Di Saverio Salomone, Catena Fausto, Santini Donatella, Ansaloni Luca, Fogacci Tommaso, Mignani Stefano, Leone Antonio, Gazzotti Filippo, Gagliardi Stefano, De Cataldis Angelo, Taffurelli Mario
Emergency and General Surgery, Department of Surgery, Breast Unit, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
Breast Cancer Res Treat. 2008 Jun;109(3):405-16. doi: 10.1007/s10549-007-9668-7. Epub 2007 Aug 9.
The Van Nuys Prognostic Index (VNPI) is a simple score for predicting the risk of local recurrence (LR) in patients with Ductal Carcinoma In Situ (DCIS) conservatively treated. This score combines three independent predictors of Local Recurrence. The VNPI has recently been updated with the addition of age as a fourth parameter into the scoring system (University of Southern California/ VNPI).
Our database consisted of 408 women with DCIS. Applying the USC/VNPI we reviewed retrospectively 259 patients who were treated with breast conserving surgery with or without radiotherapy (RT). Of these patients 63.5% had a low VNPI score, 32% intermediate and 4.5% a high score. In the low score group, the majority of the patients underwent Conservative Surgery (CS) without RT while in the intermediate group, almost half of the patients received RT. Eighty-three percent (83%) of the patients with high VNPI were treated with Conservative Surgery plus RT. Nodal assessment by Sentinel Lymph Node Biopsy was obtained in 32 patients since 2002.
Twenty-one Local Recurrences were observed (8%) with a mean follow up of 130 months: sixteen were invasive. No statistically significant differences in Disease Free Survival were reached in all groups of VNPI score between patients treated with Conservative Surgery or Conservative Surgery plus RT. However it was noted that the higher the VNPI score, the lower was the risk of local recurrence in the group treated additionally with RT, even though it was not statistically significant. Further analysis included those patients treated with Conservative Surgery alone and followed up. Disease-free survival (DFS) at 10 years was 94% with low VNPI and 83% in both intermediate and high score (P < 0.05). No significant differences were observed in the subgroups of VNPI. The Local Relapse rate after Conservative Surgery alone, increased with tumor size, margin width, and pathology classification (P < 0,05), while age was not found to be a significant factor. Lesions with only mammographic appearances are associated with lower DFS but it did not reach significance (P = ns), while assumption of estrogenic hormones and familial history of breast cancer are significant factors associated with a higher risk of local recurrence. After multivariate analysis including seven clinical and pathological factors, the only significant predictors of local recurrence remained margin width of surgical excision, previous therapy with estrogens (contraceptives or Hormone Replacement Therapy) and the Van Nuys pathologic classification. The overall survival breast cancer specific was 99% and no differences were observed between groups (P = ns). The comparison of patients treated with a total mastectomy and those conservatively treated showed a significantly better local relapse free survival rate obtained with mastectomy (98.2% vs. 89.7% at 10 years P = 0.02). However, the overall cause-specific survival did not prove any better outcome (98.7% in both groups). Of the 32 patients who underwent a Sentinel Lymph Node Biopsy, four were found to have micrometastases and all of them had a previous Directional Vacuum Assisted Biopsy.
Although in our series there is not a significant difference in LR rates by the parameter of age, the new USC/VNPI is still a simple and reliable scoring system for therapeutic management of DCIS. We did not find any statistically significant advantage in groups treated with the addition of RT. Obtaining wide surgical margins appears to be the strongest prognostic factor for local recurrence, regardless of other pathological factors or the addition of adjuvant radiation therapy. However, only prospective randomized studies can precisely predict the risk of LR of conservatively treated DCIS. The clinical significance of Sentinel Lymph Nodes micrometastases Immuno-Histo-Chemistry-detected found in DCIS patients remains uncertain. However, we hypothesize that the anatomical disruption after preoperative biopsy procedures increases the likelihood of epithelial cell displacement and the frequency of IHC-positive Sentinel Lymph Nodes, both of which are directly proportional to the degree of manipulation.
范奈斯预后指数（VNPI）是一种用于预测接受保守治疗的导管原位癌（DCIS）患者局部复发（LR）风险的简单评分系统。该评分综合了三个局部复发的独立预测因素。最近，VNPI进行了更新，将年龄作为第四个参数纳入评分系统（南加州大学/VNPI）。
我们的数据库包含408例DCIS女性患者。应用南加州大学/VNPI，我们回顾性分析了259例接受保乳手术（无论是否接受放疗）的患者。这些患者中，63.5%的VNPI评分为低分，32%为中等评分，4.5%为高分。在低分患者组中，大多数患者接受了不保乳放疗的保守手术（CS），而在中等评分组中，几乎一半的患者接受了放疗。VNPI高评分的患者中有83%接受了保乳手术加放疗。自2002年起，32例患者接受了前哨淋巴结活检以进行淋巴结评估。
平均随访130个月，观察到21例局部复发（8%），其中16例为浸润性复发。在接受保守手术或保守手术加放疗的患者中，各VNPI评分组的无病生存率无统计学显著差异。然而，值得注意的是，在接受额外放疗的组中，VNPI评分越高，局部复发风险越低，尽管这在统计学上并不显著。进一步分析包括那些仅接受保守手术并进行随访的患者。VNPI低分时，10年无病生存率（DFS）为94%，中等和高分时均为83%（P<0.05）。VNPI亚组间未观察到显著差异。单纯保守手术后的局部复发率随肿瘤大小、切缘宽度和病理分类增加（P<0.05），而年龄并非显著因素。仅表现为乳腺钼靶影像的病变与较低的DFS相关，但未达到显著水平（P=无显著性差异），而服用雌激素和乳腺癌家族史是与局部复发风险较高相关的显著因素。在纳入七个临床和病理因素的多因素分析后，局部复发的唯一显著预测因素仍然是手术切缘宽度、既往雌激素治疗（避孕药或激素替代疗法）和范奈斯病理分类。乳腺癌特异性总生存率为99%，组间未观察到差异（P=无显著性差异）。接受全乳切除术和接受保守治疗的患者比较显示，全乳切除术的局部无复发生存率显著更高（10年时为98.2%对89.7%，P=0.02）。然而，总体病因特异性生存率并未显示出更好的结果（两组均为98.7%）。在接受前哨淋巴结活检的32例患者中，4例发现有微转移，且所有患者之前均接受过定向真空辅助活检。
尽管在我们的系列研究中，年龄参数在LR率上没有显著差异，但新的南加州大学/VNPI仍然是一种用于DCIS治疗管理的简单可靠的评分系统。我们未发现在加用放疗的组中有任何统计学显著优势。无论其他病理因素或是否加用辅助放疗，获得较宽的手术切缘似乎是局部复发最强的预后因素。然而，只有前瞻性随机研究才能精确预测保守治疗DCIS的LR风险。在DCIS患者中通过免疫组化检测发现的前哨淋巴结微转移的临床意义仍不确定。然而，我们推测术前活检操作后的解剖结构破坏增加了上皮细胞移位的可能性以及免疫组化阳性前哨淋巴结的频率，这两者均与操作程度成正比。
