Introduction
Breast cancer is the most common cancer among women in Morocco. Its incidence is about 45.5 cases per 100,000 inhabitants [ 1 ]. Bone is the most favored site for breast cancer metastasis [ 2 ]. However, the appearance of bone manifestations in a patient treated for localized breast cancer is not always related to a bone relapse of this cancer. We describe through this clinical case the diagnostic difficulties of multiple myeloma in a patient with a history of breast cancer and who is at risk of delaying the management of myeloma.
Case presentation
A 68-year-old patient with no pathological history was followed for breast cancer, diagnosed after discovery by self-examination of a nodule in the left breast. The nodule was classified as ACR5 on mammographic ultrasound. The patient underwent a lumpectomy with axillary lymph node dissection. It was an infiltrating ductal carcinoma SBR III, hormone receptor positive, and Her2 negative. The tumor was classified as stage IIA. The patient received adjuvant chemotherapy (three cycles of anthracycline at a dose of 60 mg/m 2 and cyclophosphamide at a dose of 600 mg/m 2 , followed by three cycles of docetaxel at a dose of 100 mg/m 2 ), followed by radiotherapy and endocrine therapy (anastrozole 1 mg/d).
After two years, the evolution was marked by the appearance of inflammatory spinal pain, which prompted her to seek consultation. The physical examination found a patient with a performance status of 1, without tumor syndrome or signs of local relapse. The spinal MRI showed the presence of multiple vertebral lesions with hyperintensity on fat-suppressed T2-weighted imaging, mainly suggesting a relapse of her disease (Figure 1 ).
The initial biological exploration revealed a normal CA 15-3 level (7.3 U/mL) with isolated anemia (9 g/dL) on the complete blood count. The biochemical test showed hypoalbuminemia (32 g/L), moderate hypercalcemia (2.70 mmol/L), and elevated serum creatinine (160 µmol/L), indicating a glomerular filtration rate of 40 mL/min. Nevertheless, protein (89 g/L) and lactate dehydrogenase (200 U/L) levels were normal.
In light of this clinical and biological presentation, a complementary biological assessment was necessary, notably protein electrophoresis, which showed a monoclonal hypergammaglobulinemic peak (43 g/L), and urine immunofixation electrophoresis, which demonstrated the presence of Bence-Jones protein. To confirm the diagnosis of myeloma, we performed a bone marrow examination that showed 42% infiltration of the bone marrow by dystrophic plasma cells (Figure 2 ).
In the end, we ruled out the diagnosis of breast cancer recurrence and retained the diagnosis of stage II multiple myeloma. The patient underwent six cycles of chemotherapy according to the VTD protocol (bortezomib 1.3 mg/m 2 weekly, thalidomide 50 mg once a day, and dexamethasone 20 mg), marked by good tolerance. After six months of follow-up, the patient is in clinical and biological remission from her myeloma.
Discussion
Breast cancer is the most common cancer among women, accounting for approximately 30% of newly diagnosed cancers [ 3 ]. It is the second leading cause of cancer death in women [ 3 ]. Screening and the development of adjuvant therapies have improved overall patient survival [ 4 ]. The risk of metastatic recurrence of early breast cancer is not negligible and is estimated to be between 20% and 30% [ 5 ].
However, the appearance of a bone lesion in a treated patient is not always related to a metastatic relapse of the already known cancer [ 6 ]. The incidence of malignant hemopathy, particularly multiple myeloma, in patients treated for breast cancer appears to be higher than in the general population [ 7 ]. Confirmation of bone relapse from breast cancer requires careful consideration. Several factors must be taken into consideration before starting treatment, including the patient's age, biological assessment, radiological appearance of the bone lesions, presence of other metastatic sites, and tumor markers [ 8 ].
The association of cytopenia, hypercalcemia, or lytic bone lesions in a patient pretreated for breast cancer can lead to confusion between two diagnoses: metastatic bone relapse and multiple myeloma [ 9 ]. Even bone scintigraphy cannot always distinguish between the two, as it is more sensitive to osteoblastic lesions but remains less reliable for lytic lesions [ 10 , 11 ]. Moreover, the presence of a bone abnormality on scintigraphy may be related to benign inflammatory or traumatic processes [ 9 ]. Fluorodeoxyglucose (FDG)-PET/CT remains the most sensitive for detecting bone and visceral recurrences of breast cancer [ 12 ]. The biopsy and the pathology study of bone lesions remain hard to perform [ 13 ]. With the development of molecular biology, a liquid biopsy from a blood sample appears to play a role in the diagnosis of relapses [ 14 ].
In addition to the previously mentioned biological abnormalities, the deterioration of renal function, the presence of a monoclonal spike during serum protein electrophoresis, and the search for Bence-Jones protein will lead us to consider the diagnosis of multiple myeloma more closely. The presence of clonal bone marrow plasmacytosis ≥ 10% on bone marrow biopsy, combined with the CRAB criteria, confirms the diagnosis of multiple myeloma [ 9 , 15 ].
Conclusions
Breast cancer screening programs have promoted the diagnosis of this cancer in young populations and at an early stage, which has improved overall survival. The risk of developing other pathologies, particularly malignant hematological diseases in pretreated patients, does not seem negligible. Hence, it is important to ensure and conduct an etiological investigation before confirming a diagnosis of relapse and starting a treatment that may be harmful.
Disclosures
Human subjects: Informed consent for treatment and open access publication was obtained or waived by all participants in this study.
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:
Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.
Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.
Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
Author Contributions
Concept and design: Mohamed Kaakoua, Yahyaoui Hicham, Aznag Mohamed Amine, Ismail Essadi, Moussa Abdolaziz Sawadogo, Soukayna Boujmadi, Nada Ebbadi, Hamza Laabbar
Acquisition, analysis, or interpretation of data: Mohamed Kaakoua, Yahyaoui Hicham, Aznag Mohamed Amine, Ismail Essadi, Moussa Abdolaziz Sawadogo, Soukayna Boujmadi, Nada Ebbadi, Hamza Laabbar
Drafting of the manuscript: Mohamed Kaakoua, Yahyaoui Hicham, Aznag Mohamed Amine, Ismail Essadi, Moussa Abdolaziz Sawadogo, Soukayna Boujmadi, Nada Ebbadi, Hamza Laabbar
Critical review of the manuscript for important intellectual content: Mohamed Kaakoua, Yahyaoui Hicham, Aznag Mohamed Amine, Ismail Essadi, Moussa Abdolaziz Sawadogo, Soukayna Boujmadi, Nada Ebbadi, Hamza Laabbar
Supervision: Mohamed Kaakoua, Yahyaoui Hicham, Aznag Mohamed Amine, Ismail Essadi, Moussa Abdolaziz Sawadogo, Soukayna Boujmadi, Nada Ebbadi, Hamza Laabbar
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