CLINICAL BEHAVIOUR OF METASTATIC TRIPLE NEGATIVE BREAST CARCINOMA: AN INSTITUTIONAL REVIEW

Abhash Shankar 1 , PuneetNagpal 1 , Budhi Singh Yadav 1 , DivyaDahiya 2 , Rajinder Singh 2 and Sushmita Ghoshal 1 . 1. Department Of Radiotherapy, Pgimer Chandigarh. 2. Department Of General Surgery, Pgimer Chandigarh. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


ISSN: 2320-5407
Int. J. Adv. Res. 5 (6), 2301-2307 2302 Introduction:-Breast cancer is the most common cancer in women [1]. It has been divided into various subtypes depending upon oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. ER-positive comprises about 70% of cases while ER-negative breast cancer constitutes approximately 40% [2,3,4]. HER2/neu oncogene is amplified in about 15-20% of breast cancer cases [2]. Triple negative breast cancer (TNBC) is a type of breast cancer that does not express any of the markers and accounts for about 10-15% of all cases.
TNBC in general are aggressive in nature as compared to other subtypes [5].Histologically TNBC comprises of cells having high proliferation rate, are generally poorly differentiated, and, in most cases harbour mutations in the TP53gene [6,7,8].
The aim of the present study is to evaluate the clinical characteristics and outcomes of patients with metastatic triple negative breast cancer treated at our institute in last three years.

Pretreatment Evaluation:-
Diagnosis of all cases was based on biopsy specimens. Staging was based on physical examination, USG whole abdomen, Chest radiograph and bone scan.
Management:-All patients were managed by multimodality treatment, which includes chemotherapy, radiation therapy and surgery. Chemotherapy:-Chemotherapy consisted of 6 cycles of FAC chemotherapy, [F =5 FLOURO URACIL 600mg/m2 bolus injection (day 1) + A = doxorubicin 50 mg/m2 in a 1-hour infusion (day 1) + C = cyclophosphamide 600 mg/m2 as bolus injection (day 1) ] either in the neo-adjuvant or adjuvant setting. Cycles were administered at 3-week intervals. Paclitaxel[175mg/m2] for 4 cycles was added after 4 cycles of FAC depending upon patients affordability Evaluation of response to chemotherapy was performed either by physical examination or imaging, after the induction chemotherapy.
Surgery:-Surgery in the form of Breast conserving surgery(BCS) or radical like total mastectomy(TMAC) depending upon the patient's preference or tumor status was planned as a primary treatment in some patients or after induction chemotherapy depending upon the response.

Radiation:-
For patient who underwent TMAC radiation dose of 35Gy/40Gy in 15 fractions was given to chest wall and supraclavicular area respectively. The dose to patients undergoing BCS was 40Gy/40Gy in 16 fractions to whole breast and supraclavicular area respectively followed by boost to tumor bed of 10Gy in 5 fractions.
For patients with metastatic disease at presentation, 6 cycles of palliative chemotherapy with either FAC alone or 4 cycles of FAC followed by 4 cycles of paclitaxel were planned. Local radiotherapy was given with radical or palliative intent depending upon response to chemotherapy.
After treatment, patients were followed by physical check-ups. Additional studies, including if necessary biopsy, were performed when indicated. Outpatients were followed every 3 months for 2 years and then twice a year.

Statistical Analysis:-
In this retrospective study, frequency tables with counts and percentages were used to describe pre-treatment and treatment characteristics of the patients. Disease free survival (DFS) and Local control rates (LC) were calculated by the Kaplan-Meier method using statistical software SPSS for windows (version 19.0). Table 1 shows the patient profile and treatment given. The median age of presentation is 45 years(range 28-81 years).37.1% of the patients were <40 years of age while 62.9% were >40 years of age.51.6% of the tumors were right sided with most common involved quadrant being the upper outer(41.9%) 82.3% of the patients had T3-4 tumors.79% of the patients had nodal positivity.15 patients(24.2%) had metastatic disease at presentation with most common site of metastasis being bone(40%) followed by liver(20%).
TNBC comprising of 13-25% of breast cancers have a highly aggressive nature than other breast cancer subtypes accounting for a large number of metastatic disease. In our study 82.3% of the patients had T3-4 tumors.79% of the patients had nodal positivity.24.2% had metastatic disease at presentation with most common site of metastasis being bone (40%) followed by liver (20%).
Chemotherapy is the standard treatment for TNBC. It is very sensitive to cytotoxic therapy despite its aggressive nature. After treatment with chemotherapy approximately 30-45% of patients achieve complete pathological response [15,16]. In this study 12% patients who underwent neoadjuvant chemotherapy followed by surgery had complete pathological response.
As reported in two studies done on TN breast cancer 6% of patients with early stage breast cancer had brain metastasis [17,18,19]. TNBC and HER2-positive breast cancers were associated with high rates of local recurrence in comparison to other groups as shown in a meta-analysis of studies comparing breast cancer subtype and loco 2304 regional recurrence [20].Patients with TNBC have a poor prognosis as compared to luminal subtypes and this difference was most common in the first 2 years after diagnosis [21].This is in comparison with the present study which shows at median follow up period of 23 months, out of 62 patients, 34 (54.8%) patients failed the treatment. Majority of the failures (25 out of 34), were distant (40.32%). 3 patients (4.8%) had both local and distant failure, and 6(9.7%) failed locally. The most common site of distant failure was Brain (14.52%), followed by liver(11.29%) and lung (11.29%).
The 1 year, 2 year and 5 year local control rates were 91.3%, 73% and 37 % respectively. The median time to local failure was 12.5 months. The 1 year, 2 year and 5 year disease free survival were 84.9%, 72.3% and 13.5% respectively. The median time to any failure was 11 months. This is consistent with findings from the previous studies which shows that the chances of developing metastases is more common in the first 2 years after diagnosis with a decline after the fifth year [22,23,24,25].

Conclusion:-
Molecular subtyping of breast cancer is commonly done now a day as it helps in predicting the tumor behaviour and guiding further treatment. TNBCs present in younger women show variable response to chemotherapy and carry the worse prognosis. There are high chances of developing CNS metastases, especially in the first 5 years of diagnosis.