The development of all tumors originates in a multi-stage process of genetic material defects (so-called mutations) accumulating in the nucleus, which ultimately leads to transforming a previously healthy cell into a cancerous one.

In the case of a genetic susceptibility to tumors, a patient inherits, from one of the parents, a defective copy of a gene, or genes, responsible for the correct functioning of genetic material repair processes or for controlling correct cell divisions. Having a damaged gene thus increases the risk of developing cancer. However, and this ought to be clearly emphasized, it does not predetermine the actual occurrence of the disease, since that would require for the patient to also be exposed to factors damaging the organism’s cells’ genetic information.  

It is estimated that approximately 10%-20% of breast and ovarian cancer cases occur in women who carry a mutation in the BRCA1 or BRCA2 genes. In other female patients, the attempts at identifying the genetic alteration contributing to a tumor’s development have been unsuccessful, despite a sometimes evident familial burden (numerous family members suffering from breast and/or ovarian cancer, occurrences at a very young age). This results from the fact that the genetic tests which are currently available enable the identification of only chosen genetic alterations responsible for an increased susceptibility to developing cancer, while others still remain undiscovered (undetermined) or the methods allowing their identification are simply too costly.   

That is why, when determining whether a patient and her family members qualify as belonging to the group of high breast and/or ovarian cancer incidence, apart from carrying out genetic tests, a thoroughly conducted interview concerning first-degree family members (parents, siblings, children) as well as second-degree relatives (grandparents, grandchildren, mother and father’s siblings) is of fundamental importance. When analyzing genealogy, a medical geneticist pays special attention to the incidence and type of tumors as well as the age of onset. A thorough genealogical analysis makes it possible to determine whether genetic tests ought to be recommended, to identify the scope of the tests and, sometimes, a preliminary qualification of a patient to the high-risk group. It is also advisory for the patients to collect the genetic results directly from a medical geneticist along with a proper interpretation as well as a personalized list of recommendations concerning preventive testing.       

Any other person wanting to determine their carrier status for a mutation which would increase the risk of developing cancer may, of course, have  a genetic test performed. It is worth selecting a test which enables identifying both common and rare mutations, at a reasonable cost, and inquiring about the sensitivity of the identification method used – tests based on genetic material sequencing being the most sensitive (sensitivity>99.9%). In all cases, it is recommended to visit a genetic counseling office in order to consult the results and receive comprehensive genetic advice.

Families which qualify as belonging to the high-risk group are those in which:

1. a mutation in the BRCA1 or BRCA2 genes has been identified (the test result should at all times be consulted with a medical geneticist so that the result’s credibility and clinical value are ensured)
2. first and second-degree relatives (including the patient herself) developed breast and/or ovarian cancer 3 or more times
3. if among first and second-degree relatives breast and/or ovarian cancer has occurred twice – including once before the age of 50
4. at least one woman in the family (the patient herself or a first or second-degree female relative) developed bilateral breast cancer or breast and ovarian cancer
5. if the patient or her first or second-degree female relative developed cancer before the age of 40    

Recommendations for women from families at a high risk of developing breast and/or ovarian cancer (based on the recommendations issued by the European Society for Medical Oncology (ESMO 2011))

• monthly breast self-examination
• breast palpation by a physician once every 6 months (20-25 yrs and more)
• breast imaging examinations (ultrasound, mammography, magnetic resonance – depending on age and breast texture) once a year (ultrasound and magnetic resonance from the age of 25 and mammography from the age of 35)
• gynecological examination once a year (30 yrs and more)
• transvaginal ultrasound once a year (30 yrs and more)
• determining the CA 125 marker level in the blood serum once a year (30 yrs and more)

Recommendations for women who carry a mutation in the BRCA1 or BRCA2 genes (based on the recommendations issued by the European Society for Medical Oncology (ESMO 2011))

• monthly breast self-examination
• breast palpation by a physician once every 6 months (20-25 yrs and more)
• breast imaging examinations (ultrasound, mammography, magnetic resonance – depending on age and breast texture) once every 6 months (ultrasound and magnetic resonance from the age of 25 and mammography from the age of 35)
• gynecological examination once every 6 months (30 yrs and more)
• transvaginal ultrasound once every 6 months (30 yrs and more)
• determining the CA 125 marker level in the blood serum once every 6 months (30 yrs and more)

ATTENTION: In every case of an identified mutation in the BRCA1 or BRCA2 genes, it is necessary that the patient obtains counseling from a physician specializing in clinical diagnostics so as to be presented with personalized options of active prevention.

Anna Poluha, Doctor of Medicine
Expert on Clinical Genetics
GENOMED Genetic Counseling Office
ul. Tomasza Zana 29/XIX, Lublin