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Erschienen in: Lasers in Medical Science 8/2019

28.02.2019 | Original Article

Label-free detection of residual breast cancer after neoadjuvant chemotherapy using biomedical multiphoton microscopy

verfasst von: Zhonghua Han, Lianhuang Li, Deyong Kang, Zhenlin Zhan, Haohua Tu, Chuan Wang, Jianxin Chen

Erschienen in: Lasers in Medical Science | Ausgabe 8/2019

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Abstract

Neoadjuvant chemotherapy has become a standard treatment for breast cancer as it has been shown to increase the rate of breast preservation and to improve outcome in patients. However, how to accurately detect residual tumors is still a challenge. In this work, we tried to use multiphoton imaging to look for residual breast tumors after preoperative therapy. Imaging results demonstrate that multiphoton microscopy can identify remaining tumor tissues and can even detect rarely residual tumor cells, which would be helpful for surgeons to accurately assess the surgical margin in real time to confirm negative margins during operation. We also performed a quantification analysis of the nuclear area of tumor cells before and after treatment with neoadjuvant chemotherapy. The measurement data show that the tumor cell nuclei after chemotherapy are significantly larger than those without treatment, and there is a statistically significant difference in the nuclear areas between the pre-treatment and post-treatment mammary carcinoma. Our pilot study indicates the potential utility of multiphoton imaging for detecting residual breast carcinoma tissues in fresh, ex vivo specimens without the use of exogenous contrast agents. We foresee real-time intraoperative applications of multiphoton microscopy in evaluating therapy response, and thereby helping clinicians develop individualized treatment plans.
Literatur
1.
Zurück zum Zitat Mieog JS, van der Hage JA, van de Velde CJ (2007) Neoadjuvant chemotherapy for operable breast cancer. Br J Surg 94:1189–1200CrossRefPubMed Mieog JS, van der Hage JA, van de Velde CJ (2007) Neoadjuvant chemotherapy for operable breast cancer. Br J Surg 94:1189–1200CrossRefPubMed
2.
Zurück zum Zitat Liu SV, Melstrom L, Yao K et al (2010) Neoadjuvant therapy for breast cancer. J Surg Oncol 101:283–291CrossRefPubMed Liu SV, Melstrom L, Yao K et al (2010) Neoadjuvant therapy for breast cancer. J Surg Oncol 101:283–291CrossRefPubMed
3.
Zurück zum Zitat Gajdos C, Tartter PI, Estabrook A et al (2002) Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer. J Surg Oncol 80:4–11CrossRefPubMed Gajdos C, Tartter PI, Estabrook A et al (2002) Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer. J Surg Oncol 80:4–11CrossRefPubMed
4.
Zurück zum Zitat Faneyte IF, Schrama JG, Peterse JL et al (2003) Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 88:406–412CrossRefPubMedPubMedCentral Faneyte IF, Schrama JG, Peterse JL et al (2003) Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 88:406–412CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Archer CD, Parton M, Smith IE et al (2003) Early changes in apoptosis and proliferation following primary chemotherapy for breast cancer. Br J Cancer 89:1035–1041CrossRefPubMedPubMedCentral Archer CD, Parton M, Smith IE et al (2003) Early changes in apoptosis and proliferation following primary chemotherapy for breast cancer. Br J Cancer 89:1035–1041CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Charfare H, Limongelli S, Purushotham AD (2005) Neoadjuvant chemotherapy in breast cancer. Br J Surg 92:14–23CrossRefPubMed Charfare H, Limongelli S, Purushotham AD (2005) Neoadjuvant chemotherapy in breast cancer. Br J Surg 92:14–23CrossRefPubMed
7.
Zurück zum Zitat Tromberg BJ, Cerussi A, Shah N et al (2005) Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy. Breast Cancer Res 7:279–285CrossRefPubMedPubMedCentral Tromberg BJ, Cerussi A, Shah N et al (2005) Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy. Breast Cancer Res 7:279–285CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Weatherall PT, Evans GF, Metzger GJ et al (2001) MRI vs. histologic measurement of breast cancer following chemotherapy: comparison with x-ray mammography and palpation. J Magn Reson Imaging 13:868–875CrossRefPubMed Weatherall PT, Evans GF, Metzger GJ et al (2001) MRI vs. histologic measurement of breast cancer following chemotherapy: comparison with x-ray mammography and palpation. J Magn Reson Imaging 13:868–875CrossRefPubMed
9.
Zurück zum Zitat Chen JH, Feig B, Agrawal G et al (2008) MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy. Cancer 112:17–26CrossRefPubMed Chen JH, Feig B, Agrawal G et al (2008) MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy. Cancer 112:17–26CrossRefPubMed
10.
Zurück zum Zitat McKeown E, Nelson DW, Johnson EK et al (2014) Current approaches and challenges for monitoring treatment response in colon and rectal cancer. J Cancer 5:31–43CrossRefPubMedPubMedCentral McKeown E, Nelson DW, Johnson EK et al (2014) Current approaches and challenges for monitoring treatment response in colon and rectal cancer. J Cancer 5:31–43CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Rosen EL, Blackwell KL, Baker JA et al (2003) Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. Am J Roentgenol 181:1275–1282CrossRef Rosen EL, Blackwell KL, Baker JA et al (2003) Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. Am J Roentgenol 181:1275–1282CrossRef
12.
Zurück zum Zitat Martincich L, Montemurro F, De Rosa G et al (2004) Monitoring response to primary chemotherapy in breast cancer using dynamic contrast-enhanced magnetic resonance imaging. Breast Cancer Res Treat 83:67–76CrossRefPubMed Martincich L, Montemurro F, De Rosa G et al (2004) Monitoring response to primary chemotherapy in breast cancer using dynamic contrast-enhanced magnetic resonance imaging. Breast Cancer Res Treat 83:67–76CrossRefPubMed
14.
Zurück zum Zitat Tilbury K, Campagnola PJ (2015) Applications of second-harmonic generation imaging microscopy in ovarian and breast cancer. Perspect Medicin Chem 7:21–32CrossRefPubMedPubMedCentral Tilbury K, Campagnola PJ (2015) Applications of second-harmonic generation imaging microscopy in ovarian and breast cancer. Perspect Medicin Chem 7:21–32CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Alexander S, Weigelin B, Winkler F et al (2013) Preclinical intravital microscopy of the tumour-stroma interface: invasion, metastasis, and therapy response. Curr Opin Cell Biol 25:659–671CrossRefPubMed Alexander S, Weigelin B, Winkler F et al (2013) Preclinical intravital microscopy of the tumour-stroma interface: invasion, metastasis, and therapy response. Curr Opin Cell Biol 25:659–671CrossRefPubMed
16.
Zurück zum Zitat Jain M, Narula N, Aggarwal A et al (2014) Multiphoton microscopy: a potential “optical biopsy” tool for real-time evaluation of lung tumors without the need for exogenous contrast agents. Arch Pathol Lab Med 138:1037–1047CrossRefPubMed Jain M, Narula N, Aggarwal A et al (2014) Multiphoton microscopy: a potential “optical biopsy” tool for real-time evaluation of lung tumors without the need for exogenous contrast agents. Arch Pathol Lab Med 138:1037–1047CrossRefPubMed
17.
Zurück zum Zitat Li LH, Jiang WZ, Yang YH et al (2014) Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy. J Biomed Opt 19:066008CrossRefPubMed Li LH, Jiang WZ, Yang YH et al (2014) Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy. J Biomed Opt 19:066008CrossRefPubMed
18.
Zurück zum Zitat Xu X, Cheng J, Thrall MJ et al (2013) Multimodal non-linear optical imaging for label-free differentiation of lung cancerous lesions from normal and desmoplastic tissues. Biomed Opt Express 4:2855–2868CrossRefPubMedPubMedCentral Xu X, Cheng J, Thrall MJ et al (2013) Multimodal non-linear optical imaging for label-free differentiation of lung cancerous lesions from normal and desmoplastic tissues. Biomed Opt Express 4:2855–2868CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Li X, Li H, He X et al (2018) Spectrum- and time-resolved endogenous multiphoton signals reveal quantitative differentiation of premalignant and malignant gastric mucosa. Biomed Opt Express 9:453–471CrossRefPubMedPubMedCentral Li X, Li H, He X et al (2018) Spectrum- and time-resolved endogenous multiphoton signals reveal quantitative differentiation of premalignant and malignant gastric mucosa. Biomed Opt Express 9:453–471CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Sun TY, Haberman AM, Greco V (2017) Preclinical advances with multiphoton microscopy in live imaging of skin cancers. J Invest Dermatol 137:282–287CrossRefPubMed Sun TY, Haberman AM, Greco V (2017) Preclinical advances with multiphoton microscopy in live imaging of skin cancers. J Invest Dermatol 137:282–287CrossRefPubMed
21.
Zurück zum Zitat Villarreal-Garza C, Bargallo-Rocha JE, Soto-Perez-de-Celis E et al (2016) Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 157:385–394CrossRefPubMed Villarreal-Garza C, Bargallo-Rocha JE, Soto-Perez-de-Celis E et al (2016) Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 157:385–394CrossRefPubMed
22.
Zurück zum Zitat Eltahir A, Heys SD, Hutcheon AW et al (1998) Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy. Am J Surg 175:127–132CrossRefPubMed Eltahir A, Heys SD, Hutcheon AW et al (1998) Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy. Am J Surg 175:127–132CrossRefPubMed
23.
Zurück zum Zitat Gralow JR, Burstein HJ, Wood W et al (2008) Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol 26:814–819CrossRefPubMed Gralow JR, Burstein HJ, Wood W et al (2008) Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol 26:814–819CrossRefPubMed
24.
Zurück zum Zitat Bergquist JR, Murphy BL, Storlie CB et al (2017) Incorporation of treatment response, tumor grade and receptor status improves staging quality in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol 24:3510–3517CrossRefPubMed Bergquist JR, Murphy BL, Storlie CB et al (2017) Incorporation of treatment response, tumor grade and receptor status improves staging quality in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol 24:3510–3517CrossRefPubMed
25.
Zurück zum Zitat Chen Y, Shi XE, Tian JH et al (2018) Survival benefit of neoadjuvant chemotherapy for resectable breast cancer: a meta-analysis. Medicine 97:e10634CrossRefPubMedPubMedCentral Chen Y, Shi XE, Tian JH et al (2018) Survival benefit of neoadjuvant chemotherapy for resectable breast cancer: a meta-analysis. Medicine 97:e10634CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Huland DM, Jain M, Ouzounov DG et al (2014) Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo. J Biomed Opt 19:116011CrossRefPubMedPubMedCentral Huland DM, Jain M, Ouzounov DG et al (2014) Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo. J Biomed Opt 19:116011CrossRefPubMedPubMedCentral
27.
28.
Zurück zum Zitat Wu S, Huang Y, Tang Q et al (2018) Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging. Biomed Opt Express 9:1375–1388CrossRefPubMedPubMedCentral Wu S, Huang Y, Tang Q et al (2018) Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging. Biomed Opt Express 9:1375–1388CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Sun Y, You S, Tu H et al (2018) Intraoperative visualization of the tumor microenvironment and quantification of extracellular vesicles by label-free nonlinear imaging. Sci Adv 4:eaau5603CrossRefPubMedPubMedCentral Sun Y, You S, Tu H et al (2018) Intraoperative visualization of the tumor microenvironment and quantification of extracellular vesicles by label-free nonlinear imaging. Sci Adv 4:eaau5603CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Rasbridge SA, Gillett CE, Seymour AM et al (1994) The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma. Br J Cancer 70:335–341CrossRefPubMedPubMedCentral Rasbridge SA, Gillett CE, Seymour AM et al (1994) The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma. Br J Cancer 70:335–341CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Pinder SE, Provenzano E, Earl H et al (2007) Laboratory handling and histology reporting of breast specimens from patients who have received neoadjuvant chemotherapy. Histopathology 50:409–417CrossRefPubMed Pinder SE, Provenzano E, Earl H et al (2007) Laboratory handling and histology reporting of breast specimens from patients who have received neoadjuvant chemotherapy. Histopathology 50:409–417CrossRefPubMed
32.
Zurück zum Zitat Sahoo S, Lester SC (2009) Pathology of breast carcinomas after neoadjuvant chemotherapy: an overview with recommendations on specimen processing and reporting. Arch Pathol Lab Med 133:633–642PubMed Sahoo S, Lester SC (2009) Pathology of breast carcinomas after neoadjuvant chemotherapy: an overview with recommendations on specimen processing and reporting. Arch Pathol Lab Med 133:633–642PubMed
Metadaten
Titel
Label-free detection of residual breast cancer after neoadjuvant chemotherapy using biomedical multiphoton microscopy
verfasst von
Zhonghua Han
Lianhuang Li
Deyong Kang
Zhenlin Zhan
Haohua Tu
Chuan Wang
Jianxin Chen
Publikationsdatum
28.02.2019
Verlag
Springer London
Erschienen in
Lasers in Medical Science / Ausgabe 8/2019
Print ISSN: 0268-8921
Elektronische ISSN: 1435-604X
DOI
https://doi.org/10.1007/s10103-019-02754-z

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