letters to the editor

Annals of Oncology

Triple-negative breast cancers are frequently defined as

a single group identifiable using routine clinical tests. They are
negative for estrogen receptor (ER), progesterone receptor
(PR), and the human epidermal growth factor receptor 2
(HER2), the so-called triple-negative breast cancers. This term
originated from hierarchical clustering analysis of gene
expression microarray studies [1, 2]. One of the five subtypes of
breast cancer identified by these analyses characteristically
expressed very low levels of ER and related genes and did not
have HER2 overexpression, the triple-negative phenotype. This
subtype also expressed many genes expressed in myoepithelial
or basal cells in the normal breast duct and the term basal like
was given. This subgroup accounts for 15% of all types of breast
cancer. Histologically, triple-negative breast cancers are poorly
differentiated and are characterized by an aggressive clinical
history. Since there are no specific treatment guidelines for this
subgroup, triple-negative breast cancers are managed with
standard treatment; however, such treatment leaves them
associated with a high rate of local and systemic relapse [3]. In
this study, we try to investigate some demographic, clinical, and
pathological characteristics of the triple-negative breast cancers
and comparing these with non-triple-negative breast tumors in
Turkish population. Standard histological and
immunohistochemical analysis were carried out for ER, PR,
and HER2 status. ER and PR are considered negative if
immunoperoxidase staining of tumor cell nuclei is <5%. HER2
was assessed through immunohistochemistry (IHC) or FISH.
IHC is scored on a qualitative scale from 0 to 3+, based on
interpretation of staining intensity, with 0 and 1+ classified
as negative, 2+ as borderline, and 3+ as positive. FISH is
scored on a quantitative scale with <2 copies of the HER2

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Demographic, clinical, and

pathological characteristics of
Turkish triple-negative breast
cancer patients: single center
experience

letters to the editor

Annals of Oncology

is associated with an increased risk of developing basal-like

cancer [5]. Furthermore, early menarche in addition has
a stronger effect on the risk of basal-like cancers [6]. In our
study, we did not evaluate these risk factors. However,
interestingly we found a positive association between oral
contraceptive use and triple-negative breast cancer. This
finding needs further verification in larger clinical trials.
Basal-like cancers are typically high-grade tumors, with
a very high proliferative rate and central necrosis that present
with large primary tumors [7]. In accordance with the
literature, patients with triple-negative tumors in our study
population had more frequently high-grade tumors than
non-triple-negative tumors (52.9% versus 28.4%, P = 0.041).
However, this was not true in our study population for
tumor size. Studies have documented that basal-like cancers are
less likely to have metastasized to the axillary lymph nodes
(42% basal-like cancers in one series node positive versus
60% controls) [8]. In our cohort also, frequency of lymph node
metastasis was lower in patients with triple-negative tumors
than the others. Therefore, we speculate that triple-negative
tumors may prefer to disseminate to distant sites
hematogenously. Basal-like breast cancers have a different
pattern of distant metastasis, compared with ER-positive breast
cancer, with less frequent metastasis to bone and liver and more
frequent metastasis to lung and brain [8, 9]. Due to shorter
follow-up of patients in our study group, we are not able to
show metastatic pattern in our triple-negative breast cancer
patients.
Although adjuvant chemotherapy is highly effective in
the treatment of triple-negative cancers, the prognosis of
triple-negative cancers remains poor. More thorough
understanding of the biology and demographic characteristics
of triple-negative breast cancer and mechanisms of tumor
progression may allow the development of rational-targeted
treatment strategies. Preliminary preclinical and clinical results
in this area are indeed quite promising.
S. Aksoy, O. Dizdar, H. Harputluoglu & K. Altundag*

Table 1. Patient characteristics both in triple-negative and other groups

n = 160 (%)
Median age (range)
Menopausal status
Pre
Peri
Post
Oral contraceptive use
Yes
No
Grade
III
III
Lymph node
Positive
Negative
Lymphovascular invasion
Yes
No

Triple negative

The others

P value

17 (10.6)
44 (2657)

143 (89.4)
47.5 (2078)

0.2

12 (70.6%)

5 (29.4%)

61 (43.0%)
9 (6.3%)
72 (50.7%)

0.05

6 (64.7%)
11 (35.3%)

17 (12.2%)
122 (87.8%)

0.02

8 (47.1%)
9 (52.9%)

96 (71.6%)
38 (28.4%)

0.041

5 (29.4%)
12 (70.6%)

52 (38.5%)
83 (61.5%)

0.012

50 (38%)
81 (62%)

0.32

8 (47.1%)
9 (52.9%)

Volume 18 | No. 11 | November 2007

Department of Medical Oncology, Hacettepe University Institute of

Oncology, Ankara, Turkey
(*E-mail: altundag66@yahoo.com)

references
1. Perou CM, Sorlie T, Eisen MB et al. Molecular portraits of human breast tumours.
Nature 2000; 406: 747752.
2. Sorlie T, 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: 1086910874.
3. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic
options. Lancet Oncol 2007; 8: 235244.
4. Carey LA, Perou CM, Livasy CA et al. Race, breast cancer subtypes, and survival
in the Carolina Breast Cancer Study. JAMA 2006; 295: 24922502.
5. Millikan RC, Newman B, Tse CK et al. Epidemiology of basal-like breast cancer.
Breast Cancer Res Treat 2007 Jun 20; [Epub ahead of print].
6. Yang XR, Sherman ME, Rimm DL et al. Differences in risk factors for breast cancer
molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers
Prev 2007; 16: 439443.
7. Silva LD, Clarke C, Lakhani SR. Basal-like breast cancer. J Clin Pathol 2007 May
11; [Epub ahead of print].

letters to the editor | 1905

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gene classified as negative. One hundred and sixty

consecutive breast cancer patients presenting at Hacettepe
University Institute of Oncology were evaluated. Most tumors
were ER+ (76%, 123/160), PR+ (74%, 118/160), and HER2+
(59%, 94/160). Of all study population, 10.6% (17/160)
had triple-negative tumors. Patients with triple-negative
tumors were younger than those with non-triple negatives
(44 versus 47.5 years P = 0.20) (Table 1). Most of the patients
with triple-negative tumors were premenopausal at diagnosis
(70.6% versus 43.0%, P = 0.050). Frequency of oral
contraceptive use was higher in patients with triple negative
than non-triple-negative breast cancer patients (35.3%
versus 12.2%, P = 0.02). Frequency of lymph node metastasis
was lower in patients with triple-negative tumors than
non-triple-negative tumors (29.4% versus 61.5%, P = 0.012).
T stage and status of the distant metastasis were not different
at diagnosis in patients with triple-negative tumor and
non-triple-negative group. Positive family history of breast
cancer and hormone replacement therapy was not different
in patients with triple-negative tumors and those with
non-triple-negative patients. Patients with triple-negative
tumors had more frequently high-grade tumors (grade III)
than non-triple-negative tumors (52.9% versus 28.4%,
P = 0.041). There was no difference in the frequency of
lymphovascular invasion between triple-negative and other
groups.
In our small cohort study population, we found that
triple-negative patients have younger age, a history of more
frequent use of oral contraceptives, more grade III tumors, and
less lymph node metastases compared with non-triple-negative
patients. Triple-negative breast cancers are more commonly
seen in younger, premenopausal women, in women of
African descent or Hispanic, and with lower socioeconomic
status [4]. Our findings are also consistent with the literature as
younger and more premenopausal patients were included in
triple-negative group. Pregnancy not followed by breast-feeding

letters to the editor

Annals of Oncology

8. Foulkes WD, Metcalfe K, Hanna W et al. Disruption of the expected positive

correlation between breast tumor size and lymph node status in BRCA1-related
breast carcinoma. Cancer 2003; 98: 15691577.
9. Rodriguez-Pinilla SM, Sarrio D, Honrado E et al. Prognostic significance of basallike phenotype and fascin expression in node-negative invasive breast
carcinomas. Clin Cancer Res 2006; 12: 15331539.

doi:10.1093/annonc/mdm487

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Volume 18 | No. 11 | November 2007