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Table 1: Clinical, radiological and pathologic and nuclear stains were evaluated with a cumulative
characteristics in relation to each DCIS case “H score” based on proportionality score and intensity
Characteristics Nonrecurrence Recurrence scores (0-10: negative; 11-150: low; 151-250:
group group intermediate; 250-300: high). A 10% or more “nuclear”
DCIS DCIS DCIS IC staining of the tumor cells was considered “positive.”
with/IC The proliferation marker, Ki-67/MIB-1, was given
Radiology a nuclear proliferation index (1-10%: low; 11-25%:
Calcifi cations 126 41 1 10 intermediate; 26-50%: high; > 51%: very high); HER2 a
Mass 16 7 2 2 membrane stain, was interpreted as per routine guidelines
Nipple discharge 5 1 0 1 for IC (0/1 + negative, 2 + weakly positive, 3 + strongly
Chemotherapy positive) [Figure 1].
Positive 1 9 0 0 Statistical analysis
Negative 6 35 0 0
NA 140 2 0 0 Four risk groups based on ER expression were defi ned
Radiation therapy separately for subsequent invasive cancer/DCIS based
Positive 82 29 45 20 on the risk associated with clinical/histopathologic
Negative 44 14 2 1 characteristics and biomarker expression. Groups
NA 21 6 0 0 were defi ned by combining biomarker expression that
Surgery had similar strength associations and level of risk for
Segmental (bilateral) 4 1 0 1 subsequent tumor events. We used Fisher’s exact test to
Segmental (unilateral) 106 25 22 12 determine the dependence between clinical outcomes in
TM (bilateral) 17 7 10 8 the ER(+) and ER(-) groups with and without recurrence
TM (unilateral) 28 13 15 0 for each biomarker and calculation of P value. We also
Nuclear grade examined combinations of these biomarkers that were
1 20 2 0 1 found as individual markers in univariate analyses to
2 57 34 26 3 be statistically signifi cantly associated with invasive
3 70 13 21 17 cancer and/or DCIS or were previously shown to have
Size (cm) 1.8 2.0 1.6 0.8 a biological basis for association with subsequent tumors
(0.3-10) (0.35-9.0) (0.3-9.0) (0.2-2.4) after a DCIS diagnosis or were previously reported to be
Focality associated with breast cancer survival.
Unifocal 76 37 2 8
Multifocal 71 12 40 13 Results
Lymph node biopsy
Done 56 46 2 1 Of the total 219 patients selected for study, with a
Not done 91 3 45 20 median follow-up of 4.5 years (range: 1-21 years);
Margin status 88% (196/219) developed no recurrence. In
Positive 45 12 3 14 12% (26/219) patients who developed subsequent
Negative 102 34 42 7 recurrence; 6% (13/26) recurred as IC; 6% (13/26)
NA 0 0 2 0 as DCIS. In the nonrecurrence group, 67% (146/196)
Total 147 46 13 13 were pure DCIS on both biopsy and fi nal excision;
DCIS: Ductal carcinoma in situ; IC: Invasive carcinoma; TM: Total 26% (46/196) cases had subsequent IC associated with
mastectomy; Segmental: Segmental mastectomy; NA: Not available DCIS on fi nal excision. The IC associated with DCIS
were all ductal carcinomas. Their overall nuclear grade
Table 2: Antibodies used for immunohistochemical is 1, 2 and 3, which constitution ratio is 4% (2/46),
characterization of ductal carcinoma in situ 87% (40/46), 9% (4/46), respectively. The mean
Antibody Clone Dilution Source tumor size in the DCIS with subsequent IC group was
FOXA1 Goat 1:400 Santa Cruz Biotechnology, 0.4 cm (range 0.25-3.5 cm). Seventy percent (136/196)
polyclonal Inc.; Santa Cruz, CA, USA of nonrecurrence group and 92% (24/26) of recurrence
GATA-3 L50-823 1:300 BD Biosciences, USA group were treated with breast-conserving surgery
HER2-neu 485 Predilute Ventana; Tucson, AZ, USA alone. Fifty-eight percent (111/196) in the nonrecurrence
Ki-67 30-9 Predilute Ventana; Tucson, AZ, USA group and 77% (20/26) in the recurrence group were
ER SP1 Predilute Ventana; Tucson, AZ, USA treated with radiation therapy. In both the groups,
PR 1E2 Predilute Ventana; Tucson, AZ, USA negative (clear) surgical margins, defi ned as no ink
FOXA1: Forkhead-box A1; GATA-3: GATA binding protein 3; on the tumor on fi nal excision, were obtained in
HER2: Human epidermal growth factor receptor 2; ER: Estrogen 70% (136/196) nonrecurrence group and 62% (16/26)
receptor; PR: Progesterone receptor
cases of the recurrence group. The mean tumor size in
Positive and negative control tissues were used for DCIS with recurrence as IC group was 1.5 cm (mean
assessment of each marker. FOXA1, GATA-3, ER, PR, 0.1-4.5 cm). Several morphologic characteristics were

86 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦