The expansion of knowledge about the biology of breast cancer has made it possible to have increasingly precise access options that have led to improved prognosis. From diagnosis to treatment and follow-up of this neoplasia, innovation has played a vital role in understanding how the disease develops and offers the most appropriate option at each stage of the disease.
José Ángel García Sáenz, an oncologist at the Clinical Hospital of San Carlos, supports this idea by stating that “the therapeutic approach depends on the biology of the disease.” Therefore, the first step to offering the optimal approach in each case is an accurate diagnosis. “The development of cancer can be conditioned by specific molecular changes in the tumor cell, and we use massive sequencing techniques to look for those that may be present in the tumor to try to find therapeutic targets,” he explains.
As García Sáenz explains, this information makes it possible, as García Sáenz explains, to increasingly individualize treatment because, using massive sequencing techniques, “we are looking for markers that will allow us to identify whether there are markers associated with a worse prognosis or the emergence of resistance and also: If this mutation can be clinically applicable or a potential therapeutic target for the design of specific treatments aimed directly at it.”
To advance the treatment of breast cancer in general, García Sáenz suggests three goals: “We need to advance research, both in the biology of the disease and in generating hypotheses to transfer them to the clinic; We have to move towards greater individualization, practically look for à la carte treatment and all this without leaving aside humanization, bet on the quality extension of patients’ lives and that, as far as possible, they do not think so much about the disease. .”
Biology of disease
García Sáenz states that, in simplified terms, there are three types of breast cancer: luminal, HER2, and triple negative. Each case may therefore have its own specifics, which must be dealt with individually.
For luminal tumors, the oncologist points out, “the pathway involves targeting estrogen receptors; “It’s the hormone therapy route, or hormone therapy, and it occurs in about 65 percent of cases.” “There is another type in which driver The mechanism that triggers disease progression is the HER2 protein, and there are currently anti-HER2 therapies, some with recently presented results that are absolutely spectacular,” García Sáenz says, noting that this subtype affects about 15 percent of patients. And finally, there would be triple negative breast cancer. “This is a heterogeneous group that is defined as triple negative, because the expressors of estrogens, progestogens and HER2 are missing.
In addition to this classification based on the biology of the disease, there are types of breast cancer, such as metastatic cancer, which, in the words of an expert, “represents a great professional and therapeutic challenge because it is very difficult to achieve a complete remission of the disease.” “Metastatic breast cancer is inherently incurable, so the ultimate the goal of treatment is to prolong the patient’s time with a good quality of life,” he says. On a less negative note, he suggests that “in cases where remission can occur, we have to go for it,” although he points out that that “they are marginal, so the main goal in these patients is chronic and that” patients live longer and better.”
Diagnostics and monitoring
Innovation is essential in both diagnosis and disease monitoring. And some of these new tools can be used for both purposes.
Thus, García Sáenz specifies that “to evaluate and find out how the cancer develops, the first tool we have is the clinic through history and reviews; Then there are analytical tests with which we can also see dysfunctions such as the liver or the heart among others, and the third are radiodiagnostic tests that are increasingly accurate.” Following on from this thread, he highlights the advantages of techniques such as liquid biopsy, which, as shows the oncologist, “determines the circulating tumor DNA, i.e. the genetic material of tumor cells, which, thanks to mechanisms such as cell necrosis, apoptosis or secretion from the tumor cell, eliminate DNA fragments into of the bloodstream.” In this way, adds García Sáenz, “this circulating DNA can be extracted, isolated and quantified and can also be used in monitoring to identify new mutations that appear or resistance and to observe the evolution of the disease.
The main advantage that the expert emphasizes is that “this type of monitoring allows us to see the development of the disease with greater sensitivity than other tests”. The barrier that “there is still a way to go to implement liquid biopsy and see if the technique is scalable and reproducible.”
Therapeutic approach
Regarding therapeutic innovations, García Sáenz points to several alternatives, also depending on the subtype of the disease.
Speaking of the hormone-sensitive subtype, García Sáenz points out that “substances have emerged in recent years that, along with endocrine therapy, can delay resistance to hormone therapy.” “Before, cells became resistant after a short time, and with the advent of new treatments, this has been delayed,” he elaborates, adding that “treatments are now being sought to help restore hormone sensitivity.”
“In HER2-positive cases, the most important innovation is conjugated antibodies, anti-HER2 agents that act in a conjugated manner; “They are monoclonal antibodies that identify this protein and, like a ‘Trojan horse’, carry a small cytotoxic agent across the epithelial membrane antigen HER2,” he elaborates. With this option, which introduces this compound selectively, the expert expresses that it “manages to significantly increase the survival of patients”.
Finally, in the triple negative, thanks to its heterogeneity, it stands out that progress comes from two paths. “The first is to look for immunotherapy in the first line of the disease, and you can try to add chemotherapy to try to reverse the tumor capacity of the immune system and make it able to recognize and eliminate the cancer,” he points out. The second pathway for this subtype also involves conjugated antibodies, although, as García Sáenz states, “it directs them to other antigens of the epithelial membrane”. In this group, according to the oncologist, “it would be the membrane antigen TROP2, sacituzumab govitecan, which has achieved an increase in survival in the first line, which also applies to patients who do not express HER2 or do so at a low level (HER2 low)”. Finally, García Sáenz points out that “triple negative is in some cases associated with pathogenic germline mutations associated with BRCA2; “In women who have these BRCA mutations, by adding PARP inhibitors like olaparib, we see that we are able to control the disease.”
