Rosen's Breast Pathology, 4e

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Ductal Carcinoma In Situ

or the number of slides with DCIS do not provide measure- ments suitable for the VNPI. 404,405 There are likely to be many patients for whom a VNPI cannot be determined or for whom the calculated VNPI is of questionable accuracy. An updated report from the Van Nuys Center published in 1998 did not classify patients according to the VNPI. 406 The series of 707 of nonrandomized patients included 208 women treated by lumpectomy and radiotherapy and 240 treated by excision alone. Breast recurrences were detected in 36 women in each group, representing 17% and 15%, respectively, and approximately half of the recurrences were invasive in each group. Distant metastases were diagnosed in six patients, five of whom had been treated originally by lumpectomy and ra- diotherapy. Five of the patients (0.7%) in the entire series died of breast carcinoma with four in the radiated group. The me- dian follow-up for the 35 patients who had invasive recurrent carcinoma was 127 months (58 months from initial diagnosis to invasive recurrence and 69 additional months after recur- rence). The distant recurrence rate in the subset of 35 patients with invasive recurrence in the breast was 27.1%, and the mortality rate due to breast carcinoma was 14.4% at 8 years. The VNPI has evolved over the years. In 1995, the Van Nuys classification using a combination of nuclear grade and necrosis was proposed as a tool for the prediction of local recurrence. The 1996 version of VNPI (VNPI-1996) was based upon the size of DCIS, its pathologic grade and margins . The modified University of Southern California (USC)/VNPI-2003 included age as the fourth factor to the estimation, although the introduction of age did not appear to cause any significant shift in treatment modalities. In 2010, the USC-VNPI was fine-tuned further, on the basis of the observations in three times as many patients as were included 15 years previously. 407 The five quantifiable prognostic factors (size, margin width, nuclear grade, come- donecrosis, and age) were retained; however, the recommen- dations were revised. On the basis of cumulative data that included patients treated as early as l979, it was concluded that to achieve a local recurrence rate of less than 20% at 12 years, excision alone for patients scoring 4, 5, or 6, and for those with a score of 7 and margin widths of 3 mm or more, would be appropriate. Excision plus radiation therapy would achieve the same goal for patients with a score of 7 with mar- gins less than 3 mm, patients with a score of 8 and margins of 3 mm or more, and patients whose score is 9 with margins of 5 mm or more. Mastectomy was recommended for patients who score 8 and less than 3-mmmargins, those with a score 9 and margins less than 5 mm, and for all patients with a score of 10, 11, or 12. As noted above, the VNPI is not evidence based, and its formulation and reformulation have been based on a relatively small retrospective series of cases from a single institution where treatment was not randomized. In fact, it is evident that the treatment program was revised with each reanalysis of the data and lacked consistency throughout the early three decades during which the information was assem- bled. These factors, changes in the data points used to create the VNPI, and the unreliability of some of the measurements are reasons to be very cautious in accepting the VNPI cat- egories as an absolute basis for ­making therapeutic decisions.

An attempt to improve the prognostic value of VNPI 2003 through the replacement of nuclear grade by genomic grade index (GGI, a 97-gene measure of histologic tumor grade) to generate the VNPI–GGI index has been described. 408 This unusual (and currently rather impractical) attempt to merge morphologic and molecular information is unlikely to be widely applied. The novel use of USC/VNPI to assess post- mastectomy risk of recurrence has also been proposed. 409 A nomogram has been established for the risk of relapse after breast-conserving therapy on the basis of 10 predictive factors derived from a Cox multivariate analysis of retro- spective data from 1,681 patients who underwent breast- conserving surgery at Memorial Sloan-Kettering Cancer Center in New York. 410 Factors with the greatest influence on the risk of ipsilateral recurrence included age, family history of breast carcinoma, margin status, number of ex- cisions, adjuvant radiation or endocrine therapy, and treat- ment time period. Notably, neither tumor size nor any of the commonly used biomarkers (ER, PR, and HER2) were included as variables in this nomogram. This is the first no- mogram to offer such a decision tool. 410 A recent attempt to validate this nomogram in an independent data set found that it overestimated the risk of recurrence in some subsets of patients. 411 Few studies have analyzed data based exclusively on mam- mographically detected DCIS treated by breast conservation with radiotherapy. 404,405 The 10-year breast recurrence rates ranged from 4% to 7% in patients with negative final exci- sion margins to as high as 30% for women with positive or close margins. Time to recurrence appeared to be shorter for patients with positive margins (median 3.6 years) than for those with negative (median 4.3 years) or indetermi- nate (median 5.2 years) margins. 404 In patients with mam- mographically detected DCIS, pathologic features such as nuclear grade, necrosis, and architecture (comedo vs. non- comedo) were not significantly related to the risk of local recurrence. The lack of association with pathologic charac- teristics indicates the importance of stratifying patients by detection modality in the analysis of risk factors for local breast recurrence after conservation therapy. Age at diagnosis (less than 45 vs. greater than or equal to 45 years) was found to be a significant predictor of local recurrence after breast-conserving surgery with radiation in patients with mammographically detected DCIS. 269 In this study, the 10-year actuarial rate of local failure in the breast was 23.4% for women younger than 45 years when treated and 7.1% among those 45 years or older. The au- thors were unable to apply the VNPI to their analyses be- cause tumor size could not be determined in 58% of the cases. Pathologic study of the DCIS revealed several factors that might have predisposed the younger women to local recurrence. 412 These included smaller diagnostic biopsy specimens and more frequent lesions with high nuclear grade and necrosis. Breast Conservation for Mammographically Detected DCIS