T. Siddiqui  ( Departments of Medicine, The Aga Khan University Hospital Karachi. )
M. Sabih  ( Departments of Medicine, The Aga Khan University Hospital Karachi. )
A. Salam  ( Departments of Surgery, The Aga Khan University Hospital Karachi. )
S. Khan  ( Departments of Medicine, The Aga Khan University Hospital Karachi. )

Objective: To determine the overall survival of metastatic breast cancer in the Pakistani patients and compare it with published information.
Method: The design was a retrospective analysis of metastatic breast cancer patients from breast cancer database. A total of 137 patient based information was available for review and analysis.
Results: An overall median survival of 2.83 years was noted in metastatic breast cancer patients. Conclusion: This survival figure in this study compares favorably to those published in the literature (JPMA 51:120;2001).

Metastatic breast cancer (MBC) or Stage IV breast cancer is a major medical problem, which is not curable with the currently available therapies¹. Besides medical issues a significant amount of time, emotional energy and financial resources are required for its management. Therefore decision making is a medical challenge in such cases. The medical oncologist is helped in managing MBC by the knowledge of individual disease characteristics, which are known to be of prognostic significance in such a setting. Race and ethnic origin are recognized as significant prognostic factors for the outcome of many diseases including breast cancer². In the United States, black populations do worse stage for stage, than the white women with breast cancer^3,4. Breast cancer tends to present at a more advanced stage in Pakistan than what is seen the West. Factors, which contribute to the advanced stage of presentation, include poor socioeconomic circumstances, social taboos and a general lack of education leading to poor! treatment choices. Additionally the biological nature of the disease in Pakistan may be different from that reported in the literature⁵. The factors, which may contribute to these differences, include race, ethnicity, nutritional factors and perhaps interfamily marriages.
Clinicians practicing in South Asia feel that the outcome of breast cancer as a whole is poor in their part of the world. In order to understand the differences of biological behavior between different ethnic communities, a stage for stage comparison would be helpful between such groups. It may be particularly relevant to study MBC since current treatments do not prolong life substantially in this setting and the behavior of the disease itself may be a major factor which determines the ultimate outcome of survival^1,6. This study reports the survival of patients with MBC from a single tertiary care institution in Pakistan.

The records of all patients diagnosed to hance MBC between 1987 to 1999, were retrieved from the database of the Section of Oncology at the Aga Khan University Hospital in Karachi. The data was entered on a predesigned Proforma with a total of 84 variables. Only those variables, which were considered relevant for the study, were analyzed. Patients’ charts were evaluated for the endpoints of either survival or death. In those instances where this information was not available from the records, patients or other family members were contacted at home either by telephone or a letter. In 15 cases no information was retrievable and thus they were excluded from the analysis. The data was analyzed on SPSS for Windows version 8 by a qualified statistician (AS). Results were expressed as numbers (percentage) and mean ± standard deviation. Median Survival was calculated using the Kaplan-Meier method.

A total of 137 evaluable cases with histopathologically proven metastatic breast cancer of all subtypes were identified. Their mean age was 47.9±12.8 years. Eighty nine percent were married, 48.6 % were premenopausal and 51.4% postmenopausal, and 18.8% had a family history of breast cancer either in their first or second-degree relatives. There was a history of ovarian cancer in 3.6% of the cases.
Pathological features The mean size of the primary lesion available in 89 cases was 5.3cms±3.9. This size exceeds the mean size in the overall database which measures 4.5 cms. The tumor was well differentiated in 8.6%, moderately differentiated in 59.3% and poorly differentiated in 32.1%. Tumor grade was available in 81 cases. The original tumor size was TI in 4.5%, T2 in 28.4%, T3 in 32.8% and T4 in 34.3% of 89 cases. The estrogen receptor (ER) status was 34.4% negative, 24.4%weakly positive, 18% intermediate positive and 23.2% strongly positive. The progesterone receptor (PR) status by contrast was negative in 78.9%, weakly positive in 13.2% and strongly positive in 7.9%. Special molecular markers were done in approximately 20% of the cases only.
Sites of metastatic disease A chest X-ray or a CT scan, was normal in 68.5% and 24.3% of the cases showed metastatic pulmonary involvement with an additional 7.2% of the cases showing a pattern of lymphangitic carcinomatosis. Hepatic involvement was documented mostly by an ultrasound examination of the abdomen or in a few cases by a CT examination. In 70.9% the scan was normal and 29.1% showed abnormalities consistent with hepatic metastasis. An MRI or a CT scan of the head was done in 11 cases of which 7 cases (63.6%) showed cerebral metastasis. Bone scanning with Tc 99 showed metastatic involvement of the skeleton in 53.2% cases, 42.9% were normal and in 3.9% the results were indeterminate. Soft tissue metastasis was documented by a physical examination in 15% of cases.
Treatment: Numerous single agents and combinations were used in these 137 cases. Tamoxifen was used in 69% of the cases, in 22.6% megesterol acetate was used, an additional 8.4% of the cases had other hormonal combinations, including aminogluthemide and letrazole. Chemotherapy was used in 80.3% (110) of the cases only. The types of agents used were based on physician preferences. In any given case however more than one chemotherapeutic regimen was often used. In these 110 cases, in order of frequency of chemotherapy use, MMM (Mitomycin, Mitoxantrone, Methotrexate) was prescribed in 28.2%, CMF (Cyclophosphamide, Methotrexate, 5-Flourouracil) 16.3%, FAC (5-Flourouracil, Adriamycin, Cyclophosphamide)8. 1%, CA (Cyclophospham ide, Adriamycin 2.7%, FEC (5-Flourouracil, Epirubicin ,Cyclophosphamide)11%, Navelbine 5.4%, NA (Navelbine and Adriamycin) 2.7%, Taxanes 5.4%. A variety of other combinations were used in 20.2% of the cases including high dose chemotherapy with stem cell rescue as second line salvage therapy in all cases. All patients with brain metastasis were offered brain irradiation at nearby radiotherapy centers. Local radiation therapy to targeted areas for palliative purposes was used when clinically indicated.
Survival A median survival of 2.83 years was observed in this series with a standard error of 0.18 and 95% confidence interval of 2.49-3.18. As the graph indicates there were some long survivors as well. One patient having metastatic breast cancer survived for more than nineteen years (Figure).

Metastatic cancer of the breast is currently an incurable disease with a reported median survival of approximately two to three years. It is a hetrogenous disease and the inter play of a number of factors results in variations of the outcome in an individual patient. Some of these are the age of a patient, estrogen and progesterone receptor status and visceral involvement especially the liver. Patients with only bone metastasis do better than the other subtypes with a niedian survival of four years or more^1,7. In any given case however predictions of outcome are difficult and the treating physician relies very heavily on the published survival data in diverse situations to formulate a treatment plan. When confronted with such a case the physician has to be aware of some statistical figures in order to rationally discuss the treatment options with a patient and her family. The general treatment of MBC consists of hormonal therapy and chemotherapy with supportive care keeping in view the quality of life issues. Despite the vast number of agents available today to treat MBC there is very little clear cut evidence that different treatment modalities prolong life substantially¹. In a Japanese study the median survival time of patients was 28 months in 315 cases treated at the National Cancer Hospital in Tokyo⁸. In this study even though the number of patients are still relatively modest a median survival of 2.8 years is within an acceptable reported range with only one long time survival. This is probably more due to the nature of the disease biology than the treatments used. The general perception amongst physicians in Pakistan and Asia in general, except for the advanced Asian countries like Japan, is that women patients with MBC do poorly because of late presentation. The US SEER data however indicates that Asian women as a whole may do better for outcomes than either white or black women⁹. The patients in this series had patterns of metastatic disease, which were comparable to the other published reports 8, Chemotherapy in MBC is used in many ways, yet appears to have little impact on survival as such. In this study, treatments ranged from single agents to high dose chemotherapy with stem cell rescue. In this series a median survival of 2.8 years of the group as a whole is comparable to what is reported from the West. Large-scale studies are however needed to confirm this observation.

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