|Year : 2015 | Volume
| Issue : 2 | Page : 333-339
Clinical outcome and survival of breast cancer patients treated at the Clinical Oncology Department, Menoufia University
Khaled K Abd Aziz, Eman A Tawfik, Ehab A Shaltout, Rasha A Mohamed Abdel Moneum MBBCh
Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||21-Sep-2013|
|Date of Acceptance||22-Dec-2013|
|Date of Web Publication||31-Aug-2015|
Rasha A Mohamed Abdel Moneum
Demonstrator of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Menoufia University, Quisna, Shebin El Kom, Menoufia, 32512
Source of Support: None, Conflict of Interest: None
The aim of the study was to evaluate the effect of clinicopathological features and treatment modalities on clinical outcome and survival of breast cancer patients.
Breast cancer is the most common malignancy among women in developed as well as in some developing countries. In Egypt, breast cancer constitutes 33% of all female cancer cases. Axillary nodal metastases, HER-2 status, stage of disease, and appropriate treatment are the most important factors affecting survival.
Patients and methods
This study included 972 patients with breast cancer who presented at the Clinical Oncology Department, Menoufia University, from January 2000 until December 2004. Data on patient and disease characteristics and treatment modalities were collected from files, and clinical outcome and survival data were reported.
It was found that the mean age of the patients was 48.55 years (range 23-86 years). Female patients represented 99% and male patients represented 1% of cases. Among the female patients, 52.3% were premenopausal and 46.7% were postmenopausal. Invasive ductal carcinoma (IDC) was the most common (94.2%) type of cancer. Stage III was the most frequently seen stage (46.7%), followed by stage II (39.5%). Modified radical mastectomy (MRM) was the most common type of surgery performed (91.4%).
In early-stage breast cancer (stages I and II), the median overall survival was 65 months and the median Disease free survival (DFS) was 55 months. There was a statistically significant correlation between overall survival and nodal status, HER-2 status, type of surgery, hormonal treatment, and site of relapse on univariate and multivariate analyses.
In stage III, the median overall survival was 42 months and the median DFS was 26 months.
In stage IV, the median overall survival was 17 months and the median progression-free survival was 10 months.
Axillary nodal metastases, HER-2 status, stage of disease, and appropriate treatment options are strong factors affecting the survival of breast cancer patients.
Keywords: breast cancer, clinical outcome, survival
|How to cite this article:|
Abd Aziz KK, Tawfik EA, Shaltout EA, Mohamed Abdel Moneum RA. Clinical outcome and survival of breast cancer patients treated at the Clinical Oncology Department, Menoufia University. Menoufia Med J 2015;28:333-9
|How to cite this URL:|
Abd Aziz KK, Tawfik EA, Shaltout EA, Mohamed Abdel Moneum RA. Clinical outcome and survival of breast cancer patients treated at the Clinical Oncology Department, Menoufia University. Menoufia Med J [serial online] 2015 [cited 2020 Feb 17];28:333-9. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/333/163881
| Introduction|| |
Worldwide, breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women. Breast cancer accounts for 29% of new cases of cancer and 15% of cancer-related deaths and is second only to lung cancer as a cause of cancer-specific death  .
In Egypt, breast cancer constitutes 33% of all female cancer cases in the Egyptian National Cancer Institute (NCI)  .
Breast cancer is a heterogeneous disease with different molecular drivers regulating its growth, survival, and response to treatment  .
Molecular classification of breast cancer is based on the pattern of expression of hormone receptors and HER-2; luminal tumors (or HR positive) and the remaining triple-negative breast cancer  .
Histologically, the most common type of breast cancer is IDC and it represents 70% of all breast cancer cases, followed by invasive lobular carcinoma (ILC), which represents about 25%, and special subtype of breast cancer, which represents about 5% according to the predominant cell  .
Numerous prognostic factors for breast cancer have been identified, which include nodal status, tumor size, presence of distant metastasis, and hormone receptor status. These different prognostic factors stratify the patient's risk and the disease outcome  .
Most of the women with breast cancer receive a combination of treatment. For women at stage I, II, or III, the main goal of treatment is to treat the cancer and prevent its recurrence, and for women at stage IV the goal of treatment is to improve symptoms and help them live longer  .
The recent decrease in breast cancer-related death has been attributed to early diagnosis and improvement in breast cancer treatment. According to the best available data, there are huge variations in incidence, mortality, and survival between different countries and regions. Among the many complex factors underlying these variations is the population structure - for example, lifestyle, environment, and socioeconomic status  .
The tumor structure - such as pathological tumor size, histological grade, lymph node state, hormonal state, and HER-2 status, and more recently molecular markers and gene expression profiling - has a major effect in breast cancer survival. It is also influenced by the use of appropriate treatment modalities including surgery, postoperative radiation, adjuvant systemic chemotherapy and/or hormonal therapy, or targeted therapies  .
| Patients and methods|| |
This retrospective study included 972 patients with breast cancer who presented at the Clinical Oncology Department, Menoufia University Hospital, over 5 years from January 2000 until December 2004. Data were collected from files up to December 2010 and included patient characteristics (age, sex, family history, and menopausal state for females), disease characteristics (histopatholoical type, tumor size, grade, nodal status, extracapsular extension, lymph vascular invasion, hormonal status, HER-2/neu state, and stage), and treatment modalities offered (surgery, chemotherapy, radiotherapy, hormonal therapy, treatment offered for metastatic disease, and chemotherapy-related toxicities).
The clinical outcome and survival were reported with comments on relapse, type of relapse, site of metastasis, and overall survival (OS).
Data were analyzed using statistical package for social science (SPSS, version 16; SPSS Inc., Chicago, Illinois, USA) program for Windows. Two types of statistics were ascertained: descriptive statistics and analytical statistics. Progression-free survival was analyzed using the Kaplan-Meier curves. It was calculated from the date of diagnosis to the date of progression or death (all causes), whichever occurred first, and patients who did not show progression at last follow-up were censored. Differences between groups were assessed by means of the log-rank test. Two-sided P-values less than 0.05 were considered statistically significant.
| Results|| |
This retrospective study included 972 patients with breast cancer; the mean age was 48.55 years (range 23-86 years). Female patients represented 99% and male patients represented 1% of cases. Among the female patients 52.3% were premenopausal and 46.7% were postmenopausal [Table 1].
An analysis of the disease characteristics in our study [Table 2] showed that IDC was the most common histological subtype, representing 94.2% of patients, and grade II for nodal status was seen in 76.5.%. The most common was N1 representing 38.2% of patients, and T2 lesions were seen in 55.9%.
Stage III was the most common stage at diagnosis, representing 46.7% of patients, ER+ and partial response (PR+) status was seen in 57.6%, and HER-2/neu status was positive in 20.2% of patients.
For treatment options and survival analysis the patients were classified on the basis of stage into three groups: stages I and II (early breast cancer), stage III, and stage IV.
Early-stage breast cancer
Locally directed therapy including MRM was performed in 91.8% of patients, whereas body condition scoring (BCS) was performed in 8.2 and 88.2% of patients received postoperative radiotherapy.
Systemic therapy included adjuvant chemotherapy in which anthracycline-based chemotherapy was the most common type of chemotherapy received by the patients and represented 91.5% of patients, followed by adjuvant hormonal therapy in which tamoxifen (TAM) was received by 84.4% of patients and aromatase inhibitors by 11.1%.
As regards survival analysis there was a statistically significant correlation between median OS and N stage, HER-2/neu status, type of surgery, and type of adjuvant hormonal therapy (P = 0.036, 0.044, 0.000, and 0.041, respectively) [Figure 1] and [Figure 2].
|Figure 1: Kaplan– Meier curve showing the correlation between overall survival and N stage|
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|Figure 2: Kaplan– Meier curve showing the correlation between overall survival and HER-2/neu status.|
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There was no statistically significant correlation between OS and T stage and hormonal status (P = 0.897 and 0.833, respectively) [Figure 3].
|Figure 3: Kaplan– Meier curve showing the correlation between overall survival and T stage.|
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Multivariate analysis using Cox regression test was used for OS and N stage, surgery, site of relapse, adjuvant hormonal therapy, adjuvant radiotherapy, and adjuvant chemotherapy (P = 0.012, 0.036, 0.003, 0.079, 0.192, and 0.187, respectively, and hazard ratio 2.031, 0.517, 0.691. 0.513, 1.730, and 0.696, respectively) [Table 3].
|Table 3 Stepwise Cox regression multivariate analysis for overall survival in early-stage breast cancer|
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Locally advanced breast cancer (stage III)
Locally directed therapy including MRM was performed in 96.5% of patients, followed by BCS in 3.5%. Seventeen (3.7%) patients did not undergo surgery, and 96.3% were diagnosed by excisional biopsy and postoperative radiotherapy.
Systemic therapy includes chemotherapy in which anthracycline-based chemotherapy was the most common type of chemotherapy received by the patients in the adjuvant and neoadjuvant setting, representing 93.9 and 51.4%, respectively, followed by hormonal therapy in which TAM represented 84.1% and aromatase inhibitors represented 9.7% of patients.
The median OS was 42 months, and there was a statistically significant correlation between OS and stage of breast cancer (P = 0.000) [Figure 4].
|Figure 4: Kaplan– Meier curve of overall survival for all stages breast cancer|
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Metastatic breast cancer stage IV
Locally directed therapy including palliative irradiation was received by 61 (59.8%) patients; 43 (70.5%) patients received palliative irradiation to bone metastases, 11 (18%) patients received palliative irradiation to the breast, and seven (11.5%) patients received palliative irradiation to the brain.
Systemic therapy included palliative chemotherapy, received by 85 (83.3%) patients, and hormonal therapy, in which TAM was given to 50.6% and aromatase inhibitors were given to 49.4%; 17 (16.7%) patients did not receive chemotherapy.
The median OS was 17 months and there was no statistically significant correlation between OS and site of metastasis (P = 0.321).
| Discussion|| |
The mean age of 48.55 years for breast cancer patients in this study is similar to the mean age of breast cancer incidence in Egypt. According to the Egyptian NCI, it is about 49.6 years  , which is similar to that reported from other institutions of developing countries such as Pakistan. The mean age has been reported as 48 years by Malik  . This is considerably lower than that reported by developed countries and about one and a half decade earlier than that of patients in developed countries like the USA and Australia. A report of a diverse population with invasive breast cancer at the Boston University Medical School from 1998 to 2006  showed a median age of 58 years compared with 48.55 years in our study; this is explained by differences in ethnicity and genetic background.
The age of the women at the time of diagnosis of breast cancer in the present study is different from that of the developed world. The most striking difference between the developing and the developed world is the early peak age at presentation, which is 40-50 years in the former compared with 60-70 years in the latter  .
The stage at presentation of breast cancer is a major determinant of the patient's survival after treatment. In our study stage I patients represented 3.3%, stage II patients represented 39.5%, stage III represented 46.7%, and stage IV patients represented 10.5% of the study population; thus, it can be seen that most of the patients presented with stage III cancer.
This is consistent with the stage presentation in developing countries. Most patients in Egypt had advanced disease at presentation (stages III-IV constituted 68% of all breast cancer cases)  . The rates are high in Oman as well (50.8%)  .
There is a sharp contrast with developed countries in terms of established screening programs. During the year 2006, invasive cancers diagnosed at stages I, II, III, and IV represented 56%, 37%, 5%, and 2%, respectively, in Stockholm, Sweden  . In the USA, stages III and IV collectively accounted for only 10% of patients, whereas 57-61% of patients presented at stage I  .
The striking difference in the stage distribution of breast cancer patients in developing and developed countries has been largely attributed to the lack of screening facilities, delays in seeking medical attention, poor socioeconomic status, poor healthcare systems, poor screening, and poor therapeutic facilities.
In our study, IDC is the most frequently seen (94.2%), followed by ILC (3.5%) and some rare variants (2.3%). The frequency of IDC in our patients is higher and the frequency of ILC is lower than that found in developed countries. About 70-80% of patients had IDC and 5-15% had ILC in developed countries  .
As regards tumor grade, in our study, grade II was the most frequently seen grade (76.5%), followed by grade III (21.6%) and grade I (1.6%). This coincides with the observation from other developing countries like Tunisia in which grade II was the most frequently seen grade (57.2%), followed by grade III (31.4%), and grade I (11.4%)  .
As regards survival analysis in our study for early-stage breast cancer, the median OS was 65 months (95% confidence interval) and the median DFS was 55 months (95% confidence interval).
Lymph node status, tumor size, histological grade, HER-2/neu status, and hormonal receptor expression status are reported to be the main prognostic factors associated with breast cancer  .
In our study, the univariate Kaplan-Meier analysis demonstrated that there is a statistically significant correlation between OS and N stage (P = 0.036). The 5-year survival for patients with node-negative disease (N0) was 66% compared with 52% for patients with 1-3 positive nodes (N1).
There are other studies that support this observation; Li et al.  showed a significant correlation between OS and nodal status (P<</i>0.0001), and 5-year survival for patients with node-negative disease (N0) was 94% compared with 86% for N1. In other studies by Sivridis et al.  and Fisher et al.  5-year survival for patients with node-negative disease was 82.8% compared with 73% for N1 disease.
There was a statistically significant difference between N stage and site of relapse (P = 0.022).
The 5-year survival for our patients is lower than that of developed countries because of limited early screening programs, lack of treatment facilities, and financial problems.
In a study by Li et al.  there was significant correlation between OS and size of the tumor (P < 0.0001); 5-year survival for patients with T1 was 92%, for T2 was 84%, and for T3 was 43%.
This is not consistent with the results of our study in which there was nonsignificant correlation between OS and T stage (P = 0.897). The univariate Kaplan-Meier analysis for patients with T1 and T2 is overlapped and crossed [Figure 3], indicating similar survival without significant difference; 5-year survival for patients at T1 and T2 was 58% compared with 50% for T3.
In a study conducted by Debarshi et al.  , in Kolkata, India, a statistically significant correlation was found between hormonal status and OS (P = 0.0007). In all, 91.7% of patients with ER-positive tumor survived for 5 years compared with 70.3% with ER-negative tumors, in contrast with our study in which there was no significant correlation between hormonal status and OS (P = 0.833); 54% of patients with ER-positive tumor survived for 5 years compared with 48% of those with ER-negative tumors.
HER-2/neu is a prognostic marker for predicting survival and outcome of breast cancer  .
In our study there was a statistically significant correlation between OS pattern for 5 years and the HER-2/neu status (P = 0.044). Better OS was observed for patients with HER-2/neu-negative tumors; the median OS was 44 months (40%) compared with 36 months (28%) for HER-2/neu-positive tumors. Our results are similar to those of a study in Kolkata (India), which found a statistically significant association between survival pattern for 5 years and HER-2/neu status (P = 0.00001); 100% of patients with HER-2/neu-negative tumors survived for 5 years compared with 36.8% with HER-2/neu-positive tumors  . It should be noted that our patients did not receive Herceptin because of financial problems and unavailability of targeted therapy.
As regards survival from stage III breast cancer, the median OS was 42 months (95% confidence interval) and the DFS was 26 months (95% confidence interval).
There was a gradual decrease in observed survival with an increase in the clinical stage of the disease; the 5-year survival from stage III was 34% and is similar to the results of another study by Debarshi et al.  in which survival was significantly affected by the clinical stage of the disease as at stage I nine (100%), stage II 22 (95.7%), stage III 41 (83.7%), and stage IV two (40%) (P = 0.006).
In our study, the median OS for metastatic breast cancer was 17 months. Our results were similar to those reported by many previous studies in which the median survival ranged between 16 and 34 months  , and also similar to the result reported from Tunisia in which the median survival was 18 months  .
The OS was, respectively, 76, 25, and 5% at 1, 2, and 3 years, compared with the result of a study conducted in Tunisia in which the OS was, respectively, 63, 42, and 26% at 1, 2, and 3 years  , showing lower OS in the second and third years in our study because of late presentation and traditional beliefs of our patients and their families.
In our study there was no significant correlation between the site of metastasis and OS (P = 0.321). The estimated median OS for bone, visceral, CNS, and disseminated metastases was 17, 11, 14, and 13 months, respectively. Nonvisceral localizations have a better prognosis than do visceral sites  . Our study confirmed these results in which bone metastasis had better OS compared with other sites. The median OS for bone metastasis was 17 months compared with 11 months for visceral and 14 months for central nervous system (CNS) metastasis.
| Conclusion|| |
Markers of poor prognosis for survival were increasing number of positive lymph nodes, stage of disease, and HER-2 status. Clinical outcomes and survival associated for each prognostic marker were inferior when compared with those of developed countries because of low level of awareness, lack of screening programs, and late access to treatment because of financial problems and interruption of administration of treatment.
Population-based screening programs, outreach mammography, improvements in technical expertise and quality of care, and standardized treatment regimens in a tax-funded healthcare system need to be developed for countries with limited resources.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]