|Year : 2018 | Volume
| Issue : 4 | Page : 69-74
Metaplastic carcinoma of breast: A series of nine cases from a regional cancer center in Northeast India
Srigopal Mohanty, Yumkhaibam Sobita Devi, Daffilyne Lyngdoh Nongrum, Laishram Jaichand Singh, Vimal Sekar, Deep Sikha Das
Department of Radiotherapy, Regional Cancer Centre, RIMS, Imphal, Manipur, India
|Date of Web Publication||26-Dec-2018|
Dr. Srigopal Mohanty
Department of Radiotherapy, Regional Cancer Centre, RIMS, Imphal, Manipur
Source of Support: None, Conflict of Interest: None
Background: Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast carcinoma containing glandular and nonglandular components with mixed epithelial and mesenchymal differentiations. Aim of the Study: The study aimed to report clinical, radiological and pathological profiles, treatment and outcome of patients diagnosed with MCB from a tertiary care institute along with literature review. Materials and Methods: Diagnosed cases of MCB were obtained from the record over a period of January 2010 to December 2017, and data were recorded in a structured pro forma. Results: A total of 9 (0.9%) cases of MCB were identified out of 1031 breast cancer patients with the median age of presentation of 53 years. The palpable lump was the most common presentation (77.78%). The mean tumor size was 4.9 cm in greatest dimension. Sonographically, most of the lesions were solid (44.44%) followed by cystic (33.33%). Mammographically, microcalcifications were absent in eight cases. Histologically, 55.56% of cases were purely epithelial subtype (3: pure squamous and 2: adenosquamous) and 4 (44.44%) cases were mixed epithelial and mesenchymal subtypes (3: carcinosarcoma and 1: invasive lobular carcinoma with sarcomatous component and osseous metaplasia). All the cases were having triple-negative receptor status. Modified radical mastectomy (MRM) was performed in all cases and 33.33% of cases had axillary node positive. About 77.88% and 88.89% of cases received adjuvant chemotherapy and adjuvant radiotherapy, respectively. At median follow-up of 27 months, local recurrence and distant metastases were seen in 1 and 3 cases, respectively. At present, 33.33%, 22.22%, and 44.45% of patients were died, alive, and lost for follow-up, respectively. Conclusion: MCB is a rare histologic subtype of breast cancer with larger tumor size at presentation and MRM is the preferred surgical procedure over breast conservation surgery. Long-term and regular follow-up is necessary to know the outcome.
Keywords: Clinicopathological, metaplastic carcinoma of breast, outcome, radiological, treatment
|How to cite this article:|
Mohanty S, Devi YS, Nongrum DL, Singh LJ, Sekar V, Das DS. Metaplastic carcinoma of breast: A series of nine cases from a regional cancer center in Northeast India. Oncol J India 2018;2:69-74
|How to cite this URL:|
Mohanty S, Devi YS, Nongrum DL, Singh LJ, Sekar V, Das DS. Metaplastic carcinoma of breast: A series of nine cases from a regional cancer center in Northeast India. Oncol J India [serial online] 2018 [cited 2019 May 19];2:69-74. Available from: http://www.ojionline.org/text.asp?2018/2/4/69/248535
| Introduction|| |
Metaplastic carcinoma of breast (MCB) represents a rare heterogeneous malignant tumor, comprising of glandular and nonglandular patterns with epithelial and/or mesenchymal tissues. It accounts for <1% of all breast cancers and has aggressive behavior with poor outcome.,, Most MCBs are sporadic with unknown etiology; however, it may arise from preexisting lesions including complex sclerosing lesions, papilloma, or nipple adenoma., According to the morphological features of tumor cell types, MCB can be divided into two groups: purely epithelial (squamous/adenosquamous/spindle cell carcinomas) or mixed epithelial and mesenchymal (carcinoma with chondroid/osseous metaplasia and carcinosarcoma)., Wargotz et al. classified MCB into five categories: (i) matrix-producing carcinoma, (ii) spindle cell carcinoma, (iii) carcinosarcoma, (iv) squamous cell carcinoma (SCC), and (v) MCB with osteoclastic giant cells.,,,,
Due to the rarity of MCB, only a few case reports or series are published in the literature. The present study has reviewed all cases of MCBs treated at a Regional Cancer Center over the last 8 years with respect to clinicopathological and radiological features, possible therapeutic approaches, and prognostic factors along with literature review.
| Materials and Methods|| |
The present study was a retrospective analysis conducted on diagnosed cases of MCB treated at a tertiary cancer centre, Regional Institute of Medical Science, Imphal, during the period from January 2010 to December 2017. Data of all the confirmed cases of MCB were obtained from record after permission from the authority concerned. The incidence of MCB was calculated in comparison to total breast cancers diagnosed during the study period. Data were collected with regard to age, sex, menstrual history, family history, symptoms, and its duration, clinical stage, radiological findings (ultrasonography/mammography), operative details, biopsy features, adjuvant treatment received, and outcome. IBM SPSS Statistics for Windows, Version 21.0. (Armonk, NY: IBM Corp) software was used for statistical analysis.
| Results|| |
A total of nine (0.9%) confirmed cases of MCB were identified out of total 1031 number of breast cancer patients treated during the study period. The clinicoradiological and pathological features, treatment, and outcome were analyzed here.
Out of all the MCB cases, 44.44% of cases were diagnosed at age <50 years and 55.56% of cases at age >50 years with median age of 53 years at diagnosis. Majority of patients were postmenopausal at the time of presentation consisting 77.78%. One case of pure SCC of breast diagnosed at 53 years of age had a history of stomach cancer in her father. Whereas, one case of carcinosarcoma-type MCB diagnosed at 49 years of age had a history of sarcoma in her father. All the MCB cases presented with palpable breast lump and two cases were associated with discharge. Lumps were rapidly increasing in size, firm to hard in feeling, and size varied from 3 to 10 cm in maximum dimension. There was no skin or chest wall involvement in any of the cases. The mean tumor size of presentation was 4.9 cm at maximum dimension. The predominant side and quadrant of location for MCB cases were mentioned in [Table 1]. One case with large lump of size approximately 10 cm × 10 cm occupied all four quadrants of the breast. Clinically, only one patient was found to have ipsilateral axillary node (one in number, discrete, mobile, and nontender), in which postoperative biopsy report showing 12 out of 15 dissected nodes were involved by malignancy.
During initial presentation, no patient was found to have distant metastasis. Sonographically, all most all the lesions were having oval and/or rounded appearance (88.89%) and solid lesion was the predominant form consisting of 44.45% cases in comparison to cystic and mixed solid/cystic lesions [Figure 1]. Mammographically, 55.56% of the patients were having well defined dense opacity lesions [Figure 2]. Breast Imaging Reporting and Data System (BIRADS) Categories IV and V were the common findings constituting 33.33% of patients for each. Microcalcifications were not found in all available mammography reports (in 8 cases) [Table 1].
|Figure 1: Ultrasonography of the right breast showing an oval lobulated cystic lesion containing hypoechoic soft-tissue fronds|
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|Figure 2: Mammography of the right breast showing a well-circumscribed dense opacity in the posterior aspect, abutting the pectoral muscle Breast Imaging Reporting and Data System 3|
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Fine-needle aspiration cytology from the breast lump was suggestive of fibroadenoma and invasive ductal carcinoma (IDC) in four (44.45%) patients each and invasive lobular carcinoma (ILC) in one (11.10%) patient. Tru-cut biopsy from the breast lesion was performed for all cases showing positive of malignancy (5 cases: MCB, 3 cases: IDC, and 1 case: ILC).
Final histopathological characteristics
The final histopathological examination of the operated specimen revealed 55.56% of cases with pure epithelial type and 44.45% of cases with mixed epithelial and mesenchymal type. Among pure epithelial types, three cases were pure SCC and two cases were adenosquamous variant. Whereas, among mixed epithelial and mesenchymal type, three were carcinosarcoma [Figure 3] and one was ILC with sarcomatous component and osseous metaplasia (ILC-SCOM). Most of the cases (77.78%) had pathological T2 (PT2) disease, whereas rest cases were pathologically T3 (PT3) disease. About 88.89% of patients had high-grade tumor (Elston–Ellis modified Scarff–Bloom–Richardson [SBR] score of 9; i.e., 3 + 3 + 3). Whereas, only one (11.11%) case with pure squamous histology was found to have moderate-grade tumor (modified SBR score of 7, i.e., 3 + 2 + 2). Extensive intraductal component, ductal carcinoma in situ component, perineural invasion (PNI), lymphovascular invasion (LVI), and nipple areolar complex status were highlighted in [Table 2]. Node was positive in 3 (33.3%) cases with histological subtypes of ILC-SCOM (11 out of 12 nodes positive), adenosquamous variant (12 out of 15 nodes positive), and carcinosarcoma (12 out of 13 nodes positive). First 2 of these 3 cases were having extranodal extension. All nine (100%) cases in this series were found to be triple-negative breast cancer, i.e. that is, estrogen receptors (ER) negative, progesterone receptors (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative.
|Figure 3: Malignant epithelial tumor cells predominantly arranged in solid sheets with areas of malignant spindleoid cells (H and E, ×40)|
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Treatment and outcome
The treatment and outcome profiles are depicted in [Table 3]. All the patients underwent modified radical mastectomy (MRM). Of these, one case with adenosquamous variant underwent breast conservation surgery (BCS) initially with postoperative resection margin positive for which MRM was performed. Sentinel lymph node biopsy was not done for any patients and axillary node dissection was performed for all the cases. Seven patients had received adjuvant chemotherapy and eight cases received adjuvant radiotherapy (RT). Chemotherapy regimens used for MCB were FAC regimen (5-fluorouracil 750 mg/m2, adriamycin 60 mg/m2, and cyclophosphamide 600 mg/m2), AC regimen (adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2), EC regimen (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2), and docetaxel 80 mg/m2. All the regimens were given at 3 weekly intervals. Adjuvant RT was given by external beam RT of dose 50 Gy in 25 fractions to chest wall, ipsilateral supraclavicular fossa, and axilla as per requirement at 2 Gy per fraction, 5 fractions in a week over 5 weeks as per the schedule. The case of ILC-SCOM received neoadjuvant chemotherapy with 4 cycles of FAC regimen due to large tumor size with poor response and MRM was performed with resection margin positive. The case was first received adjuvant RT in view of resection margin positivity followed by received 4 cycles of adjuvant docetaxel chemotherapy. One case of carcinosarcoma histology received adjuvant chemotherapy with 4 cycles of AC regimen followed by 3 cycles of docetaxel not completing the 4th cycle of docetaxel due to toxicity and not received adjuvant RT. The patient of ILC-SCOM developed skeletal metastasis to lumbar spine L2 and L3 at 12 months of follow-up. She received palliative RT of 30 Gy in 10 fractions to local area for symptomatic relief followed by received injection zoledronic acid 4 mg on 3 weekly basis for 3 cycles and discontinued. She developed local recurrence (chest wall) 6 months after skeletal metastasis detection and planned for palliative chemotherapy with ifosfamide- and adriamycin-based regimen. However, she denied to take treatment and died after 4 months of local recurrence. One patient with adenosquamous cell carcinoma having PT3N3 disease developed lung metastasis at 27 months of follow-up and refused to take further palliative treatment and lost for follow-up. One case of carcinosarcoma with PNI and LVI positive, PT2N3 disease status develop skeletal metastasis to right iliac bone at 26 months of follow-up and received palliative RT of 30 Gy in 10 fractions to the affected area followed by received monthly injection zoledronic acid 4 mg for 12 cycles. Now, she was on follow-up crossing 4-years of completion of adjuvant treatment. One case of SCC and one case of carcinosarcoma had no evidence of disease at 16 and 28 months of follow-up and further lost to follow-up. However, at telephonic follow-up, these two cases died as per their attendant information with unknown cause. One patient with pure SCC was under regular follow-up, without having any distant metastasis at 3 years of follow-up. At present, 4 patients lost to follow-up.
| Discussion|| |
In the present study, the incidence of MCB is 0.9% when compared to other breast cancers, whereas it was 0.6% and 0.5% for Hasdemir et al. and Park et al., respectively., MCB commonly presents in women older than 50 years and 55.56% of cases in our series were presenting at >50 years age. According to Hasdemir et al., Benson et al. and Donato et al., the median age of presentation was 61-, 45- and 65-years, respectively, whereas it was 53 years in our series.,, It usually presents with a rapidly growing relatively larger breast mass with lower rate of lymph node involvement in comparison to IDC., We found lump in the breast as most common symptom and lump with discharge per nipple in two cases supporting other literature. In the present study, the mean tumor size at presentation was 4.9 cm in its maximum dimension, whereas it was 4.6 cm for Park et al. Whereas, Bensor et al. and Gultekin et al. showed median tumor size of 8.9 cm and 3.5 cm at presentation, respectively., Axillary lymph node involvement in MCB varies from 8% to 40%. Instead of larger tumor size presentation in comparison to classical breast cancer, the rate of axillary lymph node metastases is lower possibly due to different tumor proliferation mechanism of MCB than classical breast cancer. In the present series, lymph node positivity was found in 33.33% of cases supporting the literature (Gultekin et al.: 35% of cases). An analysis of surveillance, epidemiology, and end results on 1501 MCB patients revealed axillary lymph node metastases in 22% of cases.,
On histopathological examination, MCB usually reveals epithelial and mesenchymal components. Squamous metaplasia/component is seen in most of the cases supporting our data. However, Lui et al., in their case series of 19 cases of MCB, found spindle cell component in 10 cases, whereas 8 cases were having squamous cell component.
Triple-negative receptor status is found in >90% of cases. According to the Nowara et al., ER positivity is found in approximately 20% of cases. In our series, all the patients were having triple-negative receptor status, which supports the findings of the previous studies., Hasdemir et al. also reported triple-negative receptor status in 6 out of 7 cases of MCB. Tse et al. and Park et al., in their studies for MCB, found ER, PR, and HER2 positive in 12% versus 3.7%, 9% versus 7.4%, and 15% versus 8.0% of cases, respectively., Radiological (sonographic/mammographic/magnetic resonance imaging [MRI]) findings in MCBs are inconsistent, which can be similar to IDC and benign mass lesions. On ultrasonography, MCB is round or lobular, circumscribed hypoechoic solid mass with posterior acoustic enhancement and cystic component may be seen. Mammography shows round or oval mass often not showing calcifications, and MRI shows mass with high signal intensity on T2-weighted image with peripheral rim enhancement. In our series, radiological findings are supported by the previous literature and 88.89% of cases are without calcifications on mammography with rest one case having unknown calcification status supporting the literature. Mammographically, more cystic changes may be found due to squamous metaplasia.
Specific guidelines for treatment of MCB are absent due to rarity of the disease. However, the treatment is same as that of IDC. Surgery is the mainstay of treatment followed by adjuvant chemotherapy and RT treatment according to indications. Due to larger size of tumor at presentation, BCS is not feasible in majority of MCB and needs mastectomy. In our study, MRM was performed in all the cases. However, BCS was performed initially in one of our case with tumor size of 3 cm × 4 cm and have postoperative resection margin positive, for which MRM was performed. Instead of lower rate of axillary lymph node involvement than classical breast cancers, axillary lymph node dissection is commonly performed to address axilla in patients with MCB. According to Gutman et al., axillary lymph node dissection can be avoided in spindle cell and sarcomatoid variant of MCBs due to extremely rare axillary metastases in these cases. Axillary dissection was performed in all of our cases. Three cases had node positivity out of which two cases were having sarcomatous components. Two out of three pathological N3 disease were clinically N0, and one had clinically N1 disease, indicating lymph node dissection in all the cases and contradicts Gutman et al.
Although some literatures showed good response to neoadjuvant chemotherapy, adjuvant chemotherapy is the preferred options for MCB. Despite lower incidence of axillary lymph node involvement, adjuvant chemotherapy is advised in almost all the cases. Chemotherapy used for IDC is the current standard for MCB. However, MCB is less responsive to conventional chemotherapy as compared to usual ductal and lobular breast carcinomas.,, Cisplatin-based chemotherapy regimen can be used for MCB with squamous metaplasia. Whereas, doxorubicin- and ifosfamide-based chemotherapy regimen can be used for sarcomatous variant of MCBs to target nonepithelial components.,, In our study, we advised adjuvant chemotherapy to all the patients, but two patient refused to take the same.
Regardless of the type of surgery used, adjuvant radiation should be considered as part of the multimodality therapy for MCB patients. In patients undergoing mastectomy and BCS, adjuvant RT provides statistically significant overall survival (OS) and disease-specific survival benefit. In our study, 88.89% of patients received adjuvant RT. The role of adjuvant hormone therapy and trastuzumab is limited due to less positivity of ER and HER2 in MCB, respectively. Even the role of hormone therapy in ER-positive cases is controversial., In our series, hormone therapy and trastuzumab therapy are not applied due to triple-negative receptor status in all the cases.
MCBs spread through the lymph and blood vessels, but lymphatic spread is uncommon. The incidence of Stage IV disease at presentation is more common for MCB than IDC with reported incidence of distant metastasis for MCB as 3.3%–13.2% and suggests more aggressive behavior than other types of breast cancers. In our study, there is no distant metastasis at presentation for all the cases. In the present series, spinal metastasis (L2 and L3), lung metastasis, and iliac bone metastasis were found in one case each having histology of ILC-SCOM, adenosquamous variant, and carcinosarcoma, respectively. For MCB, potentially targetable mutation may affect PIK3CA/Akt/mTOR signaling pathway and patients may be benefited of using PIK3CA and mTOR inhibitors. Moulder et al., in a study, treated five metastatic MCB patients with mTOR inhibitor temsirolimus in combination with liposomal doxorubicin and bevacizumab showing promising preliminary results. Programmed death-ligand 1 (PD-L1) expression is found more in MCB cases than other triple-negative breast cancers (46% vs. 9%) and may show improved response to immune checkpoint inhibitor (anti-PD-L1 agent; pembrolizumab).
Tumor size >5 cm, lymph node involvement, and Ki-67 ≥14% are the poor prognostic factors for patients with MCB. Furthermore, one case from our series had tumor size >5 cm performing poor prognosis and all the lymph node positive cases developed distant metastases. Compared to patients with IDC, MCB has poor prognosis with 5-year OS varies from 49% to 68%. Bae et al., in their study on MCB cases, found no survival advantage with adjuvant chemotherapy. Whereas, Gultekin et al. found survival advantage with adjuvant chemotherapy showing 5-year disease-free survival (DFS) and OS rates of 76% and 80%, respectively. However, due to lack of proper follow-up schedule, we are unable to drag the percentage value of DFS and OS in our series suggesting further study evaluation with larger data and longer duration of follow-up.
| Conclusion|| |
MCB is relatively a rare entity among all the breast cancers with an incidence of 0.9% in our series. Due to larger tumor size at presentation, patients with MCB should undergo MRM instead of BCS. Adequate axillary dissection should be performed as we get 33.33% of cases showing lymph node positivity. Looking at poor prognosis and refractoriness to conventional chemotherapy in such rare entity, multi-institutional studies are needed to evaluate a new treatment paradigm with multitargeted combination therapy to improve survival outcome.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]