Genetic breast cancer
Breast Cancer
Types risk factor | genetic | malignant | stats | staging | metastic | unusual cancer


Genetic breast cancer


Most breast cancers (90%) are sporadic. This means that the cancers arise in any women, at any time, and are the result of the interplay of the risk factors mentioned above i.e. the effect of the environment on the genes. These genes cause cancer when an environmental factor induces them to mutate to true oncogenes (cancer causing genes).


Proto-oncogenes are in fact normal genes that are converted to oncogenes (cancer causing genes) by a mutation. This mutation may occur by chance during cell division (spontaneous mutation) or by some external factor such as irradiation or viruses or hormones (induced mutation).


Even hormones can affect gene function. The hormone attaches to a cell membrane receptor and via the signal transduction pathway, influences DNA activity. This is the way that oestrogen promotes breast cancer. The gene is the “initiator” and the oestrogen is the “promoter” of the cancer. Thus the oestrogen is the environmental factor that converts the proto-oncogene into the cancer causing oncogene.


Genetic causes of breast cancer account for 10% of all cases. Here the oncogenes are inherited from the parents and do not arise from mutations. Breast cancer is inherited as an autosomal dominant trait (gene) with limited penetrance and expressivity. This means that the gene can be transmitted by either mother or father and also that some family members can transmit the genetic trait without actually developing the breast cancer themselves.


The genes (or at least the ones that we can identify at the moment) incriminated are the breast cancer (BRCA) associated genes. BRCA1 is on chromosome 17 and BRCA 2 is on chromosome 13. Tests are now available to detect these genes and soon these tests will be easily obtainable. These tests will help to allay the fears of many women in high-risk families.If the gene is present, it will also help the doctor to place the patient on a very careful surveillance programme. Recently a third breast cancer gene has been discovered (BRCA3).


On the familial cancer side (Lifnamini, Camolers) are associated with genetic breaks causing breast cancer.

BRCA1 and BRCA2 are code for proteins that have an important role in genomic stability. It is estimated that mutations of these two genes contribute only 30% to 40% of hereditary susceptibility to breast cancer, implying the existence of undiscovered susceptibility genes. Because screening such women has proved to be difficult, prophylactic strategies to reduce breast cancer risk include mastectomy, which is at least 90% effective, and oophorectomy (the surgical removal of an ovary or ovaries).


Oophorectomy also reduces by 50% to 70% the risk of breast cancer in families prone to breast and ovarian cancer, reducing significantly the risk of occurrence of the latter as well. BRCA1 tumours are usually oestrogen receptor–negative, so it is unknown whether tamoxifen will reduce incidence of breast cancer in mutation carriers. Information on risks associated with the use of hormone replacement therapy is not available. There is evidence that women genetically predisposed to breast cancer may be more susceptible to the further increase in risk associated with oral contraceptives. It should be noted that these BRCA genes predispose to breast cancer, but do not make it inevitable.


BRCA1 confers an 80% risk of breast cancer (and a 40% risk of ovarian cancer). However this risk may be diminished by altering the environment (or eliminating the “promoter”) through such actions as:


Low fat, high fibre diet.


Regular exercise.


Not using HRT (for prolonged period; usually over ten years).


Regular screening mammography.


Immediate needle biopsy of all detected breast lumps.


It is clear that breast cancer is caused by a combination of DNA effect and environmental influence.Ultimately, whether the cancer is genetic (inherited – 10%) or sporadic (somatic mutation – 90%), the basic defect is in the oncogene (defective DNA). This DNA is the blueprint that codes for messenger RNA, which moves from nucleus to cytoplasm, where it forms the scaffold for protein synthesis. The abnormal DNA thus codes for abnormal protein. This is the “initiator” of the cancer.

These abnormal proteins represent the malignant characteristics of the cancer cell. Note that DNA and RNA stand for deoxy ribo- and ribo-nucleic acid. The other important concept is the one of suppressor genes. These genes (such as P53) suppress cell division and proliferation, and are thus anti-cancer. They are also a type of proto-oncogene.

When the P53 is altered into an oncogene by mutation, the brake on cell multiplication is removed, which results in unlimited and uncontrolled cell growth or cancer.


So remember if you have a strong familly history of breast cancer what should you do?


Know your family history on your father and mothers side of all cancers.


Wear a tight breast-health seatbelt. This means have:


A mammogram and ultrasound once a year from 40 years or start ten years before the youngest relative developed breast cancer.


Six to twelve months later have a breast ultrasound and possibly a breast MRI.


See your gynaecologist and a breast specialist for a breast exam once a year so you have divided your year into quarters involving two six-month radiology and two six-month clinical exams.










The reason for this is that 50% of women who are at high risk develop their cancer between their yearly mammogram exams.


Next is the discussion around genetic testing.

You should always test someone who has the cancer. (If their test is negative it is pointless testing other family members.)

Risk reducing surgery, previously known as proplylactic mastectomies are the third option for women at high risk.

These procedures are not emergency procedures and should only be done in specialist units.


All patients considering these procedures should:


Speak to other patients who have had this surgery.


Be counselled by an onco psychologist.


Discuss all the short comings around reconstruction prior to booking the surgery.