Long-Term Sacituzumab Govitecan Treatment in HR+/HER2- Advanced Breast Cancer: A Case Discussion

Long-Term Sacituzumab Govitecan Treatment in HR+/HER2- Advanced Breast Cancer: A Case Discussion | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Long-Term Sacituzumab Govitecan Treatment in HR+/HER2- Advanced Breast Cancer: A Case Discussion Yilin Lin, Yongxia Dang, Xiaotong Li, Tong Li, Jingru Yang, Xiaoling Ling This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7868904/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER 2–) breast cancer (BC) accounts for ~70% of BC cases. Guidelines recommend endocrine therapy with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor as first-line treatment, but endocrine resistance significantly impacts patient outcomes. Antibody-drug conjugates (ADCs) represent a promising advancement in treating advanced disease by targeted delivery of cytotoxic agents. Sacituzumab govitecan (SG), a first-in-class ADC targeting Trop-2, is approved for patients with metastatic HR+/HER2–, showing improved clinical outcomes and quality of life (QoL) than standard chemotherapy in patients pretreated with systemic therapy, endocrine-resistant HR+/HER2– advanced BC. Case presentation: This case presents a 24-year treatment history of a patient with metastatic HR+/HER2– BC who received SG treatment as a tenth line of therapy, after progression on multiple lines of endocrine/radio/chemo/targeted therapies. Despite initial imaging indicating progressive disease (PD), continued SG treatment improved clinical symptoms, QoL, and reduced lesion count, achieving a progression-free survival of 11 months. After subsequent progression, the patient switched to trastuzumab deruxtecan (11 th line); with no improvement after 1 cycle. The patient decided to discontinue treatment and ultimately succumbed due to PD. Conclusion : SG demonstrated long-term clinical benefit in pretreated patients with metastatic HR+/HER2− BC. Clinical and biochemical improvements occurred within 2 cycles, while reduction of target lesions became apparent in subsequent cycles (likely influenced by tumor biology and prior treatments). In advanced, post-treatment stages of HR+ BC, with complex tumor biology and progression patterns, an individualized management combining diagnostic profiling, clinical monitoring, and comprehensive assessment of treatment effect is critical. Clinical trial number: Not applicable. HR+/HER2– breast cancer Sacituzumab govitecan 24-year long survival individualized treatment improvement in quality of life Case report Figures Figure 1 Figure 2 Figure 3 1 Introduction Breast cancer (BC) is a leading cause of cancer and remains a major global health concern in women. In China, BC represents 15.6% of all female cancer incidences and contributes to 7.9% of cancer-related mortality, underscoring its substantial clinical and societal impact [ 1 ]. Hormone receptor–positive(HR+)/ human epidermal growth factor receptor 2–negative (HER2−) subtype is the most common subtype, accounting for about 70% of all cases, with an age-adjusted rate of 91.3 new cases per 100,000 women, based cases from 2018 to 2022 [ 2 ]. Endocrine therapy with tamoxifen, aromatase inhibitors or fulvestrant remains the mainstay of the treatment for HR+/HER2 − metastatic breast cancer (mBC) [ 3 ], but intrinsic or acquired resistance often limits their long-term efficacy [ 4 , 5 ]. Current American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines recommend cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy as the first-line treatment [ 6 , 7 ], improving progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) rates [ 8 – 11 ]. However, most patients eventually develop resistance to endocrine therapy, leading to disease progression [ 12 ]. Antibody-drug conjugates (ADCs), which deliver cytotoxic payloads via tumor-targeting antibodies, offer a promising strategy for patients with HR + BC, and resistant to endocrine therapy by balancing efficacy and toxicity [ 13 , 14 ]. Sacituzumab govitecan (SG) is a first-in-class Trop-2–directed ADC, with a humanized anti–Trop-2 antibody conjugated to SN-38, the active metabolite of irinotecan [ 15 ]. In the TROPiCS-02 trial SG demonstrated significantly improved median progression-free survival (mPFS) and OS in patients resistant to endocrine therapy in HR+/HER2 − mBC pretreated with 2–4 lines of chemotherapy [ 16 , 17 ]. The IMMU-132-01 and the ASCENT study [ 15 , 18 ], also confirmed its efficacy in metastatic Triple-Negative Breast Cancer (mTNBC). In this study, we present the case of a woman with HR+/HER2 − mBC who achieved clinical benefit from long-term SG treatment, after the progression through multiple lines of endocrine therapy, CDK4/6 treatments, and chemotherapy. 2 Case Report 2.1 Patient Description A 49-year-old postmenopausal woman with a history of invasive ductal carcinoma presented with recurrent metastatic HR+/HER2 − BC (initial pathological stage pT2N2M0, Stage IIIA; subsequent relapse as rT0N0M1, Stage IV). She has had lung and bone metastases for 8 years and liver metastases for the past 3 years. 2.2 Case History The patient was diagnosed in 2001 with left breast invasive ductal carcinoma estrogen receptor (ER) positive/negative (+/−), progesterone receptor (PR) positive (+), and HER-2 (+) with focal mucinous characteristics along with axillary lymph node involvement (8 in 12). She subsequently underwent modified radical mastectomy. After surgery, she received 6 cycles of docetaxel and pirarubicin (THP-D) chemotherapy regimen, and local radiotherapy. As anti-HER2- therapy was unavailable in China at that time (2002), she commenced long-term endocrine maintenance therapy with toremifene, until 2012. The subsequent treatment line of the patient is represented in Fig. 1 . The patient remained stable for more than a decade until lung and bone metastases appeared in 2016. First-line chemotherapy with a gemcitabine and cisplatin (GC) regimen for 7 cycles, resulted in a stable disease. This was followed by maintenance chemotherapy (14 cycles of capecitabine monotherapy) until October 2017, and stable disease was maintained. In October 2017, she underwent bilateral ovarian castration and began letrozole (2.5 mg once daily [0.d.]) for 1 year. In October 2018, disease progression with new pulmonary nodules and pleural effusion led to second-line treatment with albumin-bound paclitaxel (Nab-paclitaxel) for 4 cycles, resulting in a partial response. From February 2019 to June 2020, the treatment was switched to exemestane 25 mg o.d. By June 2020, worsening pleural thickening and effusion prompted 6 more cycles of Nab-paclitaxel, and the patient achieved stable disease. However, by January 2021, the pleural metastases worsened and then she received a combination of Nab-paclitaxel 400mg IV drip and apatinib 250 mg o.d for 6 cycles till April 2021, then apatinib alone, maintaining a stable disease until November 2021. Follow-up scans then revealed multiple liver metastases and increased pleural effusion. Owing to the progression of the disease, the patient commenced vinorelbine (90 mg o.d. day 1,8 and 15) in December 2021; however, she experienced worsening dyspnea and increased pleural effusion. Bevacizumab (1 cycle) was administered and then patient was initiated with sixth-line treatment with utidelone monotherapy (50mg IV drip, day 1–5) for 3 cycles until Feb 2022 and the patient’s condition remained stable. In April 2022, chest and abdominal Computed Tomography (CT) scans revealed enlarged lung and liver metastases indicating progressive disease and the patient was given three more cycles of utidelone monotherapy till May 2022. By July 2022, progressive disease with multiple lung nodules and larger liver metastases was confirmed. Consequently, as a seventh-line treatment, the regimen was changed to include abemaciclib (150 mg b.i.d.) in combination with fulvestrant (0.5g IM every 4 weeks [q4w]), which was continued until October 2023, maintaining stable disease. In October 2023, the CT scan indicated further progression of liver metastases, persistent lung lesions, enlarged patchy ground-glass shadows, and signs of carcinomatous lymphangitis. Immunohistochemistry revealed ER 80%, PR (-), HER-2 (2+) (without amplification on Fluorescence In Situ Hybridization [FISH]), Ki-67 60%. Although trastuzumab deruxtecan (T-DXd) was recommended based on guidelines and drug availability, the patient opted for another anti-HER2 ADC, disitamab vedotin (RC48), which was covered by her medical insurance, therefore initiating eighth-line therapy, receiving two cycles of RC48. However, by November 2023, CT scans revealed increased liver, rib and vertebral bone metastases, prompting ninth-line treatment with eribulin (alibulin) monotherapy (2mg IV drip, day 1 and 8) for 1 cycle. After chemotherapy, adverse effects included grade 0 gastrointestinal reactions and grade IV bone marrow suppression. In December 2023, CT scans revealed further metastases than before, with new ascites and pelvic effusion. Upon progression after the initial ADC regimen and given the patient’s prior exposure to endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy—which includes taxanes and at least one in the metastatic setting—SG was considered as a later-line treatment in accordance with the National Comprehensive Cancer Network (NCCN) guidelines. After 2 cycles of SG treatment, follow-up chest and abdominal CT scans revealed progression of liver metastases, a mild increase in bilateral pleural effusions, and the overall response was classified as progressive disease as per the RECIST v1.1 criteria. The patient developed Grade IV bone marrow suppression and was managed with a long-acting leukocyte-stimulating factor as secondary prophylaxis against severe neutropenia. Despite this, resolution of previously noted abdominal and pelvic ascites was observed. The patient also reported symptomatic improvement (chest tightness, dyspnea, fatigue, appetite), and showed improved liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT]), and tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen 125 [CA125], and carbohydrate antigen 153 [CA153]), compared to that before the initiation of SG treatment. Given the improved quality of life (QOL) and favourable clinical assessment, treatment was continued. After 2 subsequent treatment cycles, further improvements were observed in the liver enzymes and tumour markers. Follow-up chest and abdominal CT scans demonstrated a reduction in liver metastases and the bilateral pleural effusions, demonstrating a partial response. When comparing liver function tests, tumor marker trends, and imaging findings before and after treatment with SG, a favourable therapeutic response was evident. Consequently, SG was continued for ten cycles, achieving a progression-free survival of 11 months (Fig. 2 and Fig. 3 ). During the course of treatment, the patient experienced only grade II bone marrow suppression. Secondary prophylaxis with a long-acting granulocyte colony-stimulating factor was administered, which was well tolerated. Gastrointestinal side effects were mild, including grade I nausea without vomiting or diarrhea. By November 2024, subsequent follow-up CT scans revealed increase in both pleural and peritoneal effusions and elevated levels of tumor markers, indicating disease progression. As a subsequent line of therapy, the patient received 1 cycle of T-DXd monotherapy. However, the response was poor after once cycle of treatment, hence the patient decided to discontinue the treatment. Due to continued disease progression, the patient ultimately succumbed to disease complications. 3 Discussion This report describes a case of HR+/HER2 − mBC that demonstrated marked clinical benefit and tumor regression after long-term treatment with SG, following progression on endocrine therapy, radiotherapy, multiple lines of chemotherapy and targeted therapies. The patient ultimately achieved a PFS of 11 months. This special case illustrates a notable discordance between clinical and imaging assessments during the first 2 cycles with SG treatment wherein clinical improvements were observed after first 2 cycles, while significant improvement in imaging assessments was evident after subsequent cycles. This is distinct from other routine cases wherein radiological responses typically correlate with clinical improvements. Before initiating SG treatment, the patient exhibited elevated levels of AST, ALT, CEA, CA125 and CA153 along with progressive liver and lung metastases, ascites, and pelvic effusion. After 2 cycles of SG treatment, although the imaging assessment still met RECIST 1.1 criteria for progressive disease, the patient experienced clinically meaningful improvements in clinical symptoms and decline in tumor markers. Following 2 additional cycles, further biochemical improvement was observed, imaging examination demonstrated a reduction in liver metastases and decreased bilateral pleural effusion, resulting in PR. This case underscores the importance of individualized time to treatment response and highlights that early clinical improvements including early symptom relief, decreases in levels of tumor markers, and improved QOL— may occur before reduction in target lesions. These early clinical responses may justify continued SG therapy even though imaging examinations may not show immediate improvement. This is especially important considering ADCs’ pharmacokinetic and structural characteristics. ADC drugs may have delayed onset of action than other regimens. Studies have shown that the time to response (TTR) in the TROPiCS-02 and DESTINY-Breast04 trial were 2.9 and 2.7 months respectively, which was longer than that found in certain other regimens [ 16 , 19 ]. Further, the clinical assessment cycles for ADCs such as SG and T-DXd are normally performed every 21 days,[ 20 ] with the first imaging assessment taking place at ~ 1.5 months. Therefore, in cases with improving symptoms or biomarkers it is appropriate to continue treatment after initial imaging evaluations to prevent the premature discontinuation of potentially beneficial therapies. Several mechanisms attributable to the biological characteristics of HR + BC may explain this delay. Tumors often exhibit stromal fibrosis and reduced vascular density [ 21 ], which may limit efficient ADC penetration and distribution. Furthermore, prior therapies may modulate Trop-2 expression, affecting the efficacy of SG [ 22 ], delaying achievement of therapeutic intracellular concentrations. In addition, the SN-38 payload of SG requires activation by carboxylesterases (CES2) [ 23 , 24 ], and lower CES activity in BC which may further delay cytotoxic action [ 24 ]. The initial discordance between clinical improvement and radiologic progression in this case also raises the possibility of pseudo-progression, a phenomenon recognized primarily in immunotherapy [ 25 ] but potentially relevant for ADCs which may induce similar patterns because of their immunogenic potential and antibody-dependent cellular cytotoxicity (ADCC) effects [ 26 , 27 ]. Given the complex mechanisms of action of ADCs, which combine targeted delivery with immune-mediated responses, transient radiologic progression may not always indicate treatment failure. Thus, early improvements in clinical symptoms and laboratory tests indicate functional responses before tumor shrinkage. The RECIST1.1 evaluation system currently lacks specific provisions for pseudo-progression, and this highlights the limitations of relying solely on the RECIST 1.1 criteria. There is a need for more nuanced evaluation strategies that integrate clinical symptoms, biomarkers, and imaging over time to accurately assess the efficacy of ADCs and to avoid premature termination of potentially effective regimens. This case emphasizes the potential of ADCs in achieving long-term clinical response in metastatic HR+/HER2- breast cancer in the later-line treatment setting, while also demonstrating the significance of individualized assessment and the integration of multiple evaluation modalities—clinical, biochemical, and radiologic—when interpreting the efficacy of ADCs in real-world settings. As evidence evolves, ongoing trials such as ASCENT-07 trial [ 28 ], evaluating SG in chemotherapy-naïve patients, will be pivotal in establishing its role in the frontline treatment of this subtype. Thus TROP2-targeted ADCs are anticipated to not only extend clinical response but also potentially improve overall survival in patients with HR-positive/HER2-negative breast cancer. Declarations Acknowledgement The authors would like to express their sincere gratitude to The First Hospital of Lanzhou University for their invaluable support throughout the preparation of this case report. We also extend our appreciation to all the participants involved in this research for their cooperation and contribution. Funding This study was supported by the Science and Technology Bureau of Chengguan District, Lanzhou City (Grant ID: 2021SHFZ0006). Author’s contributions Yilin Lin wrote the paper and collected the case data and image data of the patient. Xiaoling Ling guided article writing. All authors contributed to the article and approved the submitted version. Conflict of Interest Yilin Lin, Yongxia Dang, Xiaotong Li, Tong Li, Jingru Yang, Xiaoling Ling declare that they have no competing interests. Ethics approval and consent to participate This study was performed in line with the principles of the Declaration of Helsinki (1964), and its later amendments. Ethical approval was granted by the Clinical Research Ethics Committee of The First Hospital of Lanzhou University, with an exemption from obtaining patient's informed consent. As the patient had succumbed to the disease complications, written informed consent was obtained from the patient’s legal representative for participation in this case report. Consent for publication Written informed consent was obtained from the patient’s legal representative for publication of this case report and any accompanying images as the patient succumbed to the disease complications. 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Abstract PO1-05-09: ASCENT-07: A phase 3, randomized, open-label study of sacituzumab govitecan versus treatment of physician’s choice in patients with HR+/HER2– inoperable, locally advanced, or metastatic breast cancer post-endocrine therapy. Cancer Research. 2024;84:PO1-05–9. https://doi.org/10.1158/1538-7445.SABCS23-PO1-05-09 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7868904","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":576391553,"identity":"a7aee61b-c9b2-4ff6-9b51-d46081a32d2a","order_by":0,"name":"Yilin Lin","email":"","orcid":"","institution":"The First Clinical Medical College of Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yilin","middleName":"","lastName":"Lin","suffix":""},{"id":576391554,"identity":"91b967fe-6963-4a18-97b7-527035214a14","order_by":1,"name":"Yongxia Dang","email":"","orcid":"","institution":"The First Clinical Medical College of Lanzhou 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1","display":"","copyAsset":false,"role":"figure","size":166268,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChronological overview of therapeutic interventions by line of therapy and the disease status after treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003eThe patient was switched to T-DXd for one month; however, the treatment showed limited efficacy, and she ultimately succumbed due to disease progression\u003c/p\u003e\n\u003cp\u003eC, cycle of treatment; Cap, Capecitabine; GP, Gemcitabine + cisplatin; Nab-paclitaxel, nanoparticle albumin-bound paclitaxel; PD, Progressive Disease; PR, Partial Response RC48, Disitamab Vedotin; SG, Sacituzumab Govitecan; SD, Stable Disease; T-DXd, Trastuzumab Deruxtecan\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7868904/v1/e83d07d12cb3a9444824d7ff.png"},{"id":100672886,"identity":"dd9cd6c4-62ae-4054-8cf7-5e978d5c1e8a","added_by":"auto","created_at":"2026-01-20 10:43:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":411111,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison CT scans of chest (A-D) and liver lesions (E-H) before and after the administration of SG\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCT, Computed Tomography; SG, Sacituzumab Govitecan\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7868904/v1/275032a2ac7246de058eced6.png"},{"id":100672628,"identity":"f780ecf0-cfd0-4617-83c0-48df0d48ab07","added_by":"auto","created_at":"2026-01-20 10:40:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":226514,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) Liver enzymes (ALT/AST) and (B) tumor markers (CA125/CA153) continued to improve after the administration of SG\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; CA 125, Cancer Antigen 12-5; CA 15-3, Cancer Antigen 153; SG Sacituzumab govitecan\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7868904/v1/025c4a5847ebc629e45e2ca7.png"},{"id":103909435,"identity":"962afe87-e8f8-4e0b-882c-bb6cbd1ab59c","added_by":"auto","created_at":"2026-03-04 11:43:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1302186,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7868904/v1/44f158a1-84ea-4743-8c0d-58566d2aa745.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-Term Sacituzumab Govitecan Treatment in HR+/HER2- Advanced Breast Cancer: A Case Discussion","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eBreast cancer (BC) is a leading cause of cancer and remains a major global health concern in women. In China, BC represents 15.6% of all female cancer incidences and contributes to 7.9% of cancer-related mortality, underscoring its substantial clinical and societal impact [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Hormone receptor\u0026ndash;positive(HR+)/ human epidermal growth factor receptor 2\u0026ndash;negative (HER2\u0026minus;) subtype is the most common subtype, accounting for about 70% of all cases, with an age-adjusted rate of 91.3 new cases per 100,000 women, based cases from 2018 to 2022 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEndocrine therapy with tamoxifen, aromatase inhibitors or fulvestrant remains the mainstay of the treatment for HR+/HER2\u0026thinsp;\u0026minus;\u0026thinsp;metastatic breast cancer (mBC) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], but intrinsic or acquired resistance often limits their long-term efficacy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Current American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines recommend cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy as the first-line treatment [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], improving progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) rates [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, most patients eventually develop resistance to endocrine therapy, leading to disease progression [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAntibody-drug conjugates (ADCs), which deliver cytotoxic payloads via tumor-targeting antibodies, offer a promising strategy for patients with HR\u0026thinsp;+\u0026thinsp;BC, and resistant to endocrine therapy by balancing efficacy and toxicity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Sacituzumab govitecan (SG) is a first-in-class Trop-2\u0026ndash;directed ADC, with a humanized anti\u0026ndash;Trop-2 antibody conjugated to SN-38, the active metabolite of irinotecan [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In the TROPiCS-02 trial SG demonstrated significantly improved median progression-free survival (mPFS) and OS in patients resistant to endocrine therapy in HR+/HER2\u0026thinsp;\u0026minus;\u0026thinsp;mBC pretreated with 2\u0026ndash;4 lines of chemotherapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The IMMU-132-01 and the ASCENT study [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], also confirmed its efficacy in metastatic Triple-Negative Breast Cancer (mTNBC).\u003c/p\u003e \u003cp\u003eIn this study, we present the case of a woman with HR+/HER2\u0026thinsp;\u0026minus;\u0026thinsp;mBC who achieved clinical benefit from long-term SG treatment, after the progression through multiple lines of endocrine therapy, CDK4/6 treatments, and chemotherapy.\u003c/p\u003e"},{"header":"2 Case Report","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Patient Description\u003c/h2\u003e \u003cp\u003eA 49-year-old postmenopausal woman with a history of invasive ductal carcinoma presented with recurrent metastatic HR+/HER2\u0026thinsp;\u0026minus;\u0026thinsp;BC (initial pathological stage pT2N2M0, Stage IIIA; subsequent relapse as rT0N0M1, Stage IV). She has had lung and bone metastases for 8 years and liver metastases for the past 3 years.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Case History\u003c/h2\u003e \u003cp\u003eThe patient was diagnosed in 2001 with left breast invasive ductal carcinoma estrogen receptor (ER) positive/negative (+/\u0026minus;), progesterone receptor (PR) positive (+), and HER-2 (+) with focal mucinous characteristics along with axillary lymph node involvement (8 in 12). She subsequently underwent modified radical mastectomy. After surgery, she received 6 cycles of docetaxel and pirarubicin (THP-D) chemotherapy regimen, and local radiotherapy. As anti-HER2- therapy was unavailable in China at that time (2002), she commenced long-term endocrine maintenance therapy with toremifene, until 2012. The subsequent treatment line of the patient is represented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient remained stable for more than a decade until lung and bone metastases appeared in 2016. First-line chemotherapy with a gemcitabine and cisplatin (GC) regimen for 7 cycles, resulted in a stable disease. This was followed by maintenance chemotherapy (14 cycles of capecitabine monotherapy) until October 2017, and stable disease was maintained. In October 2017, she underwent bilateral ovarian castration and began letrozole (2.5 mg once daily [0.d.]) for 1 year.\u003c/p\u003e \u003cp\u003eIn October 2018, disease progression with new pulmonary nodules and pleural effusion led to second-line treatment with albumin-bound paclitaxel (Nab-paclitaxel) for 4 cycles, resulting in a partial response. From February 2019 to June 2020, the treatment was switched to exemestane 25 mg o.d. By June 2020, worsening pleural thickening and effusion prompted 6 more cycles of Nab-paclitaxel, and the patient achieved stable disease.\u003c/p\u003e \u003cp\u003eHowever, by January 2021, the pleural metastases worsened and then she received a combination of Nab-paclitaxel 400mg IV drip and apatinib 250 mg o.d for 6 cycles till April 2021, then apatinib alone, maintaining a stable disease until November 2021. Follow-up scans then revealed multiple liver metastases and increased pleural effusion. Owing to the progression of the disease, the patient commenced vinorelbine (90 mg o.d. day 1,8 and 15) in December 2021; however, she experienced worsening dyspnea and increased pleural effusion. Bevacizumab (1 cycle) was administered and then patient was initiated with sixth-line treatment with utidelone monotherapy (50mg IV drip, day 1\u0026ndash;5) for 3 cycles until Feb 2022 and the patient\u0026rsquo;s condition remained stable. In April 2022, chest and abdominal Computed Tomography (CT) scans revealed enlarged lung and liver metastases indicating progressive disease and the patient was given three more cycles of utidelone monotherapy till May 2022.\u003c/p\u003e \u003cp\u003eBy July 2022, progressive disease with multiple lung nodules and larger liver metastases was confirmed. Consequently, as a seventh-line treatment, the regimen was changed to include abemaciclib (150 mg b.i.d.) in combination with fulvestrant (0.5g IM every 4 weeks [q4w]), which was continued until October 2023, maintaining stable disease.\u003c/p\u003e \u003cp\u003eIn October 2023, the CT scan indicated further progression of liver metastases, persistent lung lesions, enlarged patchy ground-glass shadows, and signs of carcinomatous lymphangitis. Immunohistochemistry revealed ER 80%, PR (-), HER-2 (2+) (without amplification on Fluorescence In Situ Hybridization [FISH]), Ki-67 60%. Although trastuzumab deruxtecan (T-DXd) was recommended based on guidelines and drug availability, the patient opted for another anti-HER2 ADC, disitamab vedotin (RC48), which was covered by her medical insurance, therefore initiating eighth-line therapy, receiving two cycles of RC48. However, by November 2023, CT scans revealed increased liver, rib and vertebral bone metastases, prompting ninth-line treatment with eribulin (alibulin) monotherapy (2mg IV drip, day 1 and 8) for 1 cycle. After chemotherapy, adverse effects included grade 0 gastrointestinal reactions and grade IV bone marrow suppression.\u003c/p\u003e \u003cp\u003eIn December 2023, CT scans revealed further metastases than before, with new ascites and pelvic effusion. Upon progression after the initial ADC regimen and given the patient\u0026rsquo;s prior exposure to endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy\u0026mdash;which includes taxanes and at least one in the metastatic setting\u0026mdash;SG was considered as a later-line treatment in accordance with the National Comprehensive Cancer Network (NCCN) guidelines. After 2 cycles of SG treatment, follow-up chest and abdominal CT scans revealed progression of liver metastases, a mild increase in bilateral pleural effusions, and the overall response was classified as progressive disease as per the RECIST v1.1 criteria. The patient developed Grade IV bone marrow suppression and was managed with a long-acting leukocyte-stimulating factor as secondary prophylaxis against severe neutropenia.\u003c/p\u003e \u003cp\u003eDespite this, resolution of previously noted abdominal and pelvic ascites was observed. The patient also reported symptomatic improvement (chest tightness, dyspnea, fatigue, appetite), and showed improved liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT]), and tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen 125 [CA125], and carbohydrate antigen 153 [CA153]), compared to that before the initiation of SG treatment. Given the improved quality of life (QOL) and favourable clinical assessment, treatment was continued. After 2 subsequent treatment cycles, further improvements were observed in the liver enzymes and tumour markers. Follow-up chest and abdominal CT scans demonstrated a reduction in liver metastases and the bilateral pleural effusions, demonstrating a partial response. When comparing liver function tests, tumor marker trends, and imaging findings before and after treatment with SG, a favourable therapeutic response was evident. Consequently, SG was continued for ten cycles, achieving a progression-free survival of 11 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). During the course of treatment, the patient experienced only grade II bone marrow suppression. Secondary prophylaxis with a long-acting granulocyte colony-stimulating factor was administered, which was well tolerated. Gastrointestinal side effects were mild, including grade I nausea without vomiting or diarrhea.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBy November 2024, subsequent follow-up CT scans revealed increase in both pleural and peritoneal effusions and elevated levels of tumor markers, indicating disease progression. As a subsequent line of therapy, the patient received 1 cycle of T-DXd monotherapy. However, the response was poor after once cycle of treatment, hence the patient decided to discontinue the treatment. Due to continued disease progression, the patient ultimately succumbed to disease complications.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Discussion","content":"\u003cp\u003eThis report describes a case of HR+/HER2\u0026thinsp;\u0026minus;\u0026thinsp;mBC that demonstrated marked clinical benefit and tumor regression after long-term treatment with SG, following progression on endocrine therapy, radiotherapy, multiple lines of chemotherapy and targeted therapies. The patient ultimately achieved a PFS of 11 months. This special case illustrates a notable discordance between clinical and imaging assessments during the first 2 cycles with SG treatment wherein clinical improvements were observed after first 2 cycles, while significant improvement in imaging assessments was evident after subsequent cycles. This is distinct from other routine cases wherein radiological responses typically correlate with clinical improvements.\u003c/p\u003e \u003cp\u003eBefore initiating SG treatment, the patient exhibited elevated levels of AST, ALT, CEA, CA125 and CA153 along with progressive liver and lung metastases, ascites, and pelvic effusion. After 2 cycles of SG treatment, although the imaging assessment still met RECIST 1.1 criteria for progressive disease, the patient experienced clinically meaningful improvements in clinical symptoms and decline in tumor markers. Following 2 additional cycles, further biochemical improvement was observed, imaging examination demonstrated a reduction in liver metastases and decreased bilateral pleural effusion, resulting in PR.\u003c/p\u003e \u003cp\u003eThis case underscores the importance of individualized time to treatment response and highlights that early clinical improvements including early symptom relief, decreases in levels of tumor markers, and improved QOL\u0026mdash; may occur before reduction in target lesions. These early clinical responses may justify continued SG therapy even though imaging examinations may not show immediate improvement. This is especially important considering ADCs\u0026rsquo; pharmacokinetic and structural characteristics. ADC drugs may have delayed onset of action than other regimens. Studies have shown that the time to response (TTR) in the TROPiCS-02 and DESTINY-Breast04 trial were 2.9 and 2.7 months respectively, which was longer than that found in certain other regimens [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFurther, the clinical assessment cycles for ADCs such as SG and T-DXd are normally performed every 21 days,[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] with the first imaging assessment taking place at ~\u0026thinsp;1.5 months. Therefore, in cases with improving symptoms or biomarkers it is appropriate to continue treatment after initial imaging evaluations to prevent the premature discontinuation of potentially beneficial therapies.\u003c/p\u003e \u003cp\u003eSeveral mechanisms attributable to the biological characteristics of HR\u0026thinsp;+\u0026thinsp;BC may explain this delay. Tumors often exhibit stromal fibrosis and reduced vascular density [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], which may limit efficient ADC penetration and distribution. Furthermore, prior therapies may modulate Trop-2 expression, affecting the efficacy of SG [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], delaying achievement of therapeutic intracellular concentrations. In addition, the SN-38 payload of SG requires activation by carboxylesterases (CES2) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and lower CES activity in BC which may further delay cytotoxic action [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The initial discordance between clinical improvement and radiologic progression in this case also raises the possibility of pseudo-progression, a phenomenon recognized primarily in immunotherapy [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] but potentially relevant for ADCs which may induce similar patterns because of their immunogenic potential and antibody-dependent cellular cytotoxicity (ADCC) effects [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Given the complex mechanisms of action of ADCs, which combine targeted delivery with immune-mediated responses, transient radiologic progression may not always indicate treatment failure.\u003c/p\u003e \u003cp\u003eThus, early improvements in clinical symptoms and laboratory tests indicate functional responses before tumor shrinkage. The RECIST1.1 evaluation system currently lacks specific provisions for pseudo-progression, and this highlights the limitations of relying solely on the RECIST 1.1 criteria. There is a need for more nuanced evaluation strategies that integrate clinical symptoms, biomarkers, and imaging over time to accurately assess the efficacy of ADCs and to avoid premature termination of potentially effective regimens.\u003c/p\u003e \u003cp\u003eThis case emphasizes the potential of ADCs in achieving long-term clinical response in metastatic HR+/HER2- breast cancer in the later-line treatment setting, while also demonstrating the significance of individualized assessment and the integration of multiple evaluation modalities\u0026mdash;clinical, biochemical, and radiologic\u0026mdash;when interpreting the efficacy of ADCs in real-world settings. As evidence evolves, ongoing trials such as ASCENT-07 trial [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], evaluating SG in chemotherapy-na\u0026iuml;ve patients, will be pivotal in establishing its role in the frontline treatment of this subtype. Thus TROP2-targeted ADCs are anticipated to not only extend clinical response but also potentially improve overall survival in patients with HR-positive/HER2-negative breast cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their sincere gratitude to The First Hospital of\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eLanzhou University for their invaluable support throughout the preparation of this case report. We also extend our appreciation to all the participants involved in this research for their cooperation and contribution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Science and Technology Bureau of Chengguan District, Lanzhou City (Grant ID: 2021SHFZ0006).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYilin Lin wrote the paper and collected the case data and image data of the patient. Xiaoling Ling guided article writing. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYilin Lin, Yongxia Dang, Xiaotong Li, Tong Li, Jingru Yang, Xiaoling Ling declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cstrong\u003eand consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki (1964), and its later amendments. Ethical approval was granted by the Clinical Research Ethics Committee of The First Hospital of Lanzhou University, with an exemption from obtaining patient\u0026apos;s informed consent. As the patient had succumbed to the disease complications, written informed consent was obtained from the patient\u0026rsquo;s legal representative for participation in this case report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s legal representative for publication of this case report and any accompanying images as the patient succumbed to the disease complications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCancer Today [Internet]. [cited 2025 May 15]. https://gco.iarc.who.int/today/. 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Signal Transduct Target Ther. 2022;7:93. https://doi.org/10.1038/s41392-022-00947-7\u003c/li\u003e\n\u003cli\u003eRugo H, Cort\u0026eacute;s J, Curigliano G, Barrios C, Punie K, Park Y, et al. Abstract PO1-05-09: ASCENT-07: A phase 3, randomized, open-label study of sacituzumab govitecan versus treatment of physician\u0026rsquo;s choice in patients with HR+/HER2\u0026ndash; inoperable, locally advanced, or metastatic breast cancer post-endocrine therapy. Cancer Research. 2024;84:PO1-05\u0026ndash;9. https://doi.org/10.1158/1538-7445.SABCS23-PO1-05-09 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"HR+/HER2– breast cancer, Sacituzumab govitecan, 24-year long survival, individualized treatment, improvement in quality of life, Case report","lastPublishedDoi":"10.21203/rs.3.rs-7868904/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7868904/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER 2–) breast cancer (BC) accounts for ~70% of BC cases. Guidelines recommend endocrine therapy with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor as first-line treatment, but endocrine resistance significantly impacts patient outcomes. Antibody-drug conjugates (ADCs) represent a promising advancement in treating advanced disease by targeted delivery of cytotoxic agents. Sacituzumab govitecan (SG), a first-in-class ADC targeting Trop-2, is approved for patients with metastatic HR+/HER2–, showing improved clinical outcomes and quality of life (QoL) than standard chemotherapy in patients pretreated with systemic therapy, endocrine-resistant HR+/HER2– advanced BC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e This case presents a 24-year treatment history of a patient with metastatic HR+/HER2– BC who received SG treatment as a tenth line of therapy, after progression on multiple lines of endocrine/radio/chemo/targeted therapies. Despite initial imaging indicating progressive disease (PD), continued SG treatment improved clinical symptoms, QoL, and reduced lesion count, achieving a progression-free survival of 11 months. After subsequent progression, the patient switched to trastuzumab deruxtecan (11\u003csup\u003eth\u003c/sup\u003e line); with no improvement after 1 cycle. The patient decided to discontinue treatment and ultimately succumbed due to PD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: SG demonstrated long-term clinical benefit in pretreated patients with metastatic HR+/HER2− BC. Clinical and biochemical improvements occurred within 2 cycles, while reduction of target lesions became apparent in subsequent cycles (likely influenced by tumor biology and prior treatments). In advanced, post-treatment stages of HR+ BC, with complex tumor biology and progression patterns, an individualized management combining diagnostic profiling, clinical monitoring, and comprehensive assessment of treatment effect is critical.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number: \u003c/strong\u003eNot applicable.\u003c/p\u003e","manuscriptTitle":"Long-Term Sacituzumab Govitecan Treatment in HR+/HER2- Advanced Breast Cancer: A Case Discussion","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 09:22:40","doi":"10.21203/rs.3.rs-7868904/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ebafa125-e902-42fe-a567-19b0e1bebff9","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-04T11:42:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-20 09:22:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7868904","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7868904","identity":"rs-7868904","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}