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There was a trend toward lower GATA-3 expression in References
all groups of ER(-) DCIS compared to the ER(+) cases. 1. Ernster VL, Barclay J, Kerlikowske K, Grady D, Henderson C.
There was not a signifi cant difference in the recurrence Incidence of and treatment for ductal carcinoma in situ of the
group; however, our numbers are low and may be breast. JAMA 1996;275:913-8.
lacking statistical power to draw meaningful conclusions. 2. Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y,
Others have shown that in IC with low/absent expression Weaver DL, Cutter G, Yankaskas BC, Rosenberg R,
of GATA-3 expression, there is an association with Carney PA, Kerlikowske K, Taplin SH, Urban N, Geller BM.
Detection of ductal carcinoma in situ in women undergoing
absence of hormone receptor expression for ER/PR, screening mammography. J Natl Cancer Inst 2002;94:1546-54.
overexpression of HER2, and most signifi cantly, shorter 3. Altintas S, Lambein K, Huizing MT, Braems G,
disease-free survival. [24] Asjoe FT, Hellemans H, Van Marck E, Weyler J, Praet M,
Van den Broecke R, Vermorken JB, Tjalma WA. Prognostic
For ER(+) luminal type-A invasive cancers, FOXA1 is a signifi cance of oncogenic markers in ductal carcinoma in situ of
signifi cant predictor of cancer survival. [10,11] Interestingly, the breast: a clinicopathologic study. Breast J 2009;15:120-32.
high FOXA1 expression in ER(-) IC has also been shown 4. Allred DC, Wu Y, Mao S, Nagtegaal ID, Lee S, Perou CM,
to confer a lower risk of recurrence, while loss of Mohsin SK, O’Connell P, Tsimelzon A, Medina D. Ductal
[12]
GATA-3 expression in ER(+) is associated with a higher carcinoma in situ and the emergence of diversity during breast
cancer evolution. Clin Cancer Res 2008;14:370-8.
rate of recurrence and/or metastasis. These data suggest 5. Tang P, Wang X, Schiffhauer L, Wang J, Bourne P, Yang Q,
[24]
that FOXA1 and GATA-3 expression in IC has a complex Quinn A, Hajdu SI. Relationship between nuclear grade of
relationship with ER. These novel transcription factors ductal carcinoma in situ and cell origin markers. Ann Clin Lab
appear to be important prognostic biomarkers associated Sci 2006;36:16-22.
with a well-differentiated state. These data help explain 6. Livasy CA, Perou CM, Karaca G, Cowan DW, Maia D,
Jackson S, Tse CK, Nyante S, Millikan RC. Identifi cation of
why our DCIS cases maintained such high expression a basal-like subtype of breast ductal carcinoma in situ. Hum
of GATA-3 and FOXA1 even within the ER(-) group. Pathol 2007;38:197-204.
It would be of importance to know the difference in the 7. Tamimi RM, Baer HJ, Marotti J, Galan M, Galaburda L, Fu Y,
level of expression between cases at recurrence and at Deitz AC, Connolly JL, Schnitt SJ, Colditz GA, Collins LC.
diagnosis, index to see if there is an incremental decrease Comparison of molecular phenotypes of ductal carcinoma
in situ and invasive breast cancer. Breast Cancer Res
in transcription factor expression at recurrence. In this 2008;10:404-13.
pilot study, we were not able to perform this comparison. 8. Provenzano E, Hopper JL, Giles GG, Marr G, Venter DJ,
Armes JE. Biological markers that predict clinical recurrence
Others have shown in DCIS that the loss of ER in ductal carcinoma in situ of the breast. Eur J Cancer
expression along with HER2-neu overexpression is 2003;39:622-30.
a predictor of recurrence. [8,28] Similarly, we saw this 9. Jordan VC, Wolf MF, Mirecki DM, Whitford DA,
pattern in our cases, with a higher percentage of ER(-), Welshons WV. Hormone receptor assays: clinical usefulness in
HER2-neu positive cases in the recurrent group compared the management of carcinoma of the breast. Crit Rev Clin Lab
Sci 1988;26:97-152.
to the nonrecurrent group. It is our hypothesis that with 10. Badve S, Turbin D, Thorat MA, Morimiya A, Nielsen TO,
greater statistical power and optimization of our antibody Perou CM, Dunn S, Huntsman DG, Nakshatri H. FOXA1
titers that we may see a small but signifi cantly lower expression in breast cancer - correlation with luminal
expression in FOXA1 and GATA-3 in recurrent cases, subtype A and survival. Clin Cancer Res 2007;13:4415-21.
as was seen with greater loss of ER expression in this 11. Thorat MA, Marchio C, Morimiya A, Savage K, Nakshatri H,
group. Reis-Filho JS, Badve S. Forkhead box A1 expression in breast
cancer is associated with luminal subtype and good prognosis.
Further work needs to be done on a larger cohort of J Clin Pathol 2008;61:327-32.
DCIS cases with recurrence to understand better which 12. Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V,
Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N,
variables are best able to predict recurrence and guide Schmitt F. Expression of FOXA1 and GATA-3 in breast cancer:
therapy decision strategies. Our study compared two the prognostic signifi cance in hormone receptor-negative
novel biomarkers, along with established biomarkers and tumours. Breast Cancer Res 2009;11:R40.
other important histopathological, clinical, and treatment 13. Habashy HO, Powe DG, Rakha EA, Ball G, Paish C, Gee J,
factors, in a novel prediction model, to determine which Nicholson RI, Ellis IO. Forkhead-box A1 (FOXA1) expression
in breast cancer and its prognostic signifi cance. Eur J Cancer
factors best predict recurrence in DCIS. The maintenance 2008;44:1541-51.
of FOXA1 and GATA-3 expression in ER(-) DCIS needs 14. Lacroix M, Leclercq G. About GATA-3, HNF3A, and XBP1,
to be evaluated further, as these transcription factors may three genes co-expressed with the oestrogen receptor-alpha
offer new promising targets for therapy. gene (ESR1) in breast cancer. Mol Cell Endocrinol
2004;219:1-7.
Acknowledgments 15. Kourzarides T. Chromatin modifi cations and their function.
Cell 2007;128:693-705.
The authors would like to thank Kim McManus (Q IHC) for 16. Williamson EA, Wolf I, O’Kelly J, Bose S, Tanosaki S,
the technical (IHC) assistance. Koeffl er HP. BRCA1 and FOXA1 proteins coregulate the

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