Rosen's Breast Pathology, 4e

398

Chapter 11

The VNPI was developed to stratify patients with DCIS, to distinguish between women who are most likely to be treated successfully by breast conservation and those who might be candidates for mastectomy because of a relatively high risk of breast recurrence. 399 The original VNPI was a numerical score of 3 to 9 based on the assessment of three variables: size of DCIS, distance between DCIS and margin, and a pathologic classification based on necrosis and nuclear grade. Each variable was divided into three categories, which were ranked (scored) from most to least favorable as 1 to 3 (Table 11.4). The original VNPI was derived from the sum of scores for individual variables. Follow-up of patients withDCIS grouped into three VNPI categories (scores 3,4; scores 5,6,7; and scores 8,9) showed significant differences in recurrence-free survival, with the most favorable outcome associated with the lowest scores. Patients were stratified within the VNPI groups according to whether they received radiotherapy in addition to excision. Radiated patients in the VNPI 3,4 group did not differ sig- nificantly from those who were not radiated, but radiation appeared to be beneficial in the intermediate VNPI group. Recurrences were “unacceptably” frequent in the VNPI 8,9 group, even when radiotherapy was administered. 399 On the basis of these observations, it was suggested that women with DCIS classified as VNPI 3,4 could be treated by exci- sion alone, that excision with radiotherapy be employed for the VNPI 5 to 7 group, and that mastectomy should be rec- ommended if the VNPI is 8 or 9. Retrospective studies have not confirmed the VNPI as a prognostic guide for local control of DCIS. For example, de Mascarel et al. 400 found a significant difference in local re- currence between women in the low- and intermediate-risk VNPI groups. In univariate analysis, the local recurrence rate increased with the size of the DCIS, with decrease in distance to the margin, with higher histologic grade, and with the percentage of paraffin blocks involved by DCIS. When these variables were considered in multivariate analysis, the per- centage of paraffin blocks with DCIS was the only significant predictor of local recurrence. Boland et al. 401 retrospectively studied 237 patients with DCIS and confirmed that margin width and grade were significant risk factors for breast re- currence. However, when stratified by VNPI, 78% of patients were in the moderate risk group, a result that led the authors to conclude that “the VNPI lacked discriminatory power for

guiding further patient management.” In this series, margin width was the strongest predictor of successful conservation treatment. When compared with patients who had a clear margin of at least 10 mm, the RR for breast recurrence was 2.5 if the margin was 1 to 9 mm and 22 for a margin of less than 1 mm. Warnberg 402 reported no statistically significant differences in relapse-free survival between patients with DCIS stratified into the three VNPI prognostic groups. The VNPI should be validated in a prospective random- ized trial before acceptance as a basis for clinical practice. This is especially important because of significant concerns about the database from which it was derived. A major is- sue is the lack of a consistent treatment program illustrated by the following quotation that described the study group 403 : Until 1988 all patients with DCIS who elected breast con- servation were advised to add breast irradiation to their treatment. Most patients accepted this recommendation; a few refused and were treated with careful clinical follow- up without irradiation. Beginning in 1989, the physicians within The Breast Center were no longer convinced of the overall value of radiation therapy for DCIS, and all breast conservation patients with uninvolved biopsy margins (clear by 1 mm or more) were offered the option of care- ful clinical follow-up without radiation therapy. Many pa- tients accepted this option; some refused and were treated with breast irradiation. Outside patients with DCIS re- ferred to our radiation oncologists for radiation therapy continued to be treated with radiation therapy in accord with the wishes of their referring physicians. Other uncontrolled variables included differing radiation schedules and inconsistent boost treatment. 403 Lesion size was one of the original three variables included in the VNPI. As discussed elsewhere in this chapter, there is no reliable or generally acceptedmethod for measuring the size or extent of DCIS, especially with the precision that is required for the VNPI scoring system. In lesions limited to a single tissue block, it may be possible to distinguish between foci smaller and larger than 15 mm, but the distinction between 15 and 40 mm and larger than 40 mm is likely to be very unreliable. De- termining size when DCIS is distributed in more than one tis- sue block from a single biopsy specimen or if it is in more than one biopsy specimen is very imprecise. The methods for de- termining lesion extent by counting 4× fields of involvement

Table 11.4  The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) Scoring System

Score

1

2

3

Size (mm)

6–40

≤ 15 ≥ 10

≥ 41

Margins (mm)

1–9

< 1

Pathologic classification

Nonhigh grade

Nonhigh grade

High grade

( − ) necrosis

( − ) necrosis

( ± ) necrosis

Age (yr)

40–60

≥ 61 ≤ 39 Modified from Silverstein MJ, Lagios MD. Choosing treatment for patients with ductal carcinoma in situ: fine tuning the University of Southern California/Van Nuys Prognostic Index. J Natl Cancer Inst Monogr 2010;2010(41):193–196.