|Year : 2014 | Volume
| Issue : 2 | Page : 163-166
Triple-negative breast cancer: An institutional analysis
A Gogia1, V Raina1, SVS Deo2, NK Shukla2, BK Mohanti3
1 Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
2 Department of Surgical oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiation Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||7-Aug-2014|
Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
Aim: Triple-negative breast cancer (TNBC) is defined by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER 2)/neu. It has been identified as an independent poor prognostic factor for survival. The aim of this study was to compare the clinico-pathological characteristics and treatment outcomes of patients with TNBC and non-TNBC. Materials and Methods: We carried out an analysis of 706 patients with invasive breast cancer between January 2007 and December 2011 in whom information on the status of ER, PR, and HER2/neu were available. Results: One hundred and fifty-five patients (21.9%) patients had TNBC. Patients with TNBC had a significantly lower median age [46.2 vs. 49.8 years; P = 0.005, 95% confidence interval (CI): 0.98 to 2.38] and a higher proportion of high-grade tumors as compared to the non-TNBC group (43 vs. 24%; P < 0.0001). After a median follow-up of 30 months, the three-year relapse-free survival (RFS) was significantly lower in the TNBC group (76 vs. 64%; log rank P = 0.002). Three-year overall survival (OS) was lower in the TNBC group but not statistically significant. Age <49 years, higher nodal stage, and larger tumor size (>5 cm) were associated with poor outcome. Conclusion: TNBC is significantly associated with younger age and high-grade tumors and constitutes 21.9% of all breast cancers in our institute. Triple negativity was a significantly poor prognostic factor for RFS but not OS.
Keywords: Institutional study, triple-negative breast cancer, treatment outcome
|How to cite this article:|
Gogia A, Raina V, Deo S, Shukla N K, Mohanti B K. Triple-negative breast cancer: An institutional analysis. Indian J Cancer 2014;51:163-6
| » Introduction|| |
In India, breast cancer is the most common cancer as reported from urban cancer registries, and accounts for around 30% of all cancers in females.  Majority of the patients present at a younger age and with advanced disease.  Breast cancer is a complex and heterogeneous disease that has been defined and classified using numerous clinical and pathologic features like involvement of axillary nodes, age, tumor size, histologic grade, angiolymphatic invasion, hormonal receptor status, and human epidermal growth factor receptor 2 (HER2)/neu amplification. These features not only help in predicting outcome, but also play a role in deciding the strategy of treatment. Although this classification is still valid at present, it has become clear that it is insufficient as a prognostic tool. Newer prognostic tools are clearly required in this era of personalized medicine, to accurately identify patients with a high risk of relapse even among the low-risk subgroups, to tailor the therapy to the need of an individual patient. Gene expression profiling has emerged as one such tool. In this context, in the year 2000, Perou et al. published a new classification based on gene-expression assays that considered four breast cancer subtypes: Luminal, HER2-positive, normal breast, and basal-like.  Further studies validated this classification and consistently correlated differences in clinical outcome with the different subtypes of tumor. , Within these four groups, basal-like breast cancer emerged as a unique subtype because of its features - absence of expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 - also showing the worst outcome and having no known therapeutic target. Despite triple-negative breast cancer (TNBC) being universally used as a surrogate marker, triple negative and basal-like are not equivalent terms. 
TNBC is defined as breast cancer negative for all three receptors, namely, ER, PR, and HER2. TNBC accounts for 12 to 24% of all breast cancers. It has been shown to be an aggressive subtype with high rates of recurrence and poorer survival. It has emerged as an independent poor prognostic subgroup apart from younger age, high grade, node positivity, and advanced stage.  Recurrences have been shown to occur more often in visceral sites with short post recurrence survival. Although survival is poor, the risk of recurrence is high in the initial five years but tends to get better thereafter. 
However, there is paucity of data on TNBC from India. Our objectives were to study the clinicopathological characteristics and survival of our patients with TNBC and to compare with non-TNBC.
| » Material and Methods|| |
A total of 1,220 patients with a diagnosis of invasive breast cancer were registered between January 2007 and December 2011 in the Department of Medical Oncology of the Institute Rotary Cancer Hospital (I.R.C.H) of the All India Institute of Medical Sciences (AIIMS). The study population consisted of 736 patients with invasive breast carcinoma, who had ER, PR, and HER2/neu information available. Thirty patients who were ER-, PR-, and HER2/neu IHC 2+ (IHC: Immunohistochemistry) [not confirmed with fluorescence in situ hybridization (FISH)] were excluded from the study. Finally, 706 patients were analyzed. Details of the patients were collected from our computer database as well as from the files of patients from the medical records section. The last follow-up of all patients was done in December 2012.
TNBC was defined as negativity for ER, PR, and HER2/neu (IHC score 0 or 1+ or FISH nonamplified). Overall survival (OS) was defined as the time period between diagnosis and death from any cause. Relapse-free survival (RFS) (only for nonmetastatic patients) was defined as the time period from diagnosis to the occurrence of relapse. Progression-free survival (PFS) (only for metastatic patients) was defined as the time period from diagnosis to the occurrence of relapse or progression. Patients who did not experience any event/death or were lost to follow-up were censored for survival analysis.
Baseline categorical variables were analyzed using the Chi-square test or Fisher's exact test. Non- categorical variables were analyzed using t-test or Mann-Whitney test. RFS, PFS, and OS were determined by Kaplan Meier survival curves. Log rank test was used to compare survival. Univariate and multivariate analyses were performed to identify prognostic factors for survival. Cox proportional hazards model was used to calculate hazard ratio. Estimates were considered statistically significant for values of P < 0.05. SPSS 16.0 software was used for statistical analysis.
| » Result|| |
Seven hundred and six patients were eligible for the study and 155 (21.9%) of them had TNBC. The median age of the whole group was 48 years. The median age of TNBC patients was significantly lower than non-TNBC patients (46.2 years vs. 49.8 years, P = 0.005). Median tumor size and tumar (T) stage and nodal (N) stage distribution were not significantly different between TNBC and non-TNBC groups [Table 1]. Similarly, there was no significant difference between both the groups with respect to pathological T and nodal stage. Grade of the tumor was available for 411 patients; 28% had high-grade tumors. Patients with TNBC had a significantly higher proportion of high-grade tumors as compared to the non-TNBC group (43 vs. 24%, P < 0.0001); 85% underwent surgery, 45% radiotherapy, and 83.5% chemotherapy. There was no difference between the two treatment groups with respect to administration of surgery, chemotherapy, or radiotherapy [Table 1].
|Table 1: Demographic and clinical characteristics of breast cancer patients|
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One hundred and eight patients received neoadjuvant chemotherapy (NACT). Response rates (clinical and pathological) after NACT were significantly high in TNBC. The overall response rate (ORR) was 85.18%; 5.5% had stable disease and 9.2% progressed. After a median duration of a follow-up of 30 months (range: 12 to 70 months), 318 events were recorded and 22% were lost to follow-up. However, there was no difference in the proportion of patients lost to follow-up between TNBC and non-TNBC groups; 127 deaths were recorded. Median time to relapse and progression was 33 months and 22 months, respectively. The proportion of patients who experienced an event as relapse was higher in the TNBC group [Table 2].
In the nonmetastatic patients, the median RFS had not been reached. The three-year RFS was 70% for the whole group. It was 78% in the non-TNBC group versus 66% in the TNBC group (P = 0.002) [Figure 1]a and b. The three-year OS rate was 80% for the whole group [Figure 1]c. TNBC patients had a lower three-year OS rate than non-TNBC patients but this was not statistically significant (76 vs. 84%, P = 0.12) [Figure 1]d.
|Figure 1: (a) Relapse-free survival of patients with nonmetastatic disease alone; (b) relapse-free survival of TNBC and non-TNBC patients; (c) overall survival of all patients with nonmetastatic disease; (d) overall survival of TNBC and non-TNBC patients|
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The median PFS was 22 months for the 101 evaluable metastatic breast cancer patients. Median PFS in TNBC group was 13 months and in non-TNBC group was 30 months, although the three-year PFS was 35% for all patients and 20 and 38% for TNBC and non-TNBC groups, respectively. The TNBC group had a significantly inferior OS than the non-TNBC group The median OS was 36 months for the whole group and 19 months for TNBC group.
Age, menopausal status, tumor size, T stage, nodal stage, clinical stage, pathological T stage, pathological nodal stage, pathological stage, and TNBC emerged as significant prognostic factors for RFS in univariate analysis. However, only age, clinical nodal stage, and TNBC were the factors found to be significantly prognostic by multivariate analysis for RFS, and pathological nodal stage and tumor size for OS for nonmetastatic disease [Table 3]. In metastatic cases, response to treatment was an independent prognostic factor for PFS and both endocrine therapy and response to treatment were factors for predicting OS.
| » Discussion|| |
TNBC has been consistently associated with younger age group and high-grade tumor in many studies. , The current study also shows that TNBC is significantly associated with younger age and high-grade tumors. Some studies have shown that TNBC patients present with larger tumor size and advanced nodal stage. ,,, The current study does not show such an association. TNBC has been considered much more chemosensitive than other subtypes. , In a study of 145 cases of stage II/III breast cancer treated with NACT, the ORR and pathological complete response (CR) rate were significantly higher in TNBC.  Liedtke et al. showed in a study of 1,118 patients with stage I to III breast cancer receiving NACT that pathological CR rate was higher in TNBC than non-TNBC (22 vs. 11%).  Another study of 106 patients of metastatic TNBC showed a similar response rate in TNBC versus non-TNBC.  The current study showed an increased response rate in patients with TNBC. Several studies have shown TNBC as an independent poor prognostic factor for disease-free survival or RFS. ,,, In this study, TNBC was a significantly poor prognostic factor for RFS. TNBC patients had an increased risk of distal recurrences rather than locoregional recurrences which has already been shown in the literature.  TNBC had a negative influence on OS in some studies. ,,,,, Conversely, some studies have not shown TNBC as a poor prognostic factor for OS. ,, It was observed that studies with a larger sample size and longer duration of follow-up with larger number of events showed TNBC as a significant prognostic factor for OS. In the current study, TNBC did not have any impact on OS. An Indian study (abstract form only) of 215 cases of breast cancer, aged 35 to 70 years, found that triple negativity had negative influence on DFS, but when controlled for other factors like age and nodal status, triple negativity lost its influence on DFS.  Another study published by Patil et al. in which they recruited 136 patients of TNBC, young age, close resected margin, and triple negativity were independent predictors of RFS.  Conventional risk factors like younger age (age < 49 years), advanced nodal stage, and larger tumor size (>5 cm) emerged significant in multivariate analysis in this study. One of the following factors may be the reason that TNBC did not emerge as a negative prognostic factor for survival in the multivariate analysis as described in western literature due to advanced stage of disease at presentation, smaller sample size, shorter duration of follow-up, and long-term data not being available in 22% of the cases. This is one of the largest studies from India but shortcomings of a retrospective analysis are obvious. Changes in patterns of referral and in therapeutic strategies may also affect the natural course of the disease and modify the relative importance of different prognostic factors for OS.
| » Conclusion|| |
TNBC constituted 21.9% of breast cancers in this study. TNBC is significantly associated with younger age, high-grade tumors, good response to chemotherapy, and earlier time to event. Triple negativity was a significantly poor prognostic factor by multivariate analysis for RFS, but not OS. Conventional risk factors like younger age, advanced nodal stage, and tumor size are predictors for RFS and OS. There were some limitations in our study. We included only the patients who had all the three receptors available. This study population may be different from the universal population of all breast cancer patients which might have introduced selection bias.
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[Table 1], [Table 2], [Table 3]