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Survival analysis of 1148 women diagnosed with breast cancer in Southern Iran

  • Abbas Rezaianzadeh1, 2Email author,
  • Janet Peacock1, 2,
  • Daniel Reidpath1, 2,
  • Abdolrasoul Talei1, 2,
  • Seyed Vahid Hosseini1, 2 and
  • Davood Mehrabani1, 2
BMC Cancer20099:168

DOI: 10.1186/1471-2407-9-168

Received: 16 June 2008

Accepted: 05 June 2009

Published: 05 June 2009

Abstract

Background

While there has been much research regarding risk factors and prognostic factors for breast cancer in general, research specific to Iran is sparse. Further, the association between breast cancer survival and socio-demographic and pathologic factors has been widely studied but the majority of these studies are from developed countries. Southern Iran has a population of approximately 4 million. To date, no research has been performed to determine breast cancer survival and to explore the association between the survival and socio-demographic and pathologic factors in Southern Iran, where this study was conducted.

Methods

The data were obtained from the cancer registry in Fars province, Southern Iran and included 1148 women diagnosed with breast cancer between 2000 and 2005. The association between survival, and sociodemographic and pathological factors, distant metastasis at diagnosis, and treatment options was investigated using Cox regression.

Results

The majority of patients were diagnosed with an advanced tumour size. Five-year overall survival was 58% (95%CI; 53%–62%). Cox regression showed that family income (good vs poor: hazard ratio 0.46, 95%CI; 0.23–0.90) smoking (HR = 1.40, 95%CI; 1.07–1.86), metastases to bone (HR = 2.25, 95%CI; 1.43–3.52) and lung (HR = 3.21, 95%CI;1.70–6.05), tumour size (≤ 2 cm vs ≥ 5 cm: HR = 2.07, 95%CI;1.39–3.09) and grade (poorly vs well differentiated HR = 2.33, 95%CI; 1.52–3.37), lymph node ratio (0 vs 1: HR = 15.31, 95%CI; 8.89–26.33) and number of involved node (1 vs >15: HR = 14.98, 95%CI; 8.83–25.33) were significantly related to survival.

Conclusion

This is the first study to evaluate breast cancer survival in Southern Iran and has used a wide range of explanatory factors, 44. The results demonstrate that survival is relatively poor and is associated with diagnosis with late stage disease. We hypothesise that this is due to low level of awareness, lack of screening programs and subsequent late access to treatment.

Background

Breast cancer is the most commonly diagnosed malignancy among women in developed countries [13], and in some developing countries [46]. According to the report of the Iranian Centre for the Prevention and Control of Disease, Ministry of Health and Medical Education, 2000, Iran; breast cancer is the most prevalent cancer among Iranian women and accounts for 21.4% of all malignancies.

The prevalence of breast cancer in Europe and the USA is estimated between 8 to 10%. However, the lowest prevalence is seen in Asian countries, at about 1% [7]. In Iran the prevalence of breast cancer was reported as 6.7/1000 in 2002, which is even less than this [8]. While there has been substantial research published on risk factors and prognostic factors for breast cancer in general, research specific to Iran is sparse. Further, the association between breast cancer survival and socio-demographic and pathologic factors has been widely studied but the majority of these studies are from developed countries.

Iran has a total population of just over 70 million and almost all studies of breast cancer in Iran are from the capital, Tehran with a population of approximately 14 million. Most of these studies have not focused on survival and prognostic factors. To our knowledge, only two studies from Tehran have investigated breast cancer survival [9, 10]. Southern Iran has a population of approximately 4 million and to date no study has determined breast cancer survival in this region or explored the relationships between the survival and socio-demographic and pathological factors. This paper presents the results of a study which fills this gap by determining five-year breast cancer survival for women with breast cancer in Southern Iran, and the impact of 44 explanatory factors.

Ethical approval for this study was obtained from the Research Ethics Committee of Shiraz University of Medical Sciences, Iran, and the Research Ethics Committee of the School of Health Sciences and Social Care of Brunel University, UK.

Methods

This study used patients' records from Shiraz University Cancer Registry Centre, which is a hospital-based registry in a tertiary care centre which delivers oncology services to a population of approximately four million. This is the only centre which delivers oncology services in Southern Iran. Therefore, most probably all cancer patients come to this hospital for treatment. However a few of them may travel to other centers for treatment. The Cancer Registry was started on 1 January 2000 and so this study includes women who were diagnosed with breast cancer between 1 January 2000 and 31 Dec. 2005. During that period, of the 6253 patients diagnosed with ten most common cancers in the area, 1192 were registered as having female breast cancer. Thirty women were excluded due to previous breast cancer (23), ductal carcinoma in situ (2), and other previous cancers (5). In addition, 14 women with bilateral tumours were excluded due to the small numbers. Thus, the study population comprised 1148 women who were diagnosed with a first primary invasive breast malignancy and who underwent breast surgery including axillary dissection.

All patients were followed-up at regular three month intervals for the first year following diagnosis and had regular six month follow-ups thereafter. The last date of follow-up was 29th July 2006. All subjects in this study underwent surgery and received radiation and all except a very small proportion received chemotherapy. These three treatment options have been offered in three sequences: surgery followed by chemotherapy and then by radiation, chemotherapy followed by surgery and then by radiation, and surgery followed only by radiation, in common with current practice in this region. About 82% received surgery followed by chemotherapy and then by radiation, 16% chemotherapy followed by surgery and then by radiation, and 2% received surgery followed only by radiation. At the time of diagnosis all patients were evaluated for metastasis to five distant sites: bone, liver, lung, brain, and ovary.

The main objective of this study was to investigate the impact of a wide range of factors on breast cancer survival. Therefore, the only outcome considered here is survival. All variables recorded at the cancer registry (44) were used in this study. The 44 explanatory variables divide naturally into three groups: socioeconomic or demographic, clinical/pathological factors, and distant metastases.

The association between each of the explanatory variables and outcome was assessed in turn using Cox's regression (unifactorial analysis).

Variables that were significantly associated with survival were considered firstly in each of the three conceptual groups: socioeconomic and demographic factors together, clinical/pathological factors, and distant metastases. Each model included all variables from the particular group that were statistically significant unifactorially, and then the variable that had the greatest regression estimate p-value was removed from the model. This process continued by remodeling and repeating removal of the next variable with the greatest p-value until all variables left in the model had p-value less than 0.05. A final model was fitted by combining all variables which were statistically significant in the three groups separately.

The proportional hazards assumption was examined at all stages in two ways: i) visually by inspecting graphs of the cumulative baseline functions against log survival time and ii) by a test based on the Schoenfeld residuals.

The results are presented as hazard ratios and 95% confidence intervals. All analysis was conducted using Stata v9.

Results

Impact of socio-demographic factors on survival

Of the 1148 patients included in the analysis 859 were alive at the end of follow-up, 269 had died, and 20 were lost to follow-up. Median follow-up time, from first pathological diagnosis until the time of death or the end of study, was 34 months. Mean age at diagnosis was 47 years (ranged from 19 to 86 years).

In unifactorial analysis of all socioeconomic and demographic factors, only family income and smoking were significantly associated with survival. (Table 1) These two factors together were entered into the first model and both remained significant. Compared to the patients with a low family income those with a higher family income were at 54% lower risk of death. (Table 2) Smokers were also at a 40% higher risk of death compared to non-smokers.
Table 1

Uni-factorial analyses and distribution of socio-demographic factors

Unifactorial analysis

 

Distribution of factors

 

Hazard ratio (95%CI)

p

Numbers

%

Area of residence

  

1148*

100

   Affluent

1

0.179

213

19

   Middle

1.12 (0.79–1.58)

 

590

51

   Deprived

1.36 (0.95–1.94)

 

345

30

Family income

  

1143

99

   Low & poor

1

0.031

426

37

   Moderate

0.88 (0.69–1.13)

 

669

58

   High

0.44 (0.22–0.87)

 

48

4

Occupation

  

1148

100

   Housewife

1

0.853

898

78

   Non-manual

0.92 (0.67–1.28)

 

199

17

   Manual

1.07 (0.63–1.80)

 

51

4

Education

  

661

57

   Illiterate

1

0.939

203

18

   Primary

1.01 (0.65–1.58)

 

223

19

   High school

1.15 (0.71–1.85)

 

148

13

   University

1.00 (0.58–1.74)

 

87

7

Smoking

  

1145

100

   Non-smoker

1

0.009

904

79

   Smoker

1.44 (1.09–1.89)

 

241

21

Marital status

  

1147

100

   Single

1

0.056

104

9

   Married

0.64 (0.44–0.93)

 

936

82

   Divorced & Widowed

0.77 (0.46–1.28)

 

107

9

Blood group

  

408

36

   O

1

0.739

153

13

   A

1.18 (0.71–1.95)

 

105

9

   B

1.32 (0.80–2.19)

 

100

9

   AB

1.08 (0.53–2.20)

 

45

4

BMI (Body Mass Index)

  

951

83

   <25

1

0.784

509

44

   25–30

1.10 (0.82–1.47)

 

317

28

   >30

1.09 (0.72–1.66)

 

125

11

No. of children

  

1143

100

   ≤ 3

1

0.218

571

50

   4–8

0.95 (0.74–1.22)

 

518

45

   >8

1.87 (1.18–2.96)

 

54

5

Age at diagnosis

  

1118

97

   ≤ 35 years

1

0.499

172

15

   36–49 years

0.96 (0.67–1.37)

 

519

45

   50–64 years

1.02 (0.69–1.50)

 

342

30

   ≥ 65 years

1.35 (0.82–2.22)

 

85

7

Age at first pregnancy

  

122

11

   ≤ 18 years

1

0.081

55

5

   19–25 years

0.30 (0.08–1.06)

 

47

4

   >25 years

0.21 (0.03–1.66)

 

20

2

OCP use

  

255

22

   ≤ 3 years

1

0.869

80

7

   >3 years

0.96 (0.59–1.57)

 

175

15

Ethnicity

  

1140

99

   Fars

1

0.821

1006

88

   Non-Fars

1.04 (0.73–1.48)

 

134

12

Religion

  

1147

100

   Islam (Shia)

1

0.931

1031

90

   Islam (Sunni)

0.93 (0.65–1.32)

 

110

9.5

   Others

1.23 (0-.)

 

6

0.05

Menarche age

  

938

82

   ≤ 13 years

1

0.934

561

49

   >13 years

0.99 (0.75–1.30)

 

377

33

History of BC in SDR

  

1148

100

   No

1

0.758

996

87

   Yes

0.94 (0.65–1.36)

 

152

13

History of BC in FDR

  

1148

100

   No

1

0.22

881

77

   Yes

0.83 (0.62–1.11)

 

267

23

Duration of breast feeding

  

205

18

   ≤ 3 years

1

0.175

78

7

   4–6 years

2.03 (0.96–4.29)

 

68

6

   >6 years

1.62 (0.71–3.69)

 

59

5

Abbreviations: OCP = Oral Contraceptive pill, BC = Breast Cancer, FDR = First Degree Relatives, SDR = Second Degree Relatives

* Total number available of 1148 subjects

Table 2

Multi-factorial analysis by three conceptual groups and final model

Variables from the other three multifactorial analyses

Result of final model

 

Hazard ratio (95%CI)

P

**

Hazard ratio (95%CI)

p

Family income

     

   Low & poor

1

0.039

99%

  

   Moderate

0.90 (0.70–1.15)

    

   Good

0.46 (0.23–0.90)

    

Smoking

     

   Non-smoker

1

0.016

99%

  

   Smoker

1.40 (1.07–1.86)

    

Metastasis to bone

     

   No

1

0.000

100%

  

   Yes

2.25 (1.43–3.52)

    

Metastasis to lung

     

   No

1

0.000

100%

  

   Yes

3.21 (1.70–6.05)

    

Tumour size

     

   ≤ 2 cm

1

0.000

88%

1

0.000

   >2 & <5 cm

1.43 (0.97–2.09)

  

1.43 (0.97–2.09)

 

   ≥ 5 cm

2.07 (1.39–3.09)

  

2.07 (1.39–3.10)

 

Tumour grade

     

   Well-differentiated

1

0.000

88%

1

0.000

   Moderately-differentiated

1.30 (0.88–1.93)

  

1.30 (0.88–1.93)

 

   Poorly-differentiated

2.33 (1.52–3.37)

  

2.33 (1.52–3.57)

 

No. of involved lymph nodes

     

   0

1

0.000

88%

1

0.000

   1–5

2.96 (1.78–4.94)

  

2.96 (1.78–4.94)

 

   6–10

5.29 (3.11–9.01)

  

5.29 (3.11–9.01)

 

   11–15

8.29 (4.98–13.80)

  

8.29 (4.98–13.80)

 

   >15

14.96 (8.83–25.33)

  

14.96 (8.83–25.33)

 

Lymph node ratio

     

   0

1

0.000

88%

1

0.000

   > 0 &≤ .3

2.02(1.30–3.13)

  

2.03 (1.09–3.76)

 

   > .3 &≤ .6

4.84 (2.72–8.60)

  

4.84 (2.72–8.60)

 

   > .6 &< 1

9.30 (5.48–15.80)

  

9.30 (5.48–15.80)

 

   1

15.31 (8.89–26.33)

  

15.31 (8.90–26.34)

 

** Proportion of subjects in multifactorial analysis

Impact of distant metastases on survival

Metastases to liver, lung and bone were all significantly associated with poorer survival in the unifactorial analyses (Table 3). Metastases to bone and lung remained significant in the multifactorial model. Compared to the patients without distant metastasis those with lung metastasis had just over three times, and those with bone metastasis had just over twice the risk of death (Table 2).
Table 3

Uni-factorial analysis and distribution of distant metastases

Unifactorial analysis

Distribution of factors

 

Hazard ratio (95%CI)

P

numbers

%

Metastasis to bone

  

1148

100

   No

1

0.001

1110

97

   Yes

2.18 (1.39–3.41)

 

38

3

Metastasis to liver

  

1148

100

   No

1

0.001

1134

99

   Yes

2.80 (1.48–5.27)

 

14

1

Metastasis to lung

  

1148

100

   No

1

0.001

1134

99

   Yes

3.06 (1.62–5.76)

 

14

1

Metastasis to brain

  

1148

100

   No

1

0.283

1142

99.5

   Yes

2.14 (0.53–8.63)

 

6

0.5

Impact of clinical/pathological factors on survival

Of 15 clinical/pathological factors, greater tumour size and higher grade, tumour calcification and necrosis, skin and nipple involvement, vascular and lymphatic invasion, higher number of excised and involved nodes, greater lymph node ratio (LNR), treatment, and type of surgery were significantly associated with poorer survival in the unifactorial analyses (Table 4). The factors that remained significant were tumour size, histological grade, number of involved nodes, and lymph node ratio. Patients with tumour size 5 cm and above had a two-fold increase in risk of death compared to the patients with tumour size 2 cm and less. Patients with poorly differentiated tumour grades had a doubling of risk of death compared to those with well differentiated tumour grades. There was a steady rise in risk with increased number of involved nodes ranging from a three-fold to a fifteen-fold increase in risk compared to node negative patients (Table 2). Hazard ratios increased steadily as the lymph node ratio increased with the hazard being greatest for patients with a ratio of one compared with zero.
Table 4

Uni-factorial analysis and distribution of clinico-pathological factors

Unifactorial analysis

Distribution of factors

 

Hazard ratio (95%CI)

p

numbers

%

Tumour side

  

1064

93

   Right

1

0.562

565

49

   Left

1.08 (0.84–1.39)

 

499

4

Tumour location

  

440

38

   Lateral

1

0.258

322

28

   Medial

0.75 (0.42–1.36)

 

68

6

   Central

0.60 (0.30–1.97)

 

50

4

Tumour size

  

1055

92

   ≤ 2 cm

1

0.000

298

26

   >2 & <5 cm

1.82 (1.30–2.70)

 

523

46

   ≥ 5 cm

3.04 (2.05–4.50)

 

234

20

Tumour grade

  

1059

92

   Well-differentiated

1

0.000

250

22

   Moderately-differentiated

1.89 (1.28–2.78)

 

637

55

   Poorly-differentiated

4.53 (2.99–6.86)

 

172

15

Nuclear grade

  

140

12

   Low

1

0.068

33

3

   Intermediate

10.88 (1.00–80.75)

 

91

8

   High

5.70 (0.59–54.90)

 

16

1

Co-morbidity

  

352

31

   GI&Respiratory

1

0.433

37

3

   Cardiovascular

0.92 (0.44–1.95)

 

122

11

   Psycho.&Neurological

0.69 (0.28–1.57)

 

55

5

   Gynaecologic

1.42 (0.61–3.29)

 

39

3

   Endocrine&Metabolic

1.13 (0.55–2.33)

 

99

9

No. of stillbirths

  

1097

96

   0

1

0.581

997

87

   1–3

1.19 (0.78–1.83)

 

92

8

   >3

1.48 (0.47–4.62)

 

8

1

No. of abortions

  

1106

96

   0

1

0.525

819

71

   1–3

0.85 (0.64–1.14)

 

269

23

   >3

0.80 (0.30–2.15)

 

18

2

Histological type

  

1062

93

   IDC

1

0.086

942

82

   ILC

0.68 (0.31–1.55)

 

33

3

   Med.C

0.35 (0.14–0.84)

 

60

5

   MLDC

1.55 (0-.)

 

3

<1

   Muc.C

0.65 (0.09–4.62)

 

6

<1

   IPC

1.33 (0.42–4.15)

 

10

1

   Met.C

3.31 (1.05–10.39)

 

8

1

No. of excised lymph nodes

  

1048

91

   0

1

0.007

20

2

   1–10

1.48 (0.46–4.74)

 

263

23

   11–20

1.93 (0.61–6.09)

 

553

48

   21–30

2.29 (0.713–7.37)

 

189

16

   >30

4.67 (1.28–17.03)

 

23

2

Lymph node ratio

  

1027

89

   0

1

0.000

331

29

   >0 & ≤ .3

1.98 (1.06–3.66)

 

246

21

   >.3 & ≤ .6

5.24 (2.96–9.29)

 

156

14

   >.6 & < 1

11.26 (6.68–18.96)

 

185

16

   1

18.87 (11.09–32.08)

 

109

9

No. of involved lymph nodes

  

1046

91

   0

1

0.000

349

30

   1–5

3.03 (1.82–5.04)

 

346

30

   6–10

6.59 (3.89–11.15)

 

146

13

   11–15

10.16 (6.13–16.84)

 

123

11

   >15

18.78 (11.21–31.45)

 

82

7

Tumour calcification

  

1022

89

   No

1

0.000

740

64

   Yes

1.67 (1.28–2.19)

 

282

25

Tumour necrosis

  

317

28

   No

1

0.017

157

14

   Yes

1.82 (1.11–2.97)

 

160

14

Nipple involvement

  

995

87

   No

1

0.000

887

77

   Yes

1.84 (1.32–2.57)

 

108

10

Skin involvement

  

1013

88

   No

1

0.000

946

82

   Yes

2.06 (1.39–3.05)

 

67

6

Vascular invasion

  

1035

90

   No

1

0.000

604

53

   Yes

1.90 (1.47–2.46)

 

431

37

Lymphatic invasion

  

1006

88

   No

1

0.000

419

36

   Yes

3.73 (2.67–5.20)

 

587

52

Treatment

  

1134

99

   S&C&R

1

0.000

927

81

   C&S&R

1.86 (1.39–2.50)

 

178

16

   S&R

1.27 (0.56–2.87)

 

29

2

Type of surgery

  

1065

93

   MRM

1

0.000

649

57

   RM

1.09 (0.64–1.86)

 

62

5

   TM

1.60 (1.13–2.28)

 

99

9

   L

0.58 (0.37–0.90)

 

164

14

   Q

0.32 (0.14–0.73)

 

85

7

   PM

2.66 (0.85–8.36)

 

6

1

Abbreviations: IDC = Invasive Ductal Carcinoma, ILC = Invasive Lobular Carcinoma, Med.C = Medullary Carcinoma, MLDC = Mixed Lobular Ductal Carcinoma, Muc.C = Mucinous Carcinoma, IPC = Invasive Papillary Carcinoma, Met.C = Metaplastic Carcinoma, S&C&R = Surgery and Chemotherapy and Radiotherapy, C&S&R = Chemotherapy and Surgery and Radiotherapy, S&R = Surgery and Radiotherapy, MRM = Modified Radical Mastectomy, RM = radical Mastectomy, TM = Total Mastectomy, L = Lumpectomy, Q = Quadrantectomy, PM = Partial Mastectomy

We modeled all statistically significant variables of the three previous models together to explore how the effect of socio-demographic variables might influence survival. This analysis showed that while the effect estimates for all variables were virtually unchanged, the socio-demographic variables and bone and lung metastases became non-significant. (Table 2) We interpret this as showing that the effects of the real and measurable effects of socio-demographic factors on survival were expressed in tumour characteristics.

Using the life-table method, five-year overall survival of this study population was 58% (95%CI; 53%–62%). The three-year overall survival was 76% (95%CI; 73%–79%).

There was no evidence that the proportional hazards assumption was violated in any of the analyses reported above.

Discussion

This study has shown that of all socioeconomic factors only family income was associated with survival after adjustment for other factors. This is in agreement with other studies which obtained family income data by interviewing patients [1113] as in this study. However, other studies which have obtained income data from a census have shown no association [2, 14, 15].

Of all demographic factors assessed, only smoking was related to breast cancer prognosis in this study, showing an adverse effect on survival which remained significant after adjustment for income. Two other studies in the UK and Sweden found a similar result [16, 17]. It is perhaps surprising that income remains significant after adjusting for smoking. This may be a true effect or may be due to inadequate control for smoking using the binary data available – smoker/non-smoker. Exploratory analysis provided evidence that the effects of smoking and income on survival were mediated through adverse tumour characteristics.

The impact of young age at diagnosis on breast cancer survival has been long debated. This study found no evidence of a relationship between younger age at diagnosis and survival. Moreover age at diagnosis was not related to tumour characteristics. These findings accord with some studies [13, 18, 19] but not others [20, 21] although in the latter studies the age categorization and settings were different.

BMI was not significantly related to survival in agreement with Carmichael's study in 2004 [22]. However four other studies reported a higher risk of death in patients with BMI > 30 compared to those with BMI < 25 [2325]. The differences in findings for BMI in our study could be due to their late stage diagnosis for our study population.

This study found no evidence for a relationship between family history of breast cancer and survival and also observed that patients with positive and negative family history had similar tumour characteristics. This is consistent with the results of several other studies [21, 26, 27]. Our findings revealed that tumour size, histological grade, and lymph node status were associated with breast cancer survival after mutual adjustment. This result is consistent with some other studies [28, 29]. We found that poorly differentiated tumours carried a higher risk of death compared to well-differentiated tumours. Patients with tumour size 5 cm and above had a higher risk of death than those with tumour size 2 cm and less.

In this study lymph node status was investigated in three different ways: number of involved nodes, lymph node ratio, and number of excised nodes. The number of involved nodes and lymph node ratio were the most powerful predictors of survival on multifactorial analysis. According to our findings not only did node positive patients have a poorer survival rate compared to node negatives, but also as the number of involved nodes increased the risk of death increased too. A similar trend has been reported elsewhere [30, 31]. Lymph node ratio (LNR) was negatively correlated with survival in agreement with studies from Canada [32], Belgium [33, 34] and the USA [35]. The number of excised lymph nodes was non-significant after adjustment for other pathological factors.

This study found no association between histological type and survival in common with other works [29, 36]. We found no evidence for an effect of intra-mammary tumour location. However, three studies reported an adverse effect of medial location [37, 38], and three others reported that central location was a negative predictor of survival [39, 40] compared to other locations. These differences might be due to missing data in our study since data regarding tumour location was only available for about one-third of the women. Skin and nipple involvement, tumour calcification and necrosis, vascular and lymphatic invasion were negatively associated with survival, but these effects became non-significant after adjustment. We note that these factors were closely correlated with each other and also with tumour size and grade, and lymph node status which may explain our findings.

Patients who underwent surgery as the first treatment option had a better prognosis than those who were treated firstly by chemotherapy. It might be due to a larger tumour size; because, women with larger tumours or metastatic diseases at diagnosis were mostly treated with chemotherapy followed by surgery. Moreover, all patients with tumour size above 1 cm received chemotherapy, which is a standard practice at the institution of study. This practice may not be standard elsewhere and this difference in treatment may contribute to the relatively poor prognosis seen.

Most other studies have reported significant effects on survival of tumour size, histological grade, and lymph node status but for other pathological factors. Our findings differed a little which could be due to the adjustment we performed – other studies have tended to adjust for only a few pathological factors whereas in our study we included 13 pathological factors that were significantly associated with survival in unifactorial analysis.

Three- and five-year overall survival rates in southern Iran were found to be 76% and 58%, respectively. To our knowledge only two studies have previously reported 5-year overall breast cancer survival rates in Iran and these were 60% [9] and 62% [10]. These studies were conducted in Tehran. The 5-year overall survival rates in Iran compare with 46% in India [41], 64% in Oman [4], 65% in Greece [42], 71% in Germany [43], 78% in Belgium [41], 89% in the USA [44], and 84% in the UK [45] and show that Iran has considerably poorer survival than European countries and the United States.

There are several possible reasons for this. In Iran women's awareness of breast cancer is limited – Iranian women have little or no information regarding breast self examination and its effect on early detection and prognosis. A study of health staff in Tehran found that only 6 percent of them reported doing breast self examination on a regular basis [46] and a study in Middle Eastern Asian Islamic immigrant women in the USA reported that none did regular breast self-examination [47]. Although, Hackshaw, 2003, concluded that breast self-examination cannot improve survival after breast cancer, women who do it, are more aware of changes in their breast and seek care earlier if there is any problem [48].

There are strong cultural barriers which hinder Iranian women from consulting with a physician for sensitive female-specific health problems. Even highly educated women are reluctant to seek treatment for breast tumours. Further to this, access to cancer treatment units is slow, delaying diagnosis and there is no screening mammography. It seems probable that all of these factors increase the chances of delayed diagnosis and hence late stage disease which is the main difference between Iranian women and women in Western countries.

There are some limitations to this study. Data for some explanatory factors were missing and some were recorded in a wrong way that made them less useful. For example, for age at first pregnancy data were available for 122 patients and for OCP usage it was available for 255 patients. In relation to OCP usage it was recorded as usage of OCP for three years and less and for above three years. It was not clear whether the others had never used OCP or they had used it but they were not asked for any information. A proportion of subjects had received hormonal therapy, but no data regarding hormone receptor status and hormonal therapy were recorded in the registry and so this factor could not be investigated. Also the type of chemotherapy drugs, doses, and duration of chemotherapy was not recorded at the registry and was not analyzed in this study.

In relation to preexisting diseases, only one disease was recorded for each patient per GP visit and so there were no data on any other preexisting diseases. In addition, preexisting diseases were categorized into five categories: gastrointestinal and respiratory, cardiovascular, psychological and neurological, gynaecological, endocrine and metabolic. This categorization differs from the international classification of diseases, and other diseases such as musculoskeletal and skin diseases were not considered. Again it was not clear whether the patients did not have these diseases or they had but it was not recorded. All of these limitations have since been addressed for future data collection but cannot be remedied for the current study.

It is strength and a weakness that this is the first study based on cancer registry data in Shiraz University of Medical Sciences, where full data collection was begun in 2000. The strengths lie in the richness of the data with many potential predictor variables tested and the uniqueness of the findings for this population. The weakness is that only 5 years of data were available for analysis, giving a relatively small sample size of 1148 women. This therefore limits the statistical power of the study. With 1148 women and power 90%, significance level 5%, a hazard ratio of 1.4 can be detected. Therefore we acknowledge that this study has insufficient statistical power to detect effects which are smaller than this and so it is possible that smaller effects have been missed. In future years when more data have been gathered, power will be greater and smaller effects can be estimated with greater confidence. In addition, in future years, the follow-up period will be longer allowing survival to be estimated with greater precision and to allow the estimation of survival beyond the 5 years possible at this time.

Conclusion

In conclusion, the results presented in this study demonstrate a relatively low five-year overall survival rate for women diagnosed with breast cancer in Iran. Following the analysis of 44 explanatory factors, the results presented in this study suggests that survival from breast cancer in southern Iran is affected by delayed diagnosis and therefore late stage disease. We hypothesize that this is due to low level of awareness, cultural barriers and slow access to treatment. Further research is needed in Iranian women to test these hypotheses and thus design appropriate interventions to ultimately improve survival.

Declarations

Authors’ Affiliations

(1)
Nemazee Hospital Cancer Registry Center, Shiraz University of Medical Sciences
(2)
School of Health Sciences and Social Care, Brunel University

References

  1. Fisch T, Pury P, Probst N, Bordoni A, Bouchardy C, Frick H, Jundt G, De Weck D, Perret E, Lutz JM: Variation in survival after diagnosis of breast cancer in Switzerland. Ann Oncol. 2005, 16 (12): 1882-1888. 10.1093/annonc/mdi404.View ArticlePubMedGoogle Scholar
  2. Grau AM, Ata A, Foster L, Ahmed NU, Gorman DR, Shyr Y, Stain SC, Pearson AS: Effect of race on long-term survival of breast cancer patients: Transinstitutional analysis from an inner city hospital and university medical center. Am Surg. 2005, 71 (2): 164-170.PubMedGoogle Scholar
  3. Nagel G, Wedding U, Hoyer H, Röhrig B, Katenkamp D: The impact of comorbidity on the survival of postmenopausal women with breast cancer. Journal of Cancer Research and Clinical Oncology. 2004, 130 (11): 664-670. 10.1007/s00432-004-0594-3.View ArticlePubMedGoogle Scholar
  4. Al-Moundhri M, Al-Bahrani B, Pervez I, Ganguly SS, Nirmala V, Al-Madhani A, Al-Mawaly K, Mawaly C, Grant C: The outcome of treatment of breast cancer in a developing country – Oman. The Breast. 2004, 13 (2): 139-145. 10.1016/j.breast.2003.10.001.View ArticlePubMedGoogle Scholar
  5. Foo CS, Su D, Chong CK, Chng HC, Tay KH, Low SC, Tan SM: Breast cancer in young Asian women: Study on survival. ANZ J Surg. 2005, 75 (7): 566-572. 10.1111/j.1445-2197.2005.03431.x.View ArticlePubMedGoogle Scholar
  6. Kim KJ, Huh SJ, Yang JH, Park W, Nam SJ, Kim JH, Lee JH, Kang SS, Lee JE, Kang MK, Park YJ, Nam HR: Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy. Jpn J Clin Oncol. 2005, 35 (3): 126-133. 10.1093/jjco/hyi039.View ArticlePubMedGoogle Scholar
  7. Farooq S, Coleman MP: Breast cancer survival in south Asian women in England and Wales. J Epidemiol Community Health. 2005, 59 (5): 402-406. 10.1136/jech.2004.030965.View ArticlePubMedPubMed CentralGoogle Scholar
  8. Hadi N, Sadeghi-Hassanabadi A, Talei AR, Arasteh MM, Kazerooni T: Assessment of a breast cancer screening programme in Shiraz, Islamic Republic of Iran. East Mediterr Health J. 2002, 8 (2–3): 386-392.PubMedGoogle Scholar
  9. Mousavi SM, Mohaghegghi MA, Mousavi-Jerrahi A, Nahvijou A, Seddighi Z: Burden of breast cancer in Iran: A study of the Tehran population based cancer registry. Asian Pac J Cancer Prev. 2006, 7 (4): 571-574.PubMedGoogle Scholar
  10. Vahdaninia M, Montazeri A: Breast cancer in Iran: A survival analysis. Asian Pac J Cancer Prev. 2004, 5 (2): 223-225.PubMedGoogle Scholar
  11. Aziz Z, Sana S, Akram M, Saeed A: Socioeconomic status and breast cancer survival in Pakistani women. J Pak Med Assoc. 2004, 54 (9): 448-453. 18PubMedGoogle Scholar
  12. Crowe JP, Patrick RJ, Rybicki LA, Grundfest-Broniatowski S, Kim JA, Lee KB: Race is a fundamental prognostic indicator for 2325 northeastern Ohio women with infiltrating breast cancer. Breast J. 2005, 11 (2): 124-128. 10.1111/j.1075-122X.2005.21564.x.View ArticlePubMedGoogle Scholar
  13. Gordon NH: Socioeconomic factors and breast cancer in black and white Americans. Cancer Metastasis Rev. 2003, 22 (1): 55-65. 10.1023/A:1022212018158.View ArticlePubMedGoogle Scholar
  14. Bradley CJ, Given CW, Roberts C: Race socioeconomic status, and breast cancer treatment and survival. J Natl Cancer Inst. 2002, 94 (7): 490-496.View ArticlePubMedGoogle Scholar
  15. Lagerlund M, Bellocco R, Karlsson P, Tejler G, Lambe M: Socio-economic factors and breast cancer survival – a population-based cohort study (Sweden). Cancer Causes Control. 2005, 16 (4): 419-430. 10.1007/s10552-004-6255-7.View ArticlePubMedGoogle Scholar
  16. Fentiman IS, Allen DS, Hamed H: Smoking and prognosis in women with breast cancer. Int J Clin Pract. 2005, 59 (9): 1051-1054. 10.1111/j.1742-1241.2005.00581.x.View ArticlePubMedGoogle Scholar
  17. Manjer J, Andersson I, Berglund G, Bondesson L, Garne JP, Janzon L, Malina J, Matson S: Survival of women with breast cancer in relation to smoking. European Journal of Surgery. 2000, 166 (11): 852-858. 10.1080/110241500447227.View ArticlePubMedGoogle Scholar
  18. Beenken SW, Urist MM, Zhang Y, Desmond R, Krontiras H, Medina H, Bland KI: Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer. Ann Surg. 2003, 237 (5): 732-738. 10.1097/00000658-200305000-00016.PubMedPubMed CentralGoogle Scholar
  19. Chia SK, Speers CH, Bryce CJ, Hayes MM, Olivotto IA: Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies. J Clin Oncol. 2004, 22 (9): 1630-1637. 10.1200/JCO.2004.09.070.View ArticlePubMedGoogle Scholar
  20. Golledge J, Wiggins JE, Callam MJ: Age-related variation in the treatment and outcomes of patients with breast carcinoma. Cancer. 2000, 88 (2): 369-374. 10.1002/(SICI)1097-0142(20000115)88:2<369::AID-CNCR18>3.0.CO;2-E.View ArticlePubMedGoogle Scholar
  21. Harris EER, Schultz DJ, Peters CA, Solin LJ: Relationship of family history and outcome after breast conservation therapy in women with ductal carcinoma in situ of the breast. International Journal of Radiation Oncology*Biology*Physics. 2000, 48 (4): 933-941. 10.1016/S0360-3016(00)00726-4.View ArticleGoogle Scholar
  22. Carmichael AR, Bendall S, Lockerbie L, Prescott RJ, Bates T: Does obesity compromise survival in women with breast cancer?. The Breast. 2004, 13 (2): 93-96. 10.1016/j.breast.2003.03.002.View ArticlePubMedGoogle Scholar
  23. Berclaz G, Li S, Price KN, Coates AS, Castilione-Gertsch M, Rudenstam CM, Holmberg SB, Lindtner J, Erien D, Collins J, Snyder R, Thurlimann B, Fey MF, Mendiola C, Werner ID, Simoncini E, Crivellari D, Gelber RD, Goldhirsch A, International Breast Cancer Study Group: Body mass index as a prognostic feature in operable breast cancer: The international breast cancer study group experience. Ann Oncol. 2004, 15 (6): 875-884. 10.1093/annonc/mdh222.View ArticlePubMedGoogle Scholar
  24. Dignam JJ, Wieand K, Johnson KA, Fisher B, Xu L, Mamounas EP: Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst. 2003, 95 (19): 1467-1476.View ArticlePubMedPubMed CentralGoogle Scholar
  25. Loi S, Milne RL, Friedlander ML, McCredie MR, Giles GG, Hopper JL, Phillips KA: Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14 (7): 1686-1691. 10.1158/1055-9965.EPI-05-0042.View ArticlePubMedGoogle Scholar
  26. Eccles D, Simmonds P, Goddard J: Familial breast cancer: An investigation into the outcome of treatment for early stage disease. Fam Cancer. 2001, 1 (2): 65-72. 10.1023/A:1013867917101.View ArticlePubMedGoogle Scholar
  27. Gonzalez-Angulo AM, Broglio K, Kau SW, Eralp Y, Erlichman J, Valero V, Theriault R, Booser D, Buzdar AU, Hortobagyi GN, Arun B: Women age < or = 35 years with primary breast carcinoma: Disease features at presentation. Cancer. 2005, 103 (12): 2466-2472. 10.1002/cncr.21070.View ArticlePubMedGoogle Scholar
  28. D'Eredita' G, Giardina C, Martellotta M, Natale T, Ferrarese F: Prognostic factors in breast cancer: The predictive value of the Nottingham prognostic index in patients with a long-term follow-up that were treated in a single institution. European Journal of Cancer. 2001, 37 (5): 591-596. 10.1016/S0959-8049(00)00435-4.View ArticlePubMedGoogle Scholar
  29. Kuru B, Camlibel M, Gulcelik MA, Alagol H: Prognostic factors affecting survival and disease-free survival in lymph node-negative breast carcinomas. J Surg Oncol. 2003, 83 (3): 167-172. 10.1002/jso.10264.View ArticlePubMedGoogle Scholar
  30. Banerjee M, George J, Song EY, Roy A, Hryniuk W: Tree-based model for breast cancer prognostication.[see comment]. J Clin Oncol. 2004, 22 (13): 2567-2575. 10.1200/JCO.2004.11.141.View ArticlePubMedGoogle Scholar
  31. Gebauer G, Fehm T, Lang N, Jäger W: Tumor size, axillary lymph node status and steroid receptor expression in breast cancer: Prognostic relevance 5 years after surgery. Breast Cancer Research and Treatment. 2002, 75 (2): 167-173. 10.1023/A:1019601928290.View ArticlePubMedGoogle Scholar
  32. Truong PT, Berthelet E, Lee J, Kader HA, Olivotto IA: The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes. Cancer. 2005, 103 (10): 2006-2014. 10.1002/cncr.20969.View ArticlePubMedGoogle Scholar
  33. Vinh-Hung V, Burzykowski T, Cserni G, Voordeckers M, Steene Van De J, Storme G: Functional form of the effect of the numbers of axillary nodes on survival in early breast cancer. Int J Oncol. 2003, 22 (3): 697-704.PubMedGoogle Scholar
  34. Voordeckers M, Vinh-Hung V, Steene Van de J, Lamote J, Storme G: The lymph node ratio as prognostic factor in node-positive breast cancer. Radiother Oncol. 2004, 70 (3): 225-230. 10.1016/j.radonc.2003.10.015.View ArticlePubMedGoogle Scholar
  35. Katz A, Buchholz TA, Thames H, Smith C, McNeese M, Theriault R, Singletary S, Strom E: Recursive partitioning analysis of locoregional recurrence patterns following mastectomy: Implications for adjuvant irradiation. International Journal of Radiation Oncology*Biology*Physics. 2001, 50 (2): 397-403. 10.1016/S0360-3016(01)01465-1.View ArticleGoogle Scholar
  36. Arpino G, Bardou VJ, Clark GM, Elledge RM: Infiltrating lobular carcinoma of the breast: Tumor characteristics and clinical outcome. Breast Cancer Res. 2004, 6 (3): R149-56. 10.1186/bcr767.View ArticlePubMedPubMed CentralGoogle Scholar
  37. Colleoni M, Zahrieh D, Gelber RD, Holmberg SB, Mattsson JE, Rudenstam CM, Lindtner J, Erzen D, Snyder R, Collins J, Fey MF, Thürlimann B, Crivellari D, Murray E, Mendiola C, Pagani O, Castiglione-Gertsch M, Coates AS, Price K, Goldhirsch A: Site of primary tumor has a prognostic role in operable breast cancer: The international breast cancer study group experience. J Clin Oncol. 2005, 23 (7): 1390-1400. 10.1200/JCO.2005.06.052.View ArticlePubMedGoogle Scholar
  38. Gaffney DK, Tsodikov A, Wiggins CL: Diminished survival in patients with inner versus outer quadrant breast cancers. J Clin Oncol. 2003, 21 (3): 467-472. 10.1200/JCO.2003.12.047.View ArticlePubMedGoogle Scholar
  39. Gill PG, Birrell SN, Luke CG, Roder DM: Tumour location and prognostic characteristics as determinants of survival of women with invasive breast cancer: South Australian hospital-based cancer registries, 1987–1998. The Breast. 2002, 11 (3): 221-227. 10.1054/brst.2001.0400.View ArticlePubMedGoogle Scholar
  40. Kroman N, Wohlfahrt J, Mouridsen HT, Melbye M: Influence of tumor location on breast cancer prognosis. International Journal of Cancer. 2003, 105 (4): 542-545. 10.1002/ijc.11116.View ArticlePubMedGoogle Scholar
  41. Yeole BB, Kumar AV, Kurkure A, Sunny L: Population-based survival from cancers of breast, cervix and ovary in women in Mumbai, India. Asian Pac J Cancer Prev. 2004, 5 (3): 308-315.PubMedGoogle Scholar
  42. Keramopoullos A, Louvrou N, Iatrakis G, Ampela K, Michalas S: Clinical course and treatment results of breast cancer patients with ten or more positive axillary nodes. The Breast. 2000, 9 (1): 17-22. 10.1054/brst.1999.0116.View ArticlePubMedGoogle Scholar
  43. Dunst J, Steil B, Furch S, Fach A, Lautenschläger C, Diestelhorst A, Lampe D, Kölbl H, Richter C: Prognostic significance of local recurrence in breast cancer after postmastectomy radiotherapy. Strahlenther Onkol. 2001, 177 (10): 504-510. 10.1007/PL00002360.View ArticlePubMedGoogle Scholar
  44. Sant M, Allemani C, Berrino F, Coleman MP, Aareleid T, Chaplain G, Coebergh JW, Colonna M, Crosignani P, Danzon A, Federico M, Gafà L, Grosclaude P, Hédelin G, Macè-Lesech J, Garcia CM, Møller H, Paci E, Raverdy N, Tretarre B, Williams EM, European Concerted Action on Survival and Care of Cancer Patients (EUROCARE) Working Group: Breast carcinoma survival in europe and the united states. Cancer. 2004, 100 (4): 715-722. 10.1002/cncr.20038.View ArticlePubMedGoogle Scholar
  45. Tejler G, Norberg B, Dufmats M, Nordenskjold B: South East Sweden Breast Cancer Group. Survival after treatment for breast cancer in a geographically defined population. British Journal of Surgery. 2004, 91 (10): 1307-12. 10.1002/bjs.4697.View ArticlePubMedGoogle Scholar
  46. Haji-Mahmoodi M, Montazeri A, Jarvandi S, Ebrahimi M, Haghighat S, Harirchi I: Breast self-examination: Knowledge, attitudes, and practices among female health care workers in Tehran, Iran. Breast J. 2002, 8 (4): 222-225. 10.1046/j.1524-4741.2002.08406.x.View ArticlePubMedGoogle Scholar
  47. Rashidi A, Rajaram SS: Middle Eastern Asian Islamic women and breast self-examination. Cancer Nurs. 2000, 23 (1): 64-70. 10.1097/00002820-200002000-00010.View ArticlePubMedGoogle Scholar
  48. Hackshaw AK, Paul EA: Breast self-examination and death from breast cancer: a meta-analysis. British Journal of Cancer. 2003, 38: 1047-1053. 10.1038/sj.bjc.6600847.View ArticleGoogle Scholar
  49. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/168/prepub

Copyright

© Rezaianzadeh et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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