level 11 – Master

1. Breast cancer case study Enter resource level 11 – Master

2. Introduction to this resource This case studyfollows the progress of a patient and her family in the genetic clinic. Different clinical areas gather family history information using different methods. Before progressing withthiscase study you may want to refresh your knowledge of family history taking in the relevant section of the learning resource “Cancer Genetics”, which is available for download from the ScotGEN Website. Next

3. The red boxes are "action boxes", and they provide suggested activities, such a discussions, reflection points and more practical activities. The light blue boxes are "content boxes", read them carefully because all the key information is there. The green boxes are "answer boxes", and they provide the answer to the previous activity. The orange boxes are “practice boxes", they suggest some practical activities aimed to deepen your knowledge about the topic. Click for suggested learning outcomes

4. Learning outcomes • Analyse the role of genes in the development of breast cancer • Appraise the relationship between the underlying basis and psychosocial impact of familial predisposition to breast cancer • Critically explore the role of the genetic services in providing risk assessment, diagnosis, management options & genetic testing in the Scottish context Next

5. Please read: This case study has be developed to enable you to use your current scientific knowledge on cancer genetics and use the skills you have gained in taking a family history and drawing a family tree. If you have background knowledge in these areas this case study can stand alone. Next

6. Breast cancer affects around 1 in 10 British women at some time in their lives. Most cases of breast cancer arise by chance. However, a few women are more likely to develop breast cancer because of their genetic make up. In this case study you will learn about how breast cancer can run in families, and what can be done to help women who have a family history of breast cancer. Start Index

7. Index • Breast Cancer case study – Part I • Confirmation of cancer • Risk assessment • Clinic appointment • Mammography • Note for educators • Family history – Part II • Family history– Part III • Genetic testing – Part I • Genetic testing – Part II Start

8. Breast Cancer case study – Part I Mollie Jenkins a 45-year-old lady has been admitted to the surgical ward for a left breast lumpectomy and removal of axillary glands. She discovered a lump in her breast about a month ago and was referred to the breast clinic. Following a mammogram, ultra-sound and fine needle biopsy she was diagnosed with breast cancer. Mollie is married with 2 teenage daughters aged 13 and 17 years and a son aged 9 years. Mollie works part-time as a primary school secretary. During the afternoon Mollie’s 42-year-old sister Wendy Adams visited her. Wendy is very concerned that Mollie is now the third person in their family to be diagnosed with breast cancer. Wendy therefore spoke to the Staff Nurse on duty to ask if she should be concerned about her own risk of developing breast cancer. The Staff Nurse recommended that she makes an appointment with her GP to discuss her family history. Her GP decided to refer Wendy to the genetic clinic. The genetic service sent Wendy a family history form to complete before a clinic appointment was activated Next

9. When the completed family history form is returned to the genetic service the family tree is drawn. Practice point Some Cancer Genetic services ask the person to bring the completed form to the clinic appointment, others draw a family tree at the appointment. Next

10. Action box • (Prior knowledge of drawing a family tree is required for this activity) • Different genetic clinics use different methods to gather family history information. The process of drawing a family tree is the same however the information is gathered. See section 2 for more information. • Open the completed family history form from Wendy Adam • Now draw the family tree (pedigree) from the form. It is important you do this to complete the case study • You may need a reminder of pedigree symbols and relationship lines • Click here to see an example of family history form used by other centres. • Click here to see a patient leaflet about filling in the family history form. • This activity should take about half an hour. Click for answer

11. Answer box • Below you will find a computer drawn family tree from Wendy’s completed family history form. • Open the correct drawing document to see what your family tree should look like. • Compare the correct drawing document with the family tree you have drawn yourself and correct any errors you have made. Keep this family tree for use in later activities. • Although your family tree will be hand drawn, and you may have a different key to represent the different types of cancers, the structure of the family tree should look the same. Next

12. Confirmation of cancer It is good practice in a genetic department to confirm the primary diagnosis of cancer from clinical records for relevant affected relatives. Click for next activity

13. Action box Why should we confirm cancers? What sources can be used to confirm a diagnosis of cancer? Click for answers

14. Answer box Note:consent If a person with cancer is alive and their cancer is required to be confirmed, a signed consent form must be sent to cancer registry with the request. Click here to see one sample form. (Each service will have their own consent forms) • Why should we confirm cancers? • Some people share the wrong information with their family. • Confirm the aetiology of specific cancers. • Confirm age at diagnosis. Sources used to confirm a cancer diagnosis. Hospital notes or electronic file, GP notes, cancer registry, births, marriages & deaths and occasionally from patient held notes or letters. You could discuss as a group, any difficulties you may experience with getting information to confirm cancers. Next

15. Optional activity • Examine the specimen documents provided • completed consent form from Mollie Jenkins, Polly Briggs and Jane Brown. • death certificate • letter from hospital notes (Jane Brown) • cancer registration form (Mollie Jenkins and Polly Briggs) • It is a common occurrence that the referred individual will be asked to provide • death certificates where possible. • Using the Family history form update the family history with the new information. Next

16. Action box • Confirmation of cancers specific to this case study • Look again at Wendy’s family history that you have drawn. • Can you say which cancers in her family history should be confirmed ? Click for answer

17. Answer box Mollie Jenkins Jane Brown Polly Brigs Beryl Smith and Sam Brigs cancer should be confirmed. Annie Silver and Kate Hare should be confirmed as well but there is not enough information about them to find them on a cancer register and confirm them. In Scotland clinical genetics centres have the support of ISD genealogy service (aim 7) for help with tracing relatives when little information is available from the family. Next

18. Cancer was confirmed in Mollie Jenkins (breast cancer at age 45), Polly Briggs (breast cancer at age 70) and Beryl Smith (breast cancer at age 70). However, Jane Brown’s ovarian cancer was not confirmed. It was noted that she had abnormal cervical cytology (no cancer) at age 29. Action box Can you add this extra information to your previous hand drawn pedigree? Click here to see updated pedigree Click for next activity

19. Risk assessment When the pedigree has been drawn and the cancers confirmed an assessment of risk is undertaken. This family history assessment is performed using appropriate evidence based guidelines. Click for next activity

20. Practice point Genetic counsellors use evidence based guidelines to estimate risk and recommend management for patients with familiar breast cancer. There are local variations in the guidelines. In Scotland, agreed guidelines were the subject of a recent health department letter (HDL). They can be viewed here. In England and Wales the NICE guidelines are used. Action box • Access guidelines • Read and understand these applied in cancer genetics practice Click for next activity

21. Action box – Level 11 • Can you assess Wendy’s risk using updated family history and Scottish Guidelines? • List elements of personal history that can be used in assessment of breast cancer risk. Next

22. Answer box Answers expected are: being older, body mass index, menarche, menopause, parity, breast feeding, COCP and HRT, history of benign breast biopsy. Read the following articles: “Breast cancer risk factors” “Breast Cancer (Female)” “Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical cancer Genetics Service setting: risk of breast/ovarian cancer quoted should reflect the cancer burden in the family” Next

23. Clinic appointment Mollie and her sister Wendy attend the genetic clinic together. The genetic counsellor explains the causes of breast cancer. Click for next activity

24. Action box Mutations in one or more genes in a cell can cause cancer. A person can inherit a mutation (gene change) from his/her parents or acquire it during his/her lifetime. A somatic (acquired) mutation can be caused by environmental factors, such a cigarette smoke, radiation, alcohol. Click for animation

25. Action box Action box Mutations in one or more genes in a cell can cause cancer. A person can inherit a mutation from his/her parents or acquire it during his/her lifetime. A somatic (acquired) mutation can be caused by environmental factors, such a cigarette smoke, radiations, alcohol. Mutations in one or more genes in a cell can cause cancer. A person can inherit a mutation (gene change) from his/her parents or acquire it during his/her lifetime. A somatic (acquired) mutation can be caused by environmental factors, such a cigarette smoke, radiation, alcohol. Click for animation Sporadic breast cancer No mutation inherited at birth Radiation Dietary and hormonal factors Other unknown factors Breast cancer Familial breast cancer Mutation inherited at birth Click for next activity

26. The counsellor explains that in Mollie’s case the cancer is unlikely to be caused by mutations in the high risk genes BRCA1 or BRCA2, but that Wendy does have a moderate risk of developing breast cancer. Moderate risk means that Wendy has at least twice the population risk of developing breast cancer. Her daughter is currently at population risk whilst Wendy remains unaffected by breast or ovarian cancer. Action box • Read these articles: • Types of genes involved in cancer • Tumour suppressor genes: guardians of our cells • Cancer and genes Next

27. Mammography Mammography is the key screening strategy in the moderate risk group. The evidence for its use is shown in the NICE guideline document. Action box Click here for more information about mammography. Next

28. Action box With the family history you have constructed, use your local breast cancer genetics guidelines to determine what surveillance and screening Mollie’ daughters will be offered and from what age. Click for answer

29. Action box With the family history you have constructed, use your local breast cancer genetics guidelines to determine what surveillance and screening Mollie’ daughters will be offered and from what age. Answer box According to both the Scottish and NICE guidelines, Wendy should be offered annual mammography from her present age until 50. Current guidelines would recommend that Molly’s daughters should start breast screening at 40. Next

30. Action box • Open this picture of a normal mammogram. • What is a mammogram? • What does it do? • What does it involve? Analyse the psychological impact that the knowledge of being at an increased risk of developing breast and ovarian cancer may have on Wendy. Read about and reflect upon how a individual’s reaction to risk may depend upon the person’s coping approach and life experience. • Read the following articles: • Psychosocial aspects of risk appraisal • Breast cancer risk perception: what do we know and understand? • Illness perceptions and distress in women at increased risk of breast cancer Next

31. Action box • Discuss the pros and cons of mammography in those increased familial risk including: • false positive and false negative rates • what happens if something found • radiation risks Answer box • Read the following articles about mammography • Advice about mammography for a young woman with a family history of breast cancer • Mammographic screening for young women with a family history of breast cancer: knowledge and views of those at risk Next

32. Action box • Read the following two articles: • Hereditary breast and ovarian cancer • Breast and ovarian cancer risk • Reflect on the differences between NICE guidance on risk assessment and the Scottish guidelines. Next

33. Note for educators First part of the learning object finishes here. The following part can be used to follow part one for a more in depth exercise. Next

34. Family History Part 2 (most relevant to genetic counsellors) A few months after Wendy attends the genetic clinic, her paternal cousin Freda aged 36 years (Harold Briggs’ daughter) starts to get anxious about all the cancers in the family. Freda asks her GP to refer her to the genetic clinic for advice about breast screening. Look at the latest version of the family history. Next

35. Action box • There are elements of personal history that can be used in assessment of breast cancer risk: being older, body mass index, menarche, menopause, parity, age at first pregnancy, breast feeding, COCP and HRT, history of benign breast biopsy. (answer box) • Read this article about breast cancer risk factors. • Summarise the risk factors and discuss how each one might impact upon Freda. Next

36. Action box • What is Freda’s risk of developing breast cancer? • Remember to refer to the Scottish guidelines. Click for answer

37. Answer box Freda is considered to be at population risk of developing breast cancer based on the information she provides and following confirmation of the cancers in her family. Next

38. Action box • Write a letter to Freda and her GP outlining her family history and including the following issues: • Background rate of breast cancer in population • Age profile • Freda’s risk assessment • National breast screening • Lifestyle advice • Breast awareness Click here to see an example of a letter to Freda Click here to see an example of a letter to the GP Next

39. Family History Part 3 (most relevant to genetic counsellors) Wendy’s maternal cousin Myra is referred for a genetic clinic appointment as her sister Winifred has recently been diagnosed with breast and ovarian cancer at the age of 35. Click for next activity

40. Action box • What is the family risk now? • Remember to refer to the Scottish guidelines. Click for answer

41. Action box • What is the family risk now? • Remember to refer to the Scottish guidelines. Answer box • The new family history information changes Wendy’s risk to high based on Scottish and NICE guidelines. Next

42. Genetic testing – Part I The genetic counsellor tells Wendy that genetic testing would now be available for her family. The counsellor explains that with Mollie’s informed consent her sample can be tested and that the result could have implications for other relatives. Next

43. Practice point It is standard practice to request a DNA sample from an affected relative. The testing and interpretation of results is complex and can take several months. Click here for more information about genetic testing. Next

44. Mollie consents to give a sample for testing of the BRCA1 and 2 genes. The test shows she has a mutation (also may be described as a gene change) in the BRCA2 gene. Click here to see Mollie’s test result Next

45. Action box • What is Wendy’s risk of breast cancer now? • Is she at risk of any other type of cancer? Click for answer

46. Answer box Working copy of BRCA gene Mum Dad Faulty copy of BRCA gene Children • Wendy has a 50% or 1:2 chance of inheriting the faulty gene. • BRCA1 risk of Breast cancer ~80%; Ovarian cancer ~65% • BRCA2 risk of Breast cancer ~88% and Ovarian ~37% • Ref: Evans DG et al. (2008). Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical cancer Genetics Service setting: risk of breast/ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer 8:155 [Electronic version] Next

47. Answer box Working copy of BRCA gene Mum Dad Faulty copy of BRCA gene Children • Women who inherit a faulty BRCA1 or BRCA2 gene will have a very high chance of developing breast and ovarian cancer. • Men who inherit a faulty gene have an increased risk of developing prostate cancer and can pass the gene on to their children. • Men with BRCA2 gene changes have an increased risk of developing breast cancer themselves. Next

48. Action box • Read about the role of BRCA1 and BRCA2 genes in the development of breast and ovarian cancer. • Breast and ovarian cancer genetics • Handbook of genetic counseling/hereditary breast cancer Next

49. Genetic testing – Part II Wendy is offered a blood test to see if she has inherited the gene change. She leaves the clinic to think about it and decides to take the test. She returns to have a blood sample taken a month later. Click for next activity

50. Action box Click below to view Wendy’s result. Click here to see Wendy’s results Next