Pathologist's health-care value in the triage of Oncotype DX® testing: a value-based pathology study of tumour biology with outcomes.

AIMS: Pathologists provide expert tissue assessment of breast cancer, yet their value to guide the appropriate use of breast cancer gene expression profile tests (GEPT) is underutilised. The specific aims of this study are to report morpho-immunohistological characteristics of breast tumours with Oncotype DX® (ODx) recurrence scores (RS) of 10 or fewer (ultra-low risk) and 25 or fewer (low risk) in order to determine if pathologists can identify prospectively patient tumours that do not require ODx testing. METHODS AND RESULTS: Oncotype DX® cases with RS < 10 from 2005 to 2010 comprised 441 of 2594 (17%) of clinical cases; this cohort had 5 years' follow-up and was treated with endocrine therapy alone. Tumours were analysed for tumour type, Nottingham grade, mitosis score (MS) semi-quantitative (H-score) hormone receptor content and Magee equation 3. Knowledge derived from this data set was used to develop algorithms in order to identify prospectively tumours with RS of 10 or fewer or 25 or fewer. Thirty-four per cent of tumours were low-grade special types, while the remainder were enriched with high hormone receptor content with MS of 1. These algorithmic selection criteria identified correctly all patient cases below the chemotherapy cut-point, i.e. RS < 25, indicating that these oncotype test orders were an unnecessary cost. CONCLUSIONS: This unique study demonstrates that (i) pathologists add great value to triage breast cancer for GEPT; and (ii) can identify prospectively low-grade tumour biology with high sensitivity and high specificity for those cases which do not require chemotherapy (RS < 25) using MS and hormone receptor content.

Program-specific cost-effectiveness analysis: breast cancer screening policies for a safety-net program.

BACKGROUND: Every Woman Counts (EWC), a California breast cancer screening program, faced challenging budget cutbacks and policy choices. METHODS: A microsimulation model evaluated costs, outcomes, and cost-effectiveness of EWC program mammography policy options on coverage for digital mammography (which has a higher cost than film mammography but recent legislation allowed reimbursement at the lower film rate); screening eligibility age; and screening frequency. Model inputs were based on analyses of program claims data linked to California Cancer Registry data, Surveillance, Epidemiology, and End Results data, and the Medi-Cal literature. Outcomes included number of procedures, cancers, cancer deaths, costs, and incremental cost per life-year. RESULTS: Projected model outcomes matched program data closely. With restrictions on the number of clients screened, strategies starting screening at age 40 years were dominated (not cost-effective). This finding was highly robust in sensitivity analyses. Compared with no screening, biennial film mammography for women aged 50 to 64 years was projected to reduce 15-year breast cancer mortality by nearly 7.8% at $18,999 per additional life-year, annual film mammography was $106,428 per additional life-year, and digital mammography $180,333 per additional life-year. This more effective, more expensive strategy was projected to reduce breast cancer mortality by 8.6%. Under equal mammography reimbursement, biennial digital mammography beginning at age 50 years was projected to decrease 15-year breast cancer mortality by 8.6% at an incremental cost per additional life-year of $17,050. CONCLUSIONS: For the EWC program, biennial screening mammography starting at age 50 years was the most cost-effective strategy. The impact of digital mammography on life expectancy was small. Program-specific cost-effectiveness analysis can be completed in a policy-relevant time frame to assist policymakers faced with difficult program choices.

Surgical "placebo" controls.

OBJECTIVE: To set ethical guidelines on the use of surgical placebo controls in the design of surgical trials. BACKGROUND DATA: Ethical concerns recently arose from surgical trials where subjects in the control arm underwent surgical procedures that had the appearance of a therapeutic intervention, but during which the essential therapeutic maneuver was omitted. Although there are ethical guidelines on the use of a placebo in drug trials, little attention has been paid to the use of a surgical placebo control in surgical trials. METHODS: The Council on Ethical and Judicial Affairs developed ethical guidelines based on a wide literature search and consultation with experts. RESULTS: Surgical placebo controls should be limited to studies of new surgical procedures aimed at treating diseases that are not amenable to other surgical therapies, and are reasonably anticipated to be susceptible to substantial placebo effects. If the standard nonsurgical treatment is efficacious and acceptable to the patient, then it must be offered as part of the study design. CONCLUSIONS: Surgical placebo controls should be used only when no other trial design will yield the requisite data and should always be accompanied by a rigorous informed consent process and a careful consideration of the related risks and benefits. The recommended ethical guidelines were adopted as AMA ethics policy and are now incorporated in the AMA's Code of Medical Ethics.