Evolutionary aspects of non-metastatic breast cancer after primary treatment in a sub-Saharan African setting: a 16-year retrospective review at the Douala general hospital, Cameroon

Breast cancer is the leading cancer among the female population in the majority of African countries [1]. More than half of women diagnosed with breast cancer in Africa die of the disease [2]. The incidence of breast cancer in Africa continues to increase and is projected to double by 2050 [3]. The rise in the rate of breast cancer has been associated with the increased prevalence of risk factors such as early menarche, late child bearing, and obesity, as well as an increase in breast cancer detection due to gradual health infrastructural development [4]. In Cameroon, the 2012 Yaounde cancer registry revealed that breast cancer accounted for about 30% of all cancers diagnosed in the community [5].

The case fatality rate of breast cancer in low and middle-income settings of sub-Saharan Africa appears to considerably exceed that in high-income countries and this is mainly as a result of advanced disease at the time of diagnosis and inadequate management resources that prevail in sub-Saharan Africa [6]. Recently, progressive refinements in breast cancer detection and treatment strategies paralleled by improvements in non-metastatic breast cancer (NMBC) management modalities have been observed in the region [7]. In Cameroon, few hospitals such as the Yaounde General Hospital and Douala General Hospital already posess multidisciplinary treatment plans [8]. Notwithstanding these advancements, NMBC patients who receive treatment are not spared of adverse events. These adverse events could be related to breast cancer itself, cancer therapy or both [9]. There is a major paucity of data regarding morbidity associated with such adverse events and it is therefore imperative to provide recent and reliable data characterizing the clinical progress of patients with NMBC after initial treatment in sub-Saharan Africa.

The objectives of this study were to determine the rates of local relapse, distant metastasis and sequelae and the time interval from initial treatment to the occurrence of these adverse events. The ultimate goal of the study is to provide data that will enable cancer treatment providers in sub-Saharan Africa to optimize the care given to patients with NMBC so as to improve on the survival of these patients.

The medical records of 568 patients diagnosed with breast cancer were reviewed amongst which 260 cases fulfilled the eligibility criteria, giving an inclusion rate of 45.8%.

African countries are characterized by extreme paucity of reports on the morbidity of NMBC following various available treatment modalities [6]. This study is one of the rare assessing the outcome of NMBC in sub-Saharan Africa in an era of progressive health infrastructural development [7]. The study contributes to solving the problem of alarming lack of data and guidelines on cancer treatment in sub-Saharan Africa where the incidence of breast cancer is on the rise.

Our study revealed that patients with non-metastatic breast cancer were relatively young and this reflects the usual early age of onset of breast cancer among black Africans. Although the reason for this is poorly elucidated, it has been suggested that breast cancer seems to have a more aggressive propensity and consequently manifests earlier in Americans of black African descent [16]. Most patients in our study had invasive ductal carcinoma and this corroborates with the findings of previous reports from Africa [17‐21]. Surgery remained the mainstay of treatment in our review and was typically non-conservative because of the prevailing locally-advanced breast cancer which may have been consequent to factors such as inadequate self-breast examination, poverty leading to delayed medical care, prolonged denial after diagnosis, fear of disfigurement from surgery and preferred alternative medicine [22]. The documented number of positive lymph nodes extracted during the surgical procedures was substantial and comparable to that of a previous report carried out in an urban setting like ours [20]. Albeit such extensive rates of positive lymph nodes could be accounted for by large tumour sizes at diagnosis as well as the aggressive variant and poor histological differentiation of breast cancer in most of the patients, it is worth noting that lymph node dissection and analysis in our setting was generally done for cases with clinical suspicion of advanced disease. This may have induced a bias towards overestimation of the pathological incidence of positive lymph nodes. Combinations of various treatment options were used in a greater majority of our cohort. Overall, after initial treatment, metastatic recurrences were frequent, even though most were local recurrences. Distant metastases usually affected bones and the lungs. Metastatic recurrences generally occurred few months after initial treatment contrary to the less observed sequelae that generally occurred much later and were mainly accounted for by lymphoedema and lung fibrosis.

The highest proportion of metastatic recurrences were observed within the first 24 months after primary treatment, which is fairly similar to the results obtained by Noufel et al. who observed the highest proportion of recurrences between 12 and 19 months [23]. Also, Donnelly et al. reported that median time to presentation of recurrence was 19 months for metastatic and 18 months for locoregional disease [24]. Chauleur et al. in France found that the period of observation for local recurrence ranged from 4 to 36 months, while distant metastatis ranged from 9 to 24 months [25]. While noting the relatively short median period of development of specific organ metastasis observed in our study, the findings in these reports and our review indicate the need to implement closer follow-up strategies especially during the first twenty four months after primary treatment since this is the period when recurrences tend to occur irrespective of the income setting. It was also noted that a considerable proportion of patients in our review presented for follow up only during the first 12 months after treatment. Aside poverty and ignorance of the seriousness of the disease, this phenomenon could be explained by the fact that after initial treatment, patients may underestimate the possibility of adverse events. This phenomenon further highlights the necessity to strengthen patient education, follow-up strategies and means of recapturing lost to follow up cases after primary treatment of NMBC.

Local recurrence was noted in 26.2% of our cases, a figure which is higher than those previously reported in low-income settings of Nigeria by Elumelu et al. (16%), Ethiopia by Ersumo et al. (15%), Afghanistan by Noufel et al. (7%), and India by Raina et al. (2.7%) [21, 23, 26, 27]. While the high rate of local recurrence in our study may be attributed to prevalent locally-advanced breast cancer and possibly non-adherence to adjuvant treatment which is known to significantly limit locoregional recurrence, it is worth noting that there were wide variations in sample sizes, clinico-pathological characteristics, treatment modalities and durations of follow-up in all the studies. These may account for the differences in the rates of local recurrences. The fair comparability in the rates of local recurrence in our report, that of Elumelu et al. in Nigeria and Ersumo et al. in Ethiopia, may be attributed to the similar ethnic and clinico-pathological characteristics as well as similar durations of follow-up of the study populations.

The proportion of patients with early breast cancer who develop distant metastases generally varies 15% to 25% at 5 years regardless of surgical technique [28]. In our report, the rate of distant metastasis was up to 28.5% which is relatively high in comparison to what was  reported in a previous study carried out in sub-Saharan Africa [29]. Apart from the high rate of locally-advanced tumour and the invasive nature of the histological type of breast cancer found in most of our patients, this observation could also be associated with the predilection of breast cancer for the upper outer quadrant in our study population. This quadrant is in close proximity to the axillary tail which is a more frequent channel for metastases when compared with the other quadrants of the breast [29, 30]. In spite of significant variations in reported rates, bones and lungs are generally the most frequent sites of distant metastasis in patients with breast cancer [31]. A previous study in Pennsylvania detected bone metastasis in up to 40% of a cohort of breast cancer patients [32] probably due to the longer follow-up period and better diagnostic resources.

The rate and mean period of occurrence of sequelae in our study is almost equivalent to what was reported by Hagigat et al. in Iran and Pawlaczyk et al. although they noted prevalence rates as high as 31.7% [33] and 22% [34] respectively. Furthermore, Kornblith et al. reported a prevalence rate of sequelae of up to 39% twenty years after the initial treatment [35]. Even though Hagigat et al. explained that postoperatively most patients usually limit movement of the surgical site which can induce lymphoedema [33] (the most frequent sequela in our study and previous reports), the relatively high rates of sequelae noted in these studies could be attributed to the longer follow-up periods and invariably lower rates of lost to follow-up which permitted detection of more sequelae.

The current report is not void of limitations. There was a possibility of selection bias given its retrospective single-center design. It is also worth mentioning that the stringent nature of our selection criteria resulted in a considerably low inclusion rate which was, nonetheless, necessary for reliable results to be generated from the poorly archived medical records in our context. Furthermore, our study like most from Africa, focused on describing morbidity data and lacked direct survival analysis. Nonetheless, we were able to derive that less than half of the patients were alive and disease-free at the end of the review period, albeit the individual follow-up periods were regrettably short in a significant proportion of the patients.

Despite progressive health infrastructural development in sub-Saharan Africa, our study reveals that adverse events were frequent and occurred relatively early among patients who received primary treatment for NMBC during the 16 year period from 1997 to 2012 at the Douala General Hospital in Cameroon. The available cancer therapeutic modalities in this setting ought to be supplemented with guidelines on efficient strategies of follow-up and monitoring so as to optimize the care provided to these patients and ultimately improve on their survival. For these to be achieved, further studies on prognostic features of patients receiving primary treatment for NMBC in the sub-Saharan African context may be warranted.