Breast cancer is the most common cancer in women worldwide, accounting for an estimated 22% of all female cancers. In Africa, it was estimated at 186,598 cases with 85,787 deaths, while in Senegal there were 1817 cases with 951 deaths in the same period, almost all due to metastases, 73% of which were bone metastases [1] [2] [3] .

The diagnosis of breast cancer metastases is based on a meticulous clinical examination, and on medical imaging examinations of the utmost importance, such as chest X-ray, abdominal ultrasound, thoraco-abdomino-pelvic computed tomography (CT) and magnetic resonance imaging (MRI): chest X-ray, abdominal ultrasound, thoraco-abdomino-pelvic computed tomography (CT), magnetic resonance imaging (MRI), sentinel lymph node technique, bone scintigraphy (BS), fluorodeoxyglucose Positron Emission Tomography (¹⁸FDG PET-CT) [4] [5] [6] . In oncology, bone scintigraphy (BS) using Hydroxyl-methylene bisphosphonate (HMDP) labelled with metastable technetium 99 (^99mTc) remains the standard examination for detecting and assessing the extension of bone metastases [7] .

The aim of our work was to evaluate the role of bone scintigraphy in the assessment and follow-up of breast cancer in Senegal.

We included a total of 142 patients out of a total of 165. Twenty-three (23) did not meet the inclusion criteria.

The limitations of our study are essentially linked to its retrospective nature, with data sometimes missing and details that should have been collected for a more exhaustive and in-depth analysis.

Breast cancer is a highly heterogeneous and complex disease, with over 90% of deaths caused by distant metastases [8] .

Bone scintigraphy is an essential part of oncology disease management.

Numerous studies have demonstrated the value of bone scintigraphy as a conventional work-up for the evaluation of metastatic disease, which has become a routine procedure for detecting metastatic bone lesions and monitoring response to treatment [9] .

However, it is tending to be replaced by fluorodeoxyglucose (FDG) positron emission tomography (PET) coupled with computed tomography (CT), which has become the most widely used examination in the initial extension assessment of breast cancers from cT2N1 or cT3Nx stages, in cases of suspected or proven recurrence, and in the evaluation of response to neo-adjuvant and adjuvant systemic treatments [10] .

But the most important aspect remains the early detection of breast cancer metastases, with the aim of improving prognosis.

• The sex

Our study population was exclusively female. Our results are in line with those of Diop O. et al. [11] , who noted female exclusivity in their study. The study by Bakhali H. et al. [12] also concerned only a population of 30 women.

In the same vein, Colombié M. [13] had identified the female sex as the most important risk factor for breast cancer, and Granier P et al. [14] had also specified that breast cancer was the most common cancer in women.

However, it can occur in men in less than 1% of cases, as reported in studies by Mousseau M. et al. [15] and Hali Fouzia et al. [16] . The study by Mahjoub N. et al. [17] found that 99.1% of cases were female, and only 0.9% male.

Camara MA et al. [18] found that 97.73% of his patients were female.

The rarity of male breast cancer can be explained by the atrophic nature of the mammary gland, the thinness of the milk ducts, the absence of acini and the abundance of fibrous tissue in men.

• Age

Age is the most important risk factor for breast cancer. Breast cancer is rare (around 10%) in women under the age of 30, and the risk increases between the ages of 50 and 75 (nearly 20% or even 2/3 of breast cancers) [19] [20] .

The age at which breast cancer is discovered differs according to the populations studied. In developing African countries, the age of discovery is often younger than in developed countries, where breast cancer is a postmenopausal cancer [19] .

In our study, the mean age of discovery of breast cancer was 46.6 years.

Our results are practically similar to those of Diop O et al. [11] , who found a mean age of 46.9 years; Aouad L [21] found a mean age of 45.76 years in his study.

Camara MA et al. [18] in Mali also found an average age of 49. Malian studies by Safini F et al. [22] , Mhamdi F et al. [23] found an average age of 49; Chatti K et al. [24] found an average age of 42.

On the other hand, other European studies have found a much older average age, in older women, such as those by Mousseau M. et al. [15] ; Colombié M. [13] reported an average age of 61, and Mayi T. [25] also found an average age of onset of 60.

In America, the study by Gordon P. Watt [26] and Hendrict RE [27] found a median age at first diagnosis of breast cancer of 55 for black women, 53 for Hispanic women and 54 for Asian women, compared with 58 for white women and 56 for North American Indians/Alaska Natives. Similarly, the study by Howlader N [28] found that the median age at diagnosis of breast cancer among women in the USA was 63; and the median age at diagnosis for black women was 60, compared with 64 for white women.

This can be explained, on the one hand, by the inversion of the age pyramid with a younger population in our developing regions and, on the other hand, by the heterogeneity and complexity of breast cancer.

• Location of breast cancer

The location of the primary tumour was unilateral in 91.55%, with 55.23% on the right and 45.77% on the left. Among the 59 cases showing bone metastases on scintigraphy, breast cancer was unilateral in 46 cases (77.97%), including 24 cases (52.17%) on the right and 22 cases (47.83%) on the left.

This predominance in the right breast was noted in the study by Diop O. et al. [11] , who found 62.5% in the right breast versus 32.5% in the left; identical in the study by Lamya A. [21] , who found 52.1% in the right breast.

Our results are not in line with those of Bakkali H et al. Bakkali H et al. [12] , who found that the left breast was the most affected. Other studies carried out in Oran found no preference for the site of breast cancer.

• Histological type of breast cancer

Invasive ductal carcinoma was the most common histological type (97.18% of cases). Among patients whose scintigraphy showed bone metastases, 57 cases (96.61%) were of the infiltrating ductal carcinoma (IDC) type. H. Bakkali et al. [12] found 90% of cases to be infiltrating ductal carcinoma; Chatti K et al. [24] in Tunisia confirmed that the most frequent histological type was infiltrating ductal carcinoma (96%); Lamya Aouad [21] in Senegal found 72.9% of IDC.

• SRB grade

Grade SRB2 was more common (61.97% of cases), followed by grade SRB3 in 32.39% of cases. These results are in line with those of Chatti K. et al. [24] , who found SRB2 and SRB3 grades in 81% of cases. In contrast, Loubna Bouggana [29] found grade 2 in 10.1% of cases and grade 3 in 8.9%; Aouad L [21] found grade SRB1 in 5 patients (5.2%), grade SRB2 in 24 patients (25%) and grade SRB3 in 12 patients (12.5%).

• Scintigraphy as part of pre-therapy assessment or follow-up assessment

The presence of bone metastases has a direct impact on a patient’s survival and quality of life, and consequently on their therapeutic management. Metastatic bone cancer is a frequent and severe complication of advanced disease. It affects up to 70% of patients with breast cancer [30] . Whole-body bone scintigraphy is widely used for the detection of bone lesions, as it is considered to have a high sensitivity for the visualization of both osteolytic and osteoblastic bone metastases [30] .

In our study, whole-body bone scintigraphy was performed in 134 cases (94.37%) for therapeutic monitoring and in 8 cases (5.63%) as part of the pre-therapeutic assessment.

Our results are in the same order as those found in Tunisia, with Chatti K. et al. [24] who reported that the most requested examination for the evaluation of metastatic treatment (100%) was planar bone scintigraphy. Similarly, Camara MA [18] found that 34.09% of BS cases were carried out in the pre-therapeutic phase, compared with 64.01% for breast cancer surveillance.

• Bone scintigraphy results

- Contribution of bone scintigraphy

In our study, 131 patients (92.25%) had a contributory bone scan, of which 72 (50.70%) were normal and 59 (41.55%) were positive or had bone metastases; 11 (7.75%) had a non-contributory or doubtful scan.

Our results appear to be similar to those of Taourel P. et al. [31] who, in a series including 784 patients with advanced breast cancer, found 48% of cases with bone metastases. The study by Mhamdi F et al. [23] showed 57 scans with secondary bone localization, compared with 18 normal cases. The study by Diop O et al. [11] found that the examination was contributive in 95% of cases (positive in 12 patients (30%); negative in 26 patients (65%)) and indeterminate in 5% of cases. The study by Granier P. et al. [14] of 267 bone scintigraphy abnormalities assessed bone location as precise in 29 cases, probable in 129 and disputed in 109.

Some authors have reported higher proportions of patients with bone metastases than in our study. Indeed, Schroeder H. et al. [32] stated that the primary site of breast cancer metastases was bone, and noted that 77% (n = 20) of patients had bone metastases at the time of diagnosis; the study by Safini F. et al. [22] found 61 patients, or 72%, with bone metastases.

On the other hand, Francon T et al. [33] reported lower proportions of bone metastases: 37% of cases (22/60) with suspected malignant foci, compared with 63% of cases (38/60) with undetermined foci; similarly, Abedi SM [34] found 19 cases (23.25%) with abnormal ^99mTc-MDP fixation among 80 bone scans.

We can testify to the high sensitivity of SO in the early detection of bone metastases, as described in the literature. Indeed, Giammarile F. [35] noted a sensitivity of 95%, Costelloe CM et al. [36] and Paycha F [7] a sensitivity close to 100% in the search for bone metastases.

- Seating and quantification of bone locations on scintigraphy

In our study, almost all patients had multiple sites, i.e. 57 cases (96.61%), and only 2 cases (3.39%) had a single or solitary site.

These bone lesions were quantified according to the Soloway [37] classification in 83 cases (58.45%) as grade I or no bone metastases; 16 cases (11.27%) as grade II or low breast cancer spread; 11 cases (7.75%) grade III or intermediate breast cancer spread; 22 cases (15.49%) grade IV or extensive breast cancer metastasis; and 10 cases (7.04%) grade V with diffuse or very extensive breast cancer metastasis.

In contrast, the study by Ndong et al. [38] found grade I: 3/15 patients (20%); grade II: 9/15 patients (60%); grade III: 3/15 patients (20%) and grade IV or super scan: no patients.

Multiple localizations were both axial and appendicular in 31 cases (54.39%); axial in 16 cases (28.07%); axial, cranial and appendicular in 10 cases (17.54%).

We thus observed a strong axial predominance, superimposed on the results of the literature. Axial secondary bone lesions were located more precisely in the thorax in 20 cases (33.90%), the spine in 17 cases (28.81%), the pelvis in 14 cases (23.73%) and the sternum in 8 cases (13.56%).

Our results are almost identical to those of Biyi A D et al. [39] (22), who noted a strong axial predominance in 80% of cases. The study by Paycha et al. [7] found metastases in the dorsolumbar spine in 50%, the costal gril in 20%, the pelvic girdle in 15% and the sternum in 10%. Similarly, the study by Ndong et al. [38] noted a predominance of spinal locations (66.66%), costal crest (58.33%), pelvis (33%) and skull (17%).

The study by Biyi A. D. [39] reported that the dorsal spine and costal grill were the sites most affected by bone metastases.

Granier P et al. [14] found 88% of bone metastases in the dorsolumbar spine and pelvis.

The study by Francon T et al. [33] found foci located on the axial skeleton in 90% of patients (54/60) and on the peripheral skeleton in 10% (6/60).

On the other hand, the Franson T et al. [33] study found 10.5% of cases presenting an isolated focus, i.e. 60 patients out of 572.

Bone metastases from breast cancer most often occur in the axial skeleton and proximal ends of the diaphysis of long bones. The most commonly affected sites are the lumbar and thoracic spine, pelvis, ribs, sternum, femurs, humerus and skull. Distal bone metastases are rarer [40] . The most common sites of single metastases from breast cancer are the sternum (34%), pelvis (18%), thoracic spine (16%), lumbar spine (10%), ribs (7%), pelvis, skull and femur [41] .

This axial preference is due to high local osteoblastic activity and abundant local blood flow to the constantly renewing bone matrix.

- Types of bone lesions on scintigraphy

Bone metastases from breast cancer are classified into three groups according to their appearance: osteolytic, osteocondensing and mixed. However, bone scintigraphy is more sensitive in detecting purely condensing lesions [42] [43] .

In our series, the scintigraphic appearance of breast cancer bone metastases was dominated mainly by hyperfixation lesions in 58 cases (98.31%), with only 1 case of a mixed lesion (1.69%).

Our results are similar to those of Ndiaye M [44] , who also found a 75% predominance of hyper-fixing lesions among patients with bone metastases.

Diop O et al. [11] who also reported that the scintigraphic appearance of bone metastases always showed bone hyperfixation of the radiotracer.

In the same vein, Mahfouz H [45] stated in his study that bone metastases observed in breast cancer were predominantly hyper-fixating.

- SO and TNM classification

In our series, bone scintigraphy correlated well with tumour T stage, with a good correlation coefficient (r = 0.9). There was a progressive increase in scintigraphy positivity with tumour size.

Safini F. et al. [22] also reported that the frequency of metastases increased with tumour size, lymph node status and disease stage.

Indeed, the study by Safini F. et al. [22] found no metastases in patients with clinical stage I disease, 14.5% of patients with clinical stage II disease had metastases, compared with 19.3% of patients with clinical stage IIIA disease, 53% with clinical stage IIIB disease and 13.2% with clinical stage IIIC disease.

Houssine Boufetta et al. [46] , in a retrospective study of 22 cases of bilateral synchronous breast cancer in a Maghreb country, found that patients with T3 or T4 tumours were nine times more likely than others to develop metastases.

Several other authors have reported an effect of tumour size on the risk of developing bone metastases, with larger tumours presenting a higher risk [47] .

Wei et al. found that tumours with bone metastases only had a mean size of 2.8 cm compared with tumours without bone metastases, which had a mean size of 1.8 cm [17] [48] .

Yamashiro H et al. [49] had shown that patients with T2 tumours had a high risk (HR) of 2.02 of being free of bone metastases, compared with patients with T3 (HR = 4.14) or T4 (HR = 6.40). Nevertheless, when considered in a multifactorial analysis, tumour size did not systematically increase the risk of bone metastases in a statistically significant way.

In contrast, a Japanese study of 9652 breast cancer patients showed no relationship between tumour size and the development of bone metastases [50] . As such, tumour size did not appear to be a major factor in the development of bone metastases [48] .

Like tumour stage, lymph node involvement is also a known risk factor for metastasis in breast cancer patients [51] .

In our study, we found that positive bone scans outnumbered negative ones as lymph node involvement became more severe. However, the absence of lymph node involvement did not totally rule out bone involvement. Indeed, we found 5 cases out of 32 of positive BS at stage N0.

In contrast, other studies showed no significant relationship between lymph node metastases and the risk of bone metastases in breast cancer patients [52] . Although it may be a factor contributing to the risk of bone metastases, lymph node metastases do not appear to play a dominant role over others such as intrinsic subtype [47] .

The isotopic sentinel node technique is a key element in the evaluation of axillary lymph nodes [53] .

The EANM and SNMMI, in their best practice guidelines for lymphoscintigraphic localization of the sentinel lymph node in breast cancer, have specified that the current indication for SPECT/CT includes: non-visualization of the sentinel lymph node on conventional planar imaging, patient obesity, presence of the sentinel lymph node extra-axillary, or drainage that is otherwise difficult to characterize (multiple drainage sites, visualization of the lymph node chain) [54] .

Bone scintigraphy has enabled good post-therapeutic monitoring of cancer in our current context. In oncology, bone scintigraphy remains the basic examination for detecting and assessing the extent of bone metastases. It has the advantage of enabling a global study of the entire skeleton in a single examination, at the price of a favourable dosimetric cost. Added to this is the excellent sensitivity of OS, evaluated at 100% in many studies. Indeed, OS can detect bone lesions earlier than CT, even at sub-clinical or asymptomatic stages. However, the main drawback of OS remains its limited specificity, which is why it should be coupled with CT (SPECT-CT or SPECT-CT).

Today, it is the nuclear exploration technique available for the proper management of bone metastases from breast cancer in Senegal. In developed countries, bone scintigraphy is increasingly giving way to PET/CT, a nuclear medicine oncology imaging technique that combines the functional information of PET with the morphological information of CT.

Improved nuclear imaging facilities in Senegal (SPECT/CT and PET/CT), improved diagnostic performance with a reduction in doubtful cases and appropriate patient management.

None.

Bathily, E.H.A.L., Djigo, M.S., Ba, D., Thiaw, G., Diop, O., Gueye, K., Fachinan, O.H., Ndong, B., Ndoye, O. and Mbodj, M. (2024) Place of Bone Scintigraphy in the Assessment of Extension and Follow-Up of Breast Cancer in Senegal: Study of 165 Cases in the Nuclear Medicine Department of Idrissa Pouye General Hospital (Dakar). Open Journal of Medical Imaging, 14, 10-30. https://doi.org/10.4236/ojmi.2024.141002