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Year : 2020  |  Volume : 16  |  Issue : 6  |  Page : 1229-1234

Clinical features of metaplastic breast carcinoma: A single-center experience

1 Department of Radiation Oncology, Ankara Oncology Training and Research Hospital, Ankara, Turkey
2 Department of Medical Oncology, Ankara Oncology Training and Research Hospital, Ankara, Turkey
3 Department of Pathology, Ankara Oncology Training and Research Hospital, Ankara, Turkey
4 Department of Surgery, Ankara Oncology Training and Research Hospital, Ankara, Turkey
5 Department of Medical Oncology, Karabuk University Faculty of Medicine, Karabuk, Turkey

Date of Submission09-Nov-2019
Date of Acceptance27-Jan-2020
Date of Web Publication18-Dec-2020

Correspondence Address:
Fatih Karatas
Department of Medical Oncology, Karabuk University Faculty of Medicine, Alparslan Street, No: 1, Karabuk
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_964_19

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 > Abstract 

Aim: Metaplastic breast cancer (MBC) is a rare subtype with unusual clinical features. We aimed to analyze treatment results and define patients' characteristic features in our large MBC patient series.
Materials and Methods: Fifty-six patients with early MBC who received adjuvant radiotherapy (RT) in our center were included in the study. The age, sex, subtypes of MBC, histopathology, hormone and nodal status, tumor size, and types of treatment were retrospectively provided from hospital records.
Results: The median tumor size was 4 (1.3–16.5) cm, and triple-negative MBC cases were 38 (67.8%) of all patients. Axillary nodal involvements were present in 25 (44.6%) patients. The median follow-up time was 45.8 (4.9–130) months; the overall survival (OS) and disease-free survival (DFS) for 5 years were 67% and 64%, respectively. While distant metastases were seen in 15 (26.7%) patients, local recurrences were seen in only 4 patients. The median OS and DFS were higher in patients with ≤5.2 cm tumor than >5.2 cm ([130 vs. 49 months, P = 0.01] and [130 vs. 30 months, P = 0.009], respectively). Nodal involvement, hormone receptor status, surgical treatment, and type of RT had no effect on survival. In multivariate analysis, tumor size was not an independent prognostic factor for OS (P = 0.068; hazard ratio [HR]: 3.4, 95% confidence interval [CI] = 0.91–12.8), whereas age >65 years was found an independent poor prognostic factor for OS ([HR: 4.25, 95% CI: 0.23–0.78, P = 0.021] and DFS [HR: 3.1, 95% CI: 0.02–0. 87; P = 0.04], respectively).
Conclusions: Distant metastasis is at the forefront rather than local recurrence in MBC patients. More studies are needed to determine the factors that affect survival independently in MBC.

Keywords: Breast cancer, chemotherapy, metaplastic, radiotherapy, tumor size

How to cite this article:
Ertas G, Başal FB, Üçer AR, Benzer E, Altundağ MB, Demirci U, Çetin B, Karatas F. Clinical features of metaplastic breast carcinoma: A single-center experience. J Can Res Ther 2020;16:1229-34

How to cite this URL:
Ertas G, Başal FB, Üçer AR, Benzer E, Altundağ MB, Demirci U, Çetin B, Karatas F. Clinical features of metaplastic breast carcinoma: A single-center experience. J Can Res Ther [serial online] 2020 [cited 2021 Dec 4];16:1229-34. Available from: https://www.cancerjournal.net/text.asp?2020/16/6/1229/303902

 > Introduction Top

Breast cancer (BC) is the most common malignancy (after skin tumors) in women.[1],[2] The most common subtypes are invasive ductal cancer and invasive lobular cancer. Metaplastic breast carcinoma (MBC) is a rare tumor first described in 1973 by Huvos et al.[3] It accounts for 0.25%–1% of all BCs.[4],[5],[6] MBC is a heterogeneous group that encompasses both malign epithelial and mesenchymal tissue components and classified purely epithelial or mixed epithelial and mesenchymal. The epithelial group is formed by squamous, adenosquamous, and spindle cell carcinomas, whereas the mesenchymal group has occurred from carcinoma with chondroid/osseous metaplasia and carcinosarcoma.

Subtypes of MBC according to the WHO 2012 are low-grade adenosquamous carcinoma, fibromatosis-like MBC, squamous cell carcinoma, spindle cell carcinoma, MBC with mesenchymal differentiation (chondroid, osseous, and other types), and mixed MBC.[7],[8],[9],[10],[11],[12]

Nearly all MBCs are negative for estrogen receptor (ER), progesterone receptor (PR) and cerb-B2 (human epidermal growth factor receptor-2 [Her2]) with a worse prognosis than the other triple-negative BC.[13] In comparison with other invasive ductal carcinomas, MBC has a larger tumor size as a rapidly growing mass and also has a lower incidence of axillary lymph node metastasis despite the tumor width.[14],[15],[16] The response of MBC to systemic chemotherapy is poor in the metastatic or neoadjuvant settings.[17] Due to poorly response with conventional chemotherapy, surgical resection should be the first and important management for nonmetastatic MBC, regardless of tumor size.[13] Considering the size of the tumor with high recurrence rate and poor prognosis, mastectomy is recommended rather than breast-conserving surgery (BCS).[18],[19] Adjuvant radiotherapy (RT) should be the component of multimodal treatment for MBC patients undergoing BCS and mastectomy with larger than 5 cm tumor size and >4 metastatic axillary lymph node involvements.[20] Despite less axillary involvement, MBC has a high potential for metastatic spread to the bone and lung through hematogenous way rather than lymphatics.[21],[22] In our research, we aimed to define patient characteristics and analyze treatment results according to some prognostic factors.

 > Materials and Methods Top

Patient selection

There were 56 patients treated adjuvant RT due to MBC between January 2006 and December 2016 in the Department of Radiation Oncology Clinic who were retrospectively analyzed. The demographics of patients (age and sex) and clinical (subtypes of MBC, features of histopathology, hormone and nodal status, tumor size, types of treatment, date of progression, and last outpatient control or the date of exitus) features were retrieved from the patients' hospital records. ER and PR were accepted positive if nuclear staining is >1%, and also, cerb-B2 was accepted positive if score 3 in immunohistochemical analysis (strong complete membrane staining >10%) and score 2 (weak and moderate complete membrane staining >10%) confirmed with fluorescent in situ hybridization.

The statistical analysis was performed using the SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics are reported as percentages, mean, and medians according to distribution type. Mean, median, or frequency evaluations were performed for demographic and clinic properties of patients. We used receiver operating characteristic (ROC) curve analyses to determine the cutoff labels.

Statistical analysis

Overall survival (OS) was described as? interval time between initiations of the diagnosis to death of any case or last follow-up. Disease-free survival (DFS) was described as interval time between initiations of the treatment to recurrence of the disease, if no recurrence was recorded, to time of last follow up. Recurrence was accepted as local recurrence and/or distant metastasis. Survival curves were generated using the Kaplan–Meier method and compared using the Log-rank (LR) test. A value of P < 0.05 was considered statistically significant. The significant factors identified in the univariate analyses were entered into a backward LR selection of Cox regression model to determine the independent prognostic factors of PFS and OS.

 > Results Top

Patient characteristics

All patients were female with a median age of 51.3 (26–88). As considering clinicopathological features, we assessed types of operation, hormone and nodal status, cerb-B2 positivity, tumor size, and types of systemic treatment, as it is shown in [Table 1]. ER was negative in 49 (87.5%) patients, positive in 6 (10.7%) patients, and unknown in 1 patient. PR was negative in 50 (89.2%) patients, positive in 5 (8.9%) patients, and unknown in 1 patient. Hormone negativity was more than positivity as expected. Cerb-B2 negativity was present more than positivity, negative in 42 (75%) patients, and positive in 10 (17.8%) patients with unknown cerb-B2 status at 4 (7.1%) patients. Triple-negative MBC cases were 38 (67.8%) patients. Despite the lack of 20 (35.7%) results of patients, the median Ki-67 value was 60% (10%–90%). Axillary nodal involvement was present in 25 (44.6%) patients and absent in 23 patients (41%) with unknown 8 patients (14.2%).
Table 1: Clinicopathological characteristics of all patients (n=56)

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In terms of other features, histopathological subtypes were squamous in 8 (14.2%) patients, adenosquamous in 6 (10.7%) patients, matrix producing in 6 (10.7%) patients, spindle-like in 1 (1.7%) patient, chondroid in 1 (1.7%) patient, and carcinosarcoma in 1 (1.7%) patient [Figure 1]. No subtype definition was reported in the other 33 (58.9%) patients. The median tumor size was 4 cm (range: 1.3–16.5 cm). According to the tumor, node, and metastasis classification for tumor size, T1, T2, and T3 tumors were seen in 8 (14.2%), 32 (57.1%), and 12 (21.4%) patients, respectively. Tumor size was unknown in 4 (7.1%) patients.
Figure 1: Squamous cell carcinoma type of MBC (x200, HE)

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Surgery management was performed as modified radical mastectomy (MRM) in 30 (53.5%) patients and as BCS in 26 (46.5%) patients. Postoperative adjuvant RT was given in 48 (85.7%) patients. Among the patients who received postoperative adjuvant RT, 23 patients were performed BCS, whereas 25 patients were performed MRM. In addition, the tumor size was =5 cm for 80.7% and >5 cm for 3.8% in BCS patients, whereas the tumor size was =5 cm for 70% and >5 cm for 30% in MRM patients. Adjuvant chemotherapy was applied in 52 patients, and adjuvant hormonotherapy was given in two patients. As far as obtained available records, chemotherapy protocols consisted of adriamycin, cyclophosphamide, taxanes, 5-fluorouracil, trastuzumab, and for one case cisplatin. The reason for a small number of anti-Her2 treatments for the other cerb-B2 patients can be explained with unable to apply trastuzumab before 2009 in our country. Due to clinical and pathological features, patients received a combination of chemotherapy of adriamycin with or without taxane. The patients who received a combination of adriamycin and taxane groups (n = 20, 35.7%) were equal to the patients who received adriamycin-based chemotherapy without taxane (n = 20, 35.7%). In the case of recurrence, multiple distant metastases were seen in 13 (23.2%) patients. Localizations of metastasis were lung (n = 8, 14.2%), brain (n = 5, 8.9%), liver (n = 6, 10.7%), and bone (n = 6, 10.7%). Chest wall recurrence was seen in three patients, and axillary recurrence was seen in only one patient.

Survival data and prognostic factors

In a median, 45.8 (4.9–130)-month follow-up time, the median OS and DFS were 118 (26.2–209.7) months and 100 (65.4–134.5) months, respectively, for all patients. At the 1st year, the cumulative OS was 91%, and for 5 years, the cumulative OS was 67% [Figure 2]. Considering DFS analysis, at the 1st year, the cumulative DFS was 80%, and for 5 years, the cumulative DFS was 64% [Figure 3].
Figure 2: OS rates (%) for 5 years

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Figure 3: DFS rates (%) for 5 years

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In the ROC curve analyses, the cutoff value of tumor size was 5.2 cm (area under the curve: 0.701, 95% confidence interval [CI]: 0.542–0.859) for DFS and OS [Table 2] and [Figure 4], [Figure 5]. We were unable to analyze ROC curve for Ki-67 due to missing data. In addition, no significant relation was detected for hormone positivity, triple negativity, type of operation, and axillary lymph node positivity in univariate analyses for both OS and DFS. The treatment of RT was not analyzed because of the small number of patients. However, we separated two groups that the first group was patients who received RT and applied MRM (n = 24, 42.9%) and the second group was patients who received RT and applied BCS (n = 24, 42.9%) that both were equal. In addition, RT according to the type of operation that while 88.4% of the patients with BCS received RT, 83.3% of the patients with MRM received adjuvant RT. Considering the differences between groups for OS and DFS, there was no significant relation; P = 0.31 and 0.53, respectively. Tumor size was not a prognostic factor for OS in the multivariate Cox regression analyses despite close to P value (P = 0.068; hazard ratio [HR]: 3.4, 95% CI = 0.91–12.8). In addition, age >65 years was found an independent poor prognostic factor for OS ([HR: 4.25, 95% CI: 0.23–0.78, P = 0.021] and DFS [HR: 3.1, 95% CI: 0.02–0. 87; P = 0.04], respectively).
Figure 4: The differences of OS according to tumor size

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Figure 5: The differences of DFS according to tumor size

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Table 2: Univariate analyses for overall survival and disease-free survival (Kaplan-Meier method)

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 > Discussion Top

MBC is a rare histologic subtype of BC.[23],[24] In addition, there is limited information about its pathogenesis and prognostic and predictive factors due to pathological heterogeneity. Thus, we aimed to evaluate the properties of MBC and search prognostic factors as a single center. MBC is seen mostly in postmenopausal women during? the fifth decade as in our study with lack of menopausal status.[25],[26],[27] ER, PR, and cerb-B2 were generally negative in MBC.[28] In this study, ER, PR, and cerb-B2 negativity was 87.5%, 89.2%, and 75%, respectively. In BC, triple-negative status is associated with poor prognosis.[29] Triple-negative immunophenotype is one of the important immunohistochemical markers which are used defining basal-like BC.[30],[31],[32],[33],[34] MBC may be in the spectrum of basal-like BC with some features such as triple negativity and higher rates of distant metastasis.[18],[34],[35],[36],[37] In our study, distant metastasis was seen in 15 (26.7%) patients and in the triple-negative group (67.8%, n = 38). Triple negativity is caused by the absence of glandular tissues in the tumor area.[34] By virtue of less information about histological subgroups, we did not perform any correlation analyses with pathological features, hormone receptor, and cerb-B2 status.

As is shown most of the studies, MBC has generally larger tumor size when compared the patients with invasive ductal carcinoma.[6],[20] In our study, the median tumor size was 4 cm and also the largest size was 16.5 cm, a great tumor. In addition, tumor size was one of the important prognostic factors as it was reported before despite in some studies no relation was shown.[13],[15],[35],[38] We found a strong effect in the univariate analyses but could not show as a prognostic factor in the multivariate analyses.

Since larger tumors are a relative contraindication to breast conservation therapy, MBC patients have generally performed mastectomy rather than lumpectomy.[36] Despite this, breast conservation therapy is appropriate for patients with smaller tumors.[28],[37] In our study, the tumor size was =5 cm for 80.7% and >5 cm for 3.8% in BCS patients. The tumor size was =5 cm for 70% and >5 cm for 30% in MRM patients. MBC has lower axillary metastasis when it compared invasive ductal carcinoma.[39],[40] However, this confirmation was not provided in all studies just like in our study.[34],[41],[42] We found that nodal negativity (41%) was nearly equal to positivity (44.6%) with unknown 14.2% patients. Although we aimed to show nodal status as a prognostic factor, we failed to find this association. We may have obtained these results due to patients whose nodal status is unknown.

In the literature, there is a huge range as 6%–96% for triple negativity for MBC.[42],[43],[44],[45] In our study, we found 67.8% triple negativity Triple negativity usually accepted as negatife prognostic factor for breast cancer, but, in MBC patients, it was seems that non prognostic factor. Budzik et al. were showed a relationship between triple negativity and lymph node involvement.[34] In addition, this association was considered as an independent factor for regional lymph node metastasis by confirmation in other recent studies.[34],[45] We failed to show this relation (P = 0.17, HR: 5.7, 95% CI: 0.80–1.56).

Tseng and Martinez investigated the impact of RT on OS and DFS in 1501 MBC patients, respectively. They showed that RT provided OS and DFS benefit.[20] However, when patients stratified according to the type of surgery, RT provided OS but not DFS benefit in BCS and mastectomy patients. In our study, postoperative adjuvant RT was given for 85.7% in all patients. While 88.4% of the patients with BCS received RT, 83.3% of the patients with MRM received adjuvant RT, and there were no statistical differences on OS and DFS according to RT and type of operation [Table 2].

In this study, unlike other studies, one patient had metachronous bilateral MBC. Treatment modalities were MRM and postoperative adjuvant RT and chemotherapy. Lung metastasis occurred after 28 months of diagnosis, and a patient died after 34 months of the treatment.

Systemic metastases are at the forefront rather than local recurrence in MBC patients. Lung and bone metastases were seen as a potential metastatic spread by the way of vasculature.[21] In our study, we supplied distant metastases more than local recurrence.

The limitations of our study were a small number of patients, lack of some information about clinical features and histopathological adverse features (i.e., grade, lymphovascular invasion, primary tumor quadrant, and type of adjuvant chemotherapy).

 > Conclusions Top

Metaplastic BC appears to be a larger tumor than other BCs. Triple negativity and less nodal involvement with more distant metastases are seen as main characteristics. We failed to show as an independent prognostic factor in this group. While today's surgical management is the main treatment with adjuvant RT and chemotherapy, because of their clinicopathological differences compared to other cancers, randomized prospective studies are needed to develop specific treatment for this BC subtype.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2]


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