Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer.

In some cases of human epidermal growth factor 2 (HER2)-negative breast cancer, including triple-negative breast cancer, HER2 expression is sporadically and strongly upregulated, a condition known as HER2 heterogeneity. We investigated the clinicopathological features of patients with HER2 heterogeneity in triple-negative breast cancers treated with neoadjuvant chemotherapy. Thirty-nine patients with triple-negative breast cancer who had undergone preoperative chemotherapy participated in this study. To assess for HER2 heterogeneity, we used dual in situ hybridization slides. We evaluated the association between HER2 heterogeneity and clinicopathological factors such as rates of pathologic complete response (pCR) and of recurrence-free survival. Of the 39 patients, 15 (38.5%) had cancers with HER2 heterogeneity. The pCR rates were 13.3% among patients with HER2 heterogeneity and 20.8% among those with HER2 nonheterogeneity, but the difference was not significant. The recurrence-free survival rate was significantly lower in patients with HER2 heterogeneity than in those without (P = 0.025). HER2 heterogeneity is a significant predictor of poor prognosis in patients with triple-negative breast cancer treated with neoadjuvant chemotherapy.

Evaluation of a Generative Adversarial Network to Improve Image Quality and Reduce Radiation-Dose during Digital Breast Tomosynthesis.

In this study, we evaluated the improvement of image quality in digital breast tomosynthesis under low-radiation dose conditions of pre-reconstruction processing using conditional generative adversarial networks [cGAN (pix2pix)]. Pix2pix pre-reconstruction processing with filtered back projection (FBP) was compared with and without multiscale bilateral filtering (MSBF) during pre-reconstruction processing. Noise reduction and preserve contrast rates were compared using full width at half-maximum (FWHM), contrast-to-noise ratio (CNR), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM) in the in-focus plane using a BR3D phantom at various radiation doses [reference-dose (automatic exposure control reference dose: AECrd), 50% and 75% reduction of AECrd] and phantom thicknesses (40 mm, 50 mm, and 60 mm). The overall performance of pix2pix pre-reconstruction processing was effective in terms of FWHM, PSNR, and SSIM. At ~50% radiation-dose reduction, FWHM yielded good results independently of the microcalcification size used in the BR3D phantom, and good noise reduction and preserved contrast. PSNR results showed that pix2pix pre-reconstruction processing represented the minimum in the error with reference FBP images at an approximately 50% reduction in radiation-dose. SSIM analysis indicated that pix2pix pre-reconstruction processing yielded superior similarity when compared with and without MSBF pre-reconstruction processing at ~50% radiation-dose reduction, with features most similar to the reference FBP images. Thus, pix2pix pre-reconstruction processing is promising for reducing noise with preserve contrast and radiation-dose reduction in clinical practice.

Multicenter Randomized Open-Label Phase II Clinical Study Comparing Outcomes of NK105 and Paclitaxel in Advanced or Recurrent Breast Cancer.

Background: NK105 is a paclitaxel (PTX)-incorporating "core-shell-type" polymeric micellar nanoparticle formulation composed of block copolymers (polyethylene glycol and a polyamino acid). The efficacy and safety of NK105 and paclitaxel in advanced or recurrent breast cancer have never been compared at equivalent dose levels. Patients and Methods: Patients were randomly assigned to either NK105 or PTX in a 1:1 ratio. The study drug was administered on Day 1, 8, and 15 of a 28-day cycle with 80 mg/m2. The primary endpoint was overall response rate (ORR), secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. Results: A total of 123 patients (NK105, n=62; PTX, n=61) received one of the two drugs. There was no significant difference in ORR, the median PFS, or OS (NK105 group: 41.9%, 9.1, and 27.5 months, respectively; PTX group: 45.9%, 7.8, and 32.4 months, respectively). Neutropenia occurred more frequently in the NK105 group, but most patients did not require granulocyte-colony stimulating factor or dose-reduction. The median time to onset of peripheral sensory neuropathy (PSN) in the NK105 group was significantly longer than that in the PTX group (p=0.001), and PSN (≥ grade 3) was not observed in the NK105 group. Conclusion: Weekly NK105 administration was well-tolerated. Efficacy was similar in both groups. The PSN profile was better in the NK105 group.

Phase II Study of Nab-paclitaxel Plus Cyclophosphamide Plus Trastuzumab Neoadjuvant Chemotherapy in Early HER-2-positive Breast Cancer.

BACKGROUND/AIM: This phase II trial evaluated the efficacy and safety of neoadjuvant nab-paclitaxel plus cyclophosphamide (CPA) plus trastuzumab (AbraC-HER) in patients with early HER2-positive breast cancer. PATIENTS AND METHODS: This was a single-arm, open-label, single-center prospective phase II study. The primary endpoint was pathological complete response rate (pCR rate). The secondary endpoints were clinical antitumor efficacy and the frequency and severity of adverse events. RESULTS: Fifty-nine patients were enrolled in this study. pCR (ypT0/is ypN0) was achieved in 29 patients (49%). The overall response rate was 88.1% (52/59) in all patients. Dose reductions because of adverse events occurred in 3 patients (5.1%) and relative dose intensity was 98%. Compared to Abra-HER, AbraC-HER induced fewer adverse effects. CONCLUSION: Treatment with nab-paclitaxel plus CPA plus trastuzumab was tolerable and effective with a high pCR rate. This AbraC-HER neoadjuvant therapy may be a feasible new treatment option for patients with early HER2-positive breast cancer.

The pathological complete response and secreted protein acidic and rich in cysteine expression in patients with breast cancer receiving neoadjuvant nab-paclitaxel chemotherapy.

Biomarkers that can accurately predict treatment response are required for indicating optimal neoadjuvant treatments. The current study assessed the predictive value of secreted protein acidic and rich in cysteine (SPARC) mRNA expression for the response to neoadjuvant nab-paclitaxel (nab-PTX) therapy in patients with breast cancer. It was hypothesized that SPARC expression can affect the response to albumin-bound taxanes, including nab-PTX since SPARC binds albumin with a high affinity. Pre-therapeutic specimens of core needle biopsies were analyzed from 50 patients in a phase II trial of neoadjuvant nab-PTX and the factors that were associated with a pathological complete response (pCR) were assessed. The pre-therapeutic tumor mRNA levels of chemotherapy-related proteins were quantified, including SPARC, and the correlations with post-therapeutic clinicopathological factors were assessed, including with pCR. The results demonstrated that pre-therapeutic SPARC mRNA expression was significantly higher in non-pCR patients compared with patients with pCR (92.37±55.33 vs. 56.53±30.19; P=0.027). A cutoff point of 48.5 was determined using receiver operating characteristic (ROC) curve analysis (sensitivity, 83.3%; specificity, 50.0%), and patients were classified into low and high SPARC expression groups. High SPARC expression was associated with histological grade (P=0.035), estrogen receptor expression (P=0.037), and progesterone receptor expression (P=0.002) but not with HER2 (P=0.895), and Ki-67 LI (P=0.743) expression. The results of the current study indicated that a high SPARC mRNA expression was a negative predictor of pCR following neoadjuvant nab-PTX therapy regardless of breast cancer subtype. The phase II study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the National Hospital Organization Takasaki General Medical Center (Registration nos. H23-9 and H23-33).

Implications of Topoisomerase (TOP1 and TOP2α) Expression in Patients With Breast Cancer.

BACKGROUND/AIM: We evaluated the usefulness of topoisomerases (TOPs) expression as prognostic predictors in breast cancer. PATIENTS AND METHODS: We retrospectively investigated sixty cases with primary breast cancer. We evaluated the tumor and non-tumor mRNA levels of TOP1 and TOP2α using quantitative reverse-transcription polymerase chain reaction. TOP1/TOP2α positivity was defined as the ratio of the mRNA expression of cancer/normal tissue of >1 for both TOP1 and TOP2α. RESULTS: TOP1 and TOP2α were markedly overexpressed in breast cancer tissues compared to normal breast tissues. Of the 60 cases, 46 (76.7%) were positive for TOP1/TOP2α. The relapse-free survival was relatively shorter for patients with positive TOP1/TOP2α. There was no recurrent disease among the 14 patients who were negative for TOP1/TOP2α, whereas four of the 46 TOP1/TOP2α-positive patients had disease recurrence. CONCLUSION: Negative TOP1 or TOP2α expression may be useful for predicting better prognoses in breast cancer patients.

Neoadjuvant weekly paclitaxel with and without trastuzumab in locally advanced or metastatic breast cancer.

A phase II clinical trial was conducted to examine the clinical and pathologic efficacy and safety of neoadjuvant paclitaxel with or without trastuzumab in women with advanced or metastatic breast cancer. A total of 49 patients with advanced or metastatic breast cancer (clinical stage IIB -IV) were included. Patients with HER2-negative tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break for 4 cycles. Patients with HER2-positive tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break and a trastuzumab 4 mg/kg loading dose, intravenously, followed by 2 mg/kg weekly for 4 cycles. The age of the patients was 51.6 +/- 1.6 years (mean +/- SE) and the size of their tumors was 5.8 +/- 0.4 cm (mean +/- SE). Thirty-two patients had HER2-negative tumors and 17 had HER2-positive tumors. Of 49 patients, 13 (26.5%) had a clinical complete response and 24 (49.0%) had a clinical partial response. Five (10.2%) patients had a pathological complete response (pCR) and three (6.1%) patients had a near pCR in the breast. A total of eight (16.3%) patients had a pCR or near pCR in the breast. The pCR or near pCR rate was 3.1% in the HER2-negative group and 41.2% in the HER2-positive group. With a median follow-up of 28 months (range, 1-45), the 3-year overall survival was 88%. Clinical responders showed a significantly better overall survival than non-responders (p < 0.01). Pathological responders showed a better overall survival than non-responders. There was no significant difference in overall survival between patients with HER2-positive and -negative tumors. In conclusion, combined neoadjuvant weekly paclitaxel and trastuzumab achieved high clinical and pathological response rates for HER2 -overexpressing breast cancers, despite the omission of an anthracycline.

[A phase I study of combination therapy with capecitabine and paclitaxel for patients with inoperable breast cancer or recurrent breast cancer].

A dose-escalation study was conducted for patients with inoperable or recurrent breast cancer in order to determine the recommended dose (RD) of capecitabine combined with a fixed dose of weekly paclitaxel. Capecitabine was administered twice daily from day 1 through day 14 combined with paclitaxel given on days 1 and 8, every 21 days. Dose-limiting toxicities(DLT)were evaluated during the first two cycles. Three patients were recruited at one of two dose levels (capecitabine 1,255 mg/m2 or 1,657 mg/m2, paclitaxel 80 mg/m2). In this study, no DLT was seen in each level, and the RD of capecitabine was determined to be 1,657 mg/m2.

[Clinical benefit of antiestrogens for breast cancer].

Tamoxifen has significantly improved mortality of both pre- and postmenopausal women with hormone receptor-positive breast cancer. Recent clinical trials have demonstrated benefits of aromatase inhibitor therapy in adjuvant regimens for postmenopausal women. Tamoxifen is now expected to demonstrate potential benefits for bone health during endocrine treatment such as switching therapy with aromatase inhibitors because aromatase inhibitors are associated with a reduction in bone mineral density. In premenopausal women, although tamoxifen remains the standard of care, combination treatment of tamoxifen and an LH-RH agonist is recommended.

Use of a Total Variation Minimization Iterative Reconstruction Algorithm to Evaluate Reduced Projections during Digital Breast Tomosynthesis.

PURPOSE: We evaluated the efficacies of the adaptive steepest descent projection onto convex sets (ASD-POCS), simultaneous algebraic reconstruction technique (SART), filtered back projection (FBP), and maximum likelihood expectation maximization (MLEM) total variation minimization iterative algorithms for reducing exposure doses during digital breast tomosynthesis for reduced projections. METHODS: Reconstructions were evaluated using normal (15 projections) and half (i.e., thinned-out normal) projections (seven projections). The algorithms were assessed by determining the full width at half-maximum (FWHM), and the BR3D Phantom was used to evaluate the contrast-to-noise ratio (CNR) for the in-focus plane. A mean similarity measure of structural similarity (MSSIM) was also used to identify the preservation of contrast in clinical cases. RESULTS: Spatial resolution tended to deteriorate in ASD-POCS algorithm reconstructions involving a reduced number of projections. However, the microcalcification size did not affect the rate of FWHM change. The ASD-POCS algorithm yielded a high CNR independently of the simulated mass lesion size and projection number. The ASD-POCS algorithm yielded a high MSSIM in reconstructions from reduced numbers of projections. CONCLUSIONS: The ASD-POCS algorithm can preserve contrast despite a reduced number of projections and could therefore be used to reduce radiation doses.

Phase II Study of S-1 plus Trastuzumab for HER2-positive Metastatic Breast Cancer (GBCCSG-01).

AIM: Treatment strategies for patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) have significantly progressed. The use of trastuzumab, a monoclonal antibody targeting the HER2 (human epidermal growth factor 2) protein, in combination with chemotherapy improves survival in patients with HER2-positive breast cancer. S-1, an oral combination of fluorouracil derivatives, is widely used in Japan and is more convenient than intravenous drugs. However, little is known about the combination of S-1 and trastuzumab in patients with HER2-positive MBC. PATIENTS AND METHODS: We conducted a single-arm, open-label, multicenter prospective phase II study to evaluate the efficacy of an S-1 plus trastuzumab regimen for HER2-positive MBC. S-1 was administered orally [80-120 mg, based on body surface area (BSA)] twice a day for 14 consecutive days in a 3-week cycle. Patients with BSA of <1.25 m2 received a total of 80 mg of S-1, those with BSA ≥1.5 m2 received 120 mg, and the remaining received 100 mg daily in two divided doses. Trastuzumab was administered intravenously at 8 mg/kg on day 1 of the first cycle and at 6 mg/kg on day 1 of subsequent cycles, i.e., every 3 weeks. RESULTS: Between December 2008 and March 2013, 10 patients were enrolled and received a median of 17 (range=3-76) cycles of treatment. Overall response and clinical benefit rates were 60.0% and 90.0%, respectively. Progression-free survival was 15.8 (95% confidence interval=9.4-29.6) months and overall survival was 45.5 (95% confidence interval=37.1-62.2) months. Grade 3/4 adverse events included were neutropenia and hyperglycemia in one patient each (10.0%). There was no clinically significant cardiotoxicity. CONCLUSION: The combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this study. S-1 plus anti-HER2 therapy is a feasible treatment option for HER2-positive MBC.

Source analysis of radiocesium in river waters using road dust tracers.

Following the Fukushima Dai-ichi Nuclear Power Station accident, regional road dust, heavily contaminated with radiocesium, now represents a potential source of radiocesium pollution in river water. To promote effective countermeasures for reducing the risk from radiocesium pollution, it is important to understand its sources. This study evaluated the utility of metals, including Al, Fe, and Zn as road dust tracers, and applied them to analyze sources of 137Cs in rivers around Fukushima during wet weather. Concentrations of Zn in road dust were higher than agricultural and forest soils, whereas concentrations of Fe and Al were the opposite. Concentrations of Zn were weakly but significantly correlated with benzothiazole, a molecular marker of tires, indicating Zn represents an effective tracer of road dust. Al, Fe, and Zn were frequently detected in suspended solids in river water during wet weather. Distribution coefficients of these metals and 137Cs exceeded 104, suggesting sorptive behavior in water. Although concentrations of Al, Fe, Zn, and 137Cs were higher in fine fractions of road dust and soils than in coarse fractions, use of ratios of 137Cs to Al, Fe, or Zn showed smaller differences among size fractions. The results demonstrate that combinations of these metals and 137Cs are useful for analyzing sources of radiocesium in water. These ratios in river water during wet weather were found to be comparable with or lower than during dry weather and were closer to soils than road dust, suggesting a limited contribution from road dust to radiocesium pollution in river water.

The regulatory effect of tamoxifen on fibronectin expression in estrogen-dependent MCF-7 breast carcinoma cells.

We investigated the regulatory effect of tamoxifen (TAM) on fibronectin (FN) expression in estrogen-dependent MCF-7 breast carcinoma cells both in vitro and in vivo. in vitro, MCF-7 cells were cultured with 17beta-estradiol (E2) and/or TAM. In the animal experiment in vivo, MCF-7 tumors were grown in ovariectomized athymic mice by implanting a sustained release E2 pellet. The E2 pellets were removed after 3 weeks of E2 treatment. Animals were then divided into four groups: 1) an E2 (0.72 mg/pellet) pellet [E2(+)]; 2) an E2 and a TAM (5 mg/pellet) pellet [E2(+)TAM]; 3) no treatment [E2(-)] and 4) a TAM pellet [E2(-)TAM]. Following each treatment for 4 weeks, all animals were sacrificed and tumors were removed. Specimens, cells (in vitro) or tumors (in vivo), were homogenized and assayed for FN by Western blots. In the in vitro experiment, FN expression in MCF-7 cells decreased by incubating with 10(-9) M E2 and increased with 10(-6) M TAM. The effect of TAM increasing FN expression was inhibited by incubation accompanied with 10(-9) M E2 or 1 microg/ml transforming growth factor-beta (TGF-beta) neutralizing antibody. In the in vivo animal experiment FN expression in the tumors of E2(+) mice was lower than that of E2(-) mice. However, TAM increased FN expression in the tumors regardless of E2 pellet. These results suggest that TAM increases FN expression of MCF-7 breast carcinoma cells and that these regulatory effects of TAM on FN expression are partly mediated by TAM-induced TGF-beta.

Significance of local recurrence as a prognostic factor in the treatment of breast cancer.

The aim of this study was to evaluate both the risk factors of local recurrence and the prognostic significance of local recurrence in relation to surgical treatment and/or radiation therapy of breast cancer. A total of 1574 primary breast cancer patients, undergoing surgical treatment and/or radiation therapy between 1980 and 2001, were included in this study. Radical mastectomy was performed in 1144 patients, subcutaneous mastectomy in 141 and breast-conserving therapy in 289. The clinical stage was significantly earlier in the subcutaneous mastectomy and breast-conserving therapy groups than in the radical mastectomy group. A positive surgical margin was observed in 9 (6.4%) out of 141 patients in the subcutaneous mastectomy group and 51 (176%) out of 289 in the breast-conserving therapy group. Local recurrence occurred more frequently in the subcutaneous mastectomy and breast-conserving therapy groups than in the radical mastectomy group. Independent prognostic factors in local recurrence were lymph node metastasis in the radical mastectomy group, and surgical margin in the subcutaneous mastectomy group and the breast-conserving therapy group. Independent prognostic factors in overall survival were local recurrence, lymph node metastasis and estrogen receptor status in the radical mastectomy group, and lymph node metastasis and estrogen receptor status in the breast-conserving therapy group. In conclusion, the surgical margin status is an important factor in the risk of local recurrence in patients who have undergone a subcutaneous mastectomy or breast-conserving therapy. The significance of local recurrence for overall survival may be different among these three treatments.

Occurrence and partition ratios of radiocesium in an urban river during dry and wet weather after the 2011 nuclear accident in Fukushima.

After the 2011 nuclear accident in Fukushima, radiocesium was released from the Fukushima Dai-ichi Nuclear Power Plant and contaminated waters in urban areas near Tokyo. By intensive field monitoring during 3 years, this study investigated the temporal trends and the occurrence of radiocesium during dry and wet weather, and analyzed the variations in radiocesium during rainfall events and factors controlling them. Concentrations of particulate radiocesium decreased rapidly from May 2012 to March 2013 and reached an equilibrium in 2014. Concentrations of particulate (137)Cs during wet weather were almost double those during dry weather in the same period. In contrast to the small variations in (137)Cs concentrations in the particulate phase on a suspended solids (SS) weight basis during events, those in the dissolved phase on a liquid-volume basis fluctuated greatly, resulting in variations in the partition coefficient (apparent Kd). The apparent Kd of (137)Cs during wet weather ranged from 30,000 to 150,000 L kg(-1) and showed a significant negative correlation with SS concentrations during wet weather. Specific surface area in solids contributed to the variations in apparent Kd.

Co-expressed type of ER and HER2 protein as a predictive factor in determining resistance to antiestrogen therapy in patients with ER-positive and HER2-positive breast cancer.

The purpose of this study was to analyze whether inter-site variation types on estrogen receptor (ER) and HER2 expression may be a predictive factor for evaluating the effectiveness of endocrine therapy in patients with ER-positive and HER2-positive breast cancer. A total of 366 consecutive women with invasive breast cancer who had undergone curative surgical treatment between 1996 and 2001 were included in this study. ER status was evaluated using the Allred score and HER-2 status was evaluated according to the HercepTest. In ER-positive and HER2-positive tumors, the expression of ER and HER2 was described as the co-expressed type or the differently expressed type using double staining with ER and HER2. Of the 366 patients, 249 (68.1%) were positive for ER and 74 (20.2%) were positive for HER2. ER-positive and HER2-negative tumors were found in 221 patients (60.4%), ER-negative and HER2-negative in 71 (19.4%), ER-negative and HER-2-positive in 46 (12.6%), and ER-positive and HER2-positive in 28 (7.7%). HER2 status was inversely correlated (p<0.01) with ER status. In ER-positive tumors, an inverse correlation between ER and HER2 was also observed. The co-expressed type was found in 10 patients, and the differently expressed type was found in 18. There was no difference in tumor size and nodal involvement between the two types. There was no significant difference in disease-free survival between patients with the co-expressed type tumor and the differently expressed type tumor. In patients with the differently expressed type tumor, those who received antiestrogen therapy showed a significantly better disease-free survival rate than those who did not receive antiestrogen therapy. As for patients with the co-expressed type of tumor, no significant difference in disease-free survival was observed between patients with and without antiestrogen treatment. The present study suggests that the co-expressed type of tumour might be a resistant factor to antiestrogen therapy in ER-positive and HER2-positive breast cancer.

Local control by breast-conserving surgery with nipple resection.

Local control was compared between patients who had undergone breast-conserving therapy with and without nipple resection. We explored whether there was any difference in local control between the two treatment methods for patients with early breast cancer. A total of 333 women with breast cancer, who had undergone breast-conserving therapy between 1991 and 2002, were included in this study. Surgery consisted of a wide local excision of the primary tumor with a 2-cm free margin as the minimum distance. When the tumor was located under the nipple or close to the nipple, breast-conserving surgery with nipple resection was selected. A total of 320 patients received breast-conserving surgery without nipple resection and radiation therapy (BCT) and 13 patients breast-conserving surgery with nipple resection and radiation therapy (BCT-NR). There were no significant differences in age, tumor size, nodal status, clinical stage, ER status, histological type or surgical margin status between the two groups. The surgical margin was positive in 55 (17.2%) out of 320 patients in the BCT group and in one (7.7%) out of 13 patients in the BCT-NR group. There was no significant difference in the breast-free survival between the two groups. In conclusion, breast-conserving surgery with nipple resection and radiation therapy may be the treatment of choice for early breast cancer patients with the tumor located under the nipple or very close to the areola.

NO donor ameliorates ischemia-reperfusion injury of the rat liver with iNOS attenuation.

This study investigated the effect of a spontaneous nitric oxide (NO) donor, FK409 (FK), in a rat model of segmental hepatic ischemia. Rats were allocated to four experimental groups. Two of the groups underwent segmental hepatic ischemia of 60 min duration and received FK (0.4 mg/kg, iv) or vehicle alone before inducing ischemia and again 5 min before reperfusion. Sham-FK and sham groups were treated identically, but did not have vascular occlusion. Serum aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) were measured, and the livers were examined for histological evidence of injury, polymorphonuclear neutrophil (PMN) infiltration, and immunohistochemical expression of inducible NO synthase (iNOS) before and 6 h after reperfusion. AST, ALT, and LDH levels were significantly (p < .05) reduced 6 h after reperfusion in the FK-treated group compared with the vehicle-treated control group. FK treatment also reduced the degree of hepatic damage apparent on histopathology and reduced PMN infiltration and iNOS expression. Thus, FK treatment is protective against hepatic ischemia reperfusion injury and attenuates neutrophil infiltration and iNOS expression.

Two cases of breast cancer with cartilaginous and osseous metaplasia.

Invasive breast cancer (IBC) with cartilaginous or osseous metaplasia is rare. Here we report two cases of this unusual variation. Case 1: The patient was a 33-year-old woman with a right breast tumor, 2.2 cm in size. Mammograms (MMG) presented no specific findings, but ultrasound (US) showed a cystic-like lesion. Excisional biopsy confirmed IBC with cartilaginous and osseous metaplasia. Biopsy was followed with a modified radical mastectomy. One lymph node was positive, and both estrogen receptor (ER) and progesterone receptor (PgR) were negative. Case 2: The patient was a 43-year-old woman with a left breast tumor, 4.2 cm in size. MMGs presented no findings but US showed an irregular shaped, low-echoic area, suggesting malignancy. Core needle biopsy confirmed IBC with cartilaginous metaplasia. A total adenectomy and lymph node dissection with breast reconstruction using a lattisimus dorsi muscle flap were performed. Two of 18 lymph nodes were positive for metastasis and both ER and PgR were negative. IBC with cartilaginous or osseus metaplasia seem to be divided into two types pathologically, with or without intervening spindle cells, which is related to the prognosis. Matrix producing carcinoma (MPC) has no intervening spindle cells and a better prognosis than other types, however, MPC has been reported to have the same prognosis as ordinary breast cancer after for adjusting its stage. Our two cases were MPC's and no recurrence has been detected 5 and 3 years from the initial therapy, respectively.