Metastatic Breast Cancer in a Tertiary Hospital in South-Western Nigeria

BC can progress to metastatic disease regardless of the initial stage at diagnosis. However, the more advanced the disease is at presentation, the more likely the chances of progression. Out of the 24 patients who developed metastasis after an initial diagnosis of localized BC in this study, 23 (95.8%) had stage 3 while only one (4.2%) was early disease. Some of these "newly diagnosed" cases might have been at stage IV of the disease ab initio: but were missed as a result of inadequate investigations either for financial reasons or lack of facility for that at our hospital. Considering the peculiarities of our setting, the ideal diagnostic imaging techniques (CT, MRI, bone scintigraphy, etc.) which are more sensitive than the routine X-rays and sonography are not available. Thus, patients requiring them would have to access these facilities at private facilities at costs which could be beyond the reach of majority of our clients. Therefore, we had to rely mainly on clinical and basic imaging studies, and for those in whom metastatic lesions are suspected, and who could afford it, we referred for newer imaging protocols where facilities for these exist.

Late presentation is very common among patients with BC in Nigeria. The mean duration of 12 months, coupled with a mean lump size of 12 cm, and about one-third presenting with ulcerated/fungating tumors are indicators of late presentation in this study. Comparing this with a study by Adisa et al.[8] who reported a mean lump duration of 5.8 months and median lump size of 8.5cm over a decade ago, nothing has really changed in terms of late presentation over the years despite seemingly widespread awareness. While efforts should be geared at improving early diagnosis and prognosis of BC patients, acceptance of diagnosis and intentional delay of treatment by patients are serious issues that still need attention among our patients in Nigeria.[,]

The majority (77.1%) of our patients had high education and this is similar to the high rates in the studies by Adisa et al.[8] and Ntekim and Nufu,[] but in contrast to Ali-Gombe et al.[] that reported a lower rate. Contrary to expectation, the high level of education was found not to have played much role in downstaging BC presentation. Thus, regardless of the patients" level of education, emphasis should still be on BC awareness at every encounter with women in any health facility.

The predominant histologic variant of the tumor in this study was invasive ductal carcinoma (97.1%). This is similar to what has been reported in previous studies.[,,-] The tumors were poorly differentiated in 40% of the patients and this was similar to 42.7% in Ali-Gombe study. More African women tend to have poorly differentiated and more biologically aggressive form of BC than their western counterparts.[] This is one of the factors responsible for poor survival outcome in the blacks.

Common sites for breast metastases are the lungs, liver, bones, and brain.[] The lungs and pleural are the most common sites of metastases in 50% of the patients followed by the liver in this study. This is in consonance with other studies from different centers though with varying rates.[,,,] In a retrospective study by Adisa et al.,[] at Ile-Ife, liver metastasis was found to be the most common while another study reported bone metastasis as the most common.[] The frequency and distribution of metastasis to the viscera and bones also vary in these centers. It is not unlikely that the incidence of bone metastasis might be underreported because most centers lack facility for bone scintigraphy which is more sensitive than X-rays. In general, risk factors for metastases include: Tumor subtypes, receptor status, nodal status, tumor grade, and size.[,]

Systemic therapies are the cornerstones of treatment in patients with MBC and they include endocrine therapy, chemotherapy, targeted drugs, and/or biologic agents. The greatest improvement in survival is mostly related to the development and widespread availability of modern systemic therapies.[] In recent times, new chemotherapeutic agents (taxanes, vinorelbine, eribulin, capecitabine, gemcitabine, liposomal anthracyclines, platinum compounds-carboplatin/cisplatin, etc.), newer hormonal agents, (third-generation aromatase inhibitors and fulvestrant), and biological therapies (trastuzumab, lapatinib, and bevacizumab), have been introduced with resultant improvements in treatment efficacy and outcome in MBC.[,] The results of the clinical trials with other agents such as cyclin-dependent kinases (CDK4/6), mTOR, and PI3K Inhibitors have been promising.[] These agents may be used alone or in combinations based on the patient"s BC subtype, receptor status, and sometimes gene mutation.

Chemotherapy and hormonal therapies are the two most commonly used for MBC in our center. The choice of the chemotherapeutic agents is restricted by availability and affordability of the agents. These encouraged the use of the available and seemingly affordable anthracycline/taxane-based regimens as mainstay of BC cytotoxic agent. Other approved second- and third-line agents were not accessible during this study. Tamoxifen was also the preferred agent for the hormonal therapy based on its availability and affordability. However, the majority (91.4%) of patients did not do immunohistochemical studies which are the main determinants of the usefulness or otherwise of the hormonal and biologic therapies. The major reason for this was the absence of such services in our center and other nearby facilities, and where available the patients could not afford it. It is hoped that with improvement in diagnostic facilities, and government efforts at making the newer drugs available and affordable, there could likely be improvement in the survival of BC patients with metastatic disease.

A few (20%) of our patients had palliative simple mastectomy after neoadjuvant chemotherapy. This was mainly considered to reduce the tumor burden and improve the quality of life. Although the role of surgery is unclear in MBC, several potential advantages have been proposed. By removing the primary tumor, the source of further metastatic spread is eradicated and reduction in the number of cancer cells may increase the efficacy of systemic therapy.[] Recent studies reported a survival benefit in those who had surgery in addition to systemic therapy especially in ER+, PR+, and HER2+ and those with the most favorable survival. [,] A French study by Pons-Tostivint et al.,[] described a 35% survival benefit with locoregional therapy (LRT). The tumor subtypes/biology, sites of metastasis and overall disease burden were the potential predictors of benefit with LRT, but this was not associated with better survival in triple-negative BC. Some patients who actually required surgery refused it because of the general belief of patients and their relatives that they will die regardless of how rigorous treatment might be and this even affected other treatments. As much as surgery is an option of treatments in our setting where patients still present with fungating tumor, all cases must be individualized and careful patient selection is crucial in the decision-making process.

Survival outcome of MBC is still very poor in Nigeria.[] The median survival of 7 months (mean 8.7 months) found in this study is far lower than what is obtained in most developed countries in recent times (12-14). In a meta-Analysis and systematic review by Caswell-Jin et al.,[] the median survival was reported to be slightly over three years, with a range from few months to many years. Some factors which influenced the survival in this study include: Site of metastasis, multiplicity of metastasis and treatment received. Patients who had bony metastasis, solitary organ metastasis and combination of surgery and chemotherapy treatments had extended survival period. Part of the reasons for the poor survival outcome might be lack of newer chemotherapeutic agents, lack of access to palliative radiotherapy, poverty, and patients/relatives" unwillingness to cooperate with the managing physicians or agree to the treatment regimen having lost hope of survival. The high mortality of BC patients in Africa is a clear evidence that there are not yet appropriate treatment strategies in place.[]

The outcome of patients with MBC still appears gloomy in our setting as nothing seems to have changed as regard its management in recent years. For there to be an improvement, there has to be a strong political will on the part of government to prioritize health, subsidize anticancer drugs and make provisions for diagnostic and treatment facilities. At present, our efforts are geared toward more awareness campaigns and BC information dissemination by working in collaboration with Non-Governmental Organizations to encourage early presentation, prompt diagnosis and treatment. Women presenting at our breast clinic are taught self-breast examination and encouraged to do yearly clinical breast examination. This will definitely reduce the number of patients presenting in advanced stage of BC.