Family History, Genes and Breast Cancer Aims: Understand risk - - PowerPoint PPT Presentation
Family History, Genes and Breast Cancer Aims: Understand risk assessment process for family history patients. Awareness of surveillance and risk reducing options in family history patients. Understand who is eligible for genetic
Understand risk assessment process for family history patients. Awareness of surveillance and risk reducing options in family history
patients.
Understand who is eligible for genetic testing. Awareness of types of gene abnormalities linked to breast cancer Understand risk reducing options for women with high risk gene
abnormalities using a case study.
550 new cases of breast cancer are diagnosed in Sheffield per year. Only 5% of breast cancers are due to a gene abnormality. Other Risk factors: female gender, family history (no single gene identified), age, race, weight, diet, alcohol, external oestrogens e.g. HRT.
Family history Clinic at RHH – run by 2
Breast Clinicians. Assess referrals from
GPs. In-house fast track clinic. Clinical genetics. Other professionals e.g.
for women who have had mantel radiotherapy.
Clinical Genetics at NGH.
Assess referrals from
GPs. Family history clinic. Oncology/ Breast
Surgeons.
Take a history of general health, lifestyle
and risk factors.
Take a detailed Family history –
maternal and paternal – at least 2 generations but as much as is known.
Assess risk level – population, moderate
Discuss self examination. Lifestyle advise – smoking, alcohol,
healthy balanced diet.
Organize screening. Discuss chemoprophylaxis. Refer on to genetics if appropriate to
consider testing.
Gene positive people seen to discuss
Population risk: Includes women with
breast cancer over age 40 at diagnosis.
Moderate risk: one first degree relative
with breast cancer diagnosed under age of 40 or several relatives but older ages, no definite pattern.
High risk: several close relatives, younger
ages, bilateral cancers, ovarian cancers, male breast cancer, Jewish ancestry, sarcomas or gliomas or multiple cancers at young ages. – refer to genetics for assessment.
Base assessment on National Institute for
Health and Care Excellence (NICE) Familial breast cancer guidelines (CG164).
Nice.org.uk/guidance/CG164
Population risk – Invited for a mammogram every 3 years on NHS Breast Screening Programme (BSP). Between around 50-70. Over 70 can self referral every 3 years. Moderate risk – annual mammograms for 40-50 then 18 monthly for 50-60 then return to NHS BSP. High risk (but low gene risk) – Annual mammogram 40-60 then NHS BSP. High risk gene abnormality – Annual MRI 30-50+ with addition of annual mammograms for 40-70. MRI continues until breast density is suitable for mammogram alone.
Chemoprophylaxis (risk reducing medication)
Women with a breast cancer risk of
moderate or above can be offered risk reducing medication i.e. anti-
For premenopausal women this is
tamoxifen 20mg daily for 5 years.
For postmenopausal women then can
also consider anastrazole 1mg or raloxifene 60mg.
Uncertain benefit in women who are
BRCA1 as they are more likely to develop oestrogen receptor negative breast cancers.
Reduces risk by 1/3, benefit lasts after
stopping treatment for several years.
Has to be considered on person by
person basis due to potential side effects, drug interactions and contraindications.
Perform risk assessment using BOADICEA. Perform diagnostic and predictive testing for gene abnormalities. Recommend appropriate early/enhanced screening. Offer counselling for Pre- implantation genetic diagnosis (PGD).
Offered in breast cancer patients; Under 40 at diagnosis or Under 50 bilateral cancers or Under 50 and triple negative or Male at any age or Strong family history Offered to women with ovarian cancer
(usually non-mucinous type).
Offered to women who have not had
cancer if at high risk of being a gene carrier ONLY if everyone who has had cancer is deceased.
Once a gene abnormality is known can
test other family members including men.
There is 50/50 chance of a gene
abnormality being passed on to each child.
If they test negative their risk is now
back to population level and their children do not need testing.
If positive then they need counselling
and other family members can be
Positive result – impact on treatment for
a patient with cancer, preventative
Negative result/inconclusive – no gene
found but may be that certain genes not yet identified.
Variant of Uncertain Significance –
alteration in a gene but not yet know if this abnormality is linked to development of breast cancer.
High risk genes: BRCA1 and BRCA2 – also increases risk of
PALB2 - breast cancer. Recently started testing for this in Sheffield. TP53 – Li-Fraumeni Syndrome- increased risk
Other genes (rare): Peutz-Jeghers syndrome (STK11) Cowden (PTEN) Hereditary diffuse gastric cancer (CDH1) Neurofibromatosis type 1 Moderate risk genes: ATM and CHEK2
BRCA1 – lifetime risk
Breast cancer 60-90% Ovarian 40-60% Male breast cancer 0.1-1% Prostate cancer – slightly higher Pancreatic cancer - population risk
BRCA2 – lifetime risk
Breast cancer 45-85% Ovarian 10-30% Male breast cancer 5-10% Prostate cancer 25% Pancreatic 3%
Case Study: female aged 39
Family tree BRCA2
25th January 2017
seen by Clinical genetics – found to
have BRCA2 gene abnormality
Referred to discuss options to avoid
passing on abnormal gene to a future child.
Referred to family history clinic. Referred to Gynaecology clinic.
9th March 2017
Seen in family history clinic. Offered high risk breast screening. Tamoxifen as chemoprophylaxis. Bilateral risk reducing mastectomies and
reconstruction discussed.
Referred to clinical psychology.
Reduces risk by 95% of developing a
future breast cancer.
With or without reconstruction. No longer need screening. Women are discussed at Oncoplastic
Multidisciplinary Team Meeting.
Seen by Surgeon and Clinical nurse
Specialist.
Psychology input – they work within the
department.
Events such as Breast Reconstruction
Awareness (BRA) evening
Women may want to avoid passing on a high risk gene abnormality to their children.
Pre-natal diagnosis (PND) – genetic
testing of the foetus.
Sample of foetal DNA taken for
assessment.
Faced then with decision of aborting an
affected foetus. OR
Pre-implantation genetic diagnosis
(PGD).
involves IVF with implantation of gene
negative embryo.
IVF rules are the same as to who is
eligible.
16th March 2017
Seen by genetics to discuss PGD.
18th May 2017
Seen by psychology department.
14th June 2017
Seen in gynaecology clinic. Offered screening Or Bilateral salpingo-ophrectomy. But still undergoing PGD so arranged to
contact when this completed. 29th June 2017
Seen in family history clinic. Pursuing fertility treatment. Referred to Oncoplastic MDT.
Ovarian cancer risk increases from age 40 in BRCA1 and 50 BRCA2. From 35 women offered: Screening – annual ultrasound and blood test (CA125) OR Bilateral Salpingo-oophorectomy reduces risk by 90-95% However, ovarian screening does not reliably pick up ovarian cancer at an early stage.
7th July 2017 -
Discussed at Oncoplastic MDT Option for implant based or autologous
reconstruction. 4th May 2018
Seen in family history clinic, Ready to pursue mastectomies and
reconstruction.
Prefers autologous options. 1 cycle of IVF failed
10th May 2018
Appointment with plastic surgeons to
discuss options 15th June 2018
Seen by Clinical Nurse Specialist. Discussed surgery, recovery times,
complications, pictures of reconstructions.
9th October 2018
Listed for breast surgery.
8th November 2018
Had prophylactic bilateral salpingo-
20th December 2018
Started tibolone due to menopausal
symptoms. 9th July 2019
Bilateral prophylactic nipple sacrificing
mastectomies with immediate DIEP reconstuctions. 23rd July 2019
No malignancy in specimens Good cosmetic outcome.
Genetic testing to be done for high gene risk women with breast cancer within the surgical/oncology setting, With referral on to Clinical Genetics if found to have a gene abnormality. Expansion of criteria for women with breast cancer to be tested.