1. South London Genomic Medicine Centre Cancer Cases Dr Alison May Berner ST4 Academic Clinical Fellow in Medical Oncology 4th June 2018

2. Lung Case – 73 year old female
Ct confirmed as only sight of disease

3. Lung Case – 73 year old female
CT guided lung biopsy
Lung adenocarcinoma
Wild-type EGFR and ALK
PDL1 3%
Sample sent for 100K
Resection of brain metastasis
Radiotherapy to tumour bed
Right lower lobe resection
pT3pN2M1b
For adjuvant therapy under oncology

4. Lung Case – 73 year old female
100K fresh frozen sample
Two tier 1 variants in EGFR gene
c.2504A>T (H835L)
c.2497T>G (L833V)
Literature search
Previous case report of patient with same dual mutation
DIRECT database
Two cases of H835L + L833V
1 documented response to Gefitinib
Three cases of L858R + L833V
Possible to offer anti-EGFR therapy in metastatic setting
Need to validate mutation
DIRECT database: DNA-mutation inventory to refine and enhance cancer treatment
(EGFR L833V, H835L; accessed ),

5. Breast Case – 36 year old female
Self-detected left breast lump
Mother also had breast cancer aged 37

6. Breast Case – 36 year old female
Biopsy
Grade 2 invasive ductal carcinoma
ER 0, PR 0, HER2 negative
100K fresh frozen sample sent
Neoadjuvant chemotherapy
Anthracycline and Taxane
Moderate response
Negative BRCA test
Left mastectomy and a sentinel node biopsy 

7. Breast Case – 36 year old female
No actionable tier 1 variants
Signature 3 identified
Compatible with defect in homologous recombination pathway
Loss of heterozygosity at BRCA1 locus
Management as BRCA?
Prophylactic surgery/screening
Treatment if recurs

8. Colorectal Case – 67 year old male
Positive faecal occult blood test
Referred for flexible sigmoidoscopy
Difficult
CT colon
Tumour at hepatic flexure
PET CT
Confirmed isolated tumour

9. Colorectal Case – 67 year old male
Right Hemicolectomy
Moderately to poorly differentiated adenocarcinoma
Dukes B
EMVI negative
0/22 lymph nodes involved
Mismatch IHC abnormal - MLH1 and PMS2 absent
Molecular analysis
BRAF V600E mutation detected
KRAS and NRAS no mutation
No family history of colorectal cancer
No adjuvant chemotherapy on balance of risk

10. Colorectal Case – 67 year old male
33 coding SNVs per megabase

11. Colorectal Case – 67 year old male
Management of follow-up
BRAF-directed trials if recurs
Consider Immunotherapy if recurs

12. St George’s 100K Cancer Team
Nirupa Murugaesu Ruth Pettegal Katie Snape Helen Hanson John Short George Morrissey Tracy Odigie Alison Berner Glen Brice Mary Brice Uzma Khan Iulia Munteanu Rahul Kurup Keith Rogerson