Genetic advice

Family history as a risk factor.

Nowadays it has been demonstrated that a personal and family history of breast cancer are major risk factors for breast cancer. When we want to find out what risks a woman has of developing breast cancer a careful study of her personal and family medical history must be carried out. We need to know the patient’s age, her personal history, and the age and pathologic history of her relatives, trying to complete a medical history of at least three generations of the family..

We suspect that there are two large groups of patients with a genetic predisposition for breast cancer.

On one hand, when a patient is diagnosed with breast cancer at an age significantly younger than normal, for example, before 30. In this case, we believe that there is a chance of a genetic predisposition to breast cancer, and that her risk is significantly higher than the population in general, as is that of her close relatives (sisters, mother, and daughters).

On the other hand, when a patient has a large number of family members who also have had breast cancer.

It has been demonstrated that when a woman has no family history of breast cancer her risk of having breast cancer increases with age. This is know as population attributable risk and is approximately 8%. When a woman has a first degree relative with breast cancer (sister, mother, or daughter), she has a higher risk, about 13%, of developing breast cancer. This risk is greater if there are two family members with breast cancer: approximately 21% during her lifetime. If there are 3 or more first degree family members with breast cancer, her risk is quite high, above 30%, and in this case we can speak about a genetic disposition to breast cancer.

BRCA1 and BRCA2 Genes indicating a hereditary disposition to breast cancer.

The discovery of the BRCA1 and BRCA2 genes in 1994 and 1995 as genes with a high correlation to breast cancer has allowed individualized risk assessment of breast cancer.

Not all the members of a family where a genetic predisposition to breast cancer is suspected have the same degree of risk. A priori, every first degree relative of someone who has had breast cancer has a 50% chance of having inherited this increased risk. Since we now know which genes indicate a predisposition to breast cancer, we can identify the family members who have inherited this predisposition. In this way we can optimize the primary or secondary preventive measures (screening) for these women. We can also stop the close follow-up measure for those family members who have not inherited the genetic predisposition.

Determining alterations in the BRCA genes is technically complex. The alterations can be located in any part of the genes, thus requiring a meticulous study be carried out, which is expensive and takes a long time.

This study is carried out on a DNA sample that usually is obtained from a blood sample. Through techniques of molecular biology, such as PCR, the DNA in the sample is replicated, and then the sequencing of the gene under study is carried out. Screening processes can be used to save time and money.

It is important to remember that a genetic study has limitations. Those that stand out most are: 1) Not all genetic alterations are identifiable, either because of technical reasons or because not all of the genes responsible for hereditary risk of cancer have been discovered, 2) not all the alterations that are detected have a simple clinical interpretation.

When is the test for genetic disposition for breast cancer indicated?

Given the complexity of the genetic study, patients should be selected carefully before undergoing this process Not everyone is a candidate for a study of BRCA1 and BRCA2 genes, and before undergoing a genetic study, the patient should receive adequate genetic evaluation from specialized personnel.

A priori, the candidates for a genetic study are those affected by breast and/or ovarian cancer and who are most likely to have a hereditary predisposition to cancer:

Families with 3 or more immediate family members affected by breast and/or ovarian cancer.

Families with just two immediate members with breast cancer and with the following specific characteristics:

Both patients diagnosed before 50.

One with breast cancer and the other with ovarian cancer.

One of the two patients is a male.

One of them had bilateral breast cancer.

Patients with no family history of breast cancer but with who are diagnosed with beast cancer before they are 30, or those diagnosed with bilateral breast cancer before 40, or diagnosed with two tumors in the breast or ovary at any age.

Follow up of patients carrying BRCA gene mutations

Women carrying a mutation (a genetic alteration) associated with breast cancer have a high risk of breast and/or ovarian cancer, but this does not mean that they will definitely develop cancer. For this reason it is important that they follow specific screening processes, such as

Monthly breast self examination starting at 18.

Breast examination by a doctor or other health specialist at least once a year.

Begin complementary examinations such as mammograms at 25 to 30. Given the low sensitivity in young patients of mammograms, a breast ultrasound can also be carried out, if the radiologist thinks it is necessary. Nowadays, the effectiveness of using MRI for the follow-up of these patients is being evaluated.

A yearly transvaginal ultrasound after 30 years of age, combined with a blood test for the tumor marker Ca 125.

Recently the usefulness of prophylactic measures in reducing the incidence and mortality of breast and/or ovarian cancer in these high-risk patients has been demonstrated.

Among these options the most promising are:
a) prophylactic salpingo-oophorectomy, removing the fallopian tubes and the ovaries when the woman does not plan to have any more children and is close to menopause,
b) preventive bilateral mastectomy, and
c) chemoprevention. These are very personal choices, and their benefits, risks and limitations should be discussed with the patient in the process of genetic evaluation.

To conclude, I would like to emphasize the following:

Breast cancer

-Normally is NOT hereditary

In the few cases where it is suspected that breast cancer is hereditary (5-10%), it is possible to study which gene is responsible.

-In families that have hereditary breast cancer we indicate a stricter follow-up that along with other measures improves the prognosis and can even prevent cancer from developing.

Dr. Ignacio Blanco


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