Photomicrograph of estrogen receptor-positive breast cancer tissue. Shown are slow-dividing cancer cells that resist therapy (red), cell nuclei (blue), and rapidly-dividing cancer cells (green).
Dana-Farber Harvard Cancer Center/National Cancer Institute/Science Photography Library at Massachusetts General Hospital
Repurposing leukemia drugs may stop the most common type of breast cancer from causing tumors elsewhere in the body, according to a study in mice, but the risk of side effects is too great for humans. may not be used for
Frances Turrell and her colleagues at the UK Cancer Institute induced estrogen receptor-positive (ER+) mammary tumors in mice. It is the most common type of breast cancer in humans, accounting for up to 80% of cases and usually occurring in people over the age of 50.
ER+ breast cancer often recurs years later, even when treatment appears successful. This is because the cells can migrate to other parts of the body before treatment and cannot be detected before treatment begins, Turrell says. Yes, and something could trigger it to reawaken.”
To learn more, the researchers fed young mice aged 8-10 weeks and older mice aged 9-18 months with ER+-positive breast cancers. Mice were not treated for these tumors. After 2-5 weeks, almost all had cancer cells at secondary sites.
In young mice, these secondary-site cancer cells did not divide, but in older mice, the cells were more likely to develop into tumors that grew primarily in the animal’s lungs.
The researchers then found that tumor growth in older mice was associated with upregulation of a growth factor called PDGF-C in the lungs.
In both humans and mice, pulmonary PDGF-C levels rise with age, which could create an environment that stimulates the division of secondary cancer cells, Turrell said.
Higher PDGF-C levels may indicate a weakened immune system, according to Claire Isaacke of the Cancer Institute.
In another part of the experiment, the researchers partially blocked tumor growth in aged mice by inhibiting PDGF-C using imatinib, a drug widely given to patients with chronic myelogenous leukemia.
Imatinib suppressed the growth rate of secondary tumors in mice, but some lesions still formed, says Turrell.
While this could potentially be used in people, she says there’s no way to predict in whom ER+ breast cancer may later recur elsewhere in the body.
Imatinib has many side effects, including stomach pain and fatigue, says Isacke. “I don’t want to treat people who don’t actually experience a relapse,” she says.
The researchers now plan to repeat this experiment in mice using drugs with more targeted effects on PDGF-C levels.
Suzanne Wardell of Duke University, North Carolina, says the study highlights the need to better understand the environmental factors in the body that drive the growth of secondary tumors. “Further work is needed to determine the overall general applicability of our findings to human cancer therapy,” she says.
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