ALSO old strategies can lead to new results. For example, when we talk about the most common breast cancer, the one that grows stimulated by female hormones (about 70% of cases), the most valid tactics are always the same: block, upstream, the synthesis of estrogen, or break , downstream, the “hooks” present on the tumor cells that capture them: what biologists call estrogen receptors. And if the tumor finds new loopholes through mutations that modify these “hooks”, then we need to look for new drugs capable of recognizing and targeting them.
Breast Health, the newsletter is born
A promising oral drug
This is one of the directions that research is looking at. And here’s why second Carlos Arteaga placeholder image, co-director of the San Antonio Breast Cancer Symposium and head of the Simmons Comprehensive Cancer Center in Dallas, one of the most interesting studies presented at the congress concerns a new drug of the “old” class of Serds. The acronym stands for Selective estrogen receptor degrader, which are drugs that damage the estrogen receptors present on cancer cells. The only Serd approved to date is fulvestrant (which requires intramuscular injections every month), but there are many studies underway on new possible molecules of this type, including oral ones. And one, elacestrant, looks particularly promising, especially for those with the ESR1 gene mutation (ie, the estrogen receptor 1 gene), which occurs in up to 40% of patients with advanced cancer.
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The data presented in San Antonio come from the Emerald study – in which the Gemelli Polyclinic of Rome and the San Gerardo Hospital of Monza also collaborated – which compared the efficacy of elacestrant with standard endocrine therapies (fulvestrant or an inhibitor of aromatase). The study was conducted in women with metastatic breast cancer whose disease progressed after at least one treatment (either with another endocrine therapy, or with a CDK 4/6 cyclin inhibitor, such as palbociclib, ribociclib and abemaciclib). . And here are the data, which could change clinical practice in the near future: the new oral drug, administered alone (on its own) reduced the risk of progression or death by 30% overall, and by 45% in those with the mutation. ESR1, compared to standard care, significantly increasing the time without disease progression. This means, among other things, that the ESR1 mutation is an important marker for personalizing treatments, following the evolution of the tumor in real time.
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Genome analysis as part of the treatment process
The goal is always the same: bypass the resistances and offer one more chance to increase survival. And the point is to figure out which sequences and combinations of drugs are best, on a case-by-case basis. Like? Undoubtedly through the sequencing of genes, in search of significant mutations. But you need a map to not get lost in this kind of ever-changing city. “Multigene sequencing is increasingly used, but its impact in the clinic and the best context in which to use it are not yet clear,” he said. Fabrice André, research director at the Gustave Roussy Cancer Campus in Villejuif, France. The study presented by André at the congress aimed precisely at understanding whether multigenic sequencing could really increase the survival of patients with metastatic “hormonal” breast cancer. The answer is yes: genomic analysis should be part of the patient’s care process, but on the condition of having a scientifically validated system to interpret the meaning of the identified mutations.
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Identification of the tumor, cell by cell
The latest study we are talking about in this newsletter is largely Italian, conducted in numerous centers and led by the IRCCS San Raffaele Hospital in Milan and the Michelangelo Foundation. This time, we are talking about triple negative breast cancer, but the question to be solved is similar to the previous one: since the response to immunotherapy varies a lot, how to identify who will have the greatest benefits? To answer this, the researchers used a very sophisticated imaging technique, which allows them to analyze the sample of the tumor and the microenvironment that surrounds it, cell by cell.
Identikit of the cell
In practice, it is possible to make the identikit of each single cell and to know its position, and this has allowed us to identify some characteristics that predict the greater effectiveness of immunotherapy. “The battle between cancer cells and the immune system is very complex,” he explains Giampaolo Bianchini, head of Breast Oncology at the IRCCS San Raffaele Hospital in Milan and researcher at the Airc Foundation: “The ability of the tumor to inhibit the action of lymphocytes (the cells of the immune system, ed.) and, on the other hand, our the ability to reactivate this action through drugs changes a great deal from case to case, based not only on the molecules that the tumor expresses but also on the way in which the tumor mass was formed, or rather on the geometry of the tumor “.
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This imaging technology – which is expensive and yet cannot be used in daily clinical practice – allows, for the first time, to build an accurate map of the tumor and microenvironment, and this information tells us how the tumor will evolve and how it will respond. to therapies. “Very complex information – says Bianchini – that we are only learning to read now. The data we obtained – he explains – help to show that precision medicine, capable of predicting the effectiveness of a therapy before it is administered, is possible. But there is still a lot of work to be done to get these discoveries applied ”.
The microenvironment of the tumor
Bianchini’s isn’t the only study investigating new ways of looking at breast cancer. Carlos Caldas, head of the Cancer Research UK Cambridge Institute, has developed a “multi-omic” system that goes in the same direction: by integrating data on DNA and Rna and thanks to artificial intelligence, it tries to better define the subtypes of breast cancer and the tumor microenvironment to predict the response to treatment before administering it. His research, published simultaneously on Nature, was awarded the Susan G. Komen Brinker Award. “This study was initiated nine years ago and was only possible thanks to the perseverance and commitment of groups of scholars and clinicians and generous funding in support of research,” Caldas said: “The ability to predict response to treatment based on the characterization of the tumor ecosystem it will transform the practice of oncology “.
