1 ABSTRACT

Breast cancer is one of the most prevalent forms of cancer in the world. More than 250,000 American women are diagnosed with breast cancer annually. Fortunately, the survival rate is relatively high and continually increasing due to improved detection techniques and treatment methods. The quality of life of breast cancer survivors is ameliorated by minimizing adverse effects on their physical appearance. Breast reconstruction is important for restoring the survivor’s appearance. In breast reconstructive surgery, there is a need to develop technologies for quantifying surgical outcomes and understanding women’s perceptions of changes in their appearance. Methods for objectively measuring breast anatomy are needed in order to help breast cancer survivors, radiation oncologists, and surgeons quantify changes in appearance that occur with different breast reconstructive surgical options. In this study, we present an automated method for computing a variant of the normalized Breast Retraction Assessment (pBRA), a common measure of symmetry, from routine clinical photographs taken to document breast cancer treatment procedures.

In this study we evaluate the influence of subject pose during image acquisition on quantitative analysis of breast morphology. Three (3D) and two-dimensional (2D) images of the torso of 12 female subjects in two different poses; (1) hands-on-hip (HH) and (2) hands-down (HD) were obtained. In order to quantify the effect of pose, we introduce a new measure; the 3D pBRA (Percentage Breast Retraction Assessment) index, and validate its use against the 2D pBRA index. Our data suggests that the 3D pBRA index is linearly correlated with the 2D counterpart for both of the poses, and is independent of the localization of fiducial points within a tolerance limit of 7 mm. The quantitative assessment of 3D asymmetry was found to be invariant of subject pose. This study further corroborates the advantages of 3D stereophotogrammetry over 2D photography. Problems with pose that are inherent in 2D photographs are avoided and fiducial point identification is made easier by being able to panoramically rotate the 3D surface enabling views from any desired angle.

The objective of this study was to determine if measurements of breast morphology computed from three-dimensional (3D) stereophotogrammetry are equivalent to traditional anthropometric measurements obtained directly on a subject using a tape measure. 3D torso images of 23 women ranged in age from 36 to 63 who underwent or were scheduled for breast reconstruction surgery were obtained using a 3dMD torso system (3Q Technologies Inc., Atlanta, GA). Two different types (contoured and line-of-sight distances) of a total of nine distances were computed from 3D images of each participant. Each participant was photographed twice, first without fiducial points marked (referred to as unmarked image) and second with fiducial points marked prior to imaging (referred to as marked image). Stereophotogrammetry was compared to traditional direct anthropometry, in which measurements were taken with a tape measure on participants. Three statistical analyses were used to evaluate the agreement between stereophotogrammetry and direct anthropometry. Seven out of nine distances showed excellent agreement between stereophotogrammetry and direct anthropometry (both marked and unmarked images). In addition, stereophotogrammetry from the unmarked image was equivalent to that of the marked image (both line-of-sight and contoured distances). A lower level of agreement was observed for some measures because of difficulty in localizing more vaguely defined fiducial points, such as lowest visible point of breast mound, and inability of the imaging system in capturing areas obscured by the breast, such as the inframammary fold. Stereophotogrammetry from 3D images obtained from the 3dMD torso system is effective for quantifying breast morphology. Tools for surgical planning and evaluation based on stereophotogrammetry have the potential to improve breast surgery outcomes.

Purpose

Separase, an endopeptidase, plays a pivotal role in chromosomal segregation by separating sister chromatids during the metaphase to anaphase transition. Using a mouse mammary tumor model we have recently demonstrated that overexpression of Separase induces aneuploidy and tumorigenesis (Zhang et al., 2008, PNAS 105:13033). In the present study, we have investigated the expression level of Separase across a wide range of human tumors.

Experimental Design

To examine the expression levels and localization of Separase in human tumors, we have performed immunofluorescence microscopy using human Separase antibody and tumor tissue arrays from osteosarcoma, colorectal, breast, and prostate cancers with appropriate normal controls.

Results

We show that Separase is significantly overexpressed in osteosarcoma, breast and prostate tumor specimens. There is a strong correlation of tumor status with the localization of Separase into the nucleus throughout all stages of the cell cycle. Unlike the normal control tissues, where Separase localization is exclusively cytoplasmic in non dividing cells, human tumor samples show significantly higher number of resting cells with a strong nuclear Separase staining. Additionally, overexpression of Separase transcript strongly correlates with high incidence of relapse, metastasis and lower 5 year overall survival rate in breast and prostate cancer patients.

Conclusion

These results further strengthen our hypothesis that Separase might be an oncogene, whose overexpression induces tumorigenesis, and indicates that Separase overexpression and aberrant nuclear localization are common in many tumor types and may predict outcome in some human cancers.

Breast cancer is one of the most prevalent forms of cancer in the US. It is estimated that more than 180,000 American women will be diagnosed with invasive breast cancer in 2008. Fortunately, the survival rate is relatively high and continually increasing due to improved detection techniques and treatment methods. However, maintaining quality of life is a factor often under emphasized for breast cancer survivors. Breast cancer treatments are invasive and can lead to deformation of the breast. Breast reconstruction is important for restoring the survivor’s appearance. However, more work is needed to develop technologies for quantifying surgical outcomes and understanding women’s perceptions of changes in their appearance. A method for objectively measuring breast anatomy is needed in order to help both the breast cancer survivors and their surgeons take expected changes to the survivor’s appearance into account when considering various treatment options. In the future, augmented reality tools could help surgeons reconstruct a survivor’s breasts to match her preferences as much as possible.