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ORIGINAL ARTICLE
Year : 2013  |  Volume : 50  |  Issue : 4  |  Page : 330-332
 

Five year retrospective survival analysis of triple negative breast cancer in North-West India


1 Department of Surgery, Acharya Tulsi Regional Cancer Treatment and Research Institute and S.P. Medical College, Bikaner, Rajasthan, India
2 Department of Radiotherapy, Acharya Tulsi Regional Cancer Treatment and Research Institute and S.P. Medical college, Bikaner, Rajasthan, India
3 Department of Medical Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute and S.P. Medical college, Bikaner, Rajasthan, India
4 MBBS Student, Acharya Tulsi Regional Cancer Treatment and Research Institute and S.P. Medical college, Bikaner, Rajasthan, India

Date of Web Publication24-Dec-2013

Correspondence Address:
A Kalwar
Department of Medical Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute and S.P. Medical college, Bikaner, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.123616

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 » Abstract 

Background: In our institute, about 10% of total cancer is female breast cancer. This analysis was performed to check triple negativity among these patients with their survival strength up to 5 years in relation to different age groups, stage and chemotherapy protocols. Materials and Methods: 208 immunohistochemistry proved triple negative breast cancer patients registered and treated until 2008 were retrospectively selected for the study. Overall survival up to 5 years was observed on the basis of stage, different age groups and chemotherapy regimens. All patients had undergone surgery, conventional external beam radiation therapy and adjuvant chemotherapy. The survival analyses were performed using the Kaplan-Meier method. Results: The majority of patients (41%) were in the age group 21-30 years. Stage IV was seen in 18% of the patients at diagnosis and mainly in 21-40 years age group. Only 3% of females were >70 years age and were of Stage I and II. Overall 5 year survival in Stage I in Cyclophosphamide, Adriamycin/Epirubicin, 5-Flurouracil group was 37.5% as compared with Docetaxel/Paclitaxel, Epirubicin group 93% (P < 0.0001). Conclusion: Triple negativity in North-West India is about 11.8%. We observed it in younger patients mainly with highly aggressive behaviors. Taxane based chemotherapy gives better result as compared with anthracycline based regimens in all stages.


Keywords: Breast cancer, North-West India, triple negative


How to cite this article:
Sharma B, Satyanarayan, Kalwar A, Sharma N, Kapoor A, Kumar N. Five year retrospective survival analysis of triple negative breast cancer in North-West India. Indian J Cancer 2013;50:330-2

How to cite this URL:
Sharma B, Satyanarayan, Kalwar A, Sharma N, Kapoor A, Kumar N. Five year retrospective survival analysis of triple negative breast cancer in North-West India. Indian J Cancer [serial online] 2013 [cited 2020 Nov 27];50:330-2. Available from: https://www.indianjcancer.com/text.asp?2013/50/4/330/123616



 » Introduction Top


Breast cancer is the most common female cancer world-wide. It is a heterogeneous disease with regard to biological behavior, responses to treatment and prognosis. [1],[2]

Nearly 70-80% of all breast cancers are positive for estrogen receptor (ER) or progesterone receptors (PRs). In contrast, the human epidermal growth factor receptor 2 (HER2) protein over expression and/or HER2 gene are over expressed and/or amplified, respectively, in approximately 15-20% of the patients only, with around half of these co-expressing hormone receptors. The remaining 15-20% of breast cancers are negative for ER, PR and HER2. These are defined as triple negative breast cancer (TNBC). [3] The primary goal of this study was to describe the relation between the triple-negative receptor status and overall survival (OS) especially with reference to age group, stage, neoadjuvant/adjuvant chemotherapy regimen.


 » Materials and Methods Top


We retrieved information of breast cancer patients registered in our institute in last ten years. Out of these, 208 were histological and immunohistochemistry (IHC) proved TNBC patients registered and treated until 2008. Stage wise (I-IV) and age wise (21-30 years to > 70 years) distribution was done. OS up to 5 years was observed on the basis of stage, different age groups and chemotherapy regimens. All patients had surgery (195 modified radical mastectomies and 13 palliative). 43 patients received neoadjuvant chemotherapy. They belonged mainly to stage IV and a few to stage III. Of this group, 26 patients received CAF/CEF and 17 TE. 2-3 cycles were given as per surgical resectability. All 208 patients received conventional external beam radiation therapy (EBRT) as per institute policy (50 Gy + 5-10 Gy chest wall boost). All patients received adjuvant chemotherapy also. This included 119 who received CAF/CEF 4-6 cycles, conventional dose and schedule and 89 who received TE (paclitaxel/docitaxel + epirubicin) 4-6 cycles, conventional doses and 3 weekly scheduled. Sequencing of surgery, chemotherapy and EBRT was done. Hematological, biochemical and radiation related toxicities were observed during treatment and were mostly acceptable and manageable. The distant metastases were managed accordingly with best possible palliative chemotherapy/symptomatic treatment. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model was used in the multivariate analysis. All statistical calculations were done with MedCalc statistical software Version 12.5.0͹ 1993-2013 (MedCalc Software, Osterd, Belgium)


 » Results Top


In our institute, the female breast cancer patients comprised 9.37% of total registered cases. We observed 1762 patients with detailed IHC; out of these, 208 (11.8%) were TNBC. We followed these cases until 5 years for survival. Majority of patients (41%) were in the age group 21-30 years. About 25% of patients were in the age group 31-40 years. Stage IV was seen in 18% of patients at diagnosis and mainly in 21-40 years age group [Table 1]. This favors aggressive triple negativity in younger females (P = 0.0021) [Figure 1]. Only 3% females were > 70 years age and were of Stage I and II. Overall 5 year survival in Stage I in CAF/CEF group was 37.5% as compared with TE group 93% (P < 0.0001) [Figure 2]. In Stage II, survival in CAF/CEF group was 47% while in TE was 88%; 33% and 74% survival was seen in Stage III; 0% and 44% in Stage IV patients for CAF/CEF and TE group respectively. TE group patients had better over all 5 year survival then CAF/CEF group.
Table 1: Age group versus stage wise number of patients


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Figure 1: Frequency table and Chi-square analysis of 21-30 years versus stage

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Figure 2: Kaplan-Meier plot of survival versus chemotherapy regimen

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 » Discussion Top


TNBC are a special subgroup of breast cancer that does not express the genes for ER, PR and HER2 neu. It is characterized by aggressive course of disease requiring special considerations in its management.

TNBC accounts for approximately 15-25% of all breast cancer cases. In our hospital based study, TNBC accounted for 11.8% of breast cancer patient's representing prevalence of TNBC in North-West Indian population. In the study by Patil et al., [4] the prevalence of TNBC in Indian population was 19.9%. Relatively lesser prevalence needs to be confirmed by other larger studies with validation of IHC procedure and method of collection of specimen.

Various studies have correlated TNBC with a younger age at diagnosis. In our study, 41% of TNBC were of age group 21-30 years and 25% of 31-40%, thus 66% of all TNBC in the age group of 21-40 years age group. These results correlate with other studies.

On comparing age group, 21-30 years to >70 years in relation to the stage, we observed a significant difference in aggressiveness of TNBC with P value of 0.0297 in Stage I, 0.014 in Stage II, 0.0001 in Stage III and 0.0003 in Stage IV. These results suggest that aggressiveness of TNBC decreases drastically with advancing age. In our study, 58% patients presented with Stage III and IV. Liedtke et al., suggested that in patients of TNBC, increasing age at diagnosis was inversely correlated with tumor grade (P < 0.0001) and positively correlated with disease-free survival (DFS) (P = 0.0003) and OS (P < 0.0001). The median DFS for patients 31-40 years and older than 60 years was 4 years (95% confidence interval [CI] 2-5, P = 0.0003) and 8 years (95% CI 5-14, P = 0.0003) respectively. [5] TNBC have an average significantly higher fluorodeoxyglucose (FDG) uptake (indicated by maximum standardized uptake value) compared with ER+/PR+/HER2-ve using 18FDG-positron emission tomography. It is speculated that enhanced glycolysis in these tumors is probably related to their aggressive biology.

On comparison of survival in relation to adjuvant/neoadjuvant CAF/CEF with TE regimen by Kaplan Meier's method, 5 years survival was significantly better in TE group (P < 0.0001). For Stage I, P value was 0.0059 (hazard ratio [HR] = 0.56, 95% CI 0.26-1.22). The data for Stage II is P = 0.0370 (HR: 0.68, 95% CI 0.40-1.16) and for Stage IV P = 0.0051 (HR = 0.42, 95% CI 0.16-1.03).

The results from published literature have shown an increased likelihood of distant recurrence and of death as compared to women with other types of breast cancer. However an important pattern to be noted is that recurrences and death rates were higher only in the first 3 years of diagnosis. Thus, despite having a high risk of early recurrence, it appears that women with TNBC who are disease free after 5 years are unlikely to die of breast cancer. The high rates of distant recurrence and relative rarity of local recurrences suggest that the mode of spread of these cancers is mainly hematogenous. The preferential site of relapse is visceral organs rather than bones. The prognostic markers for TNBC as suggested by univariate analysis include nodal status, age, tumor size and lymphovascular invasion, but these factors lost independency in multivariate analysis. [6],[7]

Today novel therapeutic options are needed to target this highly aggressive form of breast cancer. Tumors with Breast Cancer 1 gene (BRCA 1) dysfunction, the majority of which are triple negative, have defective double stranded deoxyribonucleic acid (DNA) break repair, leading to increased sensitivity to DNA damaging platinum agents.

Poly Adenosine diphosphate Ribose Polymerase inhibitors are frequently being co prescribed with platinum agents as they further inhibit DNA repair. [8] Other targeted therapies, which include epidermal growth factor receptor inhibitors (cetuximab), antiangiogenic agents (bevacizumab), inhibitors of Src-family kinases (dasatinib), transmembrane glycoprotein NMB inhibitor (glembatumumab vedotin) are under trial. A single arm trial of olaparib as a single agent showed promising results in BRCA 1 mutated population. [9]

The widely used antidiabetic drug Metformin has completed phase 2 studies for adjuvant treatment of TNBC. Epidemiologic and preclinical lab studies indicate that metformin exerts anti-tumor effects by activation of AMP activated protein kinase. [10]

In our study, TNBC was observed mainly in younger patients with highly aggressive behaviors. Taxane based chemotherapy gives better result as compared with anthracycline based regimens (P < 0.0001). However ours being a retrospective analysis, we feel that a prospective randomized control study can be carried out in Indian scenario.


 » Acknowledgment Top


We convey our sincere thanks to all our faculty members Dr. S. L. Jakhar, Dr. S. Beniwal, Dr. H. S. Kumar, Dr. A. Sharma and Dr. M. R. Bardia for contributing patients for the study. We are also thankful to Dr. Puspendra h., Dr. Saroj, Dr. Pramilla, Dr. Mukesh, Dr. Dalip, Dr. Guman, Dr. Puneet, Dr. Rajkumar, Dr. Sitaram for their support.

 
 » References Top

1.Gluz O, Liedtke C, Gottschalk N, Pusztai L, Nitz U, Harbeck N. Triple-negative breast cancer - Current status and future directions. Ann Oncol 2009;20:1913-27.  Back to cited text no. 1
[PUBMED]    
2.Podkrajsek M, Zgajnar J, Hocevar M. What is the most common mammographic appearance of T1a and T1b inasive breast cancer? Radiol Oncol 2008;42:173-80.  Back to cited text no. 2
    
3.Dawson SJ, Provenzano E, Caldas C. Triple negative breast cancers: Clinical and prognostic implications. Eur J Cancer 2009;45:27-40.  Back to cited text no. 3
[PUBMED]    
4.Patil VW, Singhai R, Patil AV, Gurav PD. Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women. Breast Cancer Targets Ther 2011;3:9-19.  Back to cited text no. 4
    
5.Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008;26:1275-81.  Back to cited text no. 5
    
6.Plesnicar A, Golicnik M, Fazarinc IK, Kralj B, Kovac V, Plesnicar BK. Attitudes of midwifery students towards teaching breast-self examination. Radiol Oncol 2010;44:52-6.  Back to cited text no. 6
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7.Viale G, Rotmensz N, Maisonneuve P, Bottiglieri L, Montagna E, Luini A, et al. Invasive ductal carcinoma of the breast with the "triple-negative" phenotype: Prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat 2009;116:317-28.  Back to cited text no. 7
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8.Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: Therapeutic options. Lancet Oncol 2007;8:235-44.  Back to cited text no. 8
[PUBMED]    
9.Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly (ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: A proof-of-concept trial. Lancet 2010;376:235-44.  Back to cited text no. 9
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10.Goodwin PJ, Ligibel JA, Stambolic V. Metformin in breast cancer: Time for action. J Clin Oncol 2009;27:3271-3.  Back to cited text no. 10
[PUBMED]    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]

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