Two research teams have announced steps forward in tackling triple negative breast cancer on the same day. The approaches are very different and the timing coincidental, but the combination provides new hope for the hardest-to-treat class of breast cancers.
The majority of breast cancers express receptor genes for estrogen, progesterone or Her2/Neu. Chemotherapies exist to target each of these, hugely improving the prospects of survival for women (and sometimes men) diagnosed with these forms. However, 15-25% of breast cancers, known as triple negative breast cancers (TNBCs), express none of these.
TNBCs are diverse: Some types have prospects as good as other forms of breast cancer, whereas others are currently very hard to treat, with high relapse rates within 3-5 years.
The Garvan Institute, Sydney, has found that the different forms of TNBC can be categorized as two distinct diseases, which the researchers believe have different origins. In Nature Communications, Dr. Alex Swarbrick and Dr. Simon Junankar report that one form of TNBC is enriched in stem cells.
Junankar and Swarbrick conclude that the inhibitor of differentiation 4 (ID4) gene suppresses specialization in mammary stem cells. When working properly, ID4 delays stem cells' transformation into specialist cells. However, if the ID4 gene is overexpressed, the stem cells it preserves can easily turn cancerous.
“We found that ID4 is produced at high levels in roughly half of all triple negative breast cancers,” said Swarbrick. “These cancers have a particularly poor prognosis.” TNBC cancers that arise from specialist cells, and appear to have no stem cell involvement, have much higher treatment success.
“We also showed that if you block the ID4 gene in experimental models of triple negative breast cancer,” Swarbrick said, “the tumour cells stop dividing.” Moreover, when the ID4 gene is suppressed, oestrogen receptors are switched on within tumors, possibly converting the cancers to the most treatable form of breast cancer, oestrogen receptor-positive, against which the drug Tamoxifen has proved highly effective.
Swarbrick admitted, “We don’t know yet whether we are seeing a real oestrogen-dependent cancer after ID4 is blocked – one with an effective oestrogen receptor – or just a caricature of one.” However, even if the oestrogen receptor treatment path proves an illusion, blocking ID4 offers considerable hope for improving the prognosis for sufferers of TNBC.
A more immediate treatment option comes with the presentation of a study at the American Society for Pharmacology and Experimental Therapeutics Annual Meeting that found that extracts of rosehip decreased the proliferation of TNBC cancers in tissue cultures, as well as boosting the effectiveness of existing chemotherapies.
Plenty of chemicals have been shown to fight cancer in vitro, but experience problems when applied to living organisms. However, rosehips make a popular tea, promoted for a variety of conditions, and North Carolina Agricultural and Technical State University's Dr. Patrick Martin claimed it has “no known side effects,” making for a much quicker path to clinical use than a potentially dangerous drug.
For unknown reasons, TNBC is particularly common among African-American women. Patrice Cagle, a PhD student who will present the work at the ASPET conference said, "I am a young African-American female so there's a higher risk for me to potentially get triple negative breast cancer. There isn't a lot of research on TNBCs and African-Americans, so we're trying to increase the profile of this particular cancer in the scientific community and in the public eye."
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