Imran Maryam, Majeed Muhammad Awais, Bin Naeem Sameen, Jamil Muhammad Ahsan, Shahzad Minahil, Akhtar Fatima, Karim Amna, Ahmad Aftab, Bano Shehar, Aqib Beenish, Abdullah Javaid Bukhari Syed
Medical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, PAK.
Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, PAK.
Cureus. 2025 Aug 20;17(8):e90634. doi: 10.7759/cureus.90634. eCollection 2025 Aug.
Introduction This study aimed to evaluate treatment outcomes of human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with non-metastatic HER2-positive breast cancer treated in a low-resource setting. Specifically, we assessed the impact of dual blockade (trastuzumab and pertuzumab), trastuzumab alone, or no HER2-targeted therapy on rates of residual disease, pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Methods We conducted a retrospective cohort study at Shaukat Khanum Memorial Cancer Hospital, including 299 patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant chemotherapy and either dual HER2 blockade, trastuzumab alone, or no HER2-targeted therapy due to financial constraints. Patient demographics, clinical features, treatments, and outcomes were analyzed using descriptive statistics, chi-square tests, and Kaplan-Meier survival analysis. Results The median age at diagnosis was 45.7 years (standard deviation±8.9). A majority of patients were premenopausal (n=222; 74.2%), and the majority presented with a palpable lump (n=275; 91.9%). Tumors were mainly located in the left (n=149; 49.8%) or right breast (n=147; 49.2%), with bilateral involvement in 3 (1.0%) cases. Invasive ductal carcinoma was the predominant histology (n=275; 91.9%), with estrogen receptor and progesterone receptor positivity observed in 185 (61.9%) and 179 (59.9%) patients, respectively. Grade III tumors were observed in 156 (52.2%) cases, and most tumors were T2 stage (n=236; 78.9%) with axillary nodal involvement in 232 (77.6%). Patients receiving dual HER2 blockade achieved a pCR in 45 (54.9%) of 82 cases, compared to 51 (45.9%) of 111 with trastuzumab alone, and 39 (36.8%) of 106 with no HER2 therapy (p=0.046). The docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen had the highest pCR rate in 19 (65.5%) of 29 patients (p<0.001). Grade III tumors were associated with higher pCR than Grade II (n=96; 56.5% vs. n=39; 30.2%; p<0.001). At 60 months, PFS was 236 (79.0%) overall, highest in the dual blockade group (n=73; 89.0%), followed by trastuzumab (n=96; 86.5%) and no HER2 therapy (n=69; 65.1%). OS at 60 months was 271 (90.6%), highest in the dual blockade group (n=78; 95.1%), then trastuzumab (n=102; 91.9%) and no HER2 therapy (n=79; 74.5%). Achieving pCR was associated with improved PFS and OS. Differences in both outcomes across groups were statistically significant (p<0.001). Conclusion Dual HER2 blockade significantly improved pCR, PFS, and OS in non-metastatic HER2-positive breast cancer. These findings support the inclusion of HER2-targeted agents in standard neoadjuvant treatment, even in resource-limited settings. Addressing barriers to access remains essential to improving global outcomes in breast cancer care.
引言 本研究旨在评估在资源匮乏地区接受治疗的非转移性人表皮生长因子受体2（HER2）阳性乳腺癌患者中，HER2靶向治疗的疗效。具体而言，我们评估了双重阻断（曲妥珠单抗和帕妥珠单抗）、单独使用曲妥珠单抗或不进行HER2靶向治疗对残留病灶率、病理完全缓解（pCR）、无进展生存期（PFS）和总生存期（OS）的影响。
方法 我们在沙卡特汗姆纪念癌症医院进行了一项回顾性队列研究，纳入了299例接受新辅助化疗的非转移性HER2阳性乳腺癌患者，这些患者因经济限制接受了双重HER2阻断、单独使用曲妥珠单抗或不进行HER2靶向治疗。使用描述性统计、卡方检验和Kaplan-Meier生存分析对患者的人口统计学、临床特征、治疗方法和结局进行分析。
结果 诊断时的中位年龄为45.7岁（标准差±8.9）。大多数患者为绝经前（n=222；74.2%），且大多数患者表现为可触及的肿块（n=275；91.9%）。肿瘤主要位于左侧（n=149；49.8%）或右侧乳房（n=147；49.2%），双侧受累3例（1.0%）。浸润性导管癌是主要的组织学类型（n=275；91.9%），分别有185例（61.9%）和179例（59.9%）患者雌激素受体和孕激素受体呈阳性。156例（52.2%）患者的肿瘤为Ⅲ级，大多数肿瘤为T2期（n=236；78.9%），232例（77.6%）有腋窝淋巴结受累。接受双重HER2阻断的82例患者中有45例（54.9%）达到pCR，单独使用曲妥珠单抗的111例中有51例（45.9%）达到pCR，未接受HER2治疗的106例中有39例（36.8%）达到pCR（p=0.046）。多西他赛、卡铂、曲妥珠单抗和帕妥珠单抗（TCHP）方案在29例患者中有19例（65.5%）的pCR率最高（p<0.001）。Ⅲ级肿瘤的pCR率高于Ⅱ级（n=96；56.5%对n=39；30.2%；p<0.001）。在60个月时，总体PFS为236例（79.0%），双重阻断组最高（n=73；89.0%），其次是曲妥珠单抗组（n=96；86.5%）和未接受HER2治疗组（n=69；65.1%）。60个月时的OS为271例（90.6%），双重阻断组最高（n=78；95.1%），其次是曲妥珠单抗组（n=102；91.9%）和未接受HER2治疗组（n=79；74.5%）。达到pCR与改善的PFS和OS相关。各组在这两个结局方面的差异具有统计学意义（p<0.001）。
结论 双重HER2阻断显著改善了非转移性HER2阳性乳腺癌的pCR、PFS和OS。这些发现支持将HER2靶向药物纳入标准新辅助治疗，即使在资源有限的环境中也是如此。解决获取障碍对于改善全球乳腺癌护理结局仍然至关重要。
