title: Tumor angiogenesis change estimated by using diffuse optical spectroscopic tomography: demonstrated correlation in women undergoing neoadjuvant chemotherapy for invasive breast cancer?
abstract: OBJECTIVE
  To investigate if changes in tumor angiogenesis associated with complete pathologic response (pCR) or partial pathologic response (pPR) to treatment can be demonstrated by using diffuse optical spectroscopic (DOS) tomography.
  
  
  METHODS
  All participants in this prospective, HIPAA-compliant, institutional review board-approved study provided written informed consent. Eleven women with invasive breast carcinoma were imaged with DOS tomography prior to, during, and at completion of neoadjuvant chemotherapeutic regimens. By using region of interest (ROI) analysis, the DOS measure of total tissue hemoglobin (Hb(T)) was temporally correlated with quantitative measures of existing (CD31-expressing) and tumor-induced (CD105-expressing) vessels, in pretreatment and posttreatment tissue specimens, to assess change.
  
  
  RESULTS
  Quantified angiogenesis alone in pretreatment core biopsy specimens did not predict treatment response, but mean vessel density (MVD) and mean vessel area (MVA) of CD105-expressing vessels were significantly decreased in women with pCR (n = 7) (P < .001 and P = .003, respectively). MVA of CD105-expressing vessels was also significantly reduced at comparison of pre- and posttreatment residual tumor for women with pPR (n = 4) (P = .033). A longitudinal analysis showed significant decreases (P = .001) in mean Hb(T) levels during neoadjuvant chemotherapy in breast abnormality ROIs for women with pCR but not women with pPR. For women with pCR, but not women with pPR, pretreatment MVD of CD105-expressing vessels correlated with pretreatment Hb(T) (P ≤ .001).
  
  
  CONCLUSIONS
  DOS tomographic examinations in women with breast cancer who are receiving neoadjuvant chemotherapy show a mean decrease in Hb(T) with time in patients with pCR only. Observed pretreatment and posttreatment correlates with quantified angiogenesis markers confirm the likely biologic origin for this DOS signature and support its potential to predict angiogenic tissue response early in the treatment cycle.
  
  
  BACKGROUND
  http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11100699/-/DC1.
authors.affiliation: Department of Pathology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Marius G
authors.initials: MG
authors.lastname: Pakalniskis
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Wells
authors.forename: Mary C
authors.initials: MC
authors.lastname: Schwab
authors.forename: Heather M
authors.initials: HM
authors.lastname: Froehlich
authors.forename: Shudong
authors.initials: S
authors.lastname: Jiang
authors.forename: Zhongze
authors.initials: Z
authors.lastname: Li
authors.forename: Tor D
authors.initials: TD
authors.lastname: Tosteson
authors.forename: Steven P
authors.initials: SP
authors.lastname: Poplack
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.forename: Keith D
authors.initials: KD
authors.lastname: Paulsen
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000071063:Endoglin; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D055096:Optical Devices; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D006454:Hemoglobins; D011956:Receptors, Cell Surface