A case of matrix-producing carcinoma of the breast treated with preoperative chemotherapy.

Background: Matrix-producing carcinoma (MPC) is a rare tumor accounting for 0.1% of all breast cancers. Although MPC is usually triple-negative breast cancer, there have been few reports of preoperative chemotherapy for MPC that is considered chemotherapy-resistant. Herein, we report a case of MPC that was successfully treated with preoperative chemotherapy. Case Description: The patient was a 47-year-old woman diagnosed with right multiple breast cancer, clinical stage IIA. One of the tumors was identified as MPC and the other was invasive ductal carcinoma. The maximum tumor diameter of MPC was 3.8-cm. On immunohistochemistry, the tumor cells of MPC tested negative for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). The Ki67 index was 90%. Preoperative chemotherapy was performed. EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) was administered every 3 weeks for a total of 4 courses, followed by 12 courses of weekly paclitaxel (80 mg/m2). Then, she underwent right skin-sparing mastectomy, sentinel lymph node biopsy, and deep inferior epigastric perforator flap reconstruction. There was no metastasis to the sentinel lymph nodes. Postoperative pathological results showed that the residual tumor of the MPC measured only 0.1 cm. On the other hand, the residual tumor of the invasive ductal carcinoma was 0.7 cm. Endocrine therapy with oral tamoxifen was initiated for the invasive ductal carcinoma. Three years after surgery, no recurrence was observed. It has been reported that prognosis was correlated with residual cancer after preoperative chemotherapy. In addition, preoperative chemotherapy is of high clinical significance for the selection of postoperative treatment. Conclusions: Although our case of MPC was successfully treated with preoperative chemotherapy, the standard of care for MPC remains uncertain. Development of a new targeted therapy for MPC is warranted. 2022 Gland Surgery. All rights reserved.

Introduction

Matrix-producing carcinoma (MPC) is a rare tumor accounting for 0.1% of all breast cancers (1). MPC is usually triple-negative breast cancer [TNBC; estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative] (2). There have been few reports on preoperative chemotherapy for MPC. We report a case of MPC treated with preoperative chemotherapy. We present the following case in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-22-179/rc).

Case presentation

A 47-year-old woman underwent ultrasonography due to feeling a mass in her right breast. Ultrasonography revealed a 3-cm mass in the right upper outer quadrant. A core needle biopsy revealed invasive ductal carcinoma. She was referred to our department for further evaluation and treatment. She had a history of endometriosis and manic-depressive illness.

Clinically, a 3.3-cm elastic, hard, smooth-surfaced mass was palpable in the right upper outer quadrant. There were no skin changes or axillary lymph node swelling.

Tumor marker tests revealed carcinoembryonic antigen levels of 1.0 ng/mL (<5.0 ng/mL) and cancer antigen 15-3 of 5.9 U/mL (<27 U/mL), which were within the normal ranges. Mammography revealed a radiopaque lump with a circular shape and a finely serrated edge in the right upper outer quadrant, which was classified as category 4 according to the Breast Imaging Reporting and Data System (). The lesion appeared as a circular, hypoechoic, and heterogeneous nodule in the upper outer quadrant of the right breast on ultrasonography. It had a maximum diameter of 2.8 cm (). Another hypoechoic lesion with a maximum diameter of 0.9 cm was observed in the lower inner quadrant of the ipsilateral breast (). Magnetic resonance imaging (MRI) revealed a 3.8 cm tumor in the upper outer quadrant of the right breast. Contrast-enhanced MRI showed a high-intensity lesion with a central low-intensity area (). In the lower inner quadrant of the ipsilateral breast, a 1 cm tumor with irregular margins was found (). Computed tomography (CT) revealed no axillary lymph node metastasis or distant metastasis. Pathological findings revealed a well-defined nodular tumor in the upper outer quadrant of the right breast. Moreover, the tumor cells directly transitioned into a cartilaginous and osseous stromal matrix without an intervening spindle cell. Thus, the patient was diagnosed with MPC (). On immunohistochemistry, the tumor cells tested negative for ER, PgR, and HER2. The Ki67 index was 90%, and the p63 minority was positive (). The S-100 protein and cytokeratin 5/6 were positive (). In the right lower inner quadrant, there was a tumor with stromal elastic fiber. Therefore, the patient was diagnosed with invasive ductal carcinoma. Immunohistochemistry revealed that the tissue of this invasive ductal carcinoma was positive for ER and PgR but negative for HER2. It had a Ki67 index of 7%.

Figure 1

Pretreatment mammography. There is a mass in the right MLO medium area (A) and CC outer area (B). Enlargements of the areas are indicated by white arrows (C). MLO, medio-lateral oblique; CC, cranio-caudal.

Figure 2

Pretreatment ultrasonography. There is a hypoechoic mass in the right upper-outer quadrant (A). Another hypoechoic lesion is observed in the right lower inner quadrant (B).

Figure 3

Pretreatment magnetic resonance image. There is a high-intensity tumor with a central low-intensity area in the right upper-outer quadrant (A). In the right lower quadrant, there is a tumor with irregular margins (B).

Figure 4

Hematoxylin-eosin staining. A well-defined nodular tumor is seen in the right upper-outer quadrant, and tumor cells directly transition to a cartilaginous and osseous stromal matrix without an intervening spindle cell (A: low magnitude, B: high magnitude). p63 minority positive (C), S-100 protein-positive (D), and cytokeratin 5/6 positive (E).

Furthermore, this tumor was staged as cT2N0M0 based on the TNM classification. As a result of the multi-disciplinary team examination, although metaplastic carcinoma has a low sensitivity to chemotherapy, it had a nature of TNBC and neoadjuvant chemotherapy (NAC) would be useful for developing a postoperative treatment strategy. Furthermore, we could discontinue chemotherapy and go forward to surgery in case of tumor progression during NAC administration. We decided to administer NAC with the consent of the patient. EC (epirubicin 90 mg/m2, cyclophosphamide 600 mg/m2) was administered every 3 weeks for a total of 4 courses, followed by 12 courses of weekly paclitaxel (80 mg/m2). After preoperative chemotherapy was completed, the contrast effect in the upper outer quadrant of the right breast mass disappeared on MRI (). The tumor in the lower inner quadrant of the ipsilateral breast exhibited only a 20% reduction at the end of chemotherapy ().

Figure 5

Post-treatment magnetic resonance image. The contrast effect in the right upper-outer quadrant mass disappeared (A). The tumor in the lower inner area of the right breast is the same as before treatment (B).

Right skin-sparing mastectomy, sentinel lymph node biopsy, and deep inferior epigastric perforator flap reconstruction were performed under general anesthesia. There was no metastasis to the sentinel lymph nodes. Pathological examination revealed that the cartilage matrix component of the MPC part was hyalinized, and only 0.1 cm of invasive cancer remained at the tumor margin. Regarding invasive ductal carcinoma, the residual tumor diameter of the infiltrated part was 0.7 cm. In both cases, the results of immunostaining for ER, PgR and HER2 in surgical specimen were the same as those of the needle biopsy specimen harvested before NAC. Since a slight residual cancer was found, we considered to administer a postoperative chemotherapy; capecitabine. However, it was not administered due to the patient’s preference. Endocrine therapy with oral tamoxifen was initiated for the invasive ductal carcinoma. Radiation therapy was not performed because there was no metastasis to the lymph nodes. Three years after surgery, no recurrence was observed. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Metaplastic carcinoma is a rare and unique histologic subtype of breast cancer. MPC is categorized as a subtype of metaplastic carcinoma based on the 4th edition of the World Health Organization classification (3). According to the 2016 Annual Breast Cancer Registry by the Japanese Breast Cancer Society, 69 (0.3%) of 25,870 patients with breast cancers were diagnosed with MPC, a rare tumor (4). MPC is an invasive breast carcinoma with a direct transition of carcinoma to the cartilaginous or osseous matrix without an intervening spindle cell component (1). The cartilaginous or osseous matrix components at the tumor center and epithelial carcinoma components at the tumor margin manifest on contrast CT and MRI as ring enhancement, which are important diagnostic findings of MPC (5).

On immunohistochemistry, MPC is usually negative for ER, PgR, and HER2 (2). In addition to the epithelial markers such as keratin and EMA in the carcinoma component, SOX6 (a mesenchymal marker indicating cartilage differentiation), p63 (a myoepithelial cell marker), and S-100 protein (which is positive in chondrocyte-derived tumors) have also been expressed in MPCs (6-8). In our case, both histological and imaging findings were consistent with these typical MPC findings.

Due to the rarity and heterogeneity of MPC, its treatment has not been standardized. Several previous studies have based their treatment plan on the typical TNBC.

In hormone receptor-negative breast cancer, response to preoperative chemotherapy was found to be a prognostic factor (9). Similarly, in patients with metaplastic carcinoma, it is known that the prognosis is good when pathological complete response (pCR) is achieved, regardless of invasive ductal carcinoma (10). Preoperative chemotherapy has a higher clinical value than does postoperative treatment. With the recent emergence of response-guided therapy for breast cancer treatment (11), preoperative chemotherapy is a viable option in patients with TNBC. The pCR rate of typical TNBC from 22% to 38.9% (12,13).

The residual cancer burden (RCB) after preoperative chemotherapy was correlated with prognosis in TNBC. Symmans et al. evaluated the state of residual cancer after preoperative chemotherapy in three stages (RCB-I to III). Their evaluation was based on combining the maximum diameter and length of residual tumor after preoperative chemotherapy, cell density of the invasive cancer in the tumor, proportion of non-invasive cancer in the tumor, number of metastatic lymph nodes, and maximum diameter of lymph node metastasis. The estimated 10-year relapse-free survival rates of the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% of TNBC (14), respectively.

There have been few reports on preoperative chemotherapy for MPC, and the pCR rate was as low as 0–23% () (2,15-18).

Table 1

pCR rate of patients who received preoperative chemotherapy for MPC

Author	Year	N*	pCR	pCR rate
Nagao et al. (15)	2012	14	0	0%
Aydiner et al. (16)	2015	8	0	0%
Cimino-Mathews et al. (17)	2016	6	1	17%
Han et al. (18)	2019	17	4	23%
Shimada et al. (2)	2019	5	0	0%

*, patients who received preoperative chemotherapy for MPC. MPC, matrix producing carcinoma; pCR, pathological complete response.

Based on previous report, MPC has a worse prognosis than typical breast cancer due to its resistance to chemotherapy, with a 5-year survival rate of approximately 60–86% (19). Recurrences were noted early, within 3 years after surgery (19). In our case, preoperative chemotherapy for MPC was administered to evaluate the patient’s response to chemotherapy and provide optimal treatment. RCB classes of the MPC part corresponded to RCB-I (20), and the patient had a good prognosis. In conclusion, we reported a case of MPC that was successfully treated with preoperative chemotherapy. Since it is rare, a standardized treatment method for MPC has not been established. To investigate the effectiveness of NAC in MPC, analysis of large case series such as national registry data is useful and development of a new targeted therapy to MPC is warranted.

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