Occurrence Delays of Metastatic Relapses of Breast Cancers Treated at University Hospital of Treichville (Abidjan-Cote d’Ivoire) ()
1. Introduction
Breast cancer is the first cancer of woman in Cote d’Ivoire as in many countries of the world [1] [2] , and its prognosis is closely related to the occurrence of metastases. Also after the curative treatment of non-metastatic forms, monitoring should be careful to quickly take care of locoregional and metastatic relapses that may occur. ASCO (American Society of Clinical Oncology) recommends clinical monitoring based on examination and clinical examination, every 4 months for 3 years, then every 6 months for the next 2 years, and once a year for the rest of life [3] . For additional examinations, only mammography and breast ultrasound should be performed annually, and other tests (chest x-ray, tumor markers, abdomino-pelvic ultrasound, bone scintigraphy, etc.) will be proposed only before functional signs [4] .
In developing countries where there is no breast cancer screening program, the management of non-metastatic tumors is late, and exposes patients to high risk of metastatic relapse after initial treatment. Yet there are few publications on metastatic relapses in African literature.
This study was conducted with the objective to describe occurrence delays of metastatic relapses observed in our department.
2. Methodology
This is a retrospective and cohort study conducted from January 2000 to December 2015 (16 years) in the gynecology department of the University Hospital of Treichville (CHUT).
It involved patients who benefited from a radical surgery with curative intent for nonmetastatic invasive breast cancer in our department between January 2000 and December 2010 and followed until December 2015.
These patients with non-metastatic invasive breast cancer have all initially benefited from a locoregional treatment and a systemic treatment. Locoregional treatment consisted in a total mastectomy, according to Patey, with axilary dissection by lack of radiotherapy and sentinel lymph nodes sampling. Regarding the systemic treatment, an adjuvant chemotherapy (FAC or FEC protocol) was performed in all patients, and only patients at Clinicalstage II and III received a neoadjuvant chemotherapy (same protocol) before surgery. At the end of the treatment and outside of any new event, the patients are followed according to ASCO recommendations.
We included in the study all patients who showed a metastatic breast cancer relapse during follow-up after initial treatment.
Patients operated outside our services, and those with breast cancer initially metastatic at initial diagnosis, were not included in the study.
Our data were collected on a survey patient records, chemotherapy registers, and anatomopathological findings.
The sample included 178 patients from whom the information was collected on a standard survey form. The analysis were done by the software Word, Excel, epi info and the statistical tests used were the calculations of the averages and frequencies.
3. Results
3.1. Epidemiological Characteristics
- Frequency of metastases
Between 2000 and 2010, 363 patients underwent radical breast cancer surgery and during surveillance until 2015, we found that 178 patients (49%) developed metastasis and we lost sight of 185 patients (51%) before the occurrence of metastases. The average follow-up duration was 3 years 7 months (extreme 9 months- 7 years 3 months) and cumulative survival without metastasis was 60% at 3 years and 43% at 5 years.
- Sociodemographic characteristics of patients
Patients had an average age of 53.4 years (extreme 38 - 74) and 62.4% were over 50 years of age, 91.6% were educated, and 88.2% did not have a high socio- economic level.
3.2. Characteristics of Metastases
- Location of metastases
Metastases were unique in 112 patients (62.9%), dominated by osseous metastases (41 patients), lung (28 patients), liver (19 patients), hollow abdominal viscera (9 patients) and peritoneal (3 patients).
- Occurrencechronology of metastases
The average occurrence delay of metastases was 2.4 years (extreme 8 months - 7 years 6 months). And they occurred in less than 24 months in 84 patients (47.2%) and over 24 months in 94 patients (52.8%). At 5 years 95.4% of patients had metastases.
3-Relation between the prognostic factors of the initial tumor and the occurrence delay of metastases.
4. Discussion
4.1. Epidemiological Characteristics
- Frequency of metastases
Metastatic relapses were frequent in our study population, estimated at 49% with a cumulative survival rate without metastasis at 3 years of 60% (Figure 1). And this frequency seems underestimated given the high rate of loss of sight (51%) that we found. In African literature we have not found any articles estimating the frequency of metastatic relapses. On the other hand, in developed countries where the breast cancer management is performed earlier, and with a better technical equipment than in our countries, metastatic relapses are generally less frequent, estimated at less than 20% in ten years [5] [6] [7] . But it is important to question these figures, as even in these developed countries, in the late-patient population, there are high rates of metastatic relapse after mastectomy : greater than 50% in 10 years [8]
- Age
Our patients had an average age of 53.4 years and the majority (62.4%) was over 50 years of age (Table 1). In the literature, it is indeed reported that metastatic relapses are more frequent in women over 50 years of age, and locoregional relapses more frequent in younger women [9] [10] . Menopausal status could affect the occurrence of these metastases, but the retrospective aspect of our study does not allow us to explore this parameter.
- Education level
The majority of our patients was educated (91.6%) (Table 1) and overall they had a sufficient level of education (secondary and higher) to better understand the interest of breast cancer screening. This screening would have permitted the management of the primary lesion at earlier stages, in order to limit the risk of metastatic relapses. But the absence of screening programs remains a reality in our regions, so that the notion of screening remains unknown to the population.
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Figure 1. Survival curve without metastatic relapses of patients who underwent radical surgery for invasive breast cancer from 2000 to 2010.
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Table 1. Distribution of patients according to their socio-demographic characteristics.
In a study conducted in our country on women having reached a secondary school level, Guié found that only 21% of women over 50 had already practiced breast cancer screening and in 42.1% of cases this screening went back to more than 4 years [11] .
- Socio-economic level
The patients in the study did not generally have a high socio-economic level (88.2%) (Table 1), constituting a real obstacle for the management of their disease (both the primary tumor and the metastases). In our country the management of cancers is expensive, and remains the responsibility of the patients because there is no social policy of health insurance. And in a study conducted in our country, Touré found that the lack of financial means caused the diagnostic delay of breast cancer in 36% of cases [1] .
4.2. Characteristics of Metastases
- Location
We found that the majority of the metastases of our patients was unique (62.9%), and affected mainly bones, lung, liver, and brain. Several authors have also highlighted the high incidence of bone and lung forms [12] [13] . As for Anhoux [14] he found, in his study conducted in our country, that the most common forms were pulmonary and hepatic. But we agree with the African authors who believe it is premature to conclude preferential locations in our conditions due to an underestimation related to insufficiency of paraclinical exploration: MRI and PET scan (Positron Emission Tomography) [14] [15] .
- Occurrence delay of metastatic relapses
After the initial treatment of our patients, metastases occurred within an average delay of 2.4 years. At 24 months, almost half of the patients (47.2%) had metastases and at 5 years almost all patients (95.4%) had metastases. It is recognized that the majority of metastases occur within the first 5 years justifying an increased surveillance during this period [3] [5] [16] . But cases of late metastases occurring beyond 20 years have been reported, imposing also a long-term monitoring of all patients for breast cancer [3] [17] [18] .
4.3. Relationship between the Prognostic Factors of the Initial Tumor and the Occurrence Delay of Metastases
1) Occurrence delay-Histological type of initial tumor
In our study 41.8% of patients having an invasive ductal carcinoma and 58.9% of patients who have had invasive lobular carcinoma, relapsed in less than 24 months (Table 2). In the literature, it is assumed that the histological type has no influence on prognosis : All invasive cancers have the same prognosis [19] [20] .
2) Occurrence delay-initial stage of tumor
In the study, the majority of patients who relapsed within 24 had an advanced stage: II and III (Table 2). In the study of Anvo [21] in which it has identified all patients with metastasis, 52.5% of the population had an initial tumor at stage III. Carter and Host [22] [23] have highlighted the pejorative role of the advanced
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Table 2. Relation between the prognostic factors of the initial tumor and the occurrence delay of metastases.
IDC: Infiltrating Ducta Carcinoma. ILC: Infiltrating Lobular Carcinoma. HR: Hormone Receptors. SBR: Scarff Bloom Richardson.
initial stage of the disease on the occurrence of relapses.
3) Occurrence delay-histological prognostic factors
Just as the initial stage of the disease, the usual histological prognostic factors govern the risk of metastatic relapse especially in the first 5 years following the initial curative treatment. [24] Thus the more the histological and prognostic grade SBR is high, the more relapses are frequent and precocious with a high mortality [25] [26] . In our series, we effectively found that metastatic relapses were more common in patients who had a higher grade (Table 2).
Concerning the other prognostic factors whose diagnosis is performed by immunohistochemistry (Receptor hormonal, Ki67, HER2), they were explored in only 58 patients (32.6%) because the laboratories were not equipped to conduct this examination during the period of study. These examinations were carried out abroad (France) at costs beyond the reach of the majority of patients. However the majority of patients who made these examinations had tumors with negative hormone receptors, an index Ki 67 high, and over expressed HER2.
The role of these various factors on the prognosis is also well known. The tumors that do not express estrogen receptors (ER-) relapse more frequently in the first 5 years, and tumors having a high index Ki 67 have a worse prognosis compared to tumors with moderate or low index [27] [28] . Moreover the HER2 overexpression is a poor prognostic factor especially for N + patients, and high grade SBR [29] [30] .
5. Conclusion
Our study has shown us that the management of breast cancer poses enormous problems. Metastases occurred early after the initial treatment. For the improvement of the survival of patients with breast cancer, we must popularize screening sessions and early diagnosis in developing countries.