Update on BRCA testing thresholds NICE guidance changes

Transcription

1 Update on BRCA testing thresholds NICE guidance changes D Gareth R Evans Christie and St Mary s Hospital Manchester UK London July 2014

2 Guideline Development Group Familial Breast Cancer Any woman with a family history of breast cancer Now INCLUDES affected women Includes those identified in Primary and secondary care

3 Risk assessment Manual approach with modified Claus Tyrer Cuzick BOADICEA

4 Genetic testing Family history and carrier probability When available in secondary care, use a carrier probability calculation method with demonstrated acceptable performance (calibration and discrimination) as well as family history to determine who should be offered referral to a specialist genetic clinic. Examples of acceptable methods include BOADICEA1 and the Manchester scoring system. [new 2013]

5 NICE FBC High Risk (tertiary care) Genetic testing Offer testing if >10% chance of BRCA1/2 or TP53 mutation in family Start with testing an affected family member Must offer full mutation testing-not partial By 2005/6 DH target of 8 weeks per gene Can now offer to an unaffected individual if no affected relative available

6 NICE genetic testing affected BC Offer people eligible for referral to a specialist genetics clinic a choice of accessing genetic testing during initial management or at any time thereafter. [new 2013] Offer fast-track genetic testing (within 4 weeks of a diagnosis of breast cancer) only as part of a clinical trial. [new 2013] Discuss the individual needs of the person with the specialist genetics team as part of the multidisciplinary approach to care. [new 2013] All requests for fast track testing to be discussed with a consultant in cancer genetics and then, if appropriate, with the laboratory. This will generally only be relevant if a woman is having neoadjuvant chemo (ie chemo before surgery) and the result may help inform treatment decisions

7 Scoring systems Manual /ballpark-use BCLC data Manchester Scoring Myriad tables (Frank JCO; 1998, 2002) Couch model BRCAPRO Cyrillic BOADICEA only available online

8 BRCA1 scoring system 5 points MBC (if BRCA1 screened) 8 points Ovary <60 yrs 5 points Ovary >59 yrs 6 points FBC <30 4 points 30-39; 3 points points 50-59; 1 point 60+

9 Assessment of score at 20% level (Evans et al 2005) Combined score numbers 0-9 0/62 0% / % /265 17% /195 21% /145 28% /112 50% /61 85% Total 230/ % percentage

10 Modified Manchester score BRCA1 BRCA2 Her Lobular -2 0 DCIS only (no -2 0 invasive cancer) LCIS only -3 0 Grade 1 IDC -2 0 Grade 2 IDC 0 0 Grade 3 IDC +2 0 ER pos -1 0 ER neg +1 0 Grade 3 triple neg +4 0

11 Assessment of Manchester score at 10% level (update 2014) Combined, Ovarian /105 (81%) Male breast All families 10/12 (83%) 104/143(73%) 68/79 (86%) /55 (59%) 6/11 (55%) 56/96 (58%) /90 (43%) 8/12 (67%) 79/170 (47%) /170 (30%) 3/15 (20%) 107/338 (32%) /180 (26%) 4/16 (25%) 119/512 (23%) /147 (14%) 2/26 (8%) 66/709 (9%) /47 (4%) 0/10 (0%) 24/515 (5%) <12 1/25 (4%) 0/4 12/565 (2%) Total 282/830 (35%) 33/106 (32%) 567/3060 (19%)

12 Sensitivity, ROC Curve 1.0 Source of the Curve Unadjusted combined score for BRCA1/2 0.8 Adjusted combined score for BRCA1/2 Reference Line C statistic 0.74: Specificity Diagonal segments are produced by ties. ROC curve with path adjusted score at 20% combined

13 Assessment of score at 10% BRCA1 level (Grade 3 TNT) BRCA1 score numbers BRCA1 BRCA2 7 1/8 0/8 1/ /39 (15%) 3/40 (7%) 3/40 (7%) /67 (18%) 9/67 (13.5%) 3/67 (4.5%) /42 (39%) 12/42 (29%) 4/42 (10%) /27 (56%) 14/27 (52%) 1/27 (4%) /49 (61%) 23/49 (47%) 7/49 (14%) /41 (92%) 33/41 (82%) 4/41 (10%) Total 116/266 (43%) 94/266 (35%) 22/266 (8%)

14 Assessment of score at 10% BRCA1 level (Grade 3 TNT) combined score numbers BRCA1 BRCA2 < /54 (7.5%) 3/54 (5.5%) 1/54 (2%) /78 (18%) 11/78 (14%) 3/78 (4%) /66 (42%) 22/68 (32%) 6/68 (9%) /48 (53%) 18/48 (38%) 7/48 (15%) /43 (77%) 28/43 (65%) 5/43 (12%) /24 (96%) 20/24 (83%) 3/24 (13%) Total 127/313(41%) 102/313 (33%) 25/313 (8%)

15 Study Countr y Age and selection Number tested BRCA1 BRCA2 Combined BRCA1/2 POSH UK <41 sporadic Manchester UK <31 unselected FBCS UK <50 mixture 43 5 (11.3%) 0 5 (11.6%) (37%) 0 11(37%) (22%) 0 11(37%) Gonzalez- Angulo USA unselected (14%) 3 (4%) 14 (18%) Young Canada <41 little or no family history 54 5 (9%) 1 (2%) 6 (11%) Comen USA Unselected Ashkenazi Jewish (30%) 6 (9%) 25 (39%)

16 Manchester POSH combined updated Cases Number BRCA1 BRCA2 isolated TNBCs aged (11%) 1 isolated TNBCs aged (11%) 0

17 High grade serous ovarian cancer 1,001 Women with nonmucinous OC 16.6% of serous cancer patients (highgrade serous, 22.6%) diagnosed 61+ with no PSFH, 16/250 (6.4%) Alsop et al JCO 2012

18 number BRCA1/2 neg % BRCA1/2 pos % Pos FH No FH Serous Clear cell Endometrioid

19 TNT >40 What about TNT 40-50? Robertson (FBCS) et al BJC 2012 suggested testing all <50 4/38 with pathology unadjusted MS <15 Detection rate not clear in sporadics >50 detection rate low only 4/101 (4%) unselected

20 What can all be tested TNBC <40 years High grade serous Ovarian <60 years

21 Do these criteria meet the 10% threshold? 1. Bilateral breast cancer and both cancers diagnosed <40 years -OK MS Triple negative breast cancer diagnosed <50 years -Evidence for sporadic lacking 3. Non- mucinous Epithelial ovarian cancer evidence for sporadic >60 well below 10% 4. Bilateral breast cancer and a relative diagnosed with breast cancer <60 years MS as low as 8! 4/78 5. A first degree relative with breast cancer and both diagnosed <40 years OK MS A first degree relative with a non-mucinous epithelial ovarian cancer -MS as low as 12! -1/16 7. A family history with a Manchester score greater than or equal to 15