Caso Clínico: Carcinoma metaplásico da mama: relato de cinco casos

Carcinoma metaplásico da mama: relato de cinco casos
Metaplastic breast carcinoma: report of five cases

Catarina Duarte | Luisa Vasconcelos | Beatriz Nunes | Vera Mendonça | Marília Jorge



Afiliação:
Serviço de Radioterapia. Hospital de Santa Maria
Lisboa, Portugal

Instituição:
Centro Hospitalar de Lisboa Norte, Hospital de Santa Maria
Serviço de Radioterapia, Lisboa, Portugal


Conflitos de interesses:
Autora declara não ter conflito de interesses

Autor para correspondência:
Catarina Duarte
Praceta Dra. Adelaide Coutinho n.º 6 - 1.º Esq.
2800-002 Almada, Portugal
Telemóvel: +351 969 312 274
Email: anacatarinaduarte@hotmail.com



Resumo

Objetivos: Relatar cinco casos clínicos de carcinoma metaplásico da mama (CMM).
Métodos: Revisão retrospectiva dos dados clínicos.
Resultados: Quatro doentes em estadio IIA, uma (envolvimento bilateral) em estadio IIA e IIIB; mediana de idades de 50 anos. Três doentes submetidas a cirurgia conservadora, duas a mastectomia. Quimioterapia adjuvante em quatro doentes e neo-adjuvante em duas. Todas realizaram radioterapia adjuvante. Aos 28 meses de follow-up três doentes sem recidiva local ou à distância e duas sofreram recidiva local e à distância tendo falecido 2 e 24 meses pós radioterapia. As doentes que apresentaram recidiva local eram mastectomizadas, ambas receberam tratamento com feixes de fotões de 6MV, uma delas também com um boost de electrões de 9MeV na cicatriz.
Conclusões: O CMM tem uma apresentação clínica semelhante ao carcinoma de mama típico, o seu comportamento localmente agressivo pode sugerir tratar-se de um tumor de tipo sarcomatoide o que explicaria a quimio-resistência na maioria dos casos. Dado tratar-se apenas de 2 casos é difícil concluir que a causa directa da recidiva local nas duas doentes mastectomizadas tenha sido uma dose insuficiente na pele.

Palavras-chave: carcinoma metaplásico da mama; cancro de mama; radioterapia.


Abstract

Aim: Report five cases of metaplastic breast carcinoma (MBC).
Methods: Retrospective review of data.
Results: Disease in four patients was classed as IIA disease and as IIA and IIIB in one patient with bilateral involvement. Median age is 50 years. Three patients were treated with conservative surgery and two with mastectomy. Four patients received adjuvant chemotherapy and two received neo-adjuvant chemotherapy. All patients received adjuvant radiotherapy. At 28 months of follow-up, three patients had no local/distant recurrence, two patients had local and distant recurrence and died, 2 and 24 months after radiotherapy.
Conclusions: MBC presents clinically as typical breast cancer. This locally aggressive behavior may suggest a sarcomatoid type explaining the chemoresistance.

Keywords: Metaplastic breast cancer; breast cancer; radiotherapy.


Introduction

Metaplastic breast cancer (MBC) is a rare subtype of breast cancer, which represents 0.25%-1% of breast cancers diagnosed annually1 and was first defined by Huvos et al in 19732. MBC is a heterogeneous group of neoplasms characterized by a combination of two or more cellular types, usually a mixture of epithelial and mesenchymal cells. The World Health Organization (WHO) has classified MBC into pure epithelial-type and mixed epithelial and mesenchymal type3.
MBC differs from typical adenocarcinoma in a number of pathologic and clinical variables such as larger tumor size, less lymph node involvement and hormone and HER2 receptor positivity rates are usually lower. 
It has been reported that the risk of tumor recurrence of MBC is higher than in typical breast cancer4. Compared to patients with invasive ductal carcinoma (IDC), those with MBC have worse outcomes with 5-year survival rates ranging from 49% to 68%5-7. 
Research on this disease process has been limited due to its rarity; a few clinical data are available in the literature regarding prognosis, the best treatment modalities and outcomes. The optimal treatment strategies for MBC are unknown. Despite growing evidence that MBC is a distinct entity1 it has been managed in the same way as IDC. Data information regarding the role of adjuvant radiation therapy (RT) for the treatment of MBC are sparse in the literature8. This study characterizes the clinical management of five patients with primary MBC treated in our department describing patient characteristics, treatment modalities and outcomes.


Case reports

Between March 2010 and March 2012, five female patients with MBC were admitted to our department. Patient’s demographic data, tumor pathological characteristics, axillary lymph node involvement, metastatic sites, treatment schedules and survival data were evaluated retrospectively using the medical records of patients. A literature search using PUBMED was performed to identify previously reported incidence, features and patient series. The median age of the five female patients at presentation was 50 years (range 39–70). Two were premenopausal (Table 1), and one had bilateral involvement. The most frequent presentation was a unilateral palpable node (4 patients). One patient presented with nipple discharge and one was asymptomatic. The median tumor size was 2.6 cm (range 2.2– 4.0 cm). Four patients were classed as IIA disease and the patient with bilateral involvement was classed as IIA and IIIB. Histopathological subtypes were classified in one patient as squamous, one as adenosquamous, two as chondroid metaplasia and one as carcinosarcoma.


Conservative surgery with sentinel node biopsy was offered in three patients. Two patients had modified radical mastectomy, one with bilateral surgery. Only one patient had positive nodes. Four patients received adjuvant chemotherapy. The regimens used were anthracyclines and taxanes. The two patients treated with mastectomy received induction chemotherapy with anthracyclines, taxanes and capecitabine. One patient received letrozole in adjuvant setting. Adjuvant RT was given to all patients with 3D conformal external beams using 6 MV photons and 9 MeV electrons in the chest wall in one of the patients to boost irradiation. These specific energies were chosen based on the best dose distribution considering the anatomical characteristics of the patients. Radiotherapy doses ranged from 50-70 Gy. Three patients receiving conservative surgery had 50 Gy/25 fractions to whole breast and a boost irradiation of 10-20 Gy/5-10 fractions. Two patients who had mastectomy were treated with a total dose of 50 Gy/25 fractions to the chest wall. One of them received a boost of 10 Gy/5 fractions at the scar and the other patient had concomitant loco-regional nodal irradiation with 50 Gy/25 fractions. 
Three patients (60%) treated with conservative surgery had no local or distant recurrence and are alive. Two (40%) patients treated with mastectomy had local and distant recurrence. The patient with bilateral involvement developed cutaneous nodules on the chest wall, both sides, during RT and died from sepsis 10 months after recurrence. The other patient who had mastectomy suffered local progression with subcutaneous metastasis 2 months after adjuvant treatment and died 24 months after RT with bone and lung metastasis. Table 2 summarizes all patient data.


Discussion

MBC is a rare and heterogeneous disease with presentation similar to typical breast carcinoma; however, with a poorer outcome. 
Of the 957 new patients with breast cancer seen in our institution over a two-year period, six (0.63%) had MBC. This incidence is similar to that reported previously. 
In our series, the median age was 50 years, which conforms with the data available in the literature4, 9-11. 
There is little information about MBC in men all the literature has been limited to case reports12. In our study, all patients were female. 
MBC tumor size is usually greater than in classic breast carcinoma, hormone receptors are negative and there is a lower incidence of axillary node disease. MBC is often classified as a variant of triple-negative breast cancer despite its heterogeneity, but it has been demonstrated to confer a poorer prognosis than with triple-negative cancers of invasive ductal histology13. 
In our series, the median tumor size was 2.6 cm, which is slightly smaller than the median tumor size reported in most series4,14,15 and there was only one patient with positive estrogen receptors and node involvement. 
There are no standard guidelines for the treatment of MBC, mastectomy being used more commonly than breast-conserving surgery16, and considering the large median size of these tumors it may be the best approach. In our study, two patients had mastectomy and three patients had conservative surgery due to smaller tumor sizes. 
Data regarding adjuvant chemotherapy are not robust16. However, poor responses to conventional chemotherapy in the metastatic setting4,16 and increasing understanding of the molecular mechanisms underlying this disease suggests that inhibitors of the EGFR, P13K-Akt, and MAPK pathways should be explored in clinical trials16. 
The two patients who received neo-adjuvant chemotherapy had a weak response to treatment; one of these patients had both neo-adjuvant and adjuvant chemotherapy and developed local recurrence during RT. 
Information regarding the role of adjuvant RT for the treatment of MBC is sparse. In a series of 43 patients with MBC, Dave et al17 reported a 10.5% rate of local recurrence for patients receiving lumpectomy and adjuvant radiation. Total radiation consisted of 50-66 Gy. Results of the Tseng et al8 study indicated that RT improved both overall survival and disease-specific survival suggesting that RT should be included in the multimodality treatment for MBC patients undergoing breast conservative surgery and those patients with tumor size ≥5 cm or >4 metastatic axillary lymph nodes undergoing mastectomy. 
Despite the small number of patients, we can observe the aggressiveness of this disease; in our series, distant metastases were seen and death occurred in two cases of five. 
MBC presents clinically as a typical breast cancer; however, it is more locally aggressive and it seems to metastasize more to lung than typical breast cancer. This behavior may suggest a sarcomatoid type of tumor more than a typical breast cancer and this may explain the chemoresistance observed in the majority of cases. 
RT is an effective treatment for local disease control in this disease and it should be offered when possible to all selected patients. 
Patients with MBC, particularly those with metastatic disease, could be suitable candidates for clinical trials with new therapeutic modalities since no standardized treatment exists.


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