Is it possible to inherit both a BRCA1 and a BRCA2 alteration?

Yes. It is possible to inherit both a BRCA1 and a BRCA2 alteration, but this is rare. Most BRCA1 or BRCA2 alteration carriers have inherited an alteration in only one of these genes. The implications of carrying both a BRCA1 and BRCA2 alteration are unclear but current evidence suggests that cancer risks in these individuals are similar to those in BRCA1 alteration carriers.

Why are alterations in BRCA1 associated with a higher cancer risk than in BRCA2?

Studies have shown a slightly higher incidence of breast cancer and a higher incidence of ovarian cancer in women with a BRCA1 alteration when compared to women with a BRCA2 alteration. It is not clear what causes the differences in these risks. BRCA1 and BRCA2 are both involved in the same DNA repair pathway in cells, but they have different roles in this pathway. This could account for the different cancer risks associated with BRCA1 and BRCA2 alterations.

Is it possible to get a more precise estimate of my own cancer risk rather than the average risks usually quoted?

Your personal risk of developing cancer depends on several factors including your family history of cancer, lifestyle factors (such as pregnancy, physical activity and weight gain) and the particular alteration that you inherited in BRCA1 or BRCA2. Your genetic counsellor will be able take these factors into account and may be able to give you a more personalised estimate of your own cancer risk. In addition, recent ongoing research has identified many small genetic alterations (called Single Nucleotide Polymorphisms or SNPs) that occur commonly in the general population and in people with BRCA alterations. These SNPs can increase or decrease the chance of cancer developing in women with BRCA alterations. These SNPs are not tested for routinely in the clinic yet, but it is likely that they will be used in the future to give BRCA carriers a more precise estimate of their cancer risk. Even with these advances in cancer risk prediction, it is impossible to say for certain whether a woman will or will not develop cancer.

Does my faulty BRCA gene put me at higher risk of developing other cancers (other than breast & ovarian) and what can I do to manage these risks?

Yes. There is some evidence that BRCA alterations (especially BRCA2 alterations) slightly increase the risk of developing pancreatic cancer. Unfortunately, there is currently no proven screening for pancreatic cancer. Research into the effectiveness of screening methods for pancreatic cancer in people with BRCA alterations is ongoing at the moment so this may change in the future.

BRCA2 alterations have also been associated with an increased risk of melanoma (an aggressive type of skin cancer). However, the absolute risk is quite low therefore routine skin clinical surveillance is not recommended. Symptoms to be aware of include new moles or existing moles that have changed in size, shape, or colour. Melanoma risk can be minimised by avoiding sunburn and wearing protective clothing and a high SPF sun cream on exposed skin. More information on melanoma prevention can be found here: https://www.hse.ie/eng/services/list/5/cancer/prevention/skin-cancer-prevention-sunsmart.html

Genetic

A short video explaining genetic inheritance.

Can I choose to have ovarian screening instead of having my ovaries removed ?

Unfortunately, at present there is no effective screening available that detects ovarian cancer at an early enough stage to improve survival in women who have been diagnosed with a BRCA 1/2 gene alteration. Ultrasounds through the vagina (transvaginal ultrasound) and blood tests to measure a protein called CA125 may sometimes be considered for a short period of time until a woman's childbearing is completed. However, it is important to remember that this approach has not been proven to detect ovarian cancers at an early stage and is not recommended in clinical guidelines. Many hospitals are therefore reluctant to off this.

What is breast density?

Breast density refers to the amount of fibrous and glandular tissue (dense tissue) in a woman’s breasts compared with the amount of fatty tissue in her breasts as seen on a mammogram.

How is Breast density measured?

When reading a mammogram, radiologists sort breast density into four categories:

1. Almost entirely fat
2. Some dense areas, but mostly fat (sometimes called scattered fibroglandular density)
3. Some fatty areas, but mostly dense (sometimes called heterogeneously dense)
4. Extremely dense

Breasts in category 3 or 4 are considered dense. The radiologist reading the mammogram chooses the category based on their expert opinion.

Are Dense Breasts Normal?

Dense breasts are normal and common. Dense breasts are not caused by illness or disease. But there are some reasons for concern as denser breast tissue can make it harder for the breast radiologist to find or see cancer on a mammogram. Also, the research shows that dense breasts also increase a women’s risk for breast cancer.

Are dense breasts a risk factor for breast cancer?

Yes, women with dense breasts have a higher risk of breast cancer than women with fatty breasts, and the risk increases with increasing breast density. Having dense breasts also makes breast cancers more difficult to see on a mammogram.

What if I have a BRCA gene alteration and dense breasts?

BRCA gene alterations and dense breasts both increase the chances that a woman will develop breast cancer independently of each other. However, BRCA1 or BRCA2 mutations put women at a much higher chance of getting breast cancer than the risk from having dense breasts. Typically MRI is used as well as mammograms as part of screening in women with BRCA alterations. In women with dense breasts, having a breast MRI improves breast cancer detection and reduces the chance of missing a breast cancer.

I have read about the possibly of having the fallopian tubes removed first and then the ovaries a few years later (‘salpingectomy with delayed oophorectomy’) to delay menopause until a woman is older- Is this an option in Ireland?

Currently this is not standard practice in Ireland. Research trials are currently in progress to test the effectiveness of removing the fallopian tubes first and then the ovaries later. If the results from these trials show that this approach is effective in preventing ovarian cancer, then surgery to remove the fallopian tubes first followed by the ovaries a few years later to delay menopause may offer a promising option in the future for women with a BRCA alteration.

Although not standard practice, some doctors in Ireland may consider performing this type of surgery in certain circumstances. This can be discussed with your individual Gynecologic Surgeon.

I’ve heard that the oral contraceptive pill ‘the pill’ can reduce a woman’s risk of developing ovarian cancer, should I take it for this reason?

It is true that the oral contraceptive pill (OCP) is associated with a lower chance of ovarian cancer, however, it does not reduce the risk enough for women with a BRCA alteration. It is therefore not recommended solely for the purpose of reducing ovarian cancer risk. It is usually fine for young women with a BRCA alteration to take the OCP for contraception (provided they do not have other conditions such as increased risk of blood clots that would make it unsuitable). See Q? for further information on the OCP.

Source: NICE 2013 Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. London: National Institute for Health and Care Excellence (NICE); 2013 (NICE Clinical Guidelines, No. 164.)

Is it safe for women with a BRCA alteration to take the oral contraceptive pill (OCP)?

Current advice from the National Institute for Health and Care Excellence (NICE) recommends that the OCP is usually suitable for use as a contraceptive by young women with a BRCA alteration. The OCP does slightly increase breast cancer risk and this needs to be considered particularly for women over 35 years given that their absolute risk increases with age. The benefits of OCP use in preventing pregnancy and reducing ovarian cancer risk may outweigh the slight increase in breast cancer risk for some women. You should discuss whether the OCP is the right contraceptive choice for you with your GP.

Source: NICE 2013 Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. London: National Institute for Health and Care Excellence (NICE); 2013 (NICE Clinical Guidelines, No. 164.)

Is there anything I can do to prevent passing my faulty BRCA gene to my future children?

Most individuals with a BRCA alteration choose to have children naturally. In this case every child you conceive has a 50% (1 in 2) chance of inheriting your BRCA alteration. Both men and women with a BRCA alteration have a 50% chance of passing their faulty BRCA gene to each of their children.

Preimplantation Genetic Diagnosis PGD is an option for some couples to prevent their faulty BRCA gene being passed to their children. This involves a couple undergoing in vitro fertilisation (IVF). When the embryos reach a certain size, a few cells are removed from the outer part of the embryo that would one day form the placenta. The removed cells are tested for the BRCA alteration and only embryo(s) that do not carry the alteration are implanted into the woman’s uterus (womb).

The decision to have PGD is a personal one and will depend on many factors such as experiences with cancer in the family and financial circumstances. PGD is expensive and can be a long and emotional journey. As with all IVF, a successful pregnancy is not guaranteed.

PGD is available in clinics in Ireland including Beacon Care Fertility and Waterstone Clinic.

Can I have my children tested for the faulty BRCA gene that I have?

Your children must be 18 years old to be tested for a BRCA alteration. At this age they are considered an adult and can therefore consent for genetic testing if they wish. BRCA alterations affect adult cancer risk and not on childhood cancer risk, therefore there is no reason to test in childhood. Even though individuals can be tested for a BRCA alteration from age 18, it is important to note that international guidelines do not recommend starting surveillance until 30 years of age. For this reason, some individuals choose to wait until they are older and closer to the age at which surveillance can begin before being tested while others wish to be tested as soon as possible.

Is there a difference in survival/mortality between cancers that occur in BRCA carriers compared to women in gen pop without these mutations?

BRCA1 or BRCA2 carriers diagnosed with breast or ovarian cancer have similar or better outcomes (survival) than those who don’t have the mutations. The reason for this may be due to BRCA carriers having a greater sensitivity to the chemotherapy often used to treat these cancers.

Source: Allison W Kurian, MD, MSc, Paul Abrahamse, MA, Irina Bondarenko, MS, Ann S Hamilton, PhD, Dennis Deapen, DrPH, Scarlett L Gomez, PhD, Monica Morrow, MD, Jonathan S Berek, MD, MMSc, Timothy P Hofer, MD, MSc, Steven J Katz, MD, MPH, Kevin C Ward, PhD, MPH, Association of Genetic Testing Results With Mortality Among Women With Breast Cancer or Ovarian Cancer, JNCI: Journal of the National Cancer Institute, Volume 114, Issue 2, February 2022, Pages 245–253, https://doi.org/10.1093/jnci/djab151

What help is there to deal with the psychological impact of a BRCA diagnosis?

Some cancer centres have Psycho-Oncology services which may offer patients appointments around the time of their diagnosis, or prior to planning risk reducing surgery. Your Doctor, Nurse or Genetic Counsellor can direct you to supports available to you. Other organisations which have relevant supports include the Irish Cancer Society and Marie Keating Foundation. Your GP can also advise you on counselling services that may be available to you. In addition, women often find peer support from other women with BRCA alterations helpful. Links to relevant organisations and groups can be found in the ‘resources’ section.

How is insurance impacted by positive BRCA gene tests?

The Disability Act (2005) prohibits genetic test results being used in relation to insurance, a mortgage, a personal pension or employment. Therefore, individuals with a BRCA alteration do not have to disclose their genetic test result to these companies and these details should not be requested by them. Questions about family history of cancer do need to be answered honestly but companies are not allowed to ask about genetic testing.
Further information is available here: http://www.justice.ie/en/JELR/DisabilityAct05Guide.pdf