Locally Advanced Breast Cancer in Pakistani Women: What Is Different from Rest of the World and Why It Is Difficult to Manage

Locally Advance Breast Cancer refers to a heterogeneous group of breast cancer with locally extensive disease, which may or may not involve the nodes, without any distant metastases. The study was conducted at Faisalabad Medical University (FMU), Oncology, Allied Hospital Faisalabad (Pakistan). Data of 100 patients with LABC was collected. Demographics were recorded in the form of age, socio-economic status. In clinical data, time of presentation, family history of breast cancer, the presenting symptom in the form of lump, ulceration and other skin changes were noted. Histo-pathological variables including tumor size, histopathology, Bloom & Richardson grading, estrogen receptor (ER), progesterone receptor status (PR) and HER2 status. Results showed that after following a standard trimodality treatment approach in LABC patients, 30 percent died within two years. Disease free survival for more than two years was observed in only 25% of patients. Whereas, 70% patients had eventful (Recurrence/metastases) survival. This poor outcome was observed due to lack of health care facilities, awareness and poor socioeco-nomic status.


Introduction
Cancer is a leading cause of death globally and is responsible for an estimated 9.6 million deaths in the world. Breast cancer is most common among women. Lo-cally advanced breast cancer (LABC) is characterized by the presence of a large primary tumor (>5 cm) or involvement of internal mammary nodes (N1b) associated with or without skin or chest-wall involvement (T4) or with fixed (matted) axillary lymph nodes in the absence of any evidence of distant metastases. LABC may be the result of neglected tumors or if tumor is rapidly growing. These cancers are classified as stage II, lllA and lllB according to the AJCC staging system [1]. Asian countries have higher incidence of LABC compared to the western developed countries due to poor socio-economic status. In India and Pakistan, incidence of LABC is 30% -60%, Malaysia 50% -60% and Singapore 21%, while in USA only 10% -20% of all breast cancers present as LABC [2] [3] [4] [5]. Current recommendation for treating LABC are neo-adjuvant chemotherapy followed by surgery and radiation therapy; hormonal treatment is added for receptor positive disease and Transtuzuumab Therapy for Her2neu positive patients [6] [7] [8] [9]. Despite of multimodality approach outcome is still very poor. Compared to patients with early breast cancer, patients with LABC are at a significantly higher risk of local recurrence and distant metastases. Even in USA, the five year survival rate for women with LABC is 55% [2]. The present study focused at all such factors and their comparison with rest of world so that treatment strategies can be developed for Pakistani women.

Materials and Methods
The study was conducted at Allied Hospital Faisalabad. One hundred patients of locally advance breast cancer were treated during the year 2013 to 2015. The data was collected retro-spectively from medical record of patients which was present in the record room of hospitals Oncology Centre. Out of 100 patients, most of the patients had T3 or N2 disease. Demographics were recorded in the form of age and socio-economic status of the patients. In clinical data, time of presentation, family history of breast cancer, the presenting symptom in the form of lump, ulceration and other skin changes were noted. Histo-pathological variables studied including tumor size, Bloom and Richardson grading, estrogen receptor (ER) and progesterone receptor status (PR) and HER2neu status. All treatment variables were recorded. Patients were put on three-month follow-up for 2 years. The treatment pattern is described in Table 1. This table describe

Results
Patient's characteristics and presenting symptoms are summarized in Table 2(a) and Table 2(b). Median age was 45 years. Mostly patients were in the age group of 30 to 60 years. Family history of breast cancer was noted in four patient. Information regarding family history was missing in medical record of five patients. Median duration between noticing lump and seeking medical help was eight months. Tumor characteristics are mentioned in Table 3. All tumors were either grade ll or grade lll, 60% of patients were ER and PR receptors positive. They all receive hormone therapy. Twenty five percent patients (25%) were HER2neu positive. Only about 40 percent were affording for transtuzumab therapy. Five percent patients (5%) did not get their receptor status done.
Clinical outcome is mentioned in Table 4.

Discussion
We have observed poor outcome of LABC in Pakistani women as compared with developed countries. Although trimodality therapy has improved the outcome but still 30% of LABC patients died at the end of two years after completing their  Node positive 74% Table 4. Clinical outcome of patients.

Survival Frequency
Mortality within 2-years 30% Alive more than 2-years 70% Disease free survival for more than two years 25% Re-currence/metastases in those survived for more than 2-years 70% treatment. This number can be even more because some patients lost to follow up. Another study on Pakistani women also reported poor outcome [10]. It's very important to figure out causes of LABC and difficulties being faced by doctors to treat such cases consequently such information will help health authorities to develop plans to deal with LABC in public sector and oncologist to develop management strategies.
In literature, many studies have identified lack of awareness, fear, lower socioeconomic status and illiteracy as main factors leading to late presentation and ending up in Locally advanced disease [11] [12] [13] [14]. These factors are common among all developing countries including Paskistan [15]. Another important factor which could be the cause of locally advanced disease is its aggressive biological behavior as node positive disease was found in 74 percent patients after surgery. Secondly despite the fact that 60 percent were ER/PR receptor positive and they also received hormone therapy even then they develop recurrence or metastatic disease. Racial differences in biology of carcinoma breast have been well described. Japanese women tend to have less aggressive breast cancer among Asians [6]. Within USA Afro-Americans and Hispanic women have more aggressive disease as compare to others USA [7] [8]. Other factors which are compromising outcome are delay in seeking the treatment and unavailability of adequate oncological services [9] [16]. Surgical services are present in every tertiary care center in Pakistan but very few tertiary centers have parallel oncological services which further compromise the management of LABC patients in our pop-ulation. When we refer them to oncology centers after surgery, most patients get lost because of economic constraints and long waiting time at such centers. These factors are totally manageable so by increasing awareness and oncological facilities to improve the outcome.

Conflicts of Interest
There is no conflict of interest. This is a research/analysis based work.