© 2007 European Society for Medical Oncology
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Demographic, clinical, and pathological characteristics of Turkish triple-negative breast cancer patients: single center experience
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 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.
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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 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.
Department of Medical Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey
* (E-mail: altundag66{at}yahoo.com)
References
1. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature (2000) 406:747–752.[CrossRef][Medline]
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) 98:10869–10874.
3. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol (2007) 8:235–244.[CrossRef][Web of Science][Medline]
4. Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA (2006) 295:2492–2502.
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].
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7. Silva LD, Clarke C, Lakhani SR. Basal-like breast cancer. J Clin Pathol. 2007 May 11; [Epub ahead of print].
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9. Rodriguez-Pinilla SM, Sarrio D, Honrado E, et al. Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas. Clin Cancer Res (2006) 12:1533–1539.
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