Background: Diffuse optical spectroscopic imaging (DOSI) can be exploited as a marker of tumor blood volume quantified by tissue hemoglobin (tHb) concentration. In DOSI, frequent measurement is possible for breast cancer patients because of its non-invasiveness. The tHb concentration determined by DOSI is expected to be a new biomarker for prediction of breast cancer response to neoadjuvant chemotherapy (NAC). Purpose: Our objective is to determine whether early change of tumor tHb concentration predicts pathological complete response (pCR) to NAC in patients with operable breast cancer. Methods: In a prospective study, one hundred patients with primary breast cancer were enrolled for primary objective analysis. The regimens of NAC were according to the standard of care. Patients underwent sequential scans using DOSI at baseline, after 1st course and 2nd course of chemotherapy. The mean value of tHb (tHbmean) concentration of the targeted lesion was measured and the percentage change in tHbmean (ΔtHbmean) concentration was calculated. Receiver operating curve analysis demonstrated diagnostic performance of DOSI for predicting a pCR. Results: In interim analysis, it was regarded as a good outcome that area under the curve (AUC) for ΔtHbmean after 1nd course was 0.797 (SE 0.104, 95%CI 0.633-0.911), and after 2st course was 0.867 (SE 0.06, 95%CI 0.715-0.956). Conclusion: DOSI could predict accurately a pCR to neoadjuvant chemotherapy in patients with primary breast cancer. Citation Format: Ogura H, Yoshizawa N, Ueda S, Hosokawa Y, Matsunuma R, Tochikubo J, Nasu H, Shigekawa T, Takeuchi H, Osaki A, Saeki T, Yoshimoto K, Ohmae E, Suzuki T, Ueda Y, Yamashita Y, Sakahara H. Near-infrared diffuse optical imaging for early prediction to neoadjuvant chemotherapy in patients with primary breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-06.

Background: The St.Gallen consensus guideline recommends the sequential administration chemotherapy followed by of endocrine therapy as postoperative therapy for the higher risk ER-positive breast cancer patients based on results of a single study (Albain et al, Lancet 2009). In metastatic settings however, several trials conducted in the 1980's demonstrated that tumor response rates were higher when chemotherapy and tamoxifen were concomitantly administered, than when chemotherapy and tamoxifen administered were given sequentially. In the preoperative settings, pathological complete response (pCR) rate can be used a surrogate marker to predict event-free survival or overall survival in Luminal B(HER2-negative) breast cancer. We therefore designed a prospective randomized safety and efficacy trial in order to test a hypothesis that the concomitant administration of an aromatase inhibitor and chemotherapy improves pathological complete response(pCR) rate than chemotherapy alone in the preoperative setting. Trial design: The trial is a prospective, multi-center, randomized comparison of chemotherapy alone versus concomitant chmo-endocrine therapy evaluating the efficacy in terms of pCR rate and safety in preoperative settings in patients with Luminal B (HER2-negative) breast cancer. 94 patients were to be accrued into this trial. - arm A (control): 12 cycles of weekly paclitaxel(80mg/m2) followed by 4 cycles of every 3-week AC(Doxorubicine 60mg/m2, Cyclophosphamide 600mg/m2). - arm B (experimental): The same chermotherapy as arm A and anastrozole in postmenopausal patients or anastrozole+leuprolerine in premenopansal patients. Eligibility criteria: 1)Female patients with operable and histologically confirmed invasive breast cancer; 2)HER2-negative; 3)Either ER -positive or PgR-positive; 4)Either Ki67-LI> = 14% and NG> = 2 or NG = 3 regardless of Ki67-LI. Endpoints : Primary endpoint is the pCR rate. Secondary endpoints are the clinical response rate(RECIST), the adverse events(CTC-AE ver.4.0), the breast conserving rate and the health related quality of life. Statistical Considerations : The pCR rates in the control arm and the experimental arm are expected to be 10% and 25%, respectively. In order to show the superiority of the experimental arm with an alfa error at 5% and beta error at 20%, calculated number of patients needed were 96. Present Accrual and Target Accrual: As of June 06, 2013, 18 patients were enrolled from 8 institutions. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-2-03.

Abstract Objectives: Optical mammography (O-MMG), which utilizes near-infrared light for the detection of abnormal breast tissue, can be a potentially useful and non-invasive tool for the screening of breast cancer patients. Here we report on the preliminary results of our clinical trial using a time-resolved O-MMG system developed by Hamamatsu Photonics (Hamamatsu, Japan). In our past examination, negative results included cases with mismatch for breast cup because of small breast, lesion outside of cup because of big breast, and bad positioning. So, size and shape of a gantry was improved (3 cup sizes; S, M and L cup). We reported the initial experience of the improved O-MMG systems. Materials and Methods: In principle, the technique involves sequential irradiation of the breast tissue with a pulsed laser with a wavelength of 760, 800 and, 830nm, which is then detected by the variable capacity gantry at multiple sites after passing through the breast tissue. Measurement time has improved to about 7 minutes (a third of the conventional measurement time). The data are analyzed and tomographic images of the absorption coefficient of the breast are then reconstructed based on our tomographic reconstruction algorithm. Between October 2011 and May 2012, fifteen patients with breast cancer and one patient with fibroadenoma participated in the trial. Results: In patients with breast cancer, S cup was used for one patient, M cup for 12 patients and L cup for two patients. Five patients after neo-adjuvant chemotherapy were excluded from the analysis. The lesions were depicted as an area of high hemoglobin concentration in 7 of 10 patients with cancer. One lesion of fibroadenoma was also identified as an area of high hemoglobin concentration. Conclusion: Further examination with our new O-MMG systems will be of interest. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-05.

Background: Activation of lipid metabolism is an early event of carcinogenesis and a central hallmark of many cancers including breast cancer. Recent findings argue that stearoyl CoA desaturase-1 (SCD1), a key regulator of the fatty acid (FA) composition and the endoplasmic reticulum resident enzyme that converts saturated FA (SFA) into monounsaturated FA (MUFA) is a novel regulator of carcinogenesis. The distinctive lipids composition of membrane in cancer cells and the biological functions of SCD1, however, still remain uncertain. Imaging mass spectrometry (IMS) is a mass spectrometry-based analyzing technique that enables visualization of the individual molecules without requiring antibodies. It allows comprehensive detection of a wide range of biomolecules, such as lipids. We attempted to visualize the localization of lipids in breast cancer by IMS for better understanding of cancer proliferation. Materials and methods: 13 specimens were obtained from the primary breast cancer patients. All were Japanese woman and aged 41–86 years (mean 61.5y.o.). Only one patient received preoperative systematic therapy. 6 were estrogen receptor (ER) and/or progesterone receptor (PgR) positive and human epidermal growth factor receptor 2 (HER2) negative, 2 were ER and/or PgR positive and HER2 positive, 2 were both ER and PgR negative and HER2 positive and 2 were triple negative. IMS: Samples were immediately chilled in liquid Hexan and stored at −80°. All specimens were sliced into 10 mm thin sections, mounted onto one indium-tin oxide-coated glass slides (Bruker Daltonics) and then sprayed by 2,5-Dihydroxybenzoic acid. Matrix assisted laser desorption ionization (MALDI) technique was used as a soft ionization method. We used time of flight (TOF)/TOF type instrument (Ultraflex, Bruker Daltonics) and all the spectrum were acquired automatically using Fleximaging software (Bruker Daltonics). Each spectral intensity at any mass-to-charge ratio (m/z) was measured at 16 regions of interest (ROI); 13 ROI were picked up from cancerous parts and 3 were from non-cancerous parts. Spectral intensities were compared and statistical analysis was performed by Mann Whitney test. The software was also used to create two-dimensional ion-density maps. Results: In the cancerous parts of all the 13 specimens, two distinct peaks of the molecular ions were detected at m/z 798.5 and 810.5, which were not found in the non-cancerous parts. Median intensity of the molecular ions at m/z 798.5 and 810.5 were 38.9 and 3.18 in the cancerous part, while they were 0.84 and 1.02 in the non-cancerous part (p=0.010 and 0.015, respectively). Tandem mass spectrometry analysis for these two molecules revealed that they were two kinds of phosphatidylcholine (PC), PC (16:0/18:1) and PC (18:0/18:1). Localization of the individual PC was visualized by means of IMS, which showed that in cancerous part accumulation of PCs containing MUFA was more pronounced than those containing SFA only. Conclusion: Two kinds of PC containing MUFA were found to highly accumulate in cancerous parts, which may suggest involvement of SCD1 in the membrane composition regulation and cancer proliferation. Further studies may thus be warranted to explore the relation between PC localization and the SCD1 expression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-05-05.

Abstract Objectives: To examine optical properties of breast cancer by time-resolved spectroscopy. Materials and Methods: We irradiated a pulsed laser of 760, 800, and 830 nm wave-length lights at multiple sites of both breasts including the site just above the cancer and detected the light transmitted through the breast with TRS-20SH (Hamamatsu Photonics K.K.). Absorption coefficient (μa), reduced scattering coefficient (μs'), total hemoglobin (tHb), and oxygen saturation (SO2) of the breast were calculated by photon diffusion equation. The clinical trial started in January 2007. A total of one hundred nine breast cancer patients participated in the trial and written informed consent were obtained from all of the patients. Results: In 800 nm wave-length, absorption coefficient (μa) of breast cancer tissue was significantly high, compared with contra-lateral normal breast (cancer:0.0677± 0.0293, normal breast;0.0479± 0.0161, p<0.001). The result was the same in 760, and 830 nm. There was no difference in reduced scattering coefficient (μs') between breast cancer tissue and contra-lateral normal breast (800 nm cancer:9.070±1.217, normal breast;9.348±1.243, p=0.10). The tHb of breast cancer tissue was significantly high, compared with normal breast (cancer:31.0± 14.7, normal breast;21.0±8.2, p<0.001). There was no difference in oxygen saturation (SO2) between breast cancer tissue and contra-lateral normal breast (cancer:72.8±4.1, normal breast;73.8±4.5, p=0.08). Conclusion: Absorption coefficient (μa) and tHb increased in breast cancer, whereas reduced scattering coefficient (μs') did not. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-03.