Table 2.
Summary of costs used in model (2010 prices)*
| Item | Cost (£) | Source |
|---|---|---|
| Cost of genetic testing | 50 | GCaPPS |
| Cost of counseling | 33 | GCaPPS, PSSRU unit costs of health and social care (89) |
| Cost of RRSO (and HRT) | 2222 | NHS reference costs (90), BNF ( 91 ) |
| Cost of ovarian cancer diagnosis and initial treatment | 15,753 | NHS reference costs (90), NICE guideline (92) |
| Yearly cost of ovarian cancer treatment and follow-up: years 1–2 | 612 | NHS reference costs (90), NICE guideline (92) |
| Yearly cost of ovarian cancer treatment and follow-up: years 3–5 | 262 | NHS reference costs (90), NICE guideline (92) |
| Terminal care cost with ovarian cancer | 14,716 | National Audit Office (93) |
| Cost of breast cancer screening general | 330 | Robertson 2011 (94), NHS reference cost (90) |
| Cost of breast cancer screening BRCA carriers | 5983 | NHS reference costs (90), NICE guideline famial breast cancer (19) |
| Cost of RRM | 3222 | NHS reference costs (90), weighted for 21% complication rate (18,95) |
| Cost of breast cancer treatment | 15039 | NHS reference costs (90), NICE guideline advanced breast cancer (50), NICE guidelines early and locally advanced breast cancer (96) |
| Yearly cost of breast cancer follow-up and adjuvant treatment if any (eg, Tamoxifen): years 1–5 | 1914 | BNF (91), Robertson 2011 (94), NHS reference costs (90), NICE guidelines early and locally advanced breast cancer (96) NICE guideline advanced breast cancer (50) National Costing Report. Implementing NICE guidance 2009 (47) |
* All costs were varied by +/-30% in one-way sensitivity analysis. BNF = British National Formulary; GCaPPS = Genetic Cancer Prediction through Population Screening study; HRT = hormone replacement therapy; NHS = National Health Service; NICE = National Institutes for Health and Clinical Excellence; PSSRU = Personal Social Services Research Unit; RRSO = risk-reducing salpingo-oophorectomy, RRM = risk-reducing mastectomy.
† Cost of genetic counseling/testing: based on pretest counseling time (45 minutes), 71% genetic testing uptake (GCaPPS study), and national unit cost assumed for genetic counselling = £44/h of client contact from PSSRU Unit costs of Health and Social Care 2010 (89,97).
RRSO costs: based on national reference costs for an upper genital tract laparoscopic/endoscopic intermediate procedure (90). Costs of HRT (from BNF [91]) assume HRT is given from average age of RRSO to the average age of menopause (51 years).
Ovarian cancer costs: Costs for ovarian cancer diagnosis and treatment were derived from national reference costs and a recent ovarian cancer guideline from NICE (90,92). We assumed cost of diagnosis includes a pelvic examination, ultrasound scan, CA125 test, CT scan, percutaneous biopsy, and peritoneal cytology.
The cost of treatment included the reference cost for a lower and upper genital tract very complex major procedure and administration of chemotherapy based on six cycles of carboplatin and paclitaxel treatment. It was assumed that in years 1 and 2 treated survivors would have a further three consultant visits, a CT scan, and four CA125 tests each year. In years three to five years postsurgery, it was assumed that survivors would have two consultant visits and two CA125 tests. We were conservative in our cost estimates and did not include costs for additional investigations, treatment of recurrence, or management of complications in the analysis.
Costs for terminal care for ovarian cancer were derived from end-of-life costs for cancer patients based on a report from the National Audit Office, UK (93).
In line with NICE recommendations, future healthcare costs not associated with ovarian cancer were not considered (25).
Breast Cancer Costs: Breast Cancer diagnosis and treatment costs were derived predominantly from: “National costing report- Implementing NICE guidance (Feb 2009),” which provides estimates of the national cost impact arising from implementation of NICE guidelines for diagnosis and treatment of early/locally advanced breast cancer and advanced breast cancer in England, UK (47); from UK Department of Health NHS reference costs 2010–2011 (90); the BNF (91) and other relevant NICE guidelines on breast cancer care in general and high risk populations (19,50,96).
Cost of breast cancer screening: assumes for noncarriers routine mammography (eight mammograms between 50–70 years), as per UK NHS breast cancer screening program (98). Cost of breast screening for BRCA carriers is based on annual mammogram from age 40 to 69 years and annual MRI from age 30 to 49 years, as per NICE guidelines for familial breast cancer (19).
Cost of RRM: obtained from NHS reference costs (90) weighted for a 21% complication rate (18,95).
Cost of breast cancer treatment: In the general population, 10% of breast cancer is noninvasive DCIS; 90% breast cancer is invasive; 95% of invasive breast cancer is early and locally advanced (41% Stage 1, 45% stage 2, 9% stage 3 [45–48]); 5% of invasive breast cancer is advanced breast cancer (stage 4) (45–47); 35% of early and locally advanced breast cancer will progress to advanced breast cancer (NICE costing report, 2009) (47). In BRCA carriers, 20% of cancers are DCIS and 80% invasive (61% stage1) (18,49).
The cost of diagnosis includes clinical examination, mammogram, ultrasound, and biopsy.
Mean prevalence of Axillary lymph node metastasis in early invasive breast cancer is 31.4% (systematic reviews within the NICE breast cancer guideline [96] and breast cancer clinical outcome measures [BCCOM] project [99]). 30% node-positive rate is assumed for BRCA breast cancer (based on screening studies in familial breast cancer, breast cancer case series, and Early Breast Cancer Trialists’ Collaborative Group data) (49,100–103).
Cost of sentinel lymph node biopsy (SLNB): from NICE national costing report (47). SLNB for staging axilla for early invasive breast cancer and no evidence of lymph node involvement on Ultrasound (US)/negative US–guided biopsy (73% of invasive cancers).
Cost of axillary lymph node dissection (ALND): assumed to be 25% of cost of breast surgery, as per NICE guideline development group recommendation (47), undertaken for lymph node–positive cancers (31% early and locally advanced invasive cancers) (47,96).
Breast surgery costs: This includes costs of breast conserving surgery (assumed for all noninvasive cancers, and 75% of early/locally advanced [stage 1–3] invasive cancers); and costs of mastectomy with reconstruction (for 25% early/locally advanced cancers). Costs are obtained from the national NHS reference costs (90).
Radiotherapy and chemotherapy: Invasive breast cancers that are not low risk (99,104,105) receive adjuvant treatment in line with NICE guidelines. Costs include radiotherapy costs for 60% of early invasive/locally advanced, radiotherapy and chemotherapy costs for 40% early invasive/locally advanced, and chemotherapy costs for all advanced cancers. Radiotherapy costs include planning and 40Gy, 15 times over three weeks (NICE guidelines [96]) or palliative treatment, taken form national NHS reference costs (90). Chemotherapy costs (based on polychemotherapy) (100) include administration costs, costs of 1st and 2nd line therapy, and toxicity from NICE guidelines (47,50).
All costs are adjusted for BRCA breast cancers for difference in stage at presentation and 20% cancers being noninvasive.
70% general population invasive breast cancers are ER-positive; 15% early invasive breast cancers and 25% advanced breast cancers are HER2-positive (50,96). 27% BRCA1 and 67% BRCA2 breast cancers are ER-positive; 5% BRCA1 and 14% BRCA2 breast cancers are HER2-positive (101–103,106–108). ER and HER2 testing costs are obtained from a local NHS trust and included for all breast cancers.
Endocrine therapy costs: As per NICE guidelines (47,96), ER-positive invasive breast cancers receive Tamoxifen 20mg/day (premenopausal)/ Anastrazole 1mg/day (postmenopausal) for five years: costs from the BNF (91). Rates are adjusted for BRCA carriers, ER positivity, and menopause status.
Biphosphonate costs: 74% patients with advanced breast cancer will develop bone metastases, and 65% patients with bone metastases are offered bisphosphonates (47,109,110). As per NICE guidelines, costs (from BNF [91]) assume that 50% patients receive oral clodronate and ibandronic acid, and 50% receive intravenous zoledronic acid or pamidronate (47).
Cost of Trastuzumab: for HER2-positive patients, given at three-week intervals for one year or until disease recurrence as per NICE guidelines. Costs obtained from NICE costing report (47).
35% of early/locally advanced breast cancer progress to advanced breast cancer (NICE guidelines) (47). Recurrence rates for early/locally advanced breast cancer (from the US National Surgical Adjuvant Breast and Bowel Project [NSABP]): 15.9% for node-positive (111) and 11% for node-negative (112) breast cancer: composite recurrence rate = 12.6% (weighted for 31% node-positive and 69% node-negative disease). Recurrence rate for advanced/metastatic breast cancer is 66% (34% relapse free five-year survival) (52).
Follow-up costs: includes annual mammograms and six monthly consultations. MRI scan for all stage 4 cancers. Costs include a progression rate of 35% from early and locally advanced to advanced disease (47), and 66% relapse rate for advanced disease (52).
Costs for terminal care for breast cancer were derived from end-of-life costs for cancer patients based on a report from the National Audit Office, UK (93). In line with NICE recommendations, future healthcare costs not associated with breast cancer were not considered (25).
Chemoprevention (sensitivity analysis): Tamoxifen/Raloxifene for five years (19,23), from BNF (91).
†For more detailed explanation, see Supplementary Table 2 (available online).