Breast and ovarian cancer gene. Hereditary breast cancer: causes, symptoms, treatment

Among the cancers that are most common in women, breast cancer takes the lead. Statistics show that one in nine women suffers from this disease, and age does not matter. In addition, 10% of cases of this type of oncology are genetic, that is, transmitted within the family. A specific gene is responsible for this pattern, and if it is passed on to the carrier’s offspring, the risk of developing breast or ovarian cancer increases significantly. With age, the risk of getting sick increases to 90%. That is 10% of the world's female population has an extremely high risk of developing breast cancer. In total, at least 6 people out of 1000 in Russia are carriers of some mutations. If we take patients with breast cancer, there are 30 carriers of the corresponding mutation per 1000 people, and 150 people per 1000 among patients with ovarian cancer. It is impossible to find out whether you carry a mutated gene without special research, because a mutation does not affect a person’s life until it causes a disease.

Molecular genetic analysis only needs to be done once, because the human genotype does not change over time. If the test result is positive, it is recommended that all blood relatives who are automatically at risk undergo this test.

The mutation carrier has a chance to live happily his whole life without developing diseases, but the risk is still too great, and therefore you need to carefully monitor your health in order to detect the disease at the earliest stages. If it is possible to diagnose oncology soon after its occurrence, there is a high probability of carrying out the necessary treatment or performing the required surgical intervention, and in 95% of cases the patient will be able to lead a full life without consequences for health in the future.

Sergey Mikhailovich Portnoy "Research of BRCA1 and BRCA2"

Should you be tested for the mutated gene?

The analysis is indicated for the following patients suffering from breast or ovarian cancer:

1. in whose families there are other people who have suffered from cancer,
2. in case of development of the disease before reaching 45 years of age,
3. with bilateral breast cancer.

These recommendations are especially relevant in Russia, where mutations are common. In addition, the analysis will help in more accurately prescribing treatment for cancer and will help relatives find out whether they have a similar heredity. In healthy people, mutations are also found quite often, therefore, in general, the analysis is recommended for everyone.

Carrying out analysis

For the study, 0.5-1 ml of the patient’s blood is taken using an EDTA tube. Such a sample can be stored at a temperature of -20 degrees long enough before analysis. In addition, a sample of the buccal epithelium is taken.

There are about a dozen genes whose mutations lead to a significant increase in the risk of developing breast cancer. Prophylactic bilateral mastectomy (removal of the mammary glands) reliably protects against the development of the disease. Naturally, if the disease has not developed, the measures that are used in its treatment are not required: removal of axillary lymph nodes, chemotherapy, radiation therapy, hormone therapy. The operation can be performed with simultaneous reconstruction of the mammary glands or without reconstruction. When performing reconstruction, additional changes in the size and shape of the mammary glands are possible.

Women who are carriers of a gene mutation responsible for the development of breast cancer may be offered the following preventive examination program. At the age of 25 to 50 years - ultrasound of the mammary glands once every 6 months, if technically possible - MRI mammography once a year. After 50 years - mammography once a year.

Bilateral prophylactic mastectomy with simultaneous breast reconstruction, the patient is 33 years old.

October is Breast Cancer Awareness Month. Actions and information campaigns are being held around the world to draw attention to the problem of diagnosing and treating this disease. This year, the Cancer Prevention Foundation decided to talk about how heredity affects the possibility of breast cancer, and what to do if one of your relatives has been diagnosed with this disease. Our campaign is supported by experts from biomedical companies Atlas and .

Why is breast cancer really worth talking about all month long? Breast cancer is an oncological disease in which the cells of the mammary glands stop working normally: they begin to divide uncontrollably and do not die. This is the second most common type of malignant tumor in the world (after lung cancer). 1.7 million new cases are diagnosed every year. According to the latest data in Russia, breast cancer is the most common cancer pathology among the female population and accounts for 20.9% of the cancer incidence structure (data for 2015).

It is known that in 5-10% of cases, breast cancer occurs due to genetic mutations that are inherited. Most often, these are mutations in the BRCA1 and BRCA2 genes; they significantly increase the risk of breast cancer. There are other genes known whose breakdowns can lead to the development of breast cancer: TP53, PTEN, STK11, CDH1, ATM, CHEK2, PALB2 and some others. If the average woman has a 5.6% chance of developing breast cancer in her lifetime, then a woman with a mutation in the BRCA1 or BRCA2 genes increases the chance to 70%.

The mutation can be inherited from both mother and father. In this case, it is the high risk of developing cancer that is inherited, and not the disease itself: not all carriers of the mutant gene will necessarily develop cancer.

In addition to breast cancer, carriers of mutations in the BRCA1 and BRCA2 genes increase the likelihood of developing cancer in other organs: the ovaries, pancreas and prostate gland. The risk of developing ovarian cancer increases especially strongly: from 1 to 35%.

In families where mutations are passed on, breast and ovarian cancer are more common than usual. In addition, hereditary forms of cancer develop at a relatively early age. The following features of family history may indicate the carriage of mutations:

Breast cancer up to 45 years old

Two cases of breast cancer in one person

One case of ovarian cancer

Two cases of breast cancer in blood relatives, at least one of which was diagnosed before age 50

Breast cancer in a male first- or second-degree blood relative

If any of the above is typical for your family, then you should consult a geneticist to decide whether genetic testing is necessary. And the test developed by the Cancer Prevention Foundation will help assess the risks of cancer and the need for genetic consultation.

In the world practice of working with patients who have a mutation in the BRCA1 and BRCA2 genes, there is the concept of prophylactic mastectomy (removal of healthy mammary glands before they are affected by a possible disease). In some cases, with a genetic predisposition to breast cancer, a woman may decide to undergo surgery, which reduces the risk of developing cancer by 90%. This is what Angelina Jolie did, for example, when she was found to have a mutation in the BRCA1 gene.

In Russia, unfortunately, such procedures are treated with caution. Patients at high risk of breast cancer rarely find the opportunity to undergo a mastectomy without traveling abroad. In this case, most often the doctor has to take on additional responsibility and correct the diagnosis so that the operation can be performed within the framework of compulsory medical insurance.

Carrying out genetic testing and consultation with a geneticist does not exclude the need for examinations that are considered most effective in the early diagnosis of breast cancer, for example, mammography. Every year, the Cancer Prevention Foundation conducts 3-5 events for the early detection of breast cancer in regional centers whose programs include this method.

Mammography is considered an effective method for diagnosing breast cancer and is recommended annually for women over 40-50 years of age. Women with a genetic predisposition should have mammograms and breast MRIs every year starting at age 30.

If you have health concerns related to a strong history of cancer in your family, get genetic testing and discuss your concerns with a genetic counselor. Fortunately, this is a well-functioning practice in Russia today.

A consultation with a geneticist can be done at the Atlas Medical Center, and genetic testing for predisposition to developing breast cancer and other cancers can be done at the company.

Modern science and medicine have provided many answers to questions regarding hereditary predispositionHowever, many media outlets misinterpret this information, misleading people. We decided to destroy myths about the role of hereditary factors in the development of breast cancer.

“I look a lot like my mom and/or grandma, and they had breast cancer. This means that I will have this disease too.” Is this statement correct? Is it a myth or a fact?

We hasten to inform you that the above statement is a myth, since the genes responsible for your similarity with your ancestors in no way affect the development of breast cancer.

However, many other questions need to be answered to understand this topic. At what age was your mother and/or grandmother diagnosed with breast cancer? Have other members of your family suffered from this disease? Has it been confirmed that the tumor is caused by genetic mutations? Let's look at the most common myths regarding the role of heredity in the development of breast cancer.

Myth: Most breast cancer cases are caused by genetic mutations

In fact, only 10% of all breast cancer cases are clearly linked to inherited genetic mutations. Men also have breast cancer, but since this pathology is quite rare in the male population, it is not possible to determine the frequency of genetically determined cases.

Thus, 1 in 10 cases of breast cancer are caused by genetic mutations. And 9 out of 10 cases of breast cancer are not associated with hereditary factors.

Myth: GenesBRCA - the only genes associated with the risk of developing breast cancer

You've probably heard about genes BRCA1 And BRCA2, especially after the sensational news about Angelina Jolie, who decided to undergo surgery to remove the mammary glands. The actress was found to have mutations in these genes, which put her health at great risk.

However, the gene family BRCA is not the only genetic cause of breast cancer development. Today, science knows more than 10 genes (in particular, P53, PTEN, STK11 and others), mutations in which can lead to the development of tumor processes in the mammary gland.

Myth: Not all people have genes associated with breast cancer.

In fact, all women and men have two copies of the above genes, which may be associated with the development of breast cancer.

The mere presence of these genes does not mean the onset of the disease. Pathology can only occur if a mutation occurs in these genes.

It is mutations that lead to a malfunction of genes, after which the cell is not able to fully perform its functions, it turns into a cancer cell.

Reader Questions

My girlfriend’s mother had breast cancer, and she has an older sister, 20 years old, who also had breast pain, what are the chances that my girlfriend could have the same situation? and does it necessarily appear after sex? October 18, 2013 My girlfriend’s mother had breast cancer, and she has an older sister, 20 years old, who also had breast pain, what are the chances that my girlfriend could have the same situation? and does it necessarily manifest itself after sex?

Myth: If a mutation is identified, cancer will definitely occur.

This is not entirely true. The truth is that if you have gene mutations, you have an increased chance of developing breast cancer. The same woman decided to have her mammary glands removed only because she had an increased risk of developing breast cancer.

If you have been identified with mutations in your genes, then this should be information for you to take action. You should regularly check with a mammologist to check for any changes in the mammary gland. In this case, even if the tumor begins to develop, it will be detected at an early stage, which will allow a successful course of treatment.

Arkady Galanin

One of the most common types of familial tumors is hereditary breast cancer (BC), it accounts for 5-10% of all cases of malignant lesions of the mammary glands. Hereditary breast cancer is often associated with a high risk of developing ovarian cancer (OC). As a rule, in the scientific and medical literature the single term “breast-ovarian cancer syndrome” is used. Moreover, with tumor diseases of the ovary, the proportion of hereditary cancer is even higher than with breast cancer: 10-20% of cases of ovarian cancer are caused by the presence of a hereditary genetic defect.

The presence of mutations in the BRCA1 or BRCA2 genes in such patients is associated with a predisposition to the occurrence of breast cancer/ovarian cancer syndrome. Mutations are hereditary - that is, literally in every cell of such a person’s body there is damage that is inherited. Patients with BRCA1 or BRCA2 mutations have an 80% chance of developing cancer by age 70.

The BRCA1 and BRCA2 genes play a key role in maintaining genome integrity, in particular in DNA repair processes. Mutations affecting these genes typically result in the synthesis of a shortened, incorrect protein. Such a protein cannot correctly perform its functions - “monitor” the stability of the entire genetic material of the cell.

However, in each cell there are two copies of each gene - from mom and from dad, so the second copy can compensate for the disruption of cellular systems. But the probability of its failure is also very high. When DNA repair processes are disrupted, other changes begin to accumulate in cells, which, in turn, can lead to malignant transformation and tumor growth.

Determination of genetic predisposition to cancer:

Based on the Laboratory of Molecular Oncology, National Medical Research Center of Oncology named after. N.N. Petrov uses a step-by-step analysis for patients:

1. the presence of the most common mutations is examined first (4 mutations)
2. in the absence of such and clinical need, it is possible to conduct an extended analysis (8 mutations) and/or analysis of the complete sequence of the BRCA1 and BRCA2 genes.

Currently, more than 2,000 variants of pathogenic mutations in the BRCA1 and BRCA2 genes are known. In addition, these genes are quite large - 24 and 27 exons, respectively. Therefore, complete analysis of the BRCA1 and BRCA2 gene sequences is labor-intensive, expensive and time-consuming.

However, some nationalities are characterized by a limited range of significant mutations (the so-called “founder effect”). Thus, in the population of Russian patients of Slavic origin, up to 90% of detected pathogenic variants of BRCA1 are represented by only three mutations: 5382insC, 4153delA, 185delAG. This fact allows us to significantly speed up genetic testing of patients with signs of hereditary breast cancer/ovarian cancer.

Analysis of the BRCA2 gene sequence, identification of the c.9096_9097delAA mutation

In what cases should you be tested for BRCA1 and BRCA2 mutations?

The National Comprehensive Cancer Network (NCCN) recommends that the following patients be referred for genetic testing:

1. Patients under 45 years of age diagnosed with breast cancer
2. Patients under the age of 50 years with breast cancer, if the family has at least one close blood relative with such a diagnosis
3. Also in the event that a patient under 50 years of age with breast cancer has an unknown family history of cancer
4. If multiple breast lesions are diagnosed before the age of 50
5. Patients with breast cancer under the age of 60 years - if, according to the results of histological examination, the tumor is triple-negative (there is no expression of ER, PR, HER2 markers).
6. If you are diagnosed with breast cancer at any age, if at least one of the following signs is present:
   • at least 1 close relative with breast cancer aged less than 50 years;
   • at least 2 close relatives with breast cancer at any age;
   • at least 1 close relative with ovarian cancer;
   • presence of at least 2 close relatives with pancreatic cancer and/or prostate cancer;
   • having a male relative with breast cancer;
   • belonging to a population with a high frequency of hereditary mutations (for example, Ashkenazi Jews);
7. All patients diagnosed with ovarian cancer.
8. If a man is diagnosed with breast cancer.
9. If prostate cancer is diagnosed (with a Gleason score >7) and there is at least one relative with ovarian cancer or breast cancer aged less than 50 years, or if there are at least two relatives with breast cancer, pancreatic cancer or prostate cancer.
10. If pancreatic cancer is diagnosed in the presence of at least one relative with ovarian cancer or breast cancer aged less than 50 years, or in the presence of at least two relatives with breast cancer, pancreatic cancer or prostate cancer.
11. If pancreatic cancer is diagnosed in an individual belonging to the Ashkenazi Jewish ethnic group.
12. If a relative has a BRCA1 or BRCA2 mutation

Molecular genetic analysis should be accompanied by genetic counseling, during which the content, meaning and consequences of testing are discussed; the meaning of positive, negative and uninformative results; technical limitations of the proposed test; the need to inform relatives if a hereditary mutation is detected; features of screening and prevention of tumors in mutation carriers, etc.

How to get tested for BRCA1 and BRCA2 mutations?

The material for analysis is blood. For genetic studies, test tubes with EDTA (purple cap) are used. You can donate blood at the National Medical Research Center laboratory or bring it from any other laboratory. Blood is stored at room temperature for up to 7 days.

No special preparation is needed for the study; the results of the study are not affected by food intake, medications, administration of contrast agents, etc.

There is no need to retake the test after some time or after treatment. An inherited mutation cannot disappear or appear during life or after receiving treatment.

What should I do if a woman has a BRCA1 or BRCA2 mutation?

For carriers of pathogenic mutations, a set of measures has been developed for early diagnosis, prevention and treatment of breast tumors and ovarian cancer. If among healthy women those who have a gene defect are promptly identified, it is possible to diagnose the development of the disease in the early stages.

Researchers have identified features of drug sensitivity of BRCA-associated tumors. They respond well to some cytostatic drugs, and treatment can be quite successful.

1. Monthly self-examination from age 18
2. Clinical examination of the mammary glands (mammography or magnetic resonance imaging) from 25 years of age.
3. Male carriers of a mutation in the BRCA1/2 genes are recommended to undergo an annual clinical examination of the mammary glands starting at the age of 35. From the age of 40, it is advisable to perform a screening examination of the prostate gland.
4. Conducting dermatological and ophthalmological examinations for the purpose of early diagnosis of melanoma.

How predisposition to breast cancer and ovarian cancer is inherited.

Often carriers of BRCA1/BRCA2 mutations have a question: has it been passed on to all children and what are the genetic causes of the appearance of hereditary forms of breast cancer? The chances of passing on the damaged gene to offspring are 50%.

The disease is equally inherited by both boys and girls. The gene associated with the development of breast and ovarian cancer is not located on the sex chromosomes, so the likelihood of carrying the mutation does not depend on the gender of the child.

If a mutation has been passed on through men for several generations, it is very difficult to analyze pedigrees, since men quite rarely get breast cancer even if they have a gene defect.

For example: the patient’s grandfather and father were carriers, and the disease did not manifest itself in them. When asked whether there have been cases of cancer in the family, such a patient will answer in the negative. In the absence of other clinical signs of hereditary tumors (early age/multiplicity of tumors), the hereditary component of the disease may not be taken into account.

If a BRCA1 or BRCA2 mutation is detected, all blood relatives are also recommended to be tested.

Why is it important to take ethnic background into account when doing genetic research?

Many ethnic groups have their own set of frequent mutations. The national roots of the subject must be taken into account when choosing the depth of research.

Scientists have proven that some nationalities are characterized by a limited range of significant mutations (the so-called “founder effect”). Thus, in the population of Russian patients of Slavic origin, up to 90% of detected pathogenic variants of BRCA1 are represented by only three mutations: 5382insC, 4153delA, 185delAG. This fact allows us to significantly speed up genetic testing of patients with signs of hereditary breast cancer/ovarian cancer.

And finally, a visual infographic: “Hereditary Breast and Ovarian Cancer Syndrome.” Author - Ekaterina Shotovna Kuligina, Ph.D., senior researcher at the Scientific Laboratory of Molecular Oncology, Federal State Budgetary Institution "National Medical Research Center of Oncology named after. N.N. Petrov" of the Russian Ministry of Health.