Monitoring the Response to Primary Medical Therapy for Breast Cancer Using Three-Dimensional Time-Resolved Optical Mammography

Abstract

Primary medical therapy is used to reduce tumour size prior to surgery in women with locally advanced breast cancer. Optical tomography is a functional imaging technique using nearinfrared light to produce three-dimensional breast images of tissue oxygen saturation and haemoglobin concentration. Its advantages include the ability to display quantitative physiological information, and to allow repeated scans without the hazards associated with exposure to ionising radiation. There is a need for a non-invasive functional imaging tool to evaluate response to treatment, so that non-responders can be given the opportunity to change their treatment regimen. Here, we evaluate the use of optical tomography for this purpose. Four women with newly diagnosed breast cancer who were about to undergo primary medical therapy gave informed and voluntary consent to take part in the study. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy. Optical imaging was performed prior to treatment, after the first cycle of chemotherapy, halfway through, and on completion of chemotherapy. Images of light absorption and scatter at two wavelengths were produced, from which images of total haemoglobin concentration and oxygen saturation were derived. All patients that showed a good or complete response to treatment on MRI showed a corresponding recovery in the haemoglobin concentration images. Changes in mean tumour total haemoglobin concentration could be seen four weeks into treatment. The tumour oxygen saturation was low compared to background in three out of four patients, and also showed a return to baseline over treatment. Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment over six months.

Review of optical breast imaging and spectroscopy

“…179 Several studies discussed the time-dependent change of the tumor functional properties over different treatment cycles, in part until the end of NAC. 141,169,172,173,[180][181][182] Pakalniskis et al 141 reported that tumor HbT decreases significantly during NAC for pathologic complete responders and not for partial responders. A similar trend is visible in the long-term tumor data of Falou et al 172,173 Schaafsma et al 182 focused on the investigation of patients with HER2-negative breast cancer, which is associated with decreased angiogenesis resulting in less pronounced differences in HbT between tumor and healthy tissue.…”

Diffuse optical imaging using spatially and temporally modulated light

“…These changes have also been noted by other researchers. [97][98][99][100][101][102] The change in DOSI values were compared between pCR (N ¼ 11) and nonpCR (N ¼ 25) groups to assess whether DOSI can predict pathological response early during NAC. At the treatment midpoint, the ratio of the TOI between tumor and normal tissue dropped 47 AE 8% for pCR and 20 AE 5% for nonpCR subjects.…”

The reproducibility of optical mammography in healthy volunteers

“…These changes in the healthy Q6 breast tissue are not surprising as certain chemotherapy agents can cause anaemia in some patients, which will affect the whole body. Other studies have shown that the background tissue physiological properties remain relatively stable in some patients, while other patients show changes in the background breast physiological properties over the course of treatment (Enfield et al 2011).…”