- The risky decision by Croatian virologist pays off
- Not everyone appreciated the self-treatment experiment
- Hereditary breast cancer syndrome
- Indications for genetic counseling
The risky decision by Croatian virologist pays off
Beata Halassi, a virologist from Zagreb, Croatia, tried oncolytic virotherapy (OVT), which is not yet approved for the treatment of breast cancer, and got rid of a breast tumor. Not all her colleagues appreciated her experiment despite the successful outcome, writes Nature.
B. Halasi stressed in the text that she does not consider her method a priority in the fight against cancer, but described how she used it in an almost hopeless situation. She had already had her mammary gland removed after her first tumor, and chemotherapy was not available[1].
She grew two viral samples in her laboratory - measles and vesicular stomatitis - and for two months, a colleague injected the material directly into her tumor. During the trial, Halasi was monitored by oncologists who were ready to offer her chemotherapy if complications began.
Eventually, the tumor shrunk noticeably, softened and moved away from the muscle, and was easy to cut out. According to Halasi, the viruses triggered the immune response needed for such treatment, immediately attacking them and the tumor. After the experiment, she absorbed a course of the drug Trastuzumab (Herceptin), which is approved in the United States to treat breast cancer.
Not everyone appreciated the self-treatment experiment
Before Halasi's paper was published in Vaccines, a scientific journal affiliated to the American Society of Virology (AVD), it received more than a dozen negative responses. The scientific community is cautious about experimenting on itself and considers such an approach unethical, as it can give false hope in the fight against disease[2].
As the publication notes, the measles virus is now being investigated as a possible treatment for breast cancer, but so far the only drug approved in the US for oncolytic virotherapy is T-Vec, which is based on herpes. It is used against melanoma (skin cancer).
According to oncolytic virotherapy specialist Stephen Russell, B. Halasi's experiment is unique in that she carried it out independently (with the necessary expertise) and used two viruses simultaneously.
B. Halasi told Nature that a paper that did not go down well with everyone eventually secured her a grant further to explore this approach in the treatment of pet cancers.
Hereditary breast cancer syndrome
Breast cancer is the most common cancer in women in Lithuania and in many parts of the western world. Any woman has a lifetime risk of developing breast cancer of around 10%. Most cancers are sporadic (accidental) and caused by external (environmental) factors, but 5-10% of breast cancers are caused by inherited genetic changes (gene mutations). Mutations in genes associated with breast cancer increase the risk of other cancers such as prostate cancer, pancreatic cancer and melanoma.
The BRCA1 and BRCA2 genes are classified as high cancer risk genes, with mutations that increase the risk of cancer by more than 4-fold compared to the general population risk. These genes protect the body from the process of oncogenesis. The BRCA1 gene is involved in the DNA repair process and in controlling the overall stability of the genome, while the BRCA2 gene is involved in the process of DNA rearrangement (recombination) and DNA repair. Harmful environmental factors (such as smoking, alcohol, diet, etc.) cause mutations in these genes. When a pathogenic sequence change (mutation) occurs in any of these genes, the protective function of its DNA is compromised and the cells become susceptible to malignancy. Cells begin to divide uncontrollably and accumulate damage, giving rise to the possibility of cancer. Carriers of the pathogenic BRCA1 or BRCA2 gene mutation have been through part of the cancer development pathway and, therefore, require fewer additional environmental factors than those with normal gene activity (Figure 1). The risk of developing cancer increases from the age of 30 years in BRCA1 or BRCA2 mutation carriers.
BRCA1 and BRCA2 genetic testing does not diagnose cancer, but it can determine the risk of breast and ovarian cancers and other genetically related cancers. If a pathogenic mutation in the BRCA1 or BRCA2 gene is detected, the patient is placed in a high-risk group and a special care plan is developed to prevent cancer. The patient is given targeted and detailed tests for early detection and treatment of cancer (e.g. mammography and/or breast MRI), or prophylactic organ removal surgery is recommended. Regular monthly breast self-examination is recommended from the age of 20.
Pathogenic mutations in the BRCA1 and BRCA2 genes are inherited and can be passed on from generation to generation. Therefore, if a pathogenic mutation is detected, genetic testing on the patient's children and other relatives is important.
Important!!! Early detection of an increased risk can lead to timely diagnosis and cure of the disease, avoidance of serious complications, or significant reduction of the risk through prophylactic surgery.
Indications for genetic counseling
BRCA1 and BRCA2 gene tests are prescribed by a geneticist when hereditary breast cancer syndrome is suspected. Public health insurance funds cover genetic counseling and genetic tests if the patient presents with a referral for genetic counseling. The referral can be issued by a family doctor and a specialist doctor following the indications for a genetic consultation listed in the Order of the Ministry of Health of the Republic of Lithuania No V-1458 of 31.12.2014 "On the Approval of the Description of the Indications for the Provision of Genetic Personal Health Care Services and the Procedures of the Payment of the Costs of These Services by the Budget of the Compulsory Health Insurance Fund".
Consultation of a geneticist for hereditary breast cancer syndrome is necessary when this pathology is detected: breast carcinoma diagnosed in a person aged 50 years or older; breast carcinoma with negative results for estrogen, progesterone and HER2 receptors (all three tests) (ER, PR, HER2 (-)); medullary breast carcinoma; bilateral (primary) breast carcinoma; male breast carcinoma; peritoneal/pancreatic/gastric carcinoma/melanoma in the same patient; breast carcinoma in at least two first-degree relatives; clinically suspected hereditary breast cancer syndrome.
BRCA1/2 gene testing shall be initiated in the affected family member who meets the above indications. If the patient's family meets the above indications, but it is not possible to test a family member with cancer, genetic counseling, and BRCA1/2 gene testing may be given to a healthy family member.
BRCA1/2 gene testing is divided into three stages. The first-line test is a test for the most common mutations in the BRCA1 and BRCA2 genes. If the most common BRCA1/2 gene mutations are not detected in the patient and if indicated, the patient may undergo a second-line test - next-generation sequencing of BRCA1 and BRCA2 genes. The second-line test is classified as an expensive genetic test and is ordered by a panel of doctors, one of whom must be a geneticist. In the absence of BRCA1/2 gene mutations and if indicated, the patient may undergo an additional (expanded) line III test, which a panel of doctors will administer.
