Multigene Predictors of Clinical Outcomes for BC
OPEN ACCESS: Commercialized Multigene Predictors of Clinical Outcome for Breast Cancer [ The Oncologist; Subscribe; Sample]
In the past 5 years, a number of commercialized multigene prognostic and predictive tests have entered the complex and expanding landscape of breast cancer companion diagnostics. These tests have used a variety of formats ranging from the familiar slide-based assays of immunohistochemistry and fluorescence in situ hybridization to the nonmorphology-driven molecular platforms of quantitative multiplex real-time polymerase chain reaction and genomic microarray profiling. In this review, 14 multigene assays are evaluated as to their scientific validation, current clinical utility, regulatory approval status, and estimated cost-benefit ratio. Emphasis is placed on two tests: oncotype DX™ and MammaPrint®. Current evidence indicates that the oncotype DX™ test has the advantages of earlier commercial launch, wide acceptance for payment by third-party payors in the U.S., ease of use of formalin-fixed paraffin-embedded tissues, recent listing by the American Society of Clinical Oncology Breast Cancer Tumor Markers Update Committee as recommended for use, continuous scoring system algorithm, ability to serve as both a prognostic test and predictive test for certain hormonal and chemotherapeutic agents, demonstrated cost-effectiveness in one published study, and a high accrual rate for the prospective validation clinical trial (Trial Assigning Individualized Options for Treatment). The MammaPrint® assay has the advantages of a 510(k) clearance by the U.S. Food and Drug Administration, a larger gene number, which may enhance further utility, and a potentially wider patient eligibility, including lymph node-positive, estrogen receptor (ER)-negative, and younger patients being accrued into the prospective trial (Microarray in Node-Negative Disease May Avoid Chemotherapy). A number of other assays have specific predictive goals that are most often focused on the efficacy of tamoxifen in ER-positive patients, such as the two-gene ratio test and the cytochrome P450 CYP2D6 genotyping assay
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*** MARYANNE *** aka HARRIECANARIE
1993: right side DCIS, lumpectomy, rads
1999: left side DCIS, lumpectomy, rads, tamoxifen
2006:
BRCA 2 positive
Stage I, invasive DCIS (6mm x 5mm)
Grade: intermediate
sentinal node biopsy: neg
HER2/neu amplified 4.7
ER+/PR+
TOPO II neg
Oncotype dx 20
Bilat mastectomy with DIEP flap reconstruction
oophorectomy
2007:
6 cycles TCH (taxotere, carboplatin, herceptin)
finished 1 yr herceptin 05/07
Arimidex, stopped after almost 1 yr
Femara
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