Patients' understanding of how genotype variation affects benefits of tamoxifen therapy for breast cancer.

BACKGROUND: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses. METHODS: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%). RESULTS: Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). CONCLUSION: Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.

Traceless multipole moment densities and transformations in macroscopic electromagnetism.

We consider whether use of traceless multipole moment densities in macroscopic electromagnetism can yield physically acceptable results. For harmonic plane wave fields it is shown that a traceless electric quadrupole density yields linear constitutive relations for which the dynamical material constants (permittivity and magnetoelectric coefficients) and response fields are unphysical. We further show that, within multipole theory, these constitutive relations cannot be transformed into physically acceptable relations. Specifically, the transformed response field D is unphysical for all orders beyond the electric dipole. This contrasts with use of primitive (traced) moment densities, for which unphysical constitutive relations have been successfully transformed up to electric octopole-magnetic quadrupole order, thereby providing also the leading contribution to the ac permeability.

Analysis of accuracy of measurement of quadratic electro-optic coefficients in uniaxial crystals: a case study of KDP.

Taking KDP as an example of a uniaxial crystal, we analyze contributions to its quadratic electro-optic response with a view to explaining differences in published values of certain quadratic coefficients. In an eigenvalue theory of light propagation we show that the linear electro-optic coefficient contributes to the quadratic response, even under ideal laboratory conditions. In addition, the effect of imperfect crystal cutting and alignment is investigated by means of computer calculations based on the Jones calculus. It is found that, for relatively small inaccuracies, the calculated values of the quadratic coefficient g(xyxy) are approximately two orders of magnitude greater when measured with a static field than with a dynamic one. This finding could explain the observed spread in some results for KDP-type crystals.

Effect of beam divergence from the optic axis in an electro-optic experiment to measure an induced Jones birefringence.

Certain optical properties can be described in terms of two linear birefringences existing in separate Jones platelets of a medium. One of these, known as Jones birefringence, although occurring naturally in some crystals is too small to be measurable. However, the two birefringences can be induced by an electric field in 4 and 6 crystals for propagation along the optic axis. For an even slightly divergent light beam, natural birefringence may affect accuracy of measurement. Calculations show that in an experiment with a static field the error depends critically on beam divergence, whereas with a modulated field this is not so.

Algebraic determination of the principal refractive indices and axes in the electro-optic effect.

A systematic algebraic approach is presented as a preferred alternative to an iterative numerical method for deriving expressions for the principal refractive indices and dielectric axes of a nonmagnetic crystal in a uniform electric field. This approach is applicable for an arbitrary field and for any symmetry point group. The results, to the chosen order in the field, are expressed algebraically in terms of measurable crystal tensors. Illustrations are given of the linear electro-optic effect for the point groups 4?3m, 3m, 4?2m, and 1 and of the quadratic effect in 4?2m. The latter serves to highlight a shortcoming in the numerical approach. Comparisons are drawn with numerical results published previously.