Original Article

A Study of Triple Negative Breast Cancer at a Tertiary

Cancer Care Center in Southern India
Lakshmaiah KC, Das U, Suresh TM, Lokanatha D, Babu GK, Jacob LA, Babu S
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Address for correspondence: Abstract

Dr. Umesh Das,
Department of Medical Oncology, Background: Triple negative breast cancers (TNBCs) are a diverse and heterogeneous group
Room no-5, OPD Block, Kidwai of tumors that by definition lack estrogen and progesterone receptors and amplification
Memorial Institute of Oncology, of the HER‑2 gene. The majority of the tumors classified as TNBCs are highly malignant,
Bengaluru ‑ 560 029, patients are usually young and only a subgroup of patients responds to conventional
Karnataka, India.
E‑mail: [email protected] chemotherapy with a favorable prognosis. Various studies have been reported in western
literature on TNBCs, all highlighting the poor prognosis of this subtype. However, extensive
data from India is lacking. Aim: The aim of this study was to analyze the epidemiological
and clinical profile of TNBCs at our institute. Materials and Methods: This was the
retrospective study carried out in Tertiary Cancer Care Center in South India. Case files
of all breast cancer patients were reviewed from the hospital database registered in 1 year
and TNBC patients were selected for the study. Patient’s characteristic, treatment, and
histological features were analyzed. Results: A total of 322 patients were registered
during the period of 1 year and 26% (84/322) of total patients were TNBC. Median age
of presentation was 44.5 years. About 94% (79/84) of patients had first full‑term delivery
before the age of 30 years. The most common presenting symptom was left sided breast
lump. Locally advanced and early breast cancer (EBC) was 51% (43/84) and 42% (36/84),
respectively. Metastatic breast cancer was seen in five patients. The highest numbers of
patients were node negative disease (36.9%) [31/84], followed by N1 30.95% (26/84).
Most of the patients had high‑grade tumor. 94% (34/36) of cases of EBC had undergone
upfront modified radical mastectomy. Invasive ductal carcinoma was the predominant
histology except one who had medullary carcinoma. Twenty‑four patients received
neoadjuvant chemotherapy (NACT). There was no pathological complete remission, but
all patients responded to NACT. Metastatic disease was seen in five patients. All patients
had bone metastasis. Conclusions: TNBCs are highly aggressive subtype, with high grade
with limited treatment options and very poor prognosis. Incidence is more in our country
than the western literature. Even in our country also the incidence is varies in different
region. TNBCs are significantly associated with young aged patients. There was a lack of
association between tumor size and lymph node positivity.

Keywords: Breast cancer, Triple negative, Invasive ductal carcinoma

Introduction cancer among females in urban India.[1] With development of

various modern technologies, with collaboration of pathology
Breast cancer is the most common female cancer and the leading and genetic study, breast cancer now no more considered as
cause of cancer deaths worldwide. It is the most common homogenous disease, it is a very heterogeneous disease despite
their common tissue of origin. Research in molecular pathology
and molecular genetics have shown a number of distinct
Access this article online
subtypes of breast cancer. Currently, only a limited number
Quick Response Code:
of clinical, pathologic, and molecular factors help clinicians
Website: www.amhsr.org make decisions on therapy selection and evaluate prognosis
at the time of diagnosis. Depending on gene expression data,
DOI:
breast cancer divided into five subtypes, consist of luminal
***** A and luminal B, HER‑2 expressing, basal‑like, and normal
breast‑like.

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 Lakshmaiah, et al.: Triple negative breast cancer

Triple negative breast cancers (TNBCs) are a group of primary distant metastasis. MBC was defined as any breast cancer
breast cancers, which lack the expressions of the estrogen with evidence of distant metastasis.
receptor (ER), the progesterone receptor (PR) and HER‑2,
in addition to being positive for basal cytokeratin (CK) 5/6 Results
or epidermal growth factor receptor (EGFR). Although the
triple‑negative phenotype has been considered as sufficient to A total of 322 patients were registered during the period
identify the “basal‑like” tumors, increasing evidence has shown of 1 year and 26% (84/322) of total patients were TNBC
the terms “basal‑like” and “TNBCs” are not synonymous.[2] on immunohistochemistry analysis of receptor status.
The definition of basal‑like breast cancers has been evolving Median age of presentation was 44.5 years with range of
and though there are no universally agreed upon criteria to 22-67 years. 72.6% (61/84) of patients were <50 years of
define it, the panel developed by Nielsen et al.[3] are generally age [Table 1]. 22% (19/84) patients were age ≤35 years.
accepted in practice ‑ basal‑like cancers are negative for The median age of menarche was 14 years. More number
hormone receptors (HRs) and HER‑2, in addition to being of patients (62%) [52/84] was rural background than
positive for CK5/6 or EGFRs. Various studies have been urban (38%) [32/84]. All patients were married in our present
reported in western literature on TNBCs, all highlighting the study and the median age of first full‑term pregnancy was
poor prognosis of this subtype of breast cancer. However, 22 years with minimum age of 15 years and maximum age was
extensive data from India is lacking. The aim of this study was 32 years except four who were nullipera. About 94% (79/84) of
to analyze the epidemiological and clinicopathological profile patients had first full term delivery before the age of 30 years.
of TNBCs at our institute. The most common presenting symptom was breast lump. Left
sided (58.3%) [49/84] was more common than the right side.
Materials and Methods Bilateral breast cancer was found in eight patients, five patients
had synchronous bilateral breast cancer and three patients had
This was the retrospective study carried out in Tertiary metachronous breast cancer. The median duration of symptom
Cancer Care Center in South India. Case files of all breast was 3 months. The average number of children was 2.4. History
cancer patients were reviewed from the hospital database of breastfeeding was present in 94% (79/84) patients. Family
registered in 1 year (August 2012 and July 2013) and TNBC history of breast cancer was elicited only in two patients. In
patients were selected for study. Patient’s characteristic (age, one patient mother died of breast cancer at 40 years of age and
pre/postmenopausal status, family history of breast/ovarian/ other patient’s elder sister had breast cancer.
other cancer), treatment and histological features were
analyzed. Diagnosis of breast cancer was primarily based In our study, of 84 TNBCs 51% (43/84) were locally advanced
on clinical presentation, imaging (mammogram, ultrasound and EBC was seen in 42% (36/84) of cases. Metastatic
of breast) and histopathological studies. Staging was done breast cancer was seen in five patients [Table 2]. T2 diseases
with X‑ray chest, ultrasound abdomen for localized disease were the most common (35.7%) [30/84] and T1 disease
with the addition of bone scan and computed tomography was the least common (1.1%) [1/84] presentation. T3 and
for locally advanced disease and metastatic disease. Patients T4 diseases were seen in 33% (28/84) and 25% (21/84)
were staged in accordance with American Joint Committee of cases, respectively. The highest numbers of patients
on Cancer (AJCC)‑7 (tumor node metastasis) staging system.
TNBC was defined as ER negative, PR negative, and HER2
Table 1: Risk factors
neu negative cancers. These tests were carried out with
standard Food and Drug Administration approved kits by Factors Number of patients (%)
Age (years)
IHC. For each patient in the database, antibody staining
of a set of paraffin embedded slides for ER and PR was <50 61 (72.61)
>50 23 (27.38)
carried out. A HER‑2 report of 3 + by IHC was considered
Median age at menarche 14 years
to be positive. Those IHC score for HER‑2 neu were 2+,
Age at full‑term pregnancy (years)
confirmation was done by fluorescence in situ hybridization.
<30 79 (94.0)
HER‑2 score of 0 or 1 was considered negative. Baseline >30 5 (5.95)
epidemiological and tumor characteristics of triple Number of children
negative cancers were analyzed for all 84 patients. Patients Average 2.35
were broadly divided into three categories, early breast Maximum 6
cancer (EBC), locally advanced breast cancer (LABC), and Breastfeeding 79(94)
metastatic breast cancer. EBC has been defined as tumors No breastfeeding 5(5.95)
of not more than 5 cm diameter, with either impalpable or Menopausal status
palpable but not fixed lymph nodes and with no evidence Premenopausal 50 (59.52)
of distant metastases. This corresponds to tumors that are Postmenopausal 34 (40.47)
T1‑2, N0‑1, M0 according to AJCC‑7. LABC was defined Family history of breast cancer/ 2 (1 mother at 40 years
as T‑stage ≥T3 and/or N‑stage ≥N2 without any evidence of ovarian cancer died, 1 sister)

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 Lakshmaiah, et al.: Triple negative breast cancer

were node negative disease (36.9%) [31/84], followed by because it is associated with a poor clinical outcome highly
N1 (30.95%) [26/84], N2 (28.58%) [24/84] and least common aggressive disease and it has no specific systemic treatment.[4]
was N3 (3.57%) [3/84] [Table 3]. High‑grade tumor was seen However, clinical data on TNBC in Indian populations are
in 74 patients (88%) and 10 (11.9%) patients were Grade 2 limited. Thus, we investigated the clinicopathological features
disease. No Grade 1 tumor was seen. of lymph node‑negative TNBC in Indian women.

About 94% (34/36) of cases of EBC had undergone In our study, TNBC was 26%. In their study Carey et al.[5] they
upfront modified radical mastectomy. Breast conservation found that the prevalence of the TNBC subtype among patients
surgery was done in one patient. Invasive ductal carcinoma with breast cancer in the US was 26.4%; among non‑African
was the predominant histology except one who had American patients with breast cancer this prevalence was 23%.
medullary carcinoma. Tumor size 2.1-5 cm was seen Bauer et al.[6] have reported that in the US the prevalence of
in 66% (24/36) patients. 80% (29/36) were high‑grade TNBC breast cancer among patients with all forms of breast
tumors. Pathological node negative disease was seen in cancer was 12.4% and that this prevalence was highest among
69% (25/36) of EBC cases, which was followed by N1 nodal nonHispanic black patients with breast cancer, at 24.6%. In India,
status (16.7%) [6/36] [Table 4]. Perinodal spread was seen in the incidence of TNBC was varies from 12.5% to 29.8%[7‑9]
three case of lymph node positive disease. Lymphovascular
emboli in histopathology, which indicate poor prognosis, were The median age of our patients was 44.5 years, quite younger
seen in five patients. than the Western data. Dent et al.[4] have reported that the
median age of TNBC patients were 53 years. Younger median
Of 43 LABC patients, 24 patients received neoadjuvant age in Indian population was supported by another two Indian
chemotherapy (NACT). Anthracycline‑based chemotherapy studies.[7,8] This finding of younger median age most likely
was the most commonly used chemotherapeutic agents. Only reflects the general trend of breast cancers occurring a decade
one patient received taxane‑based chemotherapy. There was no earlier in Indian population than western data. In our study,
pathological complete remission, but all patients had clinical premenopausal patient was more than the postmenopausal.
and pathological responded to NACT [Table 5]. 26% of patients in our study were ≤35 years, which indicate
TNBC patients were younger than other types. Our result was
Metastatic disease was seen in five patients. All patients had supported by two Indian studies.
bone metastasis. Bone and visceral metastasis was seen in
three cases. One patient had brain metastasis at presentation. In our study, clinical Stage III diseases were common (51%)
followed by Stage II (41%). This result was favored by
Ram Prabu et al.[7] and Dent et al.[4] studies [Table 6]. It is
Discussion well‑known that in HR positive breast cancers, there is a
Molecular classification of breast cancer has revealed that breast definite increase in the incidence of lymph node positivity
cancer is a heterogeneous disease. This heterogeneity of the with increasing size of the tumor. This has been nicely
disease signifies the prognosis and response to therapy. Among highlighted in the study by Dent et al.[4] where they have
the subgroups of breast cancer, TNBC is particularly feared shown that in TNBCs even small tumors have a high chance
of lymph node positivity. In our study, the most of the
patients were node negative disease (36.9%), followed by
Table 2: Stage N1 (30.95%) and N2 (28.58%). N3 (3.57%) diseases were
Factors Number of patients (%) less number.
Clinical stage
I 1 (1.1)
II 35 (41.66) Table 4: Tumor size and lymph node status
III 43 (51.19) T status Positive node Negative node
IV 5 (5.95) 0-2 0 2
Early breast cancer 36 (42.85) 2.1-5 9 20
Locally advanced breast cancer 43 (51.19) >5 1 4
Metastatic breast cancer 5 (5.95)

Table 5: Respond to NACT

Table 3: T and N stage NACT Number of pCR PR PD
T stage Number (%) N stage Number (%) patients
T1 1 (1.1) N0 31 (36.90) Anthracycline‑based 23 0 23 0
T2 30 (35.71) N1 26 (30.95) Taxen+anthracycline 1 0 1 0
T3 28 (33.33) N2 24 (28.57) Total 24 0 24 0
NACT: Neoadjuvant chemotherapy, pCR: Pathologic complete response, PR: Partial
T4 21 (25) N3 3 (3.57) remission, PD: Progressive disease

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 Lakshmaiah, et al.: Triple negative breast cancer

Table 6: Comparison of various Indian and Western Acknowledgments

studies of triple negative breast cancer
Department of surgical oncology ,department of pathology
Ram Prabu Suresh Dent Present
and radiation oncology , kidwai memorial institute of
et al.[7] et al.[8] et al.[4] study
Incidence (%) 24.4 12.5 11.2 26
oncology.
Median age of 46.6 49 53 44.5
presentation (years) References
Stage (%)
I 2.8 13 9.8 1.1 1. ICMR Cancer Registry 2004: Consolidated Reports of the
PBCR and HBCR’s. ICMR; 2001‑2003. p. 13.
II 31.8 62 24.2 41.7
III 47.7 15 66 51.2 2. Badve S, Dabbs DJ, Schnitt SJ, Baehner FL, Decker T, Eusebi V,
IV 17.7 10 ‑ 5.9
et al. Basal‑like and triple‑negative breast cancers: A critical
review with an emphasis on the implications for pathologists
Grade (%)
and oncologists. Mod Pathol 2011;24:157‑67.
Low ‑ ‑ ‑ ‑
3. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z,
High 43 61 66 88
et al. Immunohistochemical and clinical characterization of the
basal‑like subtype of invasive breast carcinoma. Clin Cancer
Preoperative or NACT is an option in patients with early‑stage Res 2004;10:5367‑74.
and LABC. Neoadjuvant treatment had been compared with 4. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK,
standard, postoperative adjuvant chemotherapy in terms Sawka CA, et al. Triple‑negative breast cancer: Clinical
features and patterns of recurrence. Clin Cancer Res
of improving survival and facilitating local therapies. 2007;13:4429‑34.
Unfortunately, NACT does not improve overall survival 5. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D,
as shown in (NSABP) B18 trial.[10,11] NACT may convert Conway K, et al. Race, breast cancer subtypes, and
a unresectable, LABC to an operable tumor, [12‑14] and in survival in the Carolina Breast Cancer Study. JAMA
primarily operable tumors, down staging results in increase 2006;295:2492‑502.
chance of breast conservation rates.[10,15,16] The preoperative 6. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive
setting could provide an opportunity to study the impact analysis of estrogen receptor (ER)‑negative, progesterone
receptor (PR)‑negative, and HER2‑negative invasive
of systemic therapies on breast cancer biology.[17] TNBCs
breast cancer, the so‑called triple‑negative phenotype:
are known to be highly chemosensitive with higher A population‑based study from the California cancer Registry.
pCR rates than HRs positive tumors. In our study, of 43 Cancer 2007;109:1721‑8.
locally advanced patients 24 patients received NACT. 7. Prabu MP, Raina V, Shukla NK, Mohanti BK, Deo SV. A study
Anthracycline‑based chemotherapy was the most commonly of triple‑negative breast cancer at a Cancer Institute in India.
used chemotherapeutic agents. Only one patient received J Clin Oncol 2011;29:15. [Suppl; abstr e11548].
taxane‑based chemotherapy. There was no pathological 8. Suresh P, Batra U, Doval DC. Epidemiological and clinical
profile of triple negative breast cancer at a cancer hospital in
complete remission, but all patients responded to NACT.
North India. Indian J Med Paediatr Oncol 2013;34:89‑95.
9. Ghosh J, Gupta S, Desai S, Shet T, Radhakrishnan S,
In our study, metastatic disease was seen in five patients. All Suryavanshi P, et al. Estrogen, progesterone and HER2
patients had bone metastasis. Bone and visceral metastasis receptor expression in breast tumors of patients, and their
was seen in three cases. One patient had brain metastasis at usage of HER2‑targeted therapy, in a tertiary care centre in
presentation. The main limitation of our study was the lack of India. Indian J Cancer 2011;48:391‑6.
testing for basal CK5/CK6. Further, large scale prospective 10. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A,
trials incorporating basal CK markers and gene expression Fisher ER, et al. Effect of preoperative chemotherapy on the
outcome of women with operable breast cancer. J Clin Oncol
profiling are required for complete characterization of these 1998;16:2672‑85.
tumors and to identify a positive marker that can facilitate
11. van der Hage JA, van de Velde CJ, Julien JP, Tubiana‑Hulin M,
targeted therapy. Vandervelden C, Duchateau L. Preoperative chemotherapy
in primary operable breast cancer: Results from the European
Conclusion Organization for Research and Treatment of Cancer trial
10902. J Clin Oncol 2001;19:4224‑37.
Triple negative breast cancers are highly aggressive subtype, 12. Hortobagyi GN, Ames FC, Buzdar AU, Kau SW, McNeese MD,
with high‑grade with limited treatment options and very poor Paulus D, et al. Management of stage III primary breast cancer
with primary chemotherapy, surgery, and radiation therapy.
prognosis following progression after standard anthracycline or
Cancer 1988;62:2507‑16.
taxane regimens. TNBCs are more common in our country than
13. Danforth DN Jr, Lippman ME, McDonald H, Bader J, Egan E,
the western literature. Even in our country also the incidence is Lampert M, et al. Effect of preoperative chemotherapy on
varies in different region. TNBCs are significantly associated mastectomy for locally advanced breast cancer. Am Surg
with young aged patients. There was a lack of association 1990;56:6‑11.
between tumor size and lymph node positivity. 14. Schwartz GF, Birchansky CA, Komarnicky LT, Mansfield CM,

936 Annals of Medical and Health Sciences Research | Nov-Dec | Vol 4 | Issue 6 |
 Lakshmaiah, et al.: Triple negative breast cancer

Cantor RI, Biermann WA, et al. Induction chemotherapy Findings from National Surgical Adjuvant Breast and Bowel
followed by breast conservation for locally advanced Project B‑18. J Clin Oncol 1997;15:2483‑93.
carcinoma of the breast. Cancer 1994;73:362‑9. 17. Gralow JR, Burstein HJ, Wood W, Hortobagyi GN,
15. Semiglazov V, Eiermann W, Zambetti M, Manikhas A, Gianni L, von Minckwitz G, et al. Preoperative therapy
Bozhok A, Lluch A, et al. Surgery following neoadjuvant in invasive breast cancer: Pathologic assessment and
therapy in patients with HER2‑positive locally advanced systemic therapy issues in operable disease. J Clin Oncol
or inflammatory breast cancer participating in the 2008;26:814‑9.
NeOAdjuvant Herceptin (NOAH) study. Eur J Surg Oncol
2011;37:856‑63. How to cite this article: ????
16. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A,
Margolese RG, et al. Effect of preoperative chemotherapy on
local‑regional disease in women with operable breast cancer: Source of Support: Nil. Conflict of Interest: None declared.

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