Volume 13 Supplement 2

IX Madrid Breast Cancer Conference

Open Access

Getting deep in the luminal B breast cancer subtype and its ki67 cut-off value

  • E Ciruelos1,
  • C Castaneda2,
  • T Pascual1,
  • E Andrés1,
  • HL Gomez2,
  • L Manso1,
  • N Valdivieso2,
  • I Ghanem1 and
  • H Cortes-Funes1
Breast Cancer Research201113(Suppl 2):P6

https://doi.org/10.1186/bcr3027

Published: 16 November 2011

Introduction

Inside the luminal breast cancer (BC) group, the B subclass carries a worse prognosis and is less responsive to hormonal treatment. Identification of the luminal B group, by Sørlie and colleagues [1], has been less consistent than other subclasses; and gene signatures based in estrogen-related genes or proliferation are better to identify this BC subclass. Cheang and colleagues genetically evaluated 144 luminal ER-positive HER2-negative tumors by IHC; they found a ki67 cutoff value of 13.25% to differentiate B from A subclasses [2]. No differentiation for PR status was done. The luminal B subgroup is usually defined as ki67 >13 if ER-positive, as well as HER2-positive or PR-negative. The target of this abstract is to evaluate behavior of different luminal B subsets.

Methods

We reviewed early BC cases evaluated at Hospital 12 de Octubre between 1995 and 2007 and selected 710 initially operated luminal B BC. We divided this group into four subsets as shown in Table 1 and analyzed their clinical-pathologic features and outcomes. Additionally, we evaluated the prognostic behavior of lowering the ki67 cutoff in the ER+PR+HER2- group (820 patients).

Table 1

  

HER2-

Variable

HER2+ER+

ER+PgR-

ER-PgR+

ER+PgR+ ki67 >13

Cases

189

126

10

385

Median age (P = 0.0021)

53.49

60.3

49.7

57.7

Ductal (P = 0.002)

173 (91.5%)

98(77.8%)

10 (100%)

314 (81.5%)

HG III (P = 0.03)

41%

47%

40%

34.1%

Lobular

5.3%

17.5%

0

14%

Median ER

85%

83%

0

90%

Median PR

60%

0

45%

80%

Median ki67

20%

17%

12.5%

20%

Recurrences total (%)

52 (27.5%)

32 (25.4%)

2 (20%)

81 (21%)

Locoregional

9 (17.3%)

3 (9.4%)

0

15 (18.5%)

Bone

6 (11.5%)

14 (43.8%)

0

25 (30.9%)

Visceral (P = 0.04)

34 (65.4%)

11 (34.4%)

0

36 (44.4%)

Median (95% CI) DFS (years)

8.1 (6.5 to 8.7)

6.4 (5.4 to 7.2)

9.2 (7.6 to 11.9)

5.6 (5.2 to 6.1)

Median (95% CI) OS (years)

8.7 (8.1 to 9.0)

7.0 (5.8 to 7.9)

10.5 (7.8 to 13.6)

6.1 (5.6 to 6.6)

Results

The median ki67 value for the ER+PR- group was 17%. A ki67 cutoff at 14% discerns two groups of different prognosis inside the luminal group (extracting HER2+ and PR-); and comparison of ki67 cutoff between 14 and 11% found overlapped CI (median: 6.31 (5.99 to 6.62) vs. 6.49 (6.21 to 6.78)). Table 1 summarizes different characteristics and prognosis based on molecular features (statistical comparisons exclude the ER-PR+ subgroup).

Conclusion

Subsets inside the luminal B subtype according to expression of HER2, ER, PgR and ki67 have different features and behaviors. In the ER+PR+HER2- subgroup, ki67 cutoff should be re-evaluated in order to avoid misclassification and subsequent under-treatment of poorer prognosis tumors as luminal A hormono-sensitive phenotype.

Authors’ Affiliations

(1)
Hospital Universitario 12 de Octubre
(2)
Instituto Nacional Enfermedades Neoplasicas

References

  1. Sørlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003, 100: 8418-8423. 10.1073/pnas.0932692100.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al: Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009, 101: 736-750. 10.1093/jnci/djp082.View ArticlePubMedPubMed CentralGoogle Scholar

Copyright

© Ciruelos et al. 2011

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