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 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. Breast cancer and Only 5% of breast cancers are due to a gene abnormality. Genetics 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. Family history Other professionals e.g. for women who have had and Genetic mantel radiotherapy. Services 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 or high risk. Discuss self examination. Family History Lifestyle advise – smoking, alcohol, Clinic at RHH healthy balanced diet. Organize screening. Discuss chemoprophylaxis. Refer on to genetics if appropriate to consider testing. Gene positive people seen to discuss options and offered annual follow-up.
Population risk: Includes women with only one person in their family 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 Determining ages, bilateral cancers, ovarian Risk 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. Enhanced Moderate risk – annual mammograms for 40-50 then 18 monthly for 50-60 then return to NHS BSP. Breast Screening 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.
Women with a breast cancer risk of moderate or above can be offered risk reducing medication i.e. anti- oestrogens. For premenopausal women this is tamoxifen 20mg daily for 5 years. For postmenopausal women then can also consider anastrazole 1mg or Chemoprophylaxis raloxifene 60mg. (risk reducing Uncertain benefit in women who are BRCA1 as they are more likely to medication) 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 Clinical testing for gene abnormalities. Genetics at NGH 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 Diagnostic Strong family history Genetic testing – who is Offered to women with ovarian cancer (usually non-mucinous type). eligible? 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 Predictive (or abnormality being passed on to each Targeted child. Testing) 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 offered testing.
Positive result – impact on treatment for a patient with cancer, preventative options for other family members. Negative result/inconclusive – no gene found but may be that certain genes Outcomes of not yet identified. testing 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 ovarian, prostate and pancreatic cancers. PALB2 - breast cancer. Recently started testing for this in Sheffield. TP53 – Li-Fraumeni Syndrome- increased risk Gene of multiple cancers. Abnormalities Other genes (rare): linked to Breast Peutz-Jeghers syndrome (STK11) Cancer Cowden (PTEN) Hereditary diffuse gastric cancer (CDH1) Neurofibromatosis type 1 Moderate risk genes: ATM and CHEK2
Cancer Risks for Gene Carriers BRCA1 – lifetime risk BRCA2 – lifetime risk Breast cancer 60-90% Breast cancer 45-85% Ovarian 40-60% Ovarian 10-30% Male breast cancer 0.1-1% Male breast cancer 5-10% Prostate cancer – slightly higher Prostate cancer 25% Pancreatic cancer - population risk Pancreatic 3%
Case Study: female aged 39 Family tree BRCA2
25 th 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. Case Study: Referred to Gynaecology clinic. female aged 39 9 th 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 Bilateral Risk Multidisciplinary Team Meeting. reducing Seen by Surgeon and Clinical nurse Specialist. Mastectomies 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 Genetics affected foetus. and children OR Pre-implantation genetic diagnosis (PGD). involves IVF with implantation of gene negative embryo. IVF rules are the same as to who is eligible.
16 th March 2017 Seen by genetics to discuss PGD. 18 th May 2017 Seen by psychology department. 14th June 2017 Case Study: Seen in gynaecology clinic. female aged Offered screening Or Bilateral salpingo-ophrectomy. 39 But still undergoing PGD so arranged to contact when this completed. 29 th 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) Ovarian OR Management: Bilateral Salpingo-oophorectomy reduces risk by 90-95% However, ovarian screening does not reliably pick up ovarian cancer at an early stage.
7 th July 2017 - Discussed at Oncoplastic MDT Option for implant based or autologous reconstruction. 4 th May 2018 Seen in family history clinic, Ready to pursue mastectomies and reconstruction. Case Study: Prefers autologous options. female aged 1 cycle of IVF failed 39 10 th May 2018 Appointment with plastic surgeons to discuss options 15 th June 2018 Seen by Clinical Nurse Specialist. Discussed surgery, recovery times, complications, pictures of reconstructions.
9 th October 2018 Listed for breast surgery. 8 th November 2018 Had prophylactic bilateral salpingo- ophrectomy. Case Study: 20 th December 2018 female aged Started tibolone due to menopausal symptoms. 39 9 th July 2019 Bilateral prophylactic nipple sacrificing mastectomies with immediate DIEP reconstuctions. 23 rd 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. The Future Expansion of criteria for women with breast cancer to be tested.
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