Download Are Triple-Negative and Basal-Like Breast Cancer Synonymous?

Letters to the Editor
Emad Rakha
Ian Ellis
Department of Histopathology,
Nottingham City Hospital NHS Trust,
Nottingham University,
Nottingham, United Kingdom
Are Triple-Negative and Basal-Like
Breast Cancer Synonymous?
To the Editor: In a recent issue of Clinical Cancer Research,
Dent and colleagues (1) have reported on the prognostic significance of estrogen negative, progesterone negative, and HER2
negative (triple-negative) class in a large cohort of breast cancer
patients. Triple-negative tumors are undeniably one of the most
relevant subgroups of breast cancer from a medical oncologist’s
perspective, given the lack of targeted therapies for this group
and their aggressive clinical behavior. We believe, however, that
equating basal-like cancers to triple-negative tumors may be
misleading because the basal-like category of tumors is
composed almost entirely of triple-negative breast cancers (1).
If expression profiling analysis using the intrinsic gene list is
considered the ‘‘gold standard’’ for the identification of basal-like
cancers, intuitively, one would claim that the majority of basallike cancers would lack hormone receptors and HER2 expression. In two studies in which the expression of hormone
receptors were analyzed in tumors classified according to the
intrinsic gene list, however, ER expression was seen in 5% to 45%
of basal-like cancers. In addition, Rouzier and coworkers (2)
have shown that 14% of basal-like cancers also express HER2.
On the other hand, triple-negative tumors are not necessarily
basal-like cancers. In fact, a significant proportion of normal
breast – like cancers as defined by expression arrays would also
lack hormone receptors and HER2. Although the latter group is
still poorly characterized, they are reported to have a prognosis
that seems to be better than that of basal-like cancers (3, 4) and
do not seem to respond to neoadjuvant chemotherapy (2, 5).
In fact, in one study, 45% of patients with basal-like cancer
showed pathologic complete response after anthracycline +
taxanes neoadjuvant chemotherapy, whereas none of the
normal breast – like cancers did so (2).
We (6) and others (7) have shown that the expression of
basal markers (i.e., basal cytokeratins and epidermal growth
factor receptor) identifies a clinically significant subgroup
within the triple-negative group. On the other hand, expression
of basal cytokeratins and/or epidermal growth factor receptor
(6 – 8), regardless of the expression of estrogen or progesterone
status, identifies a subgroup of cancers that persistently display
a poor prognosis, even at 10 years.
Caution should be exercised when using definitions based on
the lack of expression markers. As stressed by Nielsen and
colleagues (9), ‘‘lack of staining for estrogen and HER2 alone
to identify basal-like breast cancers risks misassignment based
on technical failures.’’ In fact, estrogen has a documented
technical false-negative rate (10) and problems with HER2
interpretation, in particular, when data are retrieved from
pathology reports without a central review, may lead to biased
results (11).
Clinical studies addressing triple-negative cancers are undeniably required; however, large-scale studies comparing the
expression of estrogen, progesterone, and HER2 in cases
classified as basal-like by expression arrays are required before
we can safely say that a triple-negative phenotype can be used as
an accurate surrogate for basal-like cancers.
Clin Cancer Res 2008;14(2) January 15, 2008
Jorge Reis-Filho
The Breakthrough Breast Cancer Research Centre,
Institute of Cancer Research,
London, United Kingdom
References
1. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13:4429 ^ 34.
2. Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes
respond differently to preoperative chemotherapy. Clin Cancer Res 2005;11:
5678 ^ 85.
3. Fan C, Oh DS,Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 2006;355:560 ^ 9.
4. SorlieT, Perou CM,Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci
U S A 2001;98:10869 ^ 74.
5. Rody A, KarnT, Solbach C, et al. The erbB2+ cluster of the intrinsic gene set predicts tumor response of breast cancer patients receiving neoadjuvant chemotherapy with docetaxel, doxorubicin and cyclophosphamide within the GEPARTRIO
trial. Breast 2007;16:235 ^ 40.
6. Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic
markers in triple-negative breast cancer. Cancer 2007;109:25 ^ 32.
7. Tischkowitz M, Brunet JS, Begin LR, et al. Use of immunohistochemical markers
can refine prognosis in triple negative breast cancer. BMC Cancer 2007;7:134.
8. Abd El-Rehim DM, Pinder SE, Paish CE, et al. Expression of luminal and basal
cytokeratins in human breast carcinoma. J Pathol 2004;203:661 ^ 71.
9. NielsenTO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res
2004;10:5367 ^ 74.
10. Rhodes A, Jasani B, Barnes DM, Bobrow LG, Miller KD. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems.
J Clin Pathol 2000;53:125 ^ 30.
11.Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007;25:
118 ^ 45.
F 2008 American Association for Cancer Research.
doi:10.1158/1078-0432.CCR-07-1943
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Are Triple-Negative and Basal-Like Breast Cancer
Synonymous?
Emad Rakha, Ian Ellis and Jorge Reis-Filho
Clin Cancer Res 2008;14:618.
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