells use to invade bone marrow in mice, where they may be protected from chemotherapy or hormonal therapies that could otherwise kill them.

Through years of experiments in mice however, ways have been found to outmanoeuvre this tactic.

Close up of woman in pink bra with breast cancer symbol on her chest
Breast cancer cells can lie dormant in bone marrow tissue

This can be done by both preventing the breast cancer cells from entering bone marrow and also by flushing the cells into the bloodstream, where they can be targeted by therapy.

The findings provide insight into one of the most devastating tendencies of some breast cancers, the ability to return.

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Cells from breast cancers that are hormone receptor-positive roam through the blood and tissues of mice.

These cells are on the lookout for specific blood vessels in bone marrow that contain the molecule E-selectin.

With their molecular key, molecules on their surface that bind to E-selectin, the cancer cells enter the spongy tissue inside bones, often lying dormant for years.

Breast cancer cell
The findings mean scientists could prevent breast cancer from returning

Hormone receptor-positive breast cancers are the most common type of breast cancer, according to the American Society of Clinical Oncology, and grow by exploiting the body’s oestrogen or progesterone.

In humans, these can resurge and create metastatic cancer relapse, for which there is no cure.

Biopsies of bone marrow in human breast cancer patients have shown that the roaming cancer cells are making their way into bone marrow even in the very early stages of cancer.

Associate Professor Dr Dorothy Sipkins at Duke University Medical Centre said: “Now we know how they are getting in.

“We also identified an important mechanism that allows them to remain anchored in the bone marrow.

Bone marrow cancer, X-ray
Biopsies of bone marrow in human breast cancer patients have shown that the roaming cancer cells are making their way into bone marrow even in the very early stages of cancer

“In the mouse, our findings could offer new strategies to intervene at the molecular level before dormant cells can take hold and cause relapse.”

The new discovery, if replicated in additional animal and human tests, could eventually lead to new therapies for treating breast cancer.

One strategy is finding a way to inhibit E-selectin, which could limit the cancer’s ability to travel into the bone.

One such inhibitor is currently being used in human clinical trials after the compound successfully prevented the breast cancer cells from entering the bone marrow in mice.

Cancer cells can also spread to bone marrow before patients are even diagnosed with breast cancer, so researchers also tested a strategy that kicks dormant cells out of the safety of bone marrow and back into circulation.

A consultant analyzing a mammogram
The findings could provide hope to women with breast cancer

They gave the mice plerixafor, an agent used in human bone marrow donors to push stem cells into the bloodstream for harvesting.

The drug forced the dormant cells into the blood cells, which scientists hypothesize may give the immune system, chemotherapy or hormonal therapy another opportunity to kill them off.

Associate professor Sipkins said: “We are hopeful that by understanding how these breast cancer cells migrate through the body and what their life cycle is, we can discover ways to make them more vulnerable and treatable.

“Our hope is to move forward with additional studies in mice to better understand our approach before moving on to studies in humans.”

The study was published in Science Translational Medicine.