HER2-low breast tumors should be identified

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All experts in pathological anatomy and oncology are very aware of the importance of applying Breast Cancer Their “surname is one of their HER2 expressions. Knowledge of the molecular profile of this cancer is the key to guaranteeing the patient the best possible treatment. That’s why resolution is becoming more important: “As detailed as possible of HER2 expression.”

In addition to the categories of HER2+ and HER2-tumors, which indicate whether patients should take one therapeutic route or the other, there is a need to distinguish HER2-low tumors, which have low expression of this protein, but this is not the case. . This is how it explains Dr. Begona Viets, Section Head of the UGC Pathological Anatomy at the Virgen del Rocío University Hospital in SevilleSince a therapeutic option exists for breast tumors in the metastatic stage with this characteristic,.

In 2023, the EMA approved the indication of an ADC in patients with low HER2-low expression (trastuzumab deruxtecan), which opened the door to the identification of this new molecular subtype. What is the definition of HER2-low as a new molecular group for the diagnosis and treatment of metastatic breast cancer patients?
From a diagnostic standpoint, the approach to HER2 evaluation has changed somewhat. Previously, the focus was on clearly distinguishing HER2-positive tumors from tumors that were not positive. Now, this differentiation seems easy, and the difficulty lies in separating those who are truly negative and those who are HER2-low or low expressers.

“HER2-low tumors have not received as much attention, but it is now very important to distinguish true-negative tumors from tumors that are HER2-low.”

The latter was not given as much attention before, but this has changed, and it is very important to isolate the real negatives. That is, those who graduate as zero, those who fall under HER2-low, because there is a new therapeutic possibility that we cannot stop offering to patients who meet that requirement. Therefore, it is true that the main purpose of HER2 determination has been modified from a diagnostic point of view.

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So, can we talk about a new molecular subtype?
I think it is still too early to talk about molecular subtypes. To establish a new subtype, we must demonstrate new characteristics that distinguish it from others, not just more or less expression. In this case, we are talking about a group of tumors that have a specific clinical indication based on the expression of a biomarker, even if it is low. But it has not yet been demonstrated that, as a group, they have molecular and prognostic characteristics that distinguish them.

To what extent is it important to correctly identify each case of these patients, as well as to include this group of tumors in diagnostic and treatment algorithms?
Of course, we should not only look at HER2-positive tumors but also distinguish true negative tumors from low-expressing tumors, and it is necessary to make this very clear in the report because this will lead to the selection of patient populations. Which are supportive of a specific treatment. In a specific context, in metastatic disease.

We should not only pay attention to the positives but also distinguish the real negative from the following manifestations, and it is necessary to make this very clear in the report.

Will all patients respond to treatment with conjugate drugs the same, or does it depend on the level of HER2 expressed by the tumor?
At present, there is no direct relationship between expression level and response level. It is true that the results we have are very optimistic; survival rates are improving in this group of patients. I’m sure there will be more data coming out soon, but it is true that, so far, we have results from clinical trials that have demonstrated this improvement, but quantification of expression in the trial versus There is a relationship between the amount of reaction. Furthermore, HER2 is determined semi-quantitatively; it is not a specific quantification because semi-quantitative assessment methods are used.

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Are you seeing improved outcomes in terms of breast cancer prognosis, reduced toxicity, and being able to minimize systemic distribution?
This question can be better answered by my fellow medical oncologists, but the data confirm significant improvement in progression-free survival and overall survival at the expense of fewer side effects, which is extremely important. We have the results of clinical trials, but we are still at the moment of generating evidence in a specific context, such as metastatic disease, which fortunately affects a small number of patients. It is important to find therapeutic alternatives for these patients, as they are becoming resistant to conventional treatment (recurrence). Therefore, the advent of this new treatment represents a major advance.

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“Treatment with conjugated drugs is leading to significant improvements in progression-free survival and overall survival at the expense of fewer side effects, which is very important.”

Right now, do all patients in Spain have access to tumor molecular profile studies?
Currently, any breast cancer is studied with a series of immunohistochemical markers through which we assess protein expression, which is a reflection of what is happening at the molecular level. Every diagnosis of breast cancer should be accompanied by studies that demonstrate its hormonal dependency, HER2 expression, and cell proliferation. These are the data that will determine what type of treatment each patient will receive.

How do you see the future for patients with metastatic breast cancer? Is there any hope for them with the advent of these new treatments?
Oncology is the best example of precision medicine, that is, medicine that attempts to accurately identify and differentiate each patient’s disease so that the appropriate treatment can be selected and not another. To achieve this precision medicine, the use of biomarkers is essential, which allow us to identify tumors, differentiate them from others, and identify patients. These biomarkers, in many cases, serve as therapeutic targets to guide targeted therapies. This is one of the main objectives of oncology: to better identify each patient and select the most appropriate treatment for each case, as well as to try to reduce the many side effects and morbidity associated with chemotherapy treatments.

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