Abstract
BACKGROUND:
Metaplastic breast carcinoma (MBC) is a rare type of breast cancer (0.20–1.00% of all cases). With a more aggressive clinical course, MBC frequently presents as a triple-negative subtype.
OBJECTIVE:
To describe a case series, analyzing patients survival in four MBC cases.
METHODS:
The cases were obtained from 532 medical records of breast cancer patients (0.7% of the total).
RESULTS:
All patients were female. Mean patient age was 49 years (range: 38–60 years). Mean tumor size was 8.9 cm (range: 3.0–15.5 cm). Mastectomy was performed in three cases. One patient had axillary nodal metastasis. All underwent chemotherapy and three received radiation therapy after surgery.
CONCLUSIONS:
With a mean follow-up of 36 months (range: 10–60 months), one case had a tumor recurrence (25%). Three patients (75%) died from metastatic disease and one (25%) is still alive and free of disease.
Background
Metaplastic breast carcinoma (MBC) is a rare and aggressive malignancy that accounts for only 0.20–1.00% of all breast cancers [1]. Morphologically, it is characterized by squamous and/or mesenchymal differentiation [2].
Concerning immunohistochemical profile, these tumors usually present as a triple-negative (TN) subtype. Nevertheless, these tumors are relatively refratory to chemotherapy, when compared to conventional invasive TN breast cancers [3].
MBC is notable due to its differences in clinical presentation and radiological and pathological heterogeneity. This category is frequently associated with poor prognosis and worse patients survival [4].
The aim of the study was to describe a case series of MBC, analyzing patients survival in four MBC cases treated in a Private Breast Disorder Clinic located in Teresina (PI), Brazil.
Methods
This is a retrospective observational case series study. Medical records of all MBC cases occurring from 2007 to 2020 were selected from analysis of 532 patients diagnosed with breast cancer. Age, tumor staging, histology studies, immunohistochemistry, treatment, and follow-up were analyzed.
The current study is part of a scientific project that was approved by the Research Ethics Committee of the State University of Piauí, Teresina (PI), Brasil, under CAAE no. 30154720.0.0000.5209. All ethical principles established by the National Health Council resolution no. 466/12 and international documents were followed.
Results
Of the 532 patients, four cases of MBC (representing 0.7% of the total) were found and described in Table 1. Two of these cases have already been previously published [5,6]. All patients were female. Mean patient age was 49 years (range: 38–60 years), and mean tumor size was 8.9 cm in diameter (range: 3.0–15.5 cm). Mastectomy was the surgical treatment in three cases and one patient had axillary node involvement (case 3). All underwent chemotherapy and three also received radiation therapy after surgery. Mean follow-up was 36 months (range: 10–60 months). One case had a tumor recurrence. Regarding the outcome, three patients (75%) died and already had metastatic disease. In one of these cases the cause of death was Guillain-Barré syndrome. One patient (25%) is alive and free of disease. The main metastatic focus was the lung.
Description of the four patients included
Description of the four patients included
SBR: Segmental breast resection. MT: Mastectomy. SLN: Sentinel lymph node. ACT: Adjuvant chemotherapy. ART: Adjuvant radiation therapy. AHT: Adjuvant hormone therapy. CNS: Central nervous system. AWD: Always without disease.
Of the four patients included, two (50%) had TN tumors. Table 2 shows the immunohistochemical results of the tumors presented.
Immunohistochemical results
ER: Estrogen receptors. PR: Progesterone receptors. HER2: HER2 protein. Ki67: Ki67 antigen. CK5: Cytokeratin 5. p63: p63 protein. 34BE12: Basal cell-specific cytokeratin. CK 5/6: Cytokeratin 5/6. AE1/AE3: AE1/AE3 anticytokeratin antibodies.
Concerning the treatment performed, in case 1, the patient underwent segmental breast resection, without axillary approach, removing an encapsulated tumor with free margins. She received 30 radiation therapy sessions, in addition to chemotherapy and hormone therapy with tamoxifen after surgery. In case 2, a modified radical mastectomy was performed. The patient received four cycles of adjuvant chemotherapy, with 5-fluorouracil, epirubicin and cyclophosphamide.
Treatment was modified radical mastectomy without reconstruction in case 3. In this case, histopathological analysis showed axillary lymph node metastases. The patient underwent chemotherapy and radiation therapy after surgery. Finally, in case 4, the patient underwent mastectomy with resection of the skin and pectoralis muscle segment, infiltrated by neoplasm, preserving the remaining skin and papillo-areolar complex. No metastasis was found in the sentinel lymph node. Then, she received adjuvant chemotherapy, followed by adjuvant radiation therapy.
In the current study, only 0.7% of breast cancer cases were MBC, in agreement with data in the literature, indicating that the MBC accounted for only 0.25–1.0% of breast cancer cases [7].
Usually, MBC presents as TN breast cancer (ER−/PR− and HER2−), with an even worse prognosis. It is rarer that typical TN tumors [8]. Nevertheless, the prognosis observed in this study was different from that commonly found in the literature. In this study, the mean follow-up period was 36 months, with different types of treatment (mastectomy, adjuvant chemotherapy and adjuvant radiation therapy) [4]. In cases 1 and 3, the tumor had ER+/PR+. Nevertheless, in case 3, ER/PR expression was very low (only 2%). More recent studies show that about 70% of MBC are TN. However, only 8.8% of cases are ER+/PR+ [9] and 4% are HER2+ in MBC [10], demonstrating that the results are not common.
Lymph node involvement is an important predictor of disease-free survival in this disease. Nevertheless, when compared to other types of breast cancer, axillary node metastasis is less frequent in MBC and occurs in 6.0–25.0% of cases [11]. In this study, only case 3 (25%) had axillary node involvement, with a global survival of 17 months.
Tumor size is also an important factor in breast cancer prognosis. Compared to other malignant breast tumors, MBC has larger dimensions in general. Consistently, mean tumor size was 8.9 cm, ranging from 3.0 to 15.5 cm. In cases of MBC, mastectomy is a common procedure for 75% of cases, particularly due to the aggressive nature of the disease, tumor size and poor chemotherapy response, which demands a more aggressive approach [7].
Chemotherapy is a commonly used treatment in MBC. In this study, it was the most frequent treatment used, administered to all 4 cases. Nevertheless, some isolated studies have shown that MBC is resistant to chemotherapy. There is no significant improvement in survival, occurrence of distant metastasis and local recurrence [8,12].
In the literature, a higher survival in MBC is related to the use of adjuvant radiation therapy. Nevertheless, even in MBC cases of low survival rates, the efficacy of different treatment modalities has not been compared, due to the few clinical trials in this rare condition [8,13]. Recent studies have cited immunotherapy to treat this disease, although the safe use of this therapy is still not recommended owing to the paucity of studies [12].
Finally, in this type of cancer, hormone therapy is rarely used, since tumors are generally TN. Only one patient (case 1) was treated with hormone therapy in the study. According to Wright et al., the presence of hormone receptors is not related to the prognosis of MBC [9].
MBC is a rare disease and its treatment is fraught with difficulties. Therefore, further studies on MBC are needed to enhance knowledge of the disease and more effective treatment modalities to improve survival rates, which are still quite low [14].
Conclusions
In the current study, MBC accounted for 0.7% of the breast cancer cases. With a mean follow-up period of 36 months (range: 10–60 months), 3 patients died (75%) and one (25%) is still alive and free of active disease, at 56 months after surgery.
Footnotes
Acknowledgements
None.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Funding
This research has not received any specific grant from public, commercial, or non-profit sector agencies.
Authors’ contributions
da Costa REAR, Fontinele DRS and Medeiros PCDR: study concept, data curation, formal analysis, methodology, project management, writing (original draft, review and editing). Vieira SC: study concept, data curation, formal analysis, methodology, project management, writing (review and editing). All authors have read and approved the final draft.