Abstract
IntroductionResidual cancer following breast conserving surgery increases the risk of local recurrence and mortality. Margin assessment presents an unmet clinical need. Breast tissue is markedly heterogeneous, which makes distinguishing small foci of cancer within the spectrum of normal tissue potentially challenging. This is further complicated by the heterogeneity as a function of menopausal status. Optical spectroscopy can provide surgeons with intra-operative diagnostic tools. Here, we evaluate ex-vivo breast tissue and determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition.MethodsDiffuse reflectance spectra were measured from 595 normal and 38 malignant sites from the margins of 104 partial mastectomy patients. All statistical tests were performed using Wilcoxon Rank-Sum tests. Normal and malignant sites were compared before stratifying the data by tissue type and depth and computing statistical differences. The frequencies of the normal tissue types were separated by menopausal status and compared to the corresponding optical properties.ResultsThe mean reduced scattering coefficient, < Ī¼s' >, and concentration of total hemoglobin, [THb]), showed statistical differences between malignant (< Ī¼s' > : 8.96 cm-1 Ā± 2.24MAD, [THb]: 42.70 Ī¼M Ā± 29.31MAD) compared to normal sites (< Ī¼s' > : 7.29 cm-1 Ā± 2.15MAD, [THb]: 32.09 Ī¼M Ā± 16.73MAD) (P < 0.05). The sites stratified according to normal tissue type (fibro-glandular (FG), fibro-adipose (FA), and adipose (A)) or disease type (invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS)) showed that FG exhibited increased < Ī¼s' > and A showed increased [Ī²-carotene] within normal tissues. Scattering differentiated between most malignant sites, DCIS (9.46 cm-1 Ā± 1.06MAD) and IDC (8.00 cm-1 Ā± 1.81MAD), versus A (6.50 cm-1 Ā± 1.95MAD). [Ī²-carotene] showed marginal differences between DCIS (19.00 Ī¼M Ā± 6.93MAD, and FG (15.30 Ī¼M Ā± 5.64MAD). [THb] exhibited statistical differences between positive sites (92.57 Ī¼M Ā± 18.46MAD) and FG (34.12 Ī¼M Ā± 22.77MAD), FA (28.63 Ī¼M Ā± 14.19MAD), and A (30.36 Ī¼M Ā± 14.86MAD). The diagnostic ability of the optical parameters was affected by distance of tumor from the margin as well as menopausal status. Due to decreased fibrous content and increased adipose content, normal sites in post-menopausal patients exhibited lower < Ī¼s' >, but higher [Ī²-carotene] than pre-menopausal patients.ConclusionsThe data indicate that the ability of an optical parameter to differentiate benign from malignant breast tissues may be dictated by patient demographics. Scattering differentiated between malignant and adipose sites and would be most effective in post-menopausal women. [Ī²-carotene] or [THb] may be more applicable in pre-menopausal women to differentiate malignant from fibrous sites. Patient demographics are therefore an important component to incorporate into optical characterization of breast specimens.
Highlights
Residual cancer following breast conserving surgery increases the risk of local recurrence and mortality
The sites stratified according to normal tissue type (fibro-glandular (FG), fibro-adipose (FA), and adipose (A)) or disease type (invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS)) showed that FG exhibited increased < Ī¼sā > and A showed increased [b-carotene] within normal tissues
The data indicate that the ability of an optical parameter to differentiate benign from malignant breast tissues may be dictated by patient demographics
Summary
Residual cancer following breast conserving surgery increases the risk of local recurrence and mortality. Breast tissue is markedly heterogeneous, which makes distinguishing small foci of cancer within the spectrum of normal tissue potentially challenging. Breast conserving surgery (BCS), known as a lumpectomy or partial mastectomy, is generally considered to be the recommended surgical choice for women with early stage breast cancer (Stages 0, I, II) and for those with Stage II to III disease who undergo successful neo-adjuvant treatment to reduce their tumor burden [2,3]. The meta-analyses by the Early Breast Cancer Trialists group has shown that for every four women who develop a local recurrence after BCT there is one potential mortality; evidence supporting the need to reduce the risk of local recurrence through complete tumor excision [7,8]
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