Patient’s characteristics with breast cancer
There were 337 patients with BC diagnosed from 1st January- 2013 to 30, Dec 2018 in HUCSH and YIMSC. Out of 302 patients included in the study, a telephone interview was made with 206 patients or their relatives. The second review of patient charts was made after two months of the beginning of data collection and 29 patients that are unavailable by telephone call had visited the hospitals during the second review time and thus, they were confirmed alive. Therefore, out of 302 BC patients, the outcome of 235 (77.8%) patients was confirmed (168 were alive, 67 have died), 57 (18.8%) patients were LTF and the rest 10 patients have visited the hospital within 6 months before the end date of the study. Out of 141 alive patients contacted by telephone, 101 (71.6%) reported they were working their usual job, 35 (24.8%) were ambulatory, 5 (3.5%) were bedridden. All relatives of deceased patients with BC believe the cause of patients’ death was BC.
Socio-demographic and clinical characteristics
Out of 263 patients, 189 (71.8%) of them were from urban areas. Their median travel time to Hawassa cancer treatment units is 2 hours (IQR=0.30-3.30 hours). Out of 302 women with BC recruited to this study, the majority of them, 177(58.6%) were within the age of 35-50 years, the median age being 39 (IQR=32-45) years, 79.1% of them were pre-menopause. Out of 208 patients, majorities 178 (85.6%) were married, 108 (51.9%) were house wife’s and 78 (37.5%) can’t read and write. Two hundred eleven (69.9%) of patients were diagnosed within the years 2016-2018 and the rest within 2013-2015. About one-third of BC patients, 208 (73.5%) came with complaints of a breast lump, and 171 (60.4%) were presented to the oncology unit within 7-23 months of a complaint. Out of 196 patients whose tumor grade is available 109 (56.2%) were grade II (moderately differentiated). Out of all 302 BC patients, 50 (16.6%) were early stage, 252 (83.4%) were presented with advanced stage at the first hospital visit, 161(53.3%) were stage III and 91(30.1%) were stage IV. About 173 patients (58.8%) had tumor size III/IV, 249 (83.4%) had ductal carcinoma, 240 (84.2%) had positive lymph node, and 56 (18.54%) had distance metastasis at the time of diagnosis. Thirty-five (11.5%) patients have comorbidity out of which, 23(7.6%) have hypertension, and 5 (1.6%) have HIV (Table 1).
Table 1: Socio-demographic and tumor characteristics of patients with breast cancer in HUCSH & YIMSC, 2013-2018.
Covariates
|
Frequency
|
Percentage
|
Resident
|
|
|
Urban
|
189
|
71.86
|
Rural
|
74
|
28.14
|
Total
|
263
|
100
|
Travel time
|
|
|
< 3 hours
|
197
|
74.9
|
3-6 hours
|
51
|
19.39
|
≥ 7 hours
|
15
|
5.7
|
Total
|
263
|
100
|
Age
|
|
|
<35
|
82
|
27.15
|
35-50
|
177
|
58.61
|
>50
|
43
|
14.24
|
Total
|
302
|
100
|
Menopausal status
|
|
|
Pre-menopause
|
239
|
79.1
|
Post-Menopause
|
63
|
20.86
|
Total
|
302
|
100
|
Breast complain at the first visit
|
|
|
Breast lump
|
208
|
73.5
|
Breast ulcer
|
34
|
12.01
|
Other #
|
41
|
14.49
|
Total
|
283
|
100
|
Duration of symptom
|
|
|
0 - 6 months
|
110
|
38.87
|
7 - 23 months
|
112
|
39.58
|
> 23 months
|
61
|
21.55
|
Total
|
283
|
100
|
Histological type
|
|
|
Ductal
|
249
|
82.45
|
Lobular
|
24
|
7.95
|
Other*
|
24
|
8.08
|
Total
|
297
|
100
|
Stage of BC
|
|
|
Early
|
50
|
16.55
|
Advanced
|
252
|
83.44
|
Tumor size
|
|
|
TI/II
|
121
|
41.16
|
TIII/IV
|
173
|
58.84
|
Total
|
294
|
100
|
Distant -metastasis
|
|
|
Yes
|
56
|
18.54
|
No
|
246
|
81.45
|
Total
|
302
|
100
|
Nodal status
|
|
|
Positive
|
240
|
84.21
|
Negative
|
45
|
15.79
|
Total
|
285
|
100
|
Co-morbidities
|
|
|
Yes
|
35
|
11.59
|
No
|
267
|
88.41
|
Total
|
302
|
100
|
NB: #=shortness of breath, axillary swelling, nipple retraction, nipple discharge. *=Mixed ductal & lobular, mucinous
The diagnosis and treatment given to the patients
One hundred twenty-eight (45.7%) patients had referral paper from another hospital and 69 (22.8%) are referred after they had surgery. A total of two hundred eight patients with BC were treated with breast surgery. Out of 190 patients with BC whose type of surgery is available on their chart, 173(91.05%) of them underwent MRM. Chemotherapy was administered for 219 BC patients, out of this, 54(24.7%) had completed the treatment (good adherence) while 138 (63.0 %) had discontinued (poor adherence) and 27 (12.3 %) were on schedule at the time of data collection. Out of 100 patients with BC that took hormonal therapy, 65(65%) were treated with Tamoxifen. Eight patients with BC had taken radiation therapy at Tikur Anbesa Specialized Hospital (table 2).
Table 2: Breast cancer therapies and other characteristics of patients with breast cancer in HUCSH & YIMSC, 2013-2018.
Covariates
|
Frequency
|
Percent
|
Surgical therapy
|
|
|
Yes
|
208
|
68.87
|
No
|
94
|
31.13
|
Total
|
302
|
100
|
Type of surgery
|
|
|
MRM
|
173
|
57.28
|
Toilet mastectomy
|
17
|
5.63
|
No surgery
|
112
|
37.09
|
Total
|
302
|
100
|
ACT
|
|
|
Good adherence
|
54
|
19.64
|
Poor adherence
|
138
|
50.18
|
No chemotherapy
|
83
|
30.18
|
Total
|
275
|
100
|
Hormonal therapy
|
|
|
Yes
|
100
|
33.12
|
No
|
202
|
66.89
|
Total
|
302
|
100
|
Hormonal therapy type
|
|
|
Tamoxifen
|
65
|
21.52
|
Anastrazole
|
35
|
11.59
|
No hormonal therapy
|
202
|
66.89
|
Total
|
302
|
100
|
Recurrence
|
|
|
Yes
|
22
|
7.28
|
No
|
280
|
92.72
|
Total
|
302
|
100
|
Progression
|
|
|
Yes
|
40
|
13.25
|
No
|
262
|
86.75
|
Total
|
302
|
100
|
NB: ACT: Adherence to chemotherapy
Out of 57 LTF patients, 55 (96.4%) have an advanced-stage of BC. Among these, 28 (49.1%) of them have stage IV disease, and 21 (36.8%) have distant metastasis at the time of diagnosis. The majority of them, 39 (68.4%) had breast surgery, even if 35 (61.4%) of them started chemotherapy, only 6 (10.5%) have had good adherence, only 9 (15.8%) were started hormonal therapy. For 84.2 % of them, their last date of contact was before the end of 2017.
Survival status of the patients with breast cancer
A total of 302 BC patients had followed for 4685.61person-months or at-risk time. There were 67 confirmed deaths during the follow-up period which is 72 months. The median follow-up time was 50.61 (IQR=18.38-50.80) months. The overall survival of BC patients at the end of one, two, and three years is 83%, 73.2 %, and 63.1%, respectively. The overall survival for the early and advanced stages of BC at the end of 2 years was 89.9 % and 63.8 %, while it is 73.4% and 44.3% for stage III and IV respectively (see table 3).
Table 3: Log-rank test for equality of survival function of patients with breast cancer diagnosed in HUCSH and YIMSC from 2013-2018 in Southern Ethiopia, 2020
Covariates
|
Survival time
|
Observed death
|
Expected death
|
X2 (df)
|
Log-rank test
(Pr > X2)
|
2 years
|
3 years
|
Overall survival
|
73.2 (65.8, 79.3)
|
63.0 (53.3, 71.2)
|
|
|
|
|
Residence
|
|
|
|
|
|
|
Urban
|
80.1 (71.6, 86.3)
|
71.4 (80.0, 60.1)
|
36
|
52.13
|
24.5 (1)
|
<0.001
|
Rural
|
50.5 (34.2, 64.7)
|
27.5 (07.4, 52.6)
|
30
|
13.87
|
|
|
Age in years
|
|
|
|
|
|
|
<35
|
61.5 (43.9, 75.0)
|
56.7 (38.2, 71.6)
|
23
|
14.06
|
7.93 (2)
|
0.019
|
35-50
|
76.0(66.5, 83.1)
|
70.2 (58.9, 78.9)
|
34
|
43.65
|
|
|
>50
|
81.5 (63.0, 91.3)
|
48.8 (21.1, 71.8)
|
10
|
9.28
|
|
|
Stage of BC
|
|
|
|
|
|
|
Early
|
95.1 (81.9, 98.7)
|
89.8 (69.3, 96.9)
|
5
|
17.52
|
12.76 (1)
|
<0.001
|
Advanced
|
67.4 (58.5, 74.8)
|
55.6 (44.1, 65.6)
|
62
|
49.48
|
|
|
Nodal status
|
|
|
|
|
|
|
Positive
|
70.9 (62.3, 77.8)
|
58.9 (47.4, 68.7)
|
57
|
48.74
|
7.75 (1)
|
0.005
|
Negative
|
95.0 (69.4, 99.2)
|
87.6 (58.1, 96.8)
|
3
|
11.26
|
|
|
Surgical therapy
|
|
|
|
|
|
|
Yes
|
78.7 (70.3, 85.0)
|
70.5 (59.6, 78.9)
|
37
|
53.07
|
23.81 (1)
|
<0.001
|
No
|
58.0 (41.8, 71.1)
|
42.0 (22.9, 60.1)
|
30
|
13.93
|
|
|
ACT
|
|
|
|
|
|
|
Good adherence
|
94.4 (79.0, 98.6)
|
82.2(55.7, 93.6)
|
6
|
15.79
|
|
|
Poor adherence
|
75.6 (65.0, 83.4)
|
66.1(52.7, 76.5)
|
31
|
35.27
|
19.33 (2)
|
<0.001
|
No chemotherapy
|
43.7 (27.6, 58.7)
|
36.6 (21.1, 52.3)
|
30
|
15.95
|
|
|
Hormonal therapy
|
|
|
|
|
|
|
Yes
|
94.2 (86.5, 97.5)
|
85.2 (72.0, 92.4)
|
13
|
35.64
|
32.36 (1)
|
<0.001
|
No
|
52.6 (40.5, 63.4)
|
41.3 (27.6, 54.5)
|
54
|
31.36
|
|
|
ACT: Adherence to chemotherapy
In the worst-case analysis, a total of 124 patients were considered as they developed an event. The median survival of BC patients is 30.57 (IQR=7.23-64.23) months. The overall survival of patients at the end of one, two, and three years is 67.03 %, 51.3 %, and 44.6 % respectively. The overall survival for the early and advanced stage of BC at the end of 2 years is 85.1 % and 44.1 % and for stage III and IV, it is 55.1% and 23.7% respectively. (see fig. 2 and 3).
Predictors of survival of patients
After adjusting for age, histological type, surgery, and nodal status, the hazard of death among rural patients with breast cancer were 2.71 times higher as compared to urban dwellers (AHR=2.71, 95% CI: 1.44, 5.09). Patients with BC that travel >7 hours to Hawassa for cancer treatment had 3.42 times increased risk of death as compared to those traveled less than 3 hours
(AHR=3.42, 95% CI; 1.05, 11.10). Patients that present to the oncology unit within the range of 7 to 23 months after the beginning of sign and symptoms of BC had 2.63 times increased risk of death (AHR=2.63, 95% CI; 1.22, 5.64) and those who came >23 months had 2.37 times increased risk of death (AHR=2.37, 95% CI; 1.00, 5.59) as compared to those patients presented within 6 months. Those who have advanced stage of disease had 3.01 times increased risk of death as compared to early-stage (AHR=3.01, 95% CI; 1.05, 8.59). The hazard of death for patients that took no chemotherapy was 6.69 times (AHR=6.69, 95% CI; 2.20, 20.30) higher than those patients that have good adherence to chemotherapy.
Table 4: Multivariable cox regression analysis model for survival of patients with breast cancer diagnosed in HUCSH & YIMSC 2013-2018
Covariates
|
Category
|
Main analysis
|
CHR (95%CI)
|
AHR (95%CI)
|
p-value
|
Residence
|
Urban
|
1
|
1
|
|
Rural
|
3.29 (2.00, 5.42)
|
2.71 (1.44, 5.09)
|
0.002
|
Travel time
|
<3 hours
|
1
|
1
|
|
3-6 hours
|
1.40 (0.73, 2.66)
|
1.11 (0.52, 2.38)
|
0.773
|
> 7 hours
|
2.22 (0.94, 5.20)
|
3.42 (1.05, 11.10)
|
0.041
|
Duration of symptom
|
0- 6 months
|
1
|
1
|
|
7-23 months
|
1.50 (0.84, 2.67)
|
2.63 (1.22, 5.64)
|
0.013
|
> 23 months
|
1.71 (0.87, 3.39)
|
2.37 (1.00, 5.59)
|
0.048
|
Stage of BC
|
Early
|
1
|
1
|
|
Advanced
|
4.67 (1.85, 11.76)
|
3.01 (1.05, 8.59)
|
0.040
|
ATC
|
Good adherence
|
1
|
1
|
|
Poor adherence
|
3.37 (1.19, 9.54)
|
2.87 (0.96, 8.58)
|
0.032
|
No CT
|
8.66 (3.03, 24.73)
|
6.69 (2.20, 20.30)
|
0.001
|
Global test
|
|
|
0.8358
|
|
NB: CHR: Crude hazard ratio, AHR: Adjusted hazard ratio, ACT: Adherence to chemotherapy, BC: breast cancer, *=Mixed ductal & lobular, mucinous, No CT: no chemotherapy.