Application of N-NOSE for Evaluating the Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

<b>Background:</b> Breast cancer remains a leading cause of cancer-related deaths despite advances in its diagnosis and treatment. Accurate evaluation of the response to neoadjuvant chemotherapy (NAC), especially in HER2-positive and triple-negative subtypes, is critical. The current met...

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Main Authors: Yoshihisa Tokumaru, Yoshimi Niwa, Ryutaro Mori, Mai Okawa, Akira Nakakami, Yuta Sato, Hideyuki Hatakeyama, Takaaki Hirotsu, Eric di Luccio, Nobuhisa Matsuhashi, Manabu Futamura
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/13/950
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Summary:<b>Background:</b> Breast cancer remains a leading cause of cancer-related deaths despite advances in its diagnosis and treatment. Accurate evaluation of the response to neoadjuvant chemotherapy (NAC), especially in HER2-positive and triple-negative subtypes, is critical. The current methods, including imaging and liquid biopsies, have limitations. N-NOSE, a novel urine-based cancer screening test using <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) chemotaxis, offers a non-invasive alternative. This study investigates the potential of N-NOSE to predict the NAC response in breast cancer patients for improved treatment evaluations. <b>Materials and Methods:</b> This prospective study enrolled 36 breast cancer patients undergoing NAC and surgery to assess the predictive power of the N-NOSE method using urine samples. A chemotaxis analysis of <i>C. elegans</i> was used to calculate the index reduction scores (IRS1–3), reflecting the changes in tumor-related odorants across the treatment stages. <b>Results:</b> Between August 2020 and May 2023, 36 breast cancer patients were enrolled to evaluate the predictive value of N-NOSE IRSs for NAC response. A pathological complete response (pCR) was achieved in 36.1% of the patients. Among the three IRS types analyzed in the 35 patients, IRS3, which showed the IRS at pre-treatment minus that after surgery, showed the highest predictive performance for a pCR, with an AUC of 0.75, indicating its potential utility as a non-invasive biomarker for treatment response evaluations. <b>Conclusions:</b> Index reduction scores evaluated using the N-NOSE method may reflect the efficacy of NAC in breast cancer patients. Future large-scale and multi-institutional prospective studies are warranted.
ISSN:2073-4409