Correction by the skin-to-chest wall distance in near-infrared spectroscopy and assessment of breast cancer responses to neoadjuvant chemotherapy

  • Yuko Asano
  • Nobuko YoshizawaEmail author
  • Yukio Ueda
  • Kenji Yoshimoto
  • Tetsuya Mimura
  • Etsuko Ohmae
  • Hiroko Wada
  • Shigeto Ueda
  • Toshiaki Saeki
  • Hiroyuki Ogura
  • Norihiko Shiiya
  • Harumi Sakahara
Regular Paper



The measurement of hemoglobin (Hb) concentrations in breast cancer by near-infrared spectroscopy is useful for the assessment of responses to neoadjuvant chemotherapy (NAC). However, the chest wall muscles may affect this measurement. We corrected Hb concentrations based on the skin-to-chest wall distance. Corrected Hb was compared with uncorrected Hb as a marker of treatment responses in breast cancer patients.


We measured total Hb (tHb) in breast cancer using a near-infrared time-resolved spectroscopy system in 10 patients before chemotherapy and after the first and second courses of NAC. To assess the skin-to-chest wall distance and thickness of tumors, ultrasound images were obtained using an ultrasonography probe with the spectroscopic probe. Net tHb (tHbnet) was calculated by subtracting tHb in normal breast tissue from cancer tHb. Patients underwent positron emission tomography with [18F] fluorodeoxyglucose (FDG) before chemotherapy and after the second course of NAC. FDG uptake was evaluated using the maximum standardized uptake value (SUVmax).


tHb, tHbnet, and SUVmax in cancer significantly decreased in the course of chemotherapy. The change in tHbnet was larger than that in tHb. Although a correlation was not observed between the change in tHb and that in SUVmax, a positive correlation was noted between the change in tHbnet and that in SUVmax.


Corrections by the skin-to-chest wall distance in spectroscopy led to the change in Hb concentrations being more similar to that in FDG uptake after NAC in breast cancer. tHbnet has potential as a reliable biomarker of breast cancer.


Breast cancer Near-infrared time-resolved spectroscopy Hemoglobin Neoadjuvant chemotherapy 



This study was partly supported by JSPS KAKENHI Grant numbers 15K19781, 26282144 and 17H03591.

Compliance with ethical standards

Conflict of interest

S. Ueda has research funding from Hamamatsu Photonics K.K. T. Saeki received honoraria for a speech from Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Novartis Pharma K.K., T. Saeki has research funding from Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Chugai Pharmaceutical Co., Ltd. H. Sakahara has research funding from Hamamatsu Photonics K.K. Y. Ueda, K. Yoshimoto, T. Mimura, E. Ohmae, and H. Wada are employees of Hamamatsu Photonics K.K. No other potential conflict of interest relevant to this article was reported.


  1. 1.
    Kaufmann, M., Hortobagyi, G.N., Goldhirsch, A., Scholl, S., Makris, A., Valagussa, P., Blohmer, J.U., Eiermann, W., Jackesz, R., Jonat, W., Lebeau, A., Loibl, S., Miller, W., Seeber, S., Semiglazov, V., Smith, R., Souchon, R., Stearns, V., Untch, M., von Minckwitz, G.: Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J. Clin. Oncol. 24(12), 1940–1949 (2006). CrossRefGoogle Scholar
  2. 2.
    Mieog, J.S., van der Hage, J.A., van de Velde, C.J.: Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst. Rev. 2, CD005002 (2007). CrossRefGoogle Scholar
  3. 3.
    Kong, X., Moran, M.S., Zhang, N., Haffty, B., Yang, Q.: Meta-analysis confirms achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur. J. Cancer (Oxford, England). 47(14), 2084–2090 (2011 (1990). CrossRefGoogle Scholar
  4. 4.
    Antoch, G., Saoudi, N., Kuehl, H., Dahmen, G., Mueller, S.P., Beyer, T., Bockisch, A., Debatin, J.F., Freudenberg, L.S.: Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET. J. Clin. Oncol. 22(21), 4357–4368 (2004). CrossRefGoogle Scholar
  5. 5.
    Fletcher, J.W., Djulbegovic, B., Soares, H.P., Siegel, B.A., Lowe, V.J., Lyman, G.H., Coleman, R.E., Wahl, R., Paschold, J.C., Avril, N., Einhorn, L.H., Suh, W.W., Samson, D., Delbeke, D., Gorman, M., Shields, A.F.: Recommendations on the use of 18F-FDG PET in oncology. J. Nucl. Med. 49(3), 480–508 (2008). CrossRefGoogle Scholar
  6. 6.
    Weber, W.A.: Use of PET for monitoring cancer therapy and for predicting outcome. J. Nucl. Med. 46(6), 983–995 (2005)Google Scholar
  7. 7.
    Weber, W.A., Figlin, R.: Monitoring cancer treatment with PET/CT: does it make a difference? J. Nucl. Med. 48(Suppl 1), 36 s–44 (2007) sGoogle Scholar
  8. 8.
    Wahl, R.L., Jacene, H., Kasamon, Y., Lodge, M.A.: From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J. Nucl. Med. 50(Suppl 1), 122 s–150 (2009). s ).CrossRefGoogle Scholar
  9. 9.
    Mghanga, F.P., Lan, X., Bakari, K.H., Li, C., Zhang, Y.: Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography in monitoring the response of breast cancer to neoadjuvant chemotherapy: a meta-analysis. Clin. Breast Cancer. 13(4), 271–279 (2013). CrossRefGoogle Scholar
  10. 10.
    Duch, J., Fuster, D., Munoz, M., Fernandez, P.L., Paredes, P., Fontanillas, M., Guzman, F., Rubi, S., Lomena, F.J., Pons, F.: 18F-FDG PET/CT for early prediction of response to neoadjuvant chemotherapy in breast cancer. Eur. J. Nucl. Med. Mol. Imaging. 36(10), 1551–1557 (2009). CrossRefGoogle Scholar
  11. 11.
    Kumar, A., Kumar, R., Seenu, V., Gupta, S.D., Chawla, M., Malhotra, A., Mehta, S.N.: The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Eur. Radiol. 19(6), 1347–1357 (2009). CrossRefGoogle Scholar
  12. 12.
    Wahl, R.L., Zasadny, K., Helvie, M., Hutchins, G.D., Weber, B., Cody, R.: Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J. Clin. Oncol. 11(11), 2101–2111 (1993). CrossRefGoogle Scholar
  13. 13.
    Chen, L., Yang, Q., Bao, J., Liu, D., Huang, X., Wang, J.: Direct comparison of PET/CT and MRI to predict the pathological response to neoadjuvant chemotherapy in breast cancer: a meta-analysis. Sci. Rep. 7(1), 8479 (2017). ADSCrossRefGoogle Scholar
  14. 14.
    Pahk, K., Kim, S., Choe, J.G.: Early prediction of pathological complete response in luminal B type neoadjuvant chemotherapy-treated breast cancer patients: comparison between interim 18F-FDG PET/CT and MRI. Nucl. Med. Commun. 36(9), 887–891 (2015). CrossRefGoogle Scholar
  15. 15.
    Andrade, W.P., Lima, E.N., Osorio, C.A., do Socorro Maciel, M., Baiocchi, G., Bitencourt, A.G., Fanelli, M.F., Damascena, A.S., Soares, F.A.: Can FDG-PET/CT predict early response to neoadjuvant chemotherapy in breast cancer? Eur. J. Surg. Oncol. 39(12), 1358–1363 (2013). CrossRefGoogle Scholar
  16. 16.
    Ueda, S., Saeki, T., Shigekawa, T., Omata, J., Moriya, T., Yamamoto, J., Osaki, A., Fujiuchi, N., Misumi, M., Takeuchi, H., Sakurai, T., Tsuda, H., Tamura, K., Ishida, J., Abe, Y., Imabayashi, E., Kuji, I., Matsuda, H.: 18F-fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response. Int. J. Clin. Oncol. 17(3), 276–282 (2012). CrossRefGoogle Scholar
  17. 17.
    Tromberg, B.J., Pogue, B.W., Paulsen, K.D., Yodh, A.G., Boas, D.A., Cerussi, A.E.: Assessing the future of diffuse optical imaging technologies for breast cancer management. Med. Phys. 35(6), 2443–2451 (2008). CrossRefGoogle Scholar
  18. 18.
    Ueda, Y., Yoshimoto, K., Ohmae, E., Suzuki, T., Yamanaka, T., Yamashita, D., Ogura, H., Teruya, C., Nasu, H., Ima, E., Sakahara, H., Oda, M., Yamashita, Y.: Time-resolved optical mammography and its preliminary clinical results. Technol. Cancer Res. Treat. 10(5), 393–401 (2011). CrossRefGoogle Scholar
  19. 19.
    Fantini, S., Sassaroli, A.: Near-infrared optical mammography for breast cancer detection with intrinsic contrast. Ann. Biomed. Eng. 40(2), 398–407 (2012). CrossRefGoogle Scholar
  20. 20.
    Wu, T., Feng, J.C., Tuerhong, S., Wang, B., Yang, L., Zhao, Q., Dilixiati, J., Xu, W.T., Zhu, L.P.: Ultrasound-guided diffuse optical tomography for differentiation of benign and malignant breast lesions: a meta-analysis. J. Ultrasound Med. 36(3), 485–492 (2017). CrossRefGoogle Scholar
  21. 21.
    Ueda, S., Yoshizawa, N., Shigekawa, T., Takeuchi, H., Ogura, H., Osaki, A., Saeki, T., Ueda, Y., Yamane, T., Kuji, I., Sakahara, H.: Near-infrared diffuse optical imaging for early prediction of breast cancer response to neoadjuvant chemotherapy: a comparative study using 18F-FDG PET/CT. J. Nucl. Med. 57(8), 1189–1195 (2016). CrossRefGoogle Scholar
  22. 22.
    Nakamiya, N., Ueda, S., Shigekawa, T., Takeuchi, H., Sano, H., Hirokawa, E., Shimada, H., Suzuki, H., Oda, M., Osaki, A., Saeki, T.: Clinicopathological and prognostic impact of imaging of breast cancer angiogenesis and hypoxia using diffuse optical spectroscopy. Cancer Sci. 105(7), 833–839 (2014). CrossRefGoogle Scholar
  23. 23.
    Tromberg, B.J., Zhang, Z., Leproux, A., O’Sullivan, T.D., Cerussi, A.E., Carpenter, P.M., Mehta, R.S., Roblyer, D., Yang, W., Paulsen, K.D., Pogue, B.W., Jiang, S., Kaufman, P.A., Yodh, A.G., Chung, S.H., Schnall, M., Snyder, B.S., Hylton, N., Boas, D.A., Carp, S.A., Isakoff, S.J., Mankoff, D.: Predicting responses to neoadjuvant chemotherapy in breast cancer: ACRIN 6691 trial of diffuse optical spectroscopic imaging. Cancer Res. 76(20), 5933–5944 (2016). CrossRefGoogle Scholar
  24. 24.
    Zhi, W., Liu, G., Chang, C., Miao, A., Zhu, X., Xie, L., Zhou, J.: Predicting treatment response of breast cancer to neoadjuvant chemotherapy using ultrasound-guided diffuse optical tomography. Transl. Oncol. 11(1), 56–64 (2018). CrossRefGoogle Scholar
  25. 25.
    Yoshizawa, N., Ueda, Y., Nasu, H., Ogura, H., Ohmae, E., Yoshimoto, K., Takehara, Y., Yamashita, Y., Sakahara, H.: Effect of the chest wall on the measurement of hemoglobin concentrations by near-infrared time-resolved spectroscopy in normal breast and cancer. Breast Cancer (Tokyo, Japan). 23(6), 844–850 (2016). CrossRefGoogle Scholar
  26. 26.
    Cerussi, A., Shah, N., Hsiang, D., Durkin, A., Butler, J., Tromberg, B.J.: In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy. J. Biomed. Opt. 11(4), 044005 (2006). ADSCrossRefGoogle Scholar
  27. 27.
    Ohmae, E., Yoshizawa, N., Yoshimoto, K., Hayashi, M., Wada, H., Mimura, T., Suzuki, H., Homma, S., Suzuki, N., Ogura, H., Nasu, H., Sakahara, H., Yamashita, Y., Ueda, Y.: Stable tissue-simulating phantoms with various water and lipid contents for diffuse optical spectroscopy. Biomed. Opt. Express. 9(11), 5792–5808 (2018). CrossRefGoogle Scholar

Copyright information

© The Optical Society of Japan 2018

Authors and Affiliations

  • Yuko Asano
    • 1
  • Nobuko Yoshizawa
    • 2
    Email author
  • Yukio Ueda
    • 3
  • Kenji Yoshimoto
    • 3
  • Tetsuya Mimura
    • 3
  • Etsuko Ohmae
    • 3
  • Hiroko Wada
    • 3
  • Shigeto Ueda
    • 4
  • Toshiaki Saeki
    • 4
  • Hiroyuki Ogura
    • 1
  • Norihiko Shiiya
    • 1
  • Harumi Sakahara
    • 2
  1. 1.First Department of SurgeryHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Department of Diagnostic Radiology and Nuclear MedicineHamamatsu University School of MedicineHamamatsuJapan
  3. 3.Central Research Laboratory, Hamamatsu Photonics K.K.HamamatsuJapan
  4. 4.Department of Breast OncologySaitama Medical University International Medical CenterHidakaJapan

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