A new preclinical trial (not tested in humans) for treating early-stage breast cancer has shown promise in completely eliminating the disease in a less invasive way than conventional therapies. The results were published in the scientific journal Proceedings of the National Academy of Science.
In general, breast cancer is the most common tumor in women worldwide. According to the World Health Organization (WHO) in 2020, there were 2.3 million women diagnosed with breast cancer and 685,000 global deaths.
In Brazil, estimates from the National Cancer Institute (Inca) indicate that about 66,280 people should be diagnosed with breast cancer annually. With regard to the number of deaths from the disease, the Inca survey showed that 18,032 die annually in the country as a result of the tumor.
In the United States, this type of cancer affects 69,000 women each year, and in many cases, they end up having breast removal surgery and radiation treatments for these very early cancers.
In other situations, some patients receive chemotherapy or hormone therapies, explained lead study author Saraswati Sukumar, a professor of oncology and pathology at Johns Hopkins University.
Now, work done in mice provides a strong preclinical basis for conducting feasibility and safety trials with patients who have stage 0 breast cancer, also known as ductal carcinoma in situ (DCIS), according to the authors. .
DCIS tumor is characterized by the presence of abnormal precancerous cells within the milk ducts in the breast. At this stage of the disease, cancer cells are only in the layer from which they developed and have not yet spread to other layers of the organ of origin.
less invasive
Thinking of avoiding an invasive treatment such as mastectomy (breast removal), the research team proposed a type of therapy that consists of the application of an injection with the immunotoxin drug through the breast duct, which could result in the cleaning of the DCIS.
“To our great surprise, the drugs “killed” all the lesions present in that breast duct. I had never seen such expressive results in my life,” said Sukumar.
During their investigations in mice, the researchers first evaluated the cell killing effects of HB21(Fv)-PE40, a targeted immunotoxin, on four cell lines of different molecular subtypes of breast cancer.
This toxin consists of HB21, a monoclonal antibody (a protein that can bind to a specific target — in this case, the human transferrin receptor (TRF), a carrier protein found in breast cancer).
HB21 has been fused to PE40, a fragment of a bacterial toxin that disrupts the production of proteins in cells and leads to cell death.
The findings showed that this infusion induced strong tumor killing effects in all cell lines.
The researchers also administered the treatment to 10 mice to look for toxins circulating in the blood after treatment and did not find them between five and 30 minutes after the injection.
THE CNN Inca specialists, who were not involved in the study, explained that the work manages to “potentiate the action of the immunotoxin”.
“Treatment toxicity has been circumvented with direct administration into the mammary duct for the treatment of intraductal (in situ) carcinoma of the breast, which is the target of the immunotoxin,” they wrote.
However, the experts explained that the injection “does not currently apply to invasive carcinomas at any stage.”
No tumor recurrence
The research team divided the mice into two different groups to administer the treatment in order to compare the result of MCF7 and SUM225. Both had the DCIS tumor.
The first group, MCF7, was administered once a week for three weeks. The treatments were followed up with non-invasive imaging. To compare, they also administered the injection into the body of the mice and also injected the HB21 antibody alone into the ducts in some of the animals.
The results showed that animals that received treatment injections with HB21(Fv)-PE40 toxins into the body had slower tumor growth. However, the tumors recurred after stopping treatment at around day 26.
Those who received HB21 alone in the ducts had invasive tumors on day 61 after injection.
On the other hand, mice that received direct treatment in the mammary ducts had their tumors completely eliminated two weeks after the completion of two of the three proposed treatments, and no recurrence was detected by imaging even after 61 days of HB21 (Fv)-PE40 injection.
To monitor the course of treatment, the researchers performed pathology exams of the mammary glands on the 32nd day. They found that tumor cells were absent and the architecture was consistent with normal mammary glands.
In the second group (SUM225), the researchers tried a pilot with the toxin treatment that showed the elimination of tumors in just two weeks of treatment, as seen by imaging. There was no recurrence of the disease until the end of the experiment, 48 days later.
To track, a second experiment tested the same dose in one group and 1/10 of the treatment dose in another, as well as the HB21 antibody alone, in some samples.
In most mammary glands there was no tumor incidence after full intraductal treatment, with weaker effects seen in the lower dose group.
The results also showed that SUM225 tumors grow aggressively at the duct site. Pathology studies demonstrated that HB21 antibody alone had little effect, while immunotoxin (HB21(Fv)-PE40.) conjugate treatment showed a significant tumor shrinking effect.
The treatment was well tolerated, with no side effects from the toxin or injection.
How would injection in humans work?
As the study is still in the pre-clinical phase, the Inca specialists explained that, if it goes ahead, the treatment may prove useful for other types of tumors.
“Without a doubt, the strategy can be useful for tumors that express high levels of human transferrin receptor (TRF). In breast cancer, TRF is expressed in several subtypes, which could be a promising target,” they said.
However, they point out that the tests can present other results when they change phase.
“Many substances that are successful in tests in animal models do not achieve the same response in humans. Therefore, as the research is very preliminary, although with interesting results in animals, we must wait for clinical studies to know how well it would work in the real world”, evaluated the Inca.
For the specialists of the national institute, there is still There is a long way to go before we can say anything about this study.
“In practice, it’s just another possibility. But the work follows an interesting trend that we have seen in other strategies, including for breast tumors,” said Inca.
Identifying breast cancer early
The proposed injection for breast cancer patients had good results in the preclinical phase because the tumor was at an early stage. THE CNN oncologist Débora Gagliato, from BP – A Beneficência Portuguesa de São Paulo, said that when diagnosed early, the chances of curing breast cancer tend to be “very high”.
“Today, a properly managed tumor, diagnosed early, located only in the breast, has a very high chance of cure, in the order of 95% [de chances]” he explained.
In some cases, the initial symptoms may appear through a lump (lump), fixed and usually painless: it is the main manifestation of the disease, being present in about 90% of cases when the cancer is perceived by the woman herself.
Some reddish spots, and breast retracted or resembling orange peel. Symptoms also include changes in the nipple, small lumps in the armpits or neck, and spontaneous outflow of abnormal fluid from the nipples, according to Inca.
But, the tumor is not always diagnosed early – which would hinder the chances of cure. Gagliato explained that in some cases there may not be any symptoms at all. “Often breast cancer does not show symptoms, hence the importance of screening tests”, he evaluated.
According to the oncologist, the main diagnostic tests are mammography and breast ultrasound. “Then, other additional tests, such as MRI [magnética]may be important depending on the context, breast density, family history or genetic factors”, he says.
for the Inca, the more you canWhen we direct the toxicity of drugs and toxins to the tumor, the greater the chances we have of finding treatments that change the course of the tumors that most afflict the population today, such as breast cancer, the most incident in the world.
Early diagnosis would be the ideal setting for the Johns Hopkins University researchers’ specific injection treatment.
According to Sukumar, the clinical study [em humanos] must advance. “A week or two before surgery, scientists can give women a low dose of HB21(Fv)-PE40 through a single duct and use slowly increasing doses to determine if any immunotoxins leak from the ducts into the bloodstream and affect the liver function. They would also examine the ducts after breast removal to look for tissue changes and their effect on precancerous lesions.”
Source: CNN Brasil
