[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].

We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer( invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).

[A Case of Recurrent Breast Cancer with Multiple Bone Metastasis Effectively Treated by CDK4/6 Inhibitor in Addition to Aromatase Inhibitor].

We report a case of recurrent breast cancer with multiple bone metastasis in a 62-year-old woman. Her breast cancer (invasive ductal carcinoma, T2N0M0, Stage ⅡA)was resected in 2001(partial mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(UFT)and irradiation to her left remnant breast. In February 2018, she complained of severe pain in right femoral joint and hip. CT scan showed a left cystic breast tumor(17 cm)and multiple bone metastasis. The core needle biopsy of the costal bone lesion and left mastectomy were performed. These pathological findings were recurrence of the breast cancer(ER+). The endocrine therapy(exemestane, aromatase inhibitor), the administration of denosumab and irradiation to painful bone lesions were performed, but it did not suppress tumor progression. The treatment of letrozole plus palbociclib(CDK4/6 inhibitor)were continued for 3 months from May 2018, and this therapy made her bone lesions smaller, but palbociclib were stopped due to its severe neutropenia. After that, the single administration of letrozole was continued, but the tumor marker did not become normal. In February 2019, abemaciclib was administered in addition to letrozole. One year later, her symptoms improved and her bone metastases have showed partial response.

A Case of Breast Cancer in a Patient with a Congenital Pectoralis Muscle Defect.

Congenital pectoral muscle defects are very rare, and when accompanied by limb defects, they are called Poland syndrome. A woman in her 70s, 4 years after partial mastectomy for breast cancer, underwent mastectomy for a local recurrence. During the operation, the pectoralis major and minor muscles were found to be defective. However, the patient did not have any limb defects. Although congenital pectoral muscle defects are very rare, it would be better to confirm defects of the pectoral muscle by preoperative diagnostic imaging such as CT because the postoperative treatment may be affected.

[A Useful Method of Nipple-Side HydroMARK-Marking before Neoadjuvant Chemotherapy in the Breast Preserving Surgery-A Case Report with pCR of the Triple Negative Breast Cancer].

When the primary breast cancer disappears by neoadjuvant chemotherapy, it is often difficult to detect it during the breast preserving surgery. Before neoadjuvant chemotherapy, preoperative nipple-side HydroMARK-marking, which was made of titanium coil and hydrogel, was a very useful and effective method because of its fine detection by ultrasonography. We report a case of 51-year-old female with the triple negative breast cancer(TNBC). At first, the HydroMARK was inserted between the nipple and the tumor. Its distance was about 10 mm toward the nipple. EC therapy followed by docetaxel was performed for 6 months as neoadjuvant chemotherapy. After that, her left TNBC(T1N0M0, Stage Ⅰ, invasive ductal carcinoma, ER[-], PgR[-], HER2[-])was disappeared in all imagings and resected in August 2018. The HydroMARK was clearly detected by intraoperative ultrasonography and her right breast preserving surgery was completely performed. Its pathological finding was pCR(pathological complete response).

[A Case of Pyloric Stenosis Due to Gastric Metastasis of Breast Cancer].

We report a case of left advanced breast cancer(T4N1M0, Stage ⅢA)in a 67-year-old woman. In August 2010, her breast cancer(triple-negative invasive ductal carcinoma)was resected(mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(TC)and irradiation to her chest wall. In July 2018, she experienced recurrent vomiting. Gastrointestinal endoscopy(GS)revealed type Ⅳ advanced gastric cancer-like appearance with pyloric stenosis. Pathological findings confirmed hormone-positive gastric metastasis of breast cancer. Systemic chemo-endocrine therapy(EC and anastrozole) was performed, following which her symptoms improved. In May 2019, recurrent vomiting appeared again. Thereafter, systemic chemo-endocrine therapy(paclitaxel plus bevacizumab and fulvestrant)was initiated, and her symptoms showed improvement. In November 2020, she showed obstructive jaundice due to malignant biliary stenosis. She was treated using endoscopic biliary stenting, but died 2 months later. Gastric metastasis is reported rarely in 4% of all breast cancers, and GS should be recommended in cases of recurrent abdominal complaints.

Anti-E Detected in a 7-Month-Old Infant with Acute Lymphoblastic Leukemia after Transfusion.

BACKGROUND: Only a few cases of infantile anti-red blood cell alloantibody production have been reported. METHODS: A 7-month-old girl with acute lymphoid leukemia developed anti-E alloantibody 13 days after transfusion of E-positive red blood cells. Antibody screening was performed before and at 2, 6, 13, 18, 27, 34, and 49 days after red blood cell transfusion. Identification test, direct immunoglobulin test, acid elution, and dithiothreitol test were also performed. RESULTS: Anti-E alloantibody was detected in the blood 13 days after the first transfusion. The detected antibody was IgM and it decreased below detectable levels within 49 days after the first transfusion. CONCLUSIONS: Follow-up testing for the presence of post-transfusion alloantibody at appropriate times is important, even in infants.

[A Case Report of Recurrent Bleeding and Massive Malodorous Effusion Due to Skin Invasion of Advanced Breast Cancer Successfully Treated with Mohs' Paste].

We report a case involving a 65-year-old woman with skin invasion and destruction by left large breast cancer(T4cN0M0, Stage ⅢB). She had severe anemia with recurrent bleeding on the cancer surface and needed blood transfusion, and massive malodorous effusion from the skin lesion resulted in hypoalbuminemia and recurrent bacteremia. Metronidazole gel treatment for malodorous effusion and postmenopausal hormonal therapy were administered at first. After using Mohs' paste 4 times with 1- or 2-week intervals, the bleeding and effusion stopped, and the primary cancer tumor almost disappeared. Bacteremia also improved with antibiotics, and amelioration of distress was observed. Following this, systemic chemotherapy was performed. Mohs' paste was a very useful method for symptom management of malignant skin lesions with bleeding and massive effusion.

[Subclavian Artery Hemorrhage Related to Everolimus in a Patient with Recurrent Breast Cancer--A Case Report].

A 53-year-old woman underwent breast-conserving surgery for right breast cancer (invasive ductal carcinoma, T1cN0M0, ly+, stage ⅠA, ER+, PR+, HER2-) 5 years previously. During treatment with tamoxifen, massive recurrence in the axillary lymph nodes was found. First- through fourth-line chemotherapy were tried, but they all failed. Everolimus and exemestane were administered, resulting in rapid shrinking of the tumor, but the patient developed sudden severe bleeding from the subclavian artery. Hemostasis was achieved with artery stenting. The patient also developed a thoracic duct-cutaneous fistula. The patient died from tumor regrowth 6.5 months after her first everolimus treatment. Treating tumors involving major vessels with everolimus can cause severe bleeding after rapid shrinking of the tumor.

Decreased expression of SOCS-3 mRNA in breast cancer with lymph node metastasis.

Signal transducers and activators of transcription (STATs) play a pleomorphic role in signal transduction, similarly to an oncogene. Suppressors of cytokine signaling (SOCS) inhibit STAT pathways. In breast cancer, little is known about the correlation among STATs, SOCS, and clinicopathological/biological features. Therefore, we investigated p-STAT3 (activated form of STAT3) and SOCS-1/3 expression, and clarified their correlation. Immunohistochemical staining for p-STAT3 antigen was performed in 74 surgically resected primary breast cancers. Real-time RT-PCR was used to measure mRNA expression of SOCS-1 and SOCS-3. There were no significant correlations between p-STAT3 expression and clinicopathological/biological features. SOCS-3 mRNA expression in the lymph node-positive group was significantly lower than that in the negative group (p=0.013). Among three groups divided based on the number of involved lymph nodes (node-negative group, 1-3 involved nodes group, 4 or more involved nodes group), the group with 4 or more involved nodes had the lowest expression of SOCS-3 (p=0.043). Correlations were not seen between SOCS-1 and SOCS-3 expression and other clinicopathological/biological features, except for blood vessel invasion. There were no statistical correlations between either SOCS-1 or SOCS-3 mRNA expression and p-STAT3 expression. Reduced expression of SOCS-3 is closely related to lymph node metastasis. Therefore, SOCS-3 may be a good predictor for lymph node metastasis.

Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in breast cancer predicts 5-FU sensitivity by a histocultural drug sensitivity test.

Thymidylate synthase (TS), Dihydropyrimidine dehydrogenase (DPD) and Thymidine Phosphorylase (TP) gene expressions are reported to be predictive markers for 5-fluorouracil (5-FU) sensitivity in gastrointestinal cancer. However, in breast cancer, it is still controversial whether those molecular markers predict 5-FU sensitivity or not. One possible reason for the difficulty may be the histological heterogeneity in breast cancer specimens. In this study, TS, DPD and TP mRNA expression in 40 breast cancer tumors were semi-quantified separately in cancer cells (Ca), cancerous stroma (Str) and normal glands (Nor) using laser capture microdissection and real time RT-PCR (LCM+RT-PCR). The histoculture drug response assay (HDRA) for 5-FU sensitivity was performed for 22 tumors. TS and TP mRNA expressions were higher in Ca than Str, although DPD gene expression was lower in Ca than Str. The group of high TS and high DPD gene expression in Ca was resistant to 5-FU, and the group of low TS and low DPD gene expression in Ca was sensitive to 5-FU (P=0.048 chi-square test). TS and DPD mRNA expressions measured using LCM+RT-PCR might be useful predictive markers for 5-FU sensitivity in human breast cancer.

Inverse correlation between the expression of O6-methylguanine-DNA methyl transferase (MGMT) and p53 in breast cancer.

BACKGROUND: Expression of O(6)-methylguanine-DNA methyl transferase (MGMT), a DNA repair protein, has been associated with tumor resistance to alkylating agents such as cyclophosphamide. Promoter hypermethylation of MGMT is a strong predictor of survival, and expression of mutant p53 protein may be associated with downregulated MGMT expression in brain tumors. In order to clarify further the correlation between MGMT and p53 expression, we investigated the expression levels of both MGMT and p53 in breast cancer. METHODS: MGMT and p53 expression was examined in tissues from 48 consecutive cases of primary breast cancer patients using immunohistochemical staining with antibodies specific for MGMT and p53. The prognosis for survival was analyzed based on MGMT and p53 immunoreactivity and clinicopathological characteristics. RESULTS: Expression of either MGMT or p53 was classified as negative or positive based on immunohistochemical staining. The expression of MGMT showed a significant inverse correlation with three clinicopathological characteristics, the status of the estrogen receptor, local recurrence and distant metastasis. There was a significant correlation between the expression level of p53 and the lymphatic involvement, estrogen receptor status and distant metastasis. MGMT and p53 were correlated with distant metastasis and local recurrence, but Kaplan-Meier curves did not show a significant difference. MGMT immuno-negative specimens showed a significantly higher expression of p53 (P = 0.026, chi(2) test). CONCLUSION: p53 may be associated with the regulation of MGMT expression in breast cancers.

Elevated cyclooxygenase-2 expression is associated with histological grade in invasive ductal breast carcinoma.

PURPOSE: The aim of this study was to evaluate the expression of cyclooxygenase-2 in human breast cancer using immunohistochemistry and to determine whether the expression of cyclooxygenase-2 is associated with clinicopathological factors in invasive ductal breast carcinoma. METHODS: Cyclooxygenase-2 expression was investigated by immunohistochemistry in 30 invasive ductal breast carcinoma specimens and relationships between cyclooxygenase-2 expression and age, histological grade, histological type, nodal status, and hormone receptor status were evaluated. RESULTS: Cyclooxygenase-2 expression was found in 56.7% of the tumor samples and was related to histological grade (P<0.01) and histological type (P<0.001). CONCLUSIONS: Our results suggest that cyclooxygenase-2 expression has an important role in tumor differentiation in invasive ductal breast carcinoma.

Esthetic evaluation of immediate breast reconstruction after nipple-sparing or skin-sparing mastectomy.

BACKGROUND: It has been reported that immediate autologous tissue breast reconstruction after nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) is esthetically superior to autologous tissue reconstruction after conventional mastectomy (CM). We evaluated reconstructed breasts to determine whether these methods contribute to breast appearance other than skin texture. METHODS: Between April 1992 and September 2001, forty-two patients underwent immediate breast reconstruction using autologous tissue. Mastectomy options were NSM, SSM and CM. Postoperative photographs were evaluated using a subscale (volume, contour, placement, and inframammary fold) on a 0-2 point scale. Sternal notch to nipple distances of the affected and normal sides were measured with photographs to estimate nipple-areola complex (NAC) position. No corrective procedure was performed in a later phase before evaluation. RESULTS: NSM was performed in 22, SSM in 6 and CM in 14 cases. On esthetic evaluation, the NSM and SSM groups received 4.96 and the CM group received 4.63. There were no significant differences. In the NSM and SSM group, the NAC position rose in cases with partial necrosis or fat lysis compared with the no complication group (p = 0,004). CONCLUSIONS: Autologous tissue breast reconstruction after NSM or SSM is esthetically equal to autologous tissue reconstruction after CM with regard to parameters other than skin texture. Preserved or simultaneously reconstructed NAC sometimes emphasizes nipple-areola asymmetry when breast deformity has occurred.

Magnetic resonance imaging of the metal clip in a breast: safety and its availability as a negative marker.

PURPOSE: This study assesses magnetic resonance (MR) safety of the stainless-steel clip inserted after stereotactic-guided directional vacuum-assisted biopsy (DVAB) of the breast, and evaluates its imaging value. METHODS: We used a sausage as a substitute breast and inserted the clip into it. The MR images of the substitute were scanned using a breast coil, and it was then dissected. After the substitute experimentation, MR scanning of the breast was performed using a dynamic contrast enhanced technique, in which a clip was placed after DVAB for suspicion of ductal carcinoma was seen as grouped amorphous calcifications on mammography. RESULTS: On every magnetic resonance image of the substitute, the clip was seen as a spotty signal void, with no surrounding artifact. There was no movement and no evidence of increased clip temperature on dissected of the substitute, confirming the safety of breast MR with a clip in place. There was no patient complaint of feeling heat or pain during the MRI examination and there were only biopsy scars on the surgically excised breast specimen material. On the breast MR images, a spreading region of the tumor adjoining the position of the signal void was identified as an early enhancing lesion. CONCLUSIONS: The safety and reliability of breast MR examination using a mammotome clip was demonstrated by both the mock examination and the breast examination. It is possible to localize of tumor spread regions based on the marker position using the clip as a negative signal marker.

Correlation among intratumoral blood flow in breast cancer, clinicopathological findings and Nottingham Prognostic Index.

BACKGROUND: The purpose of this study was to evaluate the correlation among intratumoral blood flow as assessed by color Doppler ultrasonography, clinicopathological findings and the Nottingham Prognostic Index (NPI). METHODS: Twenty-seven patients with breast cancer were examined. All patients received surgical treatment. Color Doppler ultrasonography was performed prior to surgery to detect arterial blood flow signals within the tumors. The lowest resistance index (RI) was recorded. Formalin-fixed, paraffin-embedded slides were reviewed by senior pathologists to evaluate the size of tumor, histological size, lymph node status and histological grade. Estrogen and progesterone receptor levels were measured by enzyme immunoassay. The Nottingham Prognostic Index was calculated using the equation NPI = 0.2 x tumor size (cm) + grade (I-III) + lymph node score (1-3). RESULTS: The lowest RI correlated well with NPI and histological grade (grade II:III = RI 1.037:0.816, P = 0.0035). Regression analysis revealed a linear relationship between the lowest RI and NPI (correlation coefficient = 0.475; P = 0.0153). CONCLUSIONS: Intratumoral blood flow analysis assessed by color Doppler ultrasonography correlates well with histological grade and NPI. Preoperative assessment using color Doppler ultrasonography provides useful information and may contribute to the determination of prognosis.

Endoscopic resection of benign breast tumors: retromammary space approach.

Endoscopic surgery is characterized by the creation of a working space. At our department, we have obtained good results with a retromammary space approach in which the tumor is resected after creation of a working space in the retromammary space. The special instruments used for this purpose comprise an endoscopic vein harvesting system to dissect the retromammary space, a dissecting balloon to compress the space to achieve hemostasis, and laparosonic coagulating shears to incise the tumor. This surgical technique provides a superior cosmetic result, and the level of patient satisfaction has been high.