Dual Diagnosis: Open Access Open Access

Trend, Treatment Outcome and Associated Factors of Breast Cancer at TGSH and FHRH, West Amhara, Ethiopia from January 2018 to December 2022: Institution-based Retrospective Study

Assefa Sisay Ayenew^1*, Alemtsehay Mekonnen² and Nebiat Embiale^{3 1}Department of Surgery, Dessie Comprehensive Specialized Hospital, Dessie, Ethiopia
²Department of Reproductive Health, Bahir Dar University, Bahir Dar, Ethiopia
³Department of General Surgery, Bahir Dar University, Bahir Dar, Ethiopia
^*Correspondence: Assefa Sisay Ayenew, Department of Surgery, Dessie Comprehensive Specialized Hospital, Dessie, Ethiopia, Email:

Received: 25-May-2024, Manuscript No. IPDDOA-24-20200; Editor assigned: 27-May-2024, Pre QC No. IPDDOA-24-20200 (PQ); Reviewed: 11-Jun-2024, QC No. IPDDOA-24-20200; Revised: 07-Mar-2025, Manuscript No. IPDDOA-24-20200 (R); Published: 14-Mar-2025, DOI: 10.36648/2472-5048.10.1.36

Keywords

Breast cancer; Treatment outcome; Recurrence; Ethiopia

Introduction

Cancer is one of the major non-communicable diseases responsible for 13% of total annual deaths worldwide [1]. Breast cancer is the 5th leading cause of death worldwide among all cancers and is the most common cause of cancer death in women in both developing and developed countries. The prevalence of breast cancer in Ethiopia accounts for 25%-34% of all female cancer cases, followed by cervical and colorectal cancer [1-3]. Male breast cancer is a rare disease representing, 1% of all breast carcinomas.

The lifetime risk of breast cancer is about 0.1% for a man, whereas it is 12% for a woman [4,5]. Breast cancer incidence rates rise steadily with age; the average age of a new breast cancer diagnosis is five years older for men (67 years) than for women (62 years). Breast cancer has geographic variations in presentation and the reasons for this disparity, however, are not as obvious and are likely to be multifactorial [3]. Risk factors such as sex, obesity, lack of physical exercise, alcohol consumption, hormone therapy during menopause, ionizing radiation, age at first menstruation and old age affect the incidence of breast cancer [3,6]. Other risk factors for male breast cancer include a family history of breast cancer; black ethnicity; exposure to radiation to the breast or chest; carrying a predisposition germline genetic mutation [7].

Approximately two-thirds of women with breast cancer in Addis Ababa are diagnosed with advanced-stage disease. This is strongly associated with the use of traditional medicine and the prolonged interval between symptom recognition and disease confirmation. Survival after the diagnosis of breast cancer is poor in Ethiopia because of the late stage at diagnosis and limited access to standard treatments [6,8]. Approximately 85% of the cases were diagnosed at stages III and IV. The predominant histological finding was ductal carcinoma and 37% of the patients had moderately differentiated tumors [9,10]. The incidence of ipsilateral supraclavicular Lymph Node (LN) metastasis without distant spread at the time of diagnosis is low (1%-4%). Hormone receptor positive tumors are the most common molecular subtype of breast cancer in Ethiopia and other East African countries. Triple-negative breast cancer accounts for 23% of all cases [3]. Another study in Nigeria demonstrated that the predominant pattern of immunohistochemistry study was estrogen positive tumor in 61.9% and triple negativity in 28.3% of breast cancer patients [11].

Breast cancer death could be reduced if appropriate treatment is provided for the patients and detection is made earlier; however, old age remains a risk factor for poorer survival [3]. The practice of BSE is very low in Ethiopia. 15 to 32.4% of the study population practiced BSE and only 26% had good knowledge of breast cancer [12,13]. Meanwhile,54.1% of the undergraduate female students knew and did BSE. The overall knowledge of women with breast cancer, family history of breast cancer, marital status and occupation were significantly associated with BSE [14]. Breast cancer screening and early detection are key strategies for reducing breast cancer-related mortality and distant complications and signifying a better outcome [13]. Most guidelines recommend screening after 50 years of age [7].

In the 19th century, most surgeons treated breast cancers with limited resections, with local recurrence as the rule. However, it was not until 1894 that William Stewart Halsted proposed radical mastectomy as the treatment of choice for breast cancers of any type and size [15]. A study conducted in Gondar showed that 65.7% of the patients had a positive surgical margin [9]. An early breast cancer is potentially curable. In the last decade, despite its increasing incidence, breast cancer mortality has been declining in the majority of developed countries. Neoadjuvant systemic treatment has emerged as a standard of care for treatment situations in which primary breast conservation is not possible because of tumor size or the association of tumor and breast size, provided that the patient has an indication for chemotherapy [16]. Endocrine mani-pulation with tamoxifen, ovarian ablation or both, is the preferred option for endocrineresponsive tumors [17]. Tamoxifen plus ovarian ablation was more effective than tamoxifen alone in premenopausal women. CHT is the treatment of choice for steroid receptornegative tumors [4].

The incidence of seromas after mastectomy ranges from 3%-85%. Flap fixation after mastectomy leads to fewer seroma aspirations than does conventional wound closure [18]. Another meta-analysis study on flap fixation after mastectomy found that 22.41% of patients experienced seroma formation after flap fixation and 43.61% of patients developed this complication without flap fixation [19]. Reducing dead spaces, leaving suction drain reduces the rate seroma formation. Flap fixations had no significant negative effect on surgical-site infections. SSI was observed in 59/686 (8.6%) patients in the flap fixation group and 67/686 (9.7%) in patients without flap fixation. BMI, the presence or absence of comorbidities, preoperative CHT and surgical factors did not affect the occurrence of skin flap necrosis. Approximately 38.7% of patients developed post-taxane-based therapy metastases and were followed up for 2 years. Of these patients, 51.3% developed metastases within 10-12 months. Ipsilateral axillary nodes were the most common locoregional sites (27.5%). ER negative patients had 2 times higher risk of recurrence than ER positive patients and those with poorly differentiated histologic tumor had almost 3 times higher risk of recurrence than histologic grade I. Similarly, positive LN status, clinical stage III and deeply involved surgical margin were significantly associated with recurrence. Overall, the breast cancer treatment outcomes were poor in the TASH study. Age, clinical stage (late stage), type of CHT, number of CHT cycles, mode of treatment and endocrine therapy were found to be the determinants of death.

Materials and Methods

A retrospective medical record review was performed by physicians and nurses working in the two hospitals. The sample size was estimated based on previous studies using the same setup. All breast cancer patients surgically treated at TGSH and FHRH from January 1, 2018, to December 30, 2022, were the source population. The medical records of patients who were referred from other hospitals after surgery and patients with unknown discharge status during the study period were excluded. First, we retrieved the medical records of all patients with breast cancer from the cancer center, surgical ward and operating theater. Second, we reviewed the records and identified variables that could be extracted from them. Completeness of the recorded data was ascertained by the primary investigator. Breast cancer treatment outcome: Short-term local complications were the dependent variables. The independent variables were socio-demographic, hormonal factors, patient and clinical related and treatmentrelated variables. The collected data were coded and entered into EPI data 3.1 software. It was cleaned, edited and exported into SPSS version 26 for further analysis and checked for missing values before analysis. Descriptive statistics were used to summarize the data in the form of mean frequency, Standard Deviation (SD) and cross-tabulation. Binary logistic regression analyses were performed to identify the association between short-term complications and independent variables. Variables associated with bivariate logistic regression with a significance level (p value ≤ 0.25) were entered into multiple logistic regressions to identify important determinants by controlling for possible confounding effects. Statistical significance was declared at a p-value ≤ 0.05 and the predictors of outcome variables were identified accordingly. AOR with 95% CI was used to describe the association. This study was conducted in accordance with the ethical guidelines of both institutions.

Results

Socio-Demographic Characteristics of Breast Cancer

Of the 138 patient charts included in this study, 132 questionnaires were ready for final data analysis, resulting in a response rate of 95.65%. Among the 132 patients, 119 (90.2%) were female. Approximately 4/13 (30.7%) of the male patients who underwent surgery for breast cancer were aged 61-70 years. The participants were aged 25-76 years with a mean age of 41.95 years and SD ± 12.948 years. By age group, over sixtytwo cases in the study (47%) were aged between 30 and 40 years and 5 (3.8%) were above 70 years of age.

Most participants were married (88.6%). Seventy-two (55.8%) breast cancer patients involved in this study were uneducated, while only two patients (1.5%) were medical personnel. Of the total participants, four (3%) and five (3.8%) had a family and personal history of breast cancer, respectively. None of the patients had a history of radiation exposure to the chest wall. All the patients with a personal and family history of breast cancer were females (Table 1).

Table 1: Frequency distribution of socio-demographic characteristics of breast cancer.

Patient and Clinical-Related Factors of Breast Cancer Management Outcome

Among all patients, only 9 (6.8%) knew about breast cancer and breast cancer screening, 8 (88.9%) used BSE as a screening method and 1 (11.1%) used ultrasound. Most patients 129 (97.7%) with breast masses were diagnosed with breast carcinoma. Approximately 67 (50.8%) patients had right-sided breast cancer, whereas only one patient had bilateral breast cancer.

The duration of presentation ranged from 1 month to 24 months, with a mean duration of 7.87 months and standard deviation of 3.283 months. Only 3.8% (5/132) of patients presented with symptoms within 3 months of the onset of symptoms of breast cancer and 66.6% presented with symptoms ≥ 7 months after the onset of symptoms. Breast lumps or masses (98.5%) were the most common finding, followed by axillary lymphadenopathy (15.9%), skin changes (5.3%) and nipple discharge (1.5%). Clinical staging of breast cancer was documented in all patients and the majorities (77.5%) of the patients were in the late stage of the disease; only 22.5% of the patients were diagnosed with stage II disease. Among the male patients, 10 (76.9%) were stage III and all stage 4 breast cancer patients were female.

Of the 132 patients studied in this paper, 125 (94.69%) investigated by FNAC were consistent with breast cancer (93.9%) and phyllodes tumor (2.4%). The histological report was conclusive for invasive breast carcinoma in 70 (53.0%) patients. Among patients with breast carcinoma, 55 (41.7%) and 52 (39.4%) were moderately differentiated and welldifferentiated, respectively. Evidence of distant metastases was noted in 2 patients (1.5%) (Table 2).

Table 2: Frequency of patient and clinical related factors of breast cancer.

Hormonal Status of Breast Cancer Patients

17 (12.9%) patients were nulliparous and non-breastfeeding. Most cases 94 (71.2%) were premenopausal. Of all patients reviewed in this study, only 19 (14.4%) had hormonal status determination, of which 14 (73.7%) expressed estrogen receptors (Table 3).

Table 3: Frequency distribution of breast cancer patients’ hormonal status.

Management of Breast Cancer

Patients with breast cancer in this study were operated between 2 and 150 days after diagnosis with a mean duration of 32.56 days ± 23.368 days. Among all patients, 124 (93.9%) underwent MRM with or without axillary LN dissection, 6 (4.5%) underwent toilet mastectomy for advanced breast cancer, and 2 patients with phyllodes tumor underwent simple mastectomy. Only 6/108 (5.56%) patients had positive surgical margins and 16 (12.1%) had lympho-vascular invasion. Amongst 132 patients who underwent surgery for breast cancer, only 1 (0.8%) case was referred for XRT. NACT was administered in the form of AC, FAC and AC-taxol to six (4.5%) patients with late disease and the response was partial in 83.3% of patients. The study participants were followed up for 1 to 15 months; with a mean of 7.88 ± 2.443 months (Figure 1 and Table 4).

Figure 1: Frequency distribution of breast cancer presenting complaints.

Table 4: Frequency of management related factors.

Management Outcome of Breast Cancer

About 32 (24.2%) and 2 (1.5%) of patients operated at both hospitals had seroma and flap necrosis respectively. The majority of case 82 (62.1%) were discharged within 5 days of operation and about 81.8% had improved condition on subsequent follow-up. Among 132 cases, only 5 (3.8%) patients had recurrence and all recurrences were loco-regional. 5 (3.8%) died (Table 5 and Figure 2).

Table 5: Frequency distribution of management outcomes of breast cancer.

Figure 2: Frequency distribution showing duration of follow up in months.

Factors Associated with Outcomes of Breast Cancer Management

Cross-tabulation and logistic regression analysis were performed to determine the association between independent variables and short-term local wound complications among operated patients with breast cancer at both institutions. Binary and multivariable logistic regression analyses were performed between short-term local complications (dependent variable) and socio-demographic, patient and clinical factors and treatment-related factors of breast cancer (independent variables). On binary logistic regression, age group, marital status, level of education, presenting complaints, duration of presentation, stage of the tumor, menstrual status, type of biopsy result, waiting time for surgery after diagnosis, surgical margin status, lympho-vascular invasion status and NACT use had a p-value of ≤ 0.25 compared to short-term complications and the above independent variables were collectively analyzed with multi-variable logistic regression.

However, in multivariable logistic regression of sociodemographic, patient and clinical factors; treatment of breast cancer; and short-term complications or outcomes of surgical management (dependent variable), only presenting symptoms and waiting time for surgery after diagnosis remained significantly associated with breast cancer complications (AOR=0.28; 95% CI (0.09,0.93)) and (AOR=0.16; 95% CI (0.03,0.89)) respectively (Table 6).

Table 6: Binary and multivariable logistic regression analysis of variables associated with treatment related complications.

Discussion

Breast cancer is the most common site-specific cancer in women worldwide and is responsible for 12.5% of cancers in both sexes. In this series, the female-to-male ratio of 9.15:1.0 showed that the disease affects more female populations in Ethiopia than in other African countries. Approximately 64.4% of the patients were within the range of 30 to 50 years of age, which is similar to the finding in TASH. Among all the participants in this study, only 9 (6.8%) had knowledge about breast cancer and used screening methods. Two (1.5%) and two (1.5%) patients presented with breast lumps together with nipple discharge, breast ulceration and pussy discharge, respectively. Most patients present late at the advanced stage. Approximately 75.8% of cases were diagnosed at stages III and IV. However, this rate was higher than that in Addis Ababa (54.2%). This gap may be due to several reasons. The absence of screening combined with the low rate of cancer awareness and practice of BSE and the unavailability of multimodality treatment are possible reasons for the late presentation. Another possible reason is that most patients came with referral papers, which resulted in delayed diagnosis and treatment.

The surgical margin status was reported in 106 patients. Among them, only 6 (5.5%) cases had a positive surgical margin. Our results were lower than those of previous studies in Gondar, in which 6 of 29 cases had a positive surgical margin. Only 19 patients underwent tests for hormonal status (expression of estrogen and progesterone receptors), and 5 (26.32%) did not express estrogen receptors. The overall rate of complications in breast cancer management was 45/132 (34.1%) in a mean follow-up period of 7.87 months. Seroma formation was the most frequent. Among these patients, only 2/132 cases had flap necrosis and lymphedema observed in 1.5% of patients, which is similar to the findings of Daniel et al. 25 This, finding is lower than that reported in a review of the literature on mastectomy flap necrosis (5-30%). 26 However, compared to Caren G. Solomon et al., study on lymphedema after breast cancer treatment the incidence of lymphedema in our study is minimal. The discrepancy in results observed among studies might be due to inadequate documentation in our setup. Five (3.8%) patients had recurrence and the most common site of the chest wall was twice that of the axilla. This finding is lower than that of the study by Addis (26.5%), but the most common site was the same.

After multivariable regression analysis, presenting symptoms and waiting time for surgery had a significant effect on the short-term complications of breast cancer treatment. Accordingly, after adjusting other covariates, the odds of having short-term complication of breast cancer among those who wait surgery ≤ 10 days were 84% less likely compared to those who wait more than 30 days (AOR=0.16; 95% CI (0.03,0.89)). This study also finds out the odds of having short-term complication of breast cancer treatment among those who presented with breast lump only were 72% less probable compared to those who presented with lump and other complaints of breast cancer (AOR=0.28; 95% CI (0.09,0.93)). However, a clinical trial on the impact of the wait time from NACT to surgery in breast cancer: Does time to surgery affect patient outcomes? Valerie et al. did not find any statistically significant differences in surgical complications (p=0.90). But, in certain breast cancer subtypes, such as triplenegative breast cancer, poorer outcomes have been observed in patients with delays greater than 30 days after surgery.

Conclusion

In conclusion, breast cancer commonly affects premenopausal women and more than half of the patients are younger than 50 years of age. The main presenting symptom was breast lump, and most patients presented with late-stage disease. The most common histological type of breast cancer is ductal carcinoma. MRM is the primary treatment modality. Approximately one-third of patients had wound-related complications. Patients who underwent surgery within the first 10 days of diagnosis and those who presented with a breast lump only had a decreased incidence of short-term complications.

Ethical Approval

Ethical clearance obtained from the Institutional Review Board (IRB) of College of Medicine and health sciences, Bahir Dar University, Ethiopia. Then, we got letter of permission from TGSH and FHRH medical director office research unit. Oral informed consent taken during a phone call while collecting missed information from the chart.

Consent and Ethical Approval

Institutionally approved letters from the TGSH and FHRH for publishing this paper are provided.

Disclosure

There is no financial interest or personal relationships that wound influence the work reported in this study.

Acknowledgement

I would like to thank those who work in TGSH and FHRH surgical department, oncology center and medical record unit for helping me in availing medical records.

References

1. Dagne S, Abate SM, Tigeneh W, Engidawork E (2019) Assessment of breast cancer treatment outcome at Tikur Anbessa Specialized Hospital Adult Oncology Unit, Addis Ababa, Ethiopia. Eur J Oncol Pharm. 2(2):13.

   [Google Scholar]

2. Hadgu E, Seifu D, Tigneh W (2018) Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa. BMC Womens Health. 18:1-8.

   [Crossref] [Google Scholar] [PubMed]

3. Guarneri V, Conte PF (2004) The curability of breast cancer and the treatment of advanced disease. Eur J Nucl Med Mol Imaging. 31: 1-61.

   [Crossref] [Google Scholar] [PubMed]

4. Giordano SH (2018) Breast cancer in men. N Engl J Med. 378(24):11-20.

   [Crossref] [Google Scholar] [PubMed]

5. Lijalem MT, Teshome AT, Muluneh EK (2020) Assessing the incidence, epidemiological description and associated risk factors of breast cancer in western Amhara, Ethiopia. Future Med J Breast Cancer Manag. 9(3):1-6.

   [Crossref] [Google Scholar]

6. Gøtzsche PC, Jørgensen KJ (2013) Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2013(6):6.

   [Crossref] [Google Scholar] [PubMed]

7. Ersumo T, Tessema G (2006) Breast cancer in an Ethiopian population. East Cent Afr J Surg. 11(6):81-86.

   [Google Scholar]

8. Tefera B, Cihoric N, Vlaskou Badra E, Tsikkinis A, Rauch D (2019) Breast cancer care in northern Ethiopia-cross-sectional analysis. BMC Cancer. 19:1-19.

   [Crossref] [Google Scholar] [PubMed]

9. Harbeck N, Gnant M (2017) Breast cancer. Lancet 389: 34-50.
10. Adebamowo CA, Famooto A, Ogundiran TO, Aniagwu T, Nkwodimmah C, et al. (2008) Immunohistochemical and molecular subtypes of breast cancer in Nigeria. Breast Cancer Res Treat. 110(1):183-188.

    [Crossref] [Google Scholar] [PubMed]

11. Tsegaye GW, Genet M (2021) Early detection practice of breast cancer and associated factors among women in Bahir Dar city, North West Ethiopia. Glob Sci J. 7:1-6.
12. Terfa BY, Kebede EB, Akuma AO (2020) Breast self-examination practice among women in Jimma, Southwest Ethiopia: A community-based cross-sectional study. Breast Cancer (Dove Med Press). 10:1-7.

    [Crossref] [Google Scholar] [PubMed]

13. Tewabe T, Mekuria Z (2019) Knowledge and practice of breast self-examination among undergraduate students in Bahir Dar University, North-West Ethiopia, 2016: A cross-sectional study. Public Health Africa J. 10(1):1-6.

    [Crossref] [Google Scholar] [PubMed]

14. Costanzo D (2020) Oncologic breast surgery: An historical perspective. Breast J. 26(7):1-26.

    [Crossref] [Google Scholar] [PubMed]

15. Haloua MH, Krekel NM, Winters HA, Rietveld DH, Meijer S, et al. (2013) A systematic review of oncoplastic breast-conserving surgery: Current weaknesses and future prospects. Ann Surg. 257(4):1-7.

    [Crossref] [Google Scholar] [PubMed]

16. Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, et al. (2005) Breast International Group (BIG) 1–98 Collaborative Group. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 354(2200): 2747-2757.
17. de Rooij L, van Kuijk SMJ, Granzier RWY, Hintzen KF, Heymans C, et al. (2021) Reducing seroma formation and its sequelae after mastectomy by closure of the dead space: A multi-center, double-blind randomized controlled trial (SAM-Trial). Ann Surg Oncol. 28: 1-9.

    [Crossref] [Google Scholar] [PubMed]

18. Velotti N, Limite G, Vitiello A, Berardi G, Musella M (2021) Flap fixation in preventing seroma formation after mastectomy: An updated meta-analysis. Updates Surg. 73(4):1307-1314.

    [Google Scholar] [PubMed]

19. van Bemmel AJM, van de Velde CJH, Schmitz RF, Liefers GJ (2011) Prevention of seroma formation after axillary dissection in breast cancer: A systematic review. Eur J Surg Oncol. 37(10):1-9.

    [Crossref] [Google Scholar] [PubMed]