Epidemiology and Challenges of Managing Breast Cancer in Keffi, North-Central Nigeria: A Preliminary Report.

BACKGROUND: Breast cancer is now the commonest female malignancy worldwide. The prognosis of such depends on the histopathological type, biological behavior, stage at presentation, availability of adequate oncological services. AIMS AND
OBJECTIVES: The aim of this this study is to evaluate the statistics and challenges of breast cancer management in the study centre and compare with other centres.
MATERIALS AND METHODS: This is a prospective, descriptive study that spanned over a period of 4 years (January 2015-December 2018). The study was carried out in the General surgery division of the Surgery Department of the Federal Medical Centre, Keffi.
RESULTS: A total of 199 patients were recruited into this study out of which 196 (98.25%) were females and 3 (1.5%) were males. Their age ranged between 20-60 years. The commonest histopathological variant diagnosed is invasive ductal carcinoma (NOS). Early presentation was seen in 54 (<30%) while 145 (>70%) patients had late clinical presentation.
CONCLUSION: Diagnosing and managing breast cancers successfully are mitigated my myriads of factors. Public awareness and provision of adequate care facilities will improve overall survival. Copyright:

INTRODUCTION

Breast cancer is the most common female malignancy worldwide, with an annual global incidence of 1.7 million newly diagnosed cases.1 The pandemicity of this disease has been noticed to be on the rise globally and more so in the sub-Saharan African population that hitherto enjoyed low incidence.2 In Africa, about 68,000 new cases are reported on an average annually.3 Although considered as a disease with low incidence in the negroids, the trend of breast cancer being diagnosed in our environment has been on the rise. Due to the increased level of awareness of this disease and the availability of screening investigations, many women are now more conscious of lumps in their breast more than ever before.45 On this premise, we decided to present the epidemiology and pattern of clinical presentation of breast cancer at our center.

METHODS

This is a retrospective study in which patients' folders were traced alongside the histopathology reports. Approval was obtained prior to commencement of the study, and data were managed in accordance with the ethical standards. The folders extracted were of the patients that presented to the general surgery divisions of the department of surgery between January 2013 and July 2018. Clinical information was extracted from the patients' clinical notes and entered into a pro forma specifically designed for this study. The following data were obtained or extracted from the case notes: sex, side of the lesion, axillary involvement, presence of metastasis and sites, estimated size of the breast mass at onset by the patient and at presentation in centimeter, size of the mass after completion of neoadjuvant chemotherapy (NAC) in centimeter, the duration of symptoms, and the type of chemotherapy received. The details of surgery and the histopathological variant of the breast tumor were also documented. The information was entered and analyzed using Epi-Info version 3.5.4 (developed by Centres for disease control and prevention, Atlanta Georgia, U.S.A, 2007). Results were presented in the form of tables and charts.

RESULTS

A total of 199 patients' records were analyzed after editing for completeness. One hundred and ninety-six (98.3%) of them were female. The patients' age ranged between 20 and 60 years. Sixty-four (32.2%) patients were in the age bracket of 31–40 years [Table 1]. The number of patients diagnosed annually during the study period is illustrated in Figure 1.

Table 1

Demographics of breast cancer at the study center

Parameter	Frequency (%)
Age group
<20	1 (0.5)
21-30	33 (16.6)
31-40	64 (32.2)
41-50	45 (22.6)
51-60	43 (21.6)
61-70	13 (6.5)
Sex
Male	3 (1.5)
Female	196 (98.5)
Affected side
Right breast	66 (33.2)
Left breast	133 (66.8)
Family history
Present	84 (30.6)
Absent	115 (69.4)
Parity
Nulliparous	2 (1.0)
Primiparous	6 (3.0)
Multiparous	191 (96.0)

Figure 1

Annual representation of newly diagnosed breast cancer at the study center

With respect to the breast pathology, the left breast was found to be twice as much affected compared to the right breast [Table 1]. The most common histopathological variant diagnosed was invasive ductal carcinoma. Other variants encountered are shown in Table 2. Table 3 below shows survival rate of patient with breast cancer.

Table 2

Pathological characteristics of breast cancers diagnosed

Parameter	Frequency (%)
Histopathological variant
Invasive ductal carcinoma (NOS)	118 (59.3)
Mucinous	11 (5.5)
Papillary	1 (0.5)
Medullary	7 (3.5)
Metaplastic	4 (2.0)
Invasive lobular carcinoma	2 (1.0)
Ductal carcinoma in situ	1 (0.5)
Malignant phyllodes tumor	11 (5.5)
Fibrosarcoma	2 (1.0)
Stage at presentation
Tx	5 (2.5)
T1	27 (13.6)
T2	22 (11.1)
T3	66 (33.2)
T4	79 (39.7)
Nodal status at presentation
No	3 (1.5)
N1	115 (57.8)
N2	8140.7)
Presence of distant metastasis at presentation
Mx	4 (2.0)
Mo	62 (31.2)
M1	13366.8)
Immunohistochemistry profile (n=77)
PR+	14 (18.2)
PR−	10 (13.0)
ER+	11 (14.3)
ER−	8 (10.4)
Her-2/neu+	5 (6.5)
Her-2/neu−	8 (10.4)
Triple negative	21 (27.3)

PR – Partial response; ER – Estrogen receptor; NOS – Not otherwise specified

Table 3

Survival rate of patients with different stages of breast cancer

Stage at presentation	6 months (% s)	1 year (% s)	2 years (% s)	3 years (% s)
Stage 1 (n=29)	29 (100.0)	25 (86.2)	19 (65.5)	15 (51.7)
Stage 2 (n=22)	22 (100.0)	19 (86.4)	15 (68.2)	10 (45.5)
Stage 3 (n=66)	55 (83.3)	37 (56.1)	28 (42.4)	21 (31.8)
Stage 4 (n=79)	58 (73.3)	11 (13.9)	7 (8.9)	0 (0.0)
Triple-negative tumor (n=21)	21 (100.0)	9 (42.9)	3 (14.3)	0 (0.0)

% s – Percentage of patients seen

A total of 145 (72.9%) patients presented with locally advanced and metastatic diseases [Table 2]. Immunohistochemical profile to determine the hormonal and Her-2/neu receptor status was carried out on 77 (38.7%) breast tissue specimens [Table 2]. The chest was the most common site of distant spread as seen in 76 (57.1%) patients, followed by the liver (28, 21.1%) [Figure 2]. Surgical treatment offered and responses to chemotherapy are shown in Figures 3 and 4, respectively.

Figure 2

Anatomical regions involved in metastasis

Figure 3

Various operations carried out. TM – Total mastectomy alone; TM + AD – Total mastectomy + axillary dissection; ToM – Toilet mastectomy

Figure 4

Breast tumor response to chemotherapy. CR – Complete response; PR – Partial response; Pro – Progressive disease; NR – No response

DISCUSSION

Breast cancer is a significant cause of morbidity and mortality globally.6 Females are highly predisposed to developing breast cancer due to hormonal influence, genetic predisposition, obesity, social lifestyle, and environmental influence.7 This is consistent with our study finding, with about 98.5% of cases seen in females. Researches over the years has led to an explosion in the knowledge with regards to the clinical behavior, cytogenetics, diagnostic investigations and novel therapies that have been introduced into the current management of breast cancer with attendant improved outcome in developed climes.8 However, most patients in the Sub-Saharan region are yet to benefit maximally from this advancement because of the poor facilities due to poor economic status in many developing nations, late presentation, delay in diagnosis and initiation of definitive treatment due to patients' financial hardship, and hospital delay in terms of definitive intervention following patient readiness, industrial actions and other logistic constraints.9 Survivor groups/associations are also springing up in order to raise awareness, encourage women to pay more attention to their breast, and also demystify certain sociocultural concepts that have constituted impediment to early treatment. For example, there are certain cultural beliefs that breast cancer is an affliction of the deity gods and hence, there is no need for orthodox treatment.10

The present study found that about a half (49%) of the patients were premenopausal in their third and fourth decades of life, a finding consistent with reports from previous studies.1112 This category of patients were observed to have tumors that ran aggressive course probably because of hormonal influence. Reports from these studies are consistent with the reports of other workers who studied the clinical and biological behavior of breast cancers among Nigerian and Senegalese female population.13 Male breast cancer represents <2% of the total breast cancers seen in our study. This finding is consistent with reports from other geographical regions of the country.1415

With regard to the affected side, the left breast was found to be more involved than the right side among our patients. Other workers have reported similar findings.16 The scientific basis for this is yet to be clinically substantiated as many of the propounded reasons (such as blunt trauma to the breast, breastfeeding, and increased physiological activities on the left breast) are anecdotal. Genetic predisposition in the etiopathogenesis of this condition has been incontrovertible, especially in familial cases. Surprisingly, about 70% of the affected women in our study denied a positive family history of breast cancer. This may be a pointer that most of the breast cancer cases in the present study are sporadic in nature probably with more of environmental, hormonal, and dietary influence as earlier posited by Abdulrahman and Rahman.3

Breast cancers are classified according to histopathological features or molecular characteristics. Based on histopathological considerations, adenocarcinomas have been found to be responsible for >95% of breast cancers.17 Our experience is not different from this as the most common histopathological variant encountered in our review is the invasive ductal adenocarcinoma (not otherwise specified). Invasive ductal carcinomas are characterized by malignant ductal proliferation along with stromal invasion in the presence or absence of ductal carcinoma in situ. Other variants that were diagnosed included medullary, papillary, and mucinous, among others. The proportion of these histopathological variants encountered in our study is consistent with reports from other centers.171819

Breast cancer belongs to a heterogeneous group of cancers that is unpredictable with variations in tumor biology; hence, current oncological guideline in the management of breast cancer demands determination of the receptor status. This will assist in individualizing patients' treatment, as this is pivotal in the selection of chemotherapeutic, biological, and hormonal agents that would be considered in the treatment regimen.20 The immunohistochemical analysis of breast cancer specimen commenced at our center in 2016 and at the time of this study, a total of 77 samples have undergone this assay. The presence of triple-negative receptor status (observed in 21 patients) was associated with aggressive tumors, notably among women in their third decade of life. Patients with triple-negative tumor were placed on capecitabine/docetaxel combination. This combination is expensive and as such, many of our patients could not readily afford to procure these drugs as they pay out of pocket. The seemingly gain noted at the commencement of treatment in few patients who procured the combination was soon eroded due to poor compliance as a result of financial hardship, resulting in aggressive recurrence within a year and leading to the demise of such patients.

Late clinical presentation has been a perennial problem that we face in the sub-Saharan Africa, as many of our patients present with late-stage diseases.2122 Reasons that may be responsible for late clinical presentation have been attributed to misconception about the disease, poor educational status, cultural beliefs, religious charlatans, fear of losing a breast, psycho-social factors, and loss of self-esteem (stigmatization).232425 Metastatic presentations are not unusual as many of such patients presented with features of respiratory difficulty on account of pleural effusion and lung parenchymal destruction by tumor secondaries. As a palliative measure, thoracostomy tube drainage of the malignant effusion with subsequent pleurodesis was achieved in such instances using povidone. Ogunrombi et al.26 from South-Western Nigeria also reported their experience with palliative management of malignant pleural effusion from breast cancer using povidone-iodine. This is a readily available and affordable agent, and the satisfactory outcome reported from their study encouraged us to use similar agents with satisfactory outcome and thus, we suggest the use of this agent in a low-resource setting for pleurodesis.

Our patients had NAC with attendant remarkable response achieved before embarking on mastectomy. Breast tumors in the African population tend to run biologically aggressive course with a demonstration of poor response to NAC as reported by Arowolo et al.27 However, in contrast to their reports, Anyanwu et al.28 recorded the gains of using NAC and therefore recommended its use especially in premenopausal women, a report consistent with our finding and protocol.

Other regimens commonly used include the cyclophosphamide/methotrexate/5-fluorouracil, 5-fluorouracil/epirubicin/cyclophosphamide, or taxane/carboplatin/herceptin regimen based on their financial capabilities and immunohistochemical properties of the tumor. Adjuvant chemotherapy was given appropriately, and patients were selectively sent to undergo radiotherapy at the end of the completion of their medications at designated centers. These centers are designated because of paucity of functional machines confounded with the long booking and waiting time for patients.

Total mastectomy with axillary dissection was the commonly done surgery for early-stage diseases and some selected cases of locally advanced diseases after NAC. Careful patient selection in advanced clinical presentations was done to find out those that will benefit from palliative mastectomy and/or medications (hormonal agents or low-dose chemotherapy).29 The postoperative management and follow-up of some of our patients was confounded by financial constraints in procuring new medications prescribed for them by the radio-oncologist and the downtime recorded with the machines in those designated centres. This is the same scenario that plays out in many of our tertiary care centers as reported by other surgeons.30

At the time of this write-up, we still have about 11 of our patients who were diagnosed with early-stage disease, have completed their chemotherapy and radiotherapy courses, are clinically free of metastasis, and are on follow-up for the past 3 years. Efforts are being made to co-opt them into establishing a breast cancer survivor group with the aim of raising awareness on the disease and also emphasizing the role of early diagnosis and treatment.

CONCLUSION

We have seen that many of our breast cancer cases are sporadic in nature and are biologically aggressive in behavior. Malignant breast cancer is no longer uncommon in our setting, and late clinical presentation is the cause for concern coupled with exorbitant prices of chemotherapeutic agents. The dearth of radiotherapy centers in the country at large is worrisome as many of our patients are left to their fate. This also puts the surgeon in a very difficult situation to carry out certain procedures such as breast-conserving surgery (in early diseases) and also manage metastatic and recurrent diseases.

Recommendations

As many of the anticancer drugs are expensive, subsidizing or inclusion in the national insurance scheme drug list will enhance affordability

Mass education and enlightenment programs through partnership with media houses, religious organizations, and social media will help in educating the general populace about this disease

We need cancer research centers to look into the cytogenetics and biology of the negroid breast cancer with the aim of proffering solutions

More functional radiotherapy centers should be made available and affordable across the country.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.