Hereditary Cancer Program’s High-Risk Clinic: Experience to Date Melissa Laing, Nurse Practitioner Mary McCullum, Nurse Educator April 2012 Objectives 1. To review the clinic’s first (almost) 15 years of experience with high-risk screening for women with confirmed BRCA1 or BRCA2 gene mutations 2. To discuss related clinical challenges Background • Provincial interdisciplinary Hereditary Cancer Program • High-risk clinic established in 1997 at BCCA-Vancouver • Eligibility criteria includes women who are: • confirmed BRCA1/2 mutation carrier OR at 50% risk for known family BRCA1/2 mutation • not currently under the care of an oncologist • able to attend appointments in Vancouver • have not completed risk-reducing bilateral mastectomy • Referred by their genetic counsellor • Also provide breast screening for a small number of women with other hereditary cancer syndromes Results to March 31, 2012 Chart review and basic database to describe: • clinic participants • new cancers diagnosed • method of detection • risk-reducing surgeries completed • ongoing follow-up Clinic Participants • 498 women in total have been assessed to date • 250 women are currently followed by the high-risk clinic – majority are BRCA1/2+ – other syndromes: • Ataxia Telangiectasia (n=3) • Li-Fraumeni (n=2) • Hereditary Diffuse Gastric Cancer (n=4) • age 18-79 at initial consult • majority from greater Vancouver area Health Region % popln % clinic pts Fraser 35 33 Vancouver Coastal 25 34 Vancouver Island 17 17 Interior 16 13 Northern 7 1.5 Yukon <1 1.5 Cancers diagnosed prior to participation in high risk clinic Clinic participants (n=485) n (%) No. with breast ca No. with ovarian ca No. with other cancer > 1 cancer diagnosis Declined carrier test 41 (8%) 0 0 0 0 BRCA1+ 243 (50%) 59 Unilat 50 Bilat 9 9 2 Hodgkins 1 endometrial 1* cervical and colorectal 71 *also had br ca BRCA2+ 199 (41%) 48 6* DCIS 2 Unilat 43 Bilat 3 *1 also had breast cancer 1 scc H/N 1 rectal 1 lymphoma 1 cervical 1* endometrial 58 *also had br ca BRCA1 & BRCA2+ 2 (0.4%) 0 0 0 0 Total BRCA1/2+ 444 (92%) 107 (24%) 15 (3.4%) 9 (2%) 129 (29%) * includes 1 who also had breast cancer * includes 1 who also had breast cancer Clinic Appointments • • • • Initial consultation with Nurse Practitioner and Nurse Educator Regular follow-up every 6 months or annually Clinical breast exam, imaging, referrals, decision support Discussion includes: – High-risk breast screening – Prophylactic mastectomy with breast reconstruction – Ovarian cancer screening not recommended – Bilateral salpingo-oophorectomy recommendation; effects of surgical menopause Breast Screening Guidelines • • • • • Detailed clinical breast exam every 6 months starting at age 20 Annual bilateral breast MRI from age 25-65 Annual mammogram beginning at age 30 Mammograms and MRIs alternate at 6 month intervals (ideally) Breast ultrasound if recommended by the radiologist – eg. follow-up of abnormal finding, unable to tolerate MRI • During pregnancy and lactation: – clinical breast examination every 3 months – MRI and mammogram are not recommended – Breast ultrasound used to investigate abnormalities detected on breast examination – Regular MRI and mammogram resumes 3 months after completion of breastfeeding Ovarian Cancer • Ovarian cancer screening methodologies (pelvic examination, transvaginal ultrasound and CA-125) have limited sensitivity and specificity and are therefore not recommended in British Columbia • Oral contraceptive pills have been proven to reduce rates of endometrial and ovarian cancer by 50% or more • This benefit increases with duration of use and persists for up to 20 years after the oral contraceptives are stopped • A protective effect, proportional to duration of use, was also demonstrated for women with BRCA1/2 mutations • The Society of Obstetricians and Gynecologists of Canada’s position statement indicates that there is evidence that the use of oral contraceptives in BRCA carriers does not increase their risk of breast cancer above that related to their genetic risk New Cancers Diagnosed 68 mutation carriers (15%) have had at least 1 new cancer dx • 27 of those had a previous breast or ovarian cancer • 5 had deferred carrier testing - proceeded after diagnosis • 3 were diagnosed at their 1st clinic visit • 5 have had 2 new diagnoses: 1) Bilateral breast ca (BRCA2+) 2) Invasive breast cancer + DCIS on contralateral mastectomy (BRCA2+) 3) Bilateral DCIS (one detected on contralateral mastectomy) (BRCA1+) 4) DCIS + peritoneal after BSO (BRCA1+) 5) 2nd breast cancer (multifocal) + ovarian cancer on BSO (BRCA2+) New Cancers Diagnosed n BRCA1+ BRCA2+ 38 22 16 26 11 1 15 7 0 11 4 1 DCIS 9 5 4 LCIS 1 1 0 Ovarian ca 7 4 3 Fallopian tube ca 2 1 1 Peritoneal ca (after PBSO) 3 1 2 Pancreatic ca 2 0 2 Malignant melanoma 3 2 1 Gastric cancer 1 0 1 Colorectal cancer 1 1 0 Lung cancer 1 1 0 TOTAL 68 38 30 Invasive breast ca #1 breast ca #2 breast ca #3 breast ca Method of Cancer Detection • Chart review for women with new breast or ovary cancer to identify method by which an abnormality was initially reported • Additional imaging required for confirmation in some cases • Numbers too small to report by BRCA1/2 status • 8 new cancers (breast or ovarian) diagnosed on pathology review at time of prophylactic surgery New breast cancers Detection Method Breast ca DCIS LCIS Screening MRI 21 0 0 Screening mammo 8 7 0 Self-exam 6 0 1 Clinical exam 0 0 0 2 (one while 0 0 2 (contralateral) 0 Screening ultrasound lactating) Prophylactic mastectomy 1 New “ovarian” cancers Detection Method Ovarian cancer Fallopian tube cancer Peritoneal cancer after BSO Screening ultrasound 1 1 n/a Symptomatic 3 0 3 Prophylactic Surgery 3 1 0 Risk-Reducing Mastectomy • Reviewed with each woman who attends the clinic • Reduces the probability of breast cancer by 90-95% • Option of nipple-sparing mastectomy is reviewed with the surgeon • Breast reconstructive options are briefly reviewed • Most choose reconstruction (but not all) • After bilateral mastectomy, women are discharged to their family physicians for routine examination of reconstructed breasts and regional nodes; routine imaging of reconstructed breasts is not recommended Risk-Reducing BSO • Bilateral salpingo-oophorectomy • Recommended to all BRCA1/2+ women between the ages of 35-40 and once childbearing is complete • Reduces the probability of ovarian cancer by 85-95% and reduces the risk of breast cancer by approximately 50% when performed prior to menopause • Small number of women have “actively declined” surgeries • 2 women who declined carrier testing have completed BSO • 3 women have completed salpingectomy alone (with plans to proceed with oophorectomy prior to age 40) • The effects of surgical menopause, the impact on bone, heart and brain health, as well as hormone replacement therapy are reviewed with women pre-operatively; ongoing management of related concerns is provided • Short-term HRT does not negate the protective effect of BSO on subsequent breast cancer risk Surgery Completed Unaffected (br/ov) n = 324 Previous br ca n = 107* Previous ov ca n = 15* * 1 with previous br + ov ca * 1 with previous br + ov ca Bilateral Mastectomy (only) 25 (7%) 2 BM as tx 2 CPM 1 BM after GT BSO (only) 101 (31%) 45 15 had BSO as part of treatment Excludes: 1 with previous ov ca Includes: 1 with previous br ca 16 BM as br ca tx & BSO 20 CPM & BSO 11 BM & BSO after GT 1 BM and BSO +/hysterectomy Both BM and BSO 57 (18%) BSO: bilateral salpingo-oophorectomy; BPM: bilateral prophylactic mastectomy; CPM: contralateral prophylactic mastectomy Ongoing Follow-up & Discharge from Clinic 247 women (~50%) who attended at least one clinic appt are not currently being followed: • 45% discharged after risk-reducing surgeries complete • 15% discharged to oncologist re new cancer • 11% discharged to GP (e.g. older & ineligible for MRI) • 9% lost to follow-up • 7% moved out of province • 7% deceased • 6% declined further appointments Clinical Challenges • Breast screening as an emotional rollercoaster • MRI access – Priority booking system/waiting list – Coordination with menstrual cycle • Breast reconstruction – Vancouver waiting list – Other locations • BSO decision-making – Young and single/childless – Surgical menopause • “lost to follow-up” – Recent letter to pt/MD • Appts missed/cancelled on short notice – Weather, travel, forgot Future Directions • Access to high-risk screening in each health region • Enhanced data collection & analysis • Research opportunities e.g. – – – – – – C Wilson project re outcomes of imaging Breast reconstruction waiting list Long-term follow-up (after risk-reducing surgeries) J Kwon project to model BSO vs salpingectomy Sexual health after BSO ? New ovarian screening methods • Screening for other high-risk populations