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  Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 55  |  Issue : 4  |  Page : 344-347
 

Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experience


1 Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medical Oncology, Fortis Memorial Research Institute, Gurgaon, Haryana, India
3 Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
4 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
5 Department of Radiation Oncology, Fortis Memorial Research Institute, Gurgaon, Haryana, India
6 Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication28-Feb-2019

Correspondence Address:
Ajay Gogia
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_428_18

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 ╗ Abstract 


BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer and accounts for 10%–15% of all breast cancers in the west. There is a scarcity of data on ILC from the Indian subcontinent. This report intends to present the patterns of care, survival outcomes, and prognostic factors of ILC treated in a tertiary care institute. MATERIALS AND METHODS: This retrospective analysis included consecutive patients diagnosed with ILC and registered at our Institute between 2009 and 2016. RESULTS: We included 97 patients with a median age of 53 years (range 28–80). American Joint Committee on Cancer (7th edition) stage distribution was stage I-8.24%, stage II-45.36%, stage III- 34.10%, and stage IV-12.30%. Bilateral breast cancer was seen in 8 cases. Estrogen receptor, progesterone receptor, and HER 2/neu positivity was 90%, 85%, and 9%, respectively. Triple-negative breast cancer constituted 5% of cases. Twenty-nine events were recorded (systemic and locoregional relapse) with a median follow-up of 3.5 years. Three years relapse-free survival (RFS) and overall survival were 80% and 60%, respectively. Bones were the most common site of metastasis. Ageá<45 years [HR-1.4 (0.8–2.1), P < 0.001] and advanced clinical tumor stage [T4, HR-2.1 (1.1–3.8), P = 0.001] were associated with poor RFS. CONCLUSION: ILC constituted 2.5% of breast cancer cases at our institute. Triple negativity and HER-2/neu positivity were seen in 9% and 5% of cases, respectively. Ageá<45 years and advanced clinical tumor stage were associated with poor RFS.


Keywords: Invasive lobular carcinoma, outcome, pathological characteristics


How to cite this article:
Gogia A, Raina V, Deo SV, Shukla NK, Mathur S, Mohanti BK, Sharma DN. Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experience. Indian J Cancer 2018;55:344-7

How to cite this URL:
Gogia A, Raina V, Deo SV, Shukla NK, Mathur S, Mohanti BK, Sharma DN. Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experience. Indian J Cancer [serial online] 2018 [cited 2019 Jun 16];55:344-7. Available from: http://www.indianjcancer.com/text.asp?2018/55/4/344/253294





 ╗ Introduction Top


Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer and accounts for 10%–15% of all cases.[1] ILC differs from invasive ductal carcinoma (IDC) in clinic-pathological features, molecular biology, and natural history of the disease.[2] ILC is frequently associated with older age, larger tumor size, lower histologic grade, and positive hormone receptor status.[2] ILC is more prone to spread to gastrointestinal (GI), peritoneal, and ovarian tissues.[3] Genomic profiling of ILC is also distinct in terms of high frequency of CDH1 mutations, loss of phosphatase and tensin homolog, activation of AKT, and mutations in TBX3 and FOXA1.[4] Several studies have demonstrated that the overall long-term outcome for patients diagnosed with ILC might be better, similar, or worse than for patients diagnosed with IDC.[2],[5] There is a scarcity of data on ILC from India. To identify the prognosis and treatment outcome, we have performed a retrospective analysis.


 ╗ Materials and Methods Top


In this retrospective study, we included consecutive patients diagnosed with invasive lobular breast cancer and registered at Institute Rotary Cancer Hospital (I.R.C.H) of All India Institute of Medical Sciences between January 2009 and December 2016. The last follow-up of all patients was done till 31st January 2017. Those diagnosed with mixed ductal lobular histology and incomplete file records (5 cases) were excluded from the study. Patients' details were collected from our computer database and patients' files from medical records section using international classification of disease code-50. This protocol was approved by the ethical committee of the Institute.

The usual work-up for these patients included a complete hemogram, biochemistry, bilateral mammogram, and 2D-ECHO. As a part of the metastatic work-up, the patients with locally advanced breast cancer underwent a contrast-enhanced computed tomography and bone scan, whereas patients with early breast cancer underwent a chest X-ray and ultrasonography of the abdomen and pelvis. Immunohistochemical (IHC) testing to determine estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu receptor status was performed using standard procedures on 4-μm sections of paraffin-embedded tissue specimens stained with the monoclonal antibodies (1:400;Thermo, USA), (1:400;Spring, USA), and (1:100;Thermo, USA) for ER, PR, and HER-2/neu, respectively. Nuclear staining >1% of tumor cell was considered as positive for ER and PR. Patients were considered HER-2-positive, if they had IHC 3+ or fluorescence in situ hybridization was amplified (more than 6 copies of HER-2/neu gene or HER-2/neu: CEP17 ratio of more than 2 by DAKO Hercep test). Overall survival (OS) was defined as the time period between diagnosis and death from any cause. Relapse free survival (RFS) (only for non-metastatic patients) was defined as the time period from diagnosis to the occurrence of relapse. Patients who did not experience any event/death or lost to follow-up were censored for survival analysis. Baseline categorical variables were analyzed using Chi-square test or Fisher's exact test. Non-categorical variables were analyzed using t test or Mann-Whitney test. RFS 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. The Cox proportional hazards model was used to calculate hazard ratios. Estimates were considered statistically significant for values of P < 0.05. Stata 14.0 software was used for statistical analysis.


 ╗ Results Top


We included 97 patients during the study period. The common descriptive baseline characteristics of these patients are presented in [Table 1]. The median age at diagnosis was 53 years (range 28–80 years). Only one case of male breast cancer with ILC histopathology was diagnosed during the study period. Of the 96 women included in the study, 54 (56.2%) patients were postmenopausal. The most common symptoms were breast lumps followed by pain, nipple retraction, ulcer, and bleeding. The median duration of symptoms was 7 months. The median clinical tumor size was 5.1 cm. The clinical stage distribution was stage I-8 (8.24%), stage II-44 (45.36%), stage III-33 (34.02%), and stage IV-12 (12.37%). ER, PR, and HER-2/neu positivity was seen in 90%, 85%, and 9% of patients, respectively. Triple negative breast cancer constituted 5% of our cohort. After a median follow-up of 3.5 years, 29 cases developed metastasis. The most common sites for metastasis were bone (10 cases), liver (6 cases), GI/peritoneum/ovary (6 cases), lung (3 cases), brain and bone marrow (1 case each), locoregional (6 cases), and in combination (8 cases).
Table 1: Patient and disease characteristics

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The modified radical mastectomy (MRM) was done for 60 patients, whereas 15 patients underwent a breast conservation surgery. Twenty patients received neoadjuvant chemotherapy (NACT). Fifty-five patients received adjuvant chemotherapy. The remaining 22 patients received hormonal/endocrine therapy (16 patients with early breast cancer as adjuvant and 6 patients with metastatic breast cancer as palliative treatment). Sequential anthracycline and taxane [four cycles of FEC (5-fluorouracil 600 mg/m 2, epirubicin 75 mg/m 2, and cyclophosphamide 600 mg/m 2) followed by 4 cycles docetaxel (85 mg/m 2, 3 weekly) were used in most of the cases with curative intent. Out of 7 HER-2/neu positive cases, only one patient had received trastuzumab.

The median time to relapse was 30 months. Three years RFS (non-metastatic group) and OS was 80% and 60%, respectively. Ageá<45, clinical tumor size, clinical nodal stage, pathological tumor size, and pathological nodal stage were associated with poor RFS and OS in univariate analysis [Table 2]. Ageá<45 years and clinical tumor stage-T4 (for RFS) and pathological nodal stage (for OS) emerged as significant prognostic factors in multivariate analysis [Table 3].
Table 2: Univariate analysis of relapse free survival (RFS) in invasive lobular carcinoma

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Table 3: Multivariate analysis of relapse free and overall survival

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 ╗ Discussion Top


In our study, lobular carcinoma subtype constituted 2.5% of all histologic subtypes of breast cancer diagnosed in the study duration, which is less when compared to that reported in other series from western countries.[1] This discrepancy could be explained by ethnic and genetic differences between these populations. Another factor contributing to this difference could be that we excluded other variant subtypes such as ILC-IDC mixed type. The median age of diagnosis of ILC was 53 years in our study. It has been reported that ILC occurs more among older women than IDC. The median age for IDC in India is 47 years.[6] ILC is associated with good prognostic factors such as low Ki-67 expression, positive ER and PR expression, or/and low HER-2/neu amplification.[7] In our study, ER and PR were 90% and 88%, respectively, which is similar to published literature.[7] The frequency of aggressive immune-phenotypic expression: HER2-/neu and triple negativity were found in 9% and 5% of cases, respectively, which is less when compared with invasive ductal cancer.[6] Several studies with long-term follow-up have demonstrated that breast conservation therapy and MRM have comparable locoregional and survival for early stage breast cancer (IDC and ILC).[8],[9],[10] In our study, MRM was performed in the majority of cases. ILCs are more prone to spread to GI, peritoneal, and ovarian tissue.[11] This metastatic pattern might be different due to loss of expression of cell–cell adhesion molecule E-cadherin in ILC, but in our study, we found that bone was the most common site of systemic relapse, whereas GI, peritoneal, and ovarian metastasis were found in 6 cases. The majority of patients with ILC had a low-grade ER positive tumor and were therefore unlikely to derive significant benefit from either adjuvant therapy or NACT.[12],[13] In our study, we used NACT in 20 cases but with poor clinical and pathological outcomes.[14],[15] The 3-year RFS of IDC was 76% as compared to 80% for ILC.[6]

Recent studies have shown the understanding of the landscape of somatic mutations in ILC.[4],[16] These studies have found that mutations such as CDH1, RUNX1, TBX3, and FOXA1 are more prevalent in ILCs relative to IDCs. We could not perform mutation analysis in our study.

The limitations of this study was the small sample size, referral bias, and unavailability of complete histological profile regarding Ki-67, p53, and variants of ILC such as pleomorphic or alveolar.


 ╗ Conclusion Top


ILC constitutes 2.5% of all histopathologic subtypes of breast cancer at our institute. Triple negative and HER-2/neu positive breast cancer were seen in 9% and 5% of cases, respectively. Ageá<45 years and advanced clinical tumor stage were associated with poor RFS. Bone is the most common site of metastasis. The role of FOXA1 and GATA3 genes in modulating the ER transcription program in ILC needs to be further investigated. Multicenter prospective clinical trials would be necessary to know predictive and prognostic factor to improve outcomes in ILC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 ╗ References Top

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Sledge GW, Chagpar A, Perou C. Collective wisdom: Lobular carcinoma of the breast. Am Soc Clin Oncol Educ Book 2016;35:18-21.  Back to cited text no. 1
    
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Rakha EA, Ellis IO. Lobular breast carcinoma and its variants. Semin Diagn Pathol 2010;27:49-61.  Back to cited text no. 2
    
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Wasif N, Maggard MA, Ko CY, Giuliano AE. Invasive lobular vs. ductal breast cancer: A stage-matched comparison of outcomes. Ann Surg Oncol 2010;7:1862-9.  Back to cited text no. 3
    
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Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, et al. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 2015;163:506-19.  Back to cited text no. 4
    
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Iorfida M, Maiorano E, Orvieto E, Maisonneuve P, Bottiglieri L, Rotmensz N, et al. Invasive lobular breast cancer: Subtypes and outcome. Breast Cancer Res Treat 2012;133:713-23.  Back to cited text no. 5
    
6.
Gogia A, Raina V, Deo SV, Shukla NK, Mohanti BK. Triple-negative breast cancer: An institutional analysis. Indian J Cancer 2014;51:163-6.  Back to cited text no. 6
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7.
Christgen M, Steinemann D, Kuhnle E, Kühnle E, Länger F, Gluz O, et al. Lobular breast cancer: Clinical, molecular and morphological characteristics. Pathol Res Pract 2016;212:583-97.  Back to cited text no. 7
    
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Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, et al. Prognosis after ipsilateral breast tumorrecurrence and locoregional recurrences in patients treated by breast conservingtherapy in five National Surgical Adjuvant Breast and Bowel Projectprotocols of node-negative breast cancer. J Clin Oncol 2009;27:2466-73.  Back to cited text no. 8
    
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Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. Effect of radiotherapy after breast-conservingsurgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 2011;378:1707-16.  Back to cited text no. 9
    
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Fodor J, Major T, To´th J, Sulyok Z, Polgár C. Comparison of mastectomy with breast-conservingsurgery in invasive lobular carcinoma: 15-year results. Rep Pract Oncol Radiother 2011;16:227-31.  Back to cited text no. 10
    
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Metzger Filho O, Giobbie-Hurder A, Mallon E, Gusterson B, Viale G, Winer EP, et al. Relative effectiveness of letrozole compared with tamoxifen for patients with lobular carcinoma in the BIG1-98 trial. J Clin Oncol 2015;33:2772-9.  Back to cited text no. 11
    
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Truin W, Voogd AC, Vreugdenhil G, van der Heiden-van der Loo M, Siesling S, Roumen RM. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer. Ann Oncol 2012;23:2859-65.  Back to cited text no. 12
    
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Moreno-Elola A, Aguilar A, Roman JM, Hernandez A, Martin M, Diaz Rubio E, et al. Prognostic factors in invasive lobular carcinoma of the breast: A multivariate analysis. A multicentre study after seventeen years of follow-up. Ann Chir Gynaecol 1999;88:252-8.  Back to cited text no. 13
    
14.
Gogia A, Raina V, Deo SV, Shukla NK, Mohanti BK. Taxane and anthracycline based neoadjuvant chemotherapy for locally advanced breast cancer: Institutional experience. Asian Pac J Cancer Prev 2014;15:1989-92.  Back to cited text no. 14
    
15.
Gogia A, Raina V, Deo SV, Shukla NK, Mathur S, Sharma DN. Neoadjuvant chemotherapy in locally advanced invasive lobular carcinoma: A limited institutional experience. South Asian J Cancer 2018;1:64-5.  Back to cited text no. 15
    
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Sikora MJ, Cooper KL, Bahreini A, Luthra S, Wang G, Chandran UR, et al. Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response. Cancer Res 2014;74:1463-74.  Back to cited text no. 16
    



 
 
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  [Table 1], [Table 2], [Table 3]



 

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