[Incidence of Secondary Malignancy of Chronic Myeloid Leukemia during Treatment of Breast Cancer with Hormone Therapy].

It is expected that the number of long-term breast cancer survivors will increase owing to the improvements in chemotherapy and irradiation, while the risk of double cancers, including secondary malignancy, may become an issue. There are many unclear points in the treatment policy with regard to when a secondary malignancy occurs or the primary cancer relapses during the management of a secondary malignancy. A 54-year-old woman who was diagnosed with ER/PgR-positive HER2 negative breast cancer Stage ⅢB received neoadjuvant chemotherapy FEC and docetaxel followed by breast surgery, adjuvant hormone therapy, and radiation therapy. Chronic myeloid leukemia diagnosed by the abnormal findings of leukocytosis and bone marrow aspiration emerged after 3 years of the diagnosis of the first breast cancer. After 3 years of imatinib therapy that achieved a major molecular response(MMR)of CML, a recurrence of sacral metastasis of breast cancer was revealed by MRI. The combination of imatinib and hormone or S-1 chemotherapy could be maintained without serious adverse events after the relapse of the primary cancer.

[A Case of Ipsilateral Breast Tumor Recurrence(IBTR)after Breast-Conserving Surgery Which Successfully Resected after Chemotherapy Using Carboplatin plus Gemcitabine].

A 39-year-old woman underwent partial mastectomy with sentinel lymph node biopsy for right triple negative breast cancer(T2N0M0, Stage ⅡA). Six months later, ipsilateral breast tumor recurrence(IBTR)was observed and paclitaxel plus bevacizumab therapy was started, but anaphylactoid symptoms appeared and the patient was discontinued. Subsequently, eribulin was started, but the IBTR was increased ineffectively. At that point, IBTR had progressed, apparently unresectable, with no distant metastases. We predicted from the patient's background that the patient may be associated with BRCA1 gene mutation and was sensitive to the platinum salts. Carboplatin plus gemcitabine was selected and 6 courses were performed. After the 6 courses, the IBTR were remarkably reduced and resectable, and mastectomy with axillary lymph node dissection were performed. One year after the operation, contralateral breast cancer develop and found to be hereditary breast and ovarian cancer syndrome (HBOC) by Genetic test. About 6 years have passed since local recurrence, but no distant metastases have been observed.

[A Case of Recurrent Premenopausal Hormone Receptor Positive Breast Cancer with Liver, Lung and Bone Metastasis Successfully Treated with Endocrine Therapy].

Here we report a 48-year-old female with recurrent breast cancer. She had received chest muscle-conserving mastectomy and lymph node dissection at another hospital, diagnosed as pStage ⅡB, T2N1M0 premenopausal left endocrine positive/ HER2 negative breast cancer at the age of 45. Although postoperative adjuvant therapy was started with LH-RH agonist plus tamoxifen, and chest radiation, tamoxifen therapy was intolerantly discontinued due to severe adverse events of hot flash after 1 year later. Three years later, she presented with back pain and was referred to our hospital. As PET-CT revealed recurrence of multiple bone and lung metastases and solitary liver metastasis which did not seem to be life-threatening, palliative radiation therapy and endocrine therapy with leuprorelin and anastrozole(LA)were started. Eighteen months later, PET-CT showed complete disappearance of liver and lung metastases and remarkable regression of bone metastases except for the right sciatic bone. LA therapy could be maintained for a total of 30 months until metastatic recurrence on liver and bone emerged. LA endocrine therapy may be effective for patients with premenopausal hormone-positive breast cancer even if the difficult situation such as tamoxifen intolerance.

[MASTECTOMY AND BREAST-CONSERVING SURGERY].

Mastectomy and breast-conserving surgery (BCS) are common procedures for treating breast cancer at present. The discovery rate of tumors 2 cm or less in size has risen with the increase in the number of women who receive breast physical examinations, and because of the wider usage of preoperative chemotherapy, BCS has become possible. As a result, the number of women undergoing BCS has increased, whereas the number of those undergoing mastectomy has decreased. However, if radical cure or good cosmetic results cannot be achieved, mastectomy is often offered to patients. Recently, patients have come to expect good cosmetic results after BCS, and because breast reconstruction with implants is now covered by health insurance, it is possible to perform it with mastectomy with the help of plastic surgery if patients desire. Oncoplastic surgery is now the focus of public attention, because it differs from conventional BCS in that it results in no deformity, since the defect created by wide resections is filled with a local tissue flap. It is psychologically important for patients to have satisfactory cosmetic results after BSC.

Problems experienced when swallowing solid oral dosage forms in older Japanese patients with dysphagia: A cross-sectional study.

AIMS: We aimed to assess the difficulty in taking solid oral dosage forms (SODFs) among older people with dysphagia and clarify the relationship between difficulty in swallowing SODFs and swallowing function. METHODS AND RESULTS: Outpatients from a dysphagia clinic aged ≥65 years were asked yes-or-no questions about the applicability of eight items regarding difficulty in taking SODFs. Additionally, a videofluorographic swallowing study (VFSS) was performed to assess their swallowing function. The Kruskal-Wallis test and Spearman's rank correlation coefficient were used to analyze the relationship between difficulty in taking SODFs and swallowing function. RESULTS: Among the 93 participants, the average number of SODFs consumed was 5.8 ± 3.1. In the questionnaire, the average number of "yes" answers was 2.2 ± 2.2, and 65 patients (71.0%) answered "yes" to at least one question. Additionally, no significant relationship was observed between the perceived difficulty in swallowing SODFs and VFSS findings. CONCLUSION: Approximately 70% of participants reported subjective difficulty in taking SODFs, showing that patients uniformly reported perceived difficulty in taking SODFs regardless of actual swallowing function. The results of this study suggest that patients must be questioned thoroughly about their SODFs use, regardless of the objective severity of their dysphagia.

[A case of T4bN3c breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after systemic chemotherapy].

A 40 year-old woman had right T4bN3c breast cancer without distant metastasis. A partial response was achieved in the primary lesion and right supraclavicular and axillary lymph node involvement was no longer noted after systemic chemotherapy (weekly paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide [FEC]). The patient wished to undergo immediate reconstruction of the right breast, and therefore, modified radical mastectomy with tissue expander reconstruction was performed. Adverse effects due to chemotherapy were of Grade 2. Six months after post-mastectomy radiation therapy, the tissue expander was removed and the right breast was reconstructed using an implant. No complications were noted. Six years have passed since the operation, and no local recurrence or distant metastasis has been noted. In addition, the cosmetic appearance of the right breast is satisfactory.

[A case of recurrent breast cancer with carcinomatous pleurisy responding to bevacizumab and paclitaxel therapy].

A 57-year-old woman who had undergone muscle-preserving radical mastectomy at the age of 38 presented with a 5 cm mass in front of the breastbone. She was diagnosed as having recurrent breast cancer( estrogen receptor[ ER] positive, progesterone receptor[ PgR] positive, human epidermal growth factor receptor[ HER] -2 negative) by core needle biopsy. She received an aromatase inhibitor (AI) and showed partial response. At the age of 54, PgR status became negative. At the age of 55, the recurrent tumor increased in size, and the patient received 50 Gy of radiation therapy for its treatment and AI administration was continued. At the age of 57, tumor marker levels increased and detailed examination revealed that the recurrent tumor had increased in size and carcinomatous pleurisy was noted. Bevacizumab and paclitaxel therapy was initiated. Tumor marker levels decreased and the pleural fluid disappeared in 2 weeks. After 3 courses, positron emission tomography( PET) -computed tomography( CT) showed a reduction in the tumor size and a decrease in fluorodeoxyglucose (FDG) uptake. Bevacizumab and paclitaxel therapy could be effective for the treatment of patients with recurrent breast cancer with a life-threatening status, after hormone therapy failure. Bevacizumab and paclitaxel could be effective as first- line chemotherapy because of its good treatment efficiency.

Pounding score of intracranial lipomas.

Most intracranial lipomas are asymptomatic, but headache is the most common symptom. The pounding score is sometimes high. Therefore, it is necessary to monitor imaging findings in parallel with the treatment of migraine.

Safety and immunogenicity of BK-SE36/CpG malaria vaccine in healthy Burkinabe adults and children: a phase 1b randomised, controlled, double-blinded, age de-escalation trial.

Background: BK-SE36/CpG is a recombinant blood-stage malaria vaccine candidate based on the N-terminal Plasmodium falciparum serine repeat antigen5 (SE36), adsorbed to aluminium hydroxide gel and reconstituted, prior to administration, with synthetic oligodeoxynucleotides bearing CpG motifs. In healthy Japanese adult males, BK-SE36/CpG was well tolerated. This study assessed its safety and immunogenicity in healthy malaria-exposed African adults and children. Methods: A double-blind, randomised, controlled, age de-escalating clinical trial was conducted in an urban area of Ouagadougou, Burkina Faso. Healthy participants (n=135) aged 21-45 years (Cohort 1), 5-10 years (Cohort 2) and 12-24 months (Cohort 3) were randomised to receive three vaccine doses (Day 0, 28 and 112) of BK-SE36/CpG or rabies vaccine by intramuscular injection. Results: One hundred thirty-four of 135 (99.2%) subjects received all three scheduled vaccine doses. Vaccinations were well tolerated with no related Grade 3 (severe) adverse events (AEs). Pain/limitation of limb movement, headache in adults and fever in younger children (all mild to moderate in intensity) were the most frequently observed local and systemic AEs. Eighty-three of BK-SE36/CpG (91%) recipients and 37 of control subjects (84%) had Grade 1/2 events within 28 days post vaccination. Events considered by the investigator to be vaccine related were experienced by 38% and 14% of subjects in BK-SE36/CpG and control arms, respectively. Throughout the trial, six Grade 3 events (in 4 subjects), not related to vaccination, were recorded in the BK-SE36/CpG arm: 5 events (in 3 subjects) within 28 days of vaccination. All serious adverse events (SAEs) (n=5) were due to severe malaria (52-226 days post vaccination) and not related to vaccination. In all cohorts, BK-SE36/CpG arm had higher antibody titres after Dose 3 than after Dose 2. Younger cohorts had stronger immune responses (12-24-month-old > 5-10 years-old > 21-45 years-old). Sera predominantly reacted to peptides that lie in intrinsically unstructured regions of SE36. In the control arm, there were no marked fold changes in antibody titres and participants' sera reacted poorly to all peptides spanning SE36. Conclusion: BK-SE36/CpG was well-tolerated and immunogenic. These results pave the way for further proof-of-concept studies to demonstrate vaccine efficacy. Clinical trial registration: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1921, PACTR201701001921166.

[A case of breast cancer liver metastases with jaundice responding to trastuzumab monotherapy].

We report the case of a 60-year-old female with liver dysfunction resulting from diffuse liver metastases, which, atypically, had originated from breast cancer. She responded remarkably well to trastuzumab monotherapy. She was referred to our hospital because of left breast cancer with multiple general lymphadenopathies. She presented with jaundice and liver dysfunction without a space-occupying lesion or a dilatation of the intrahepatic bile duct on computed tomography images. A liver biopsy was done to rule out autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis, and histopathological examination showed adenocarcinoma in the lymph duct of the liver. Both the primary breast cancer and the liver metastases were negative for hormone receptor expression(ER-, PR-), but overexpressed HER2(HercepTest 3+). She was diagnosed as invasive ductal carcinoma(T1N3cM1, Stage IV). We started trastuzumab monotherapy, which improved her jaundice and liver dysfunction, and resulted in a decrease in lymph node size.

[A case of cardiac tamponade due to breast cancer treated with weekly paclitaxel].

A 44-year-old woman who underwent surgery for left breast cancer 2 years ago presented with dyspnea. Her pathological stage of breast cancer was T2N1M0, ER (3+), PgR (3+), and HER2: 1+. She was treated with tamoxifen only as adjuvant therapy. Pleural effusion in both lungs and pericardial effusion were detected by computed tomography. We aspirated 1,100 mL of the pleural effusion and 700 mL of the pericardial effusion; the cytologies of both were class V. Because her dyspnea disappeared, she was administered weekly paclitaxel. Her pleural effusion and pericardial fluid have not re- emerged. The therapy of choice for pericardial effusion is local chemotherapy or systemic chemotherapy. Systemic chemotherapy after pericardial drainage was effective for this patient. Key words: Breast cancer.

[A long-surviving case of HER2-positive breast cancer with brain metastasis treated by multidisciplinary therapy].

We present a case of a 55-year-old woman who visited our hospital aware of a lump in her right breast. We diagnosed it as bilateral breast cancer [Rt: ABCDE, T3N1M0, ER (-), PgR (-), HER2: 3+, Stage IIIA; Lt: C, T2N0M0, ER (-), PgR (-), HER2: 1+, Stage IIA]. She underwent NAC with EC followed by docetaxel. After cPR, an operation (Rt Bt+Ax, Lt Bp+Ax) was performed. Liver metastases were identified 9 months after the operation, and she was administered weekly paclitaxel+trastuzumab for 12 courses. After cPR, the treatment was changed to trastuzumab only. Because a cerebellar metastasis appeared in postoperative month 19, she underwent an operation using a gamma-knife. Because a new cerebellar metastasis appeared in postoperative month 26, she underwent another gamma-knife operation. Furthermore, liver metastases were diagnosed as PD, and treatment was changed to vinorelbine and trastuzumab. Because third new cerebellar metastasis appeared in postoperative month 45, she underwent another gamma-knife operation. Lung metastases were identified 59 months after the operation, and the therapy was changed to lapatinib and capecitabine. There was no subsequent growth of metastatic tumors, and good control was obtained.

[A case of metastatic breast cancer with bilateral hydronephrosis effectively treated with capecitabine].

A 54-year-old female was diagnosed with invasive ductal carcinoma (pT3N1M0, Stage IIIA, estrogen receptor positive [ER (+)], progesterone receptor positive [PgR (+)], human epidermal growth factor receptor type 2 [HER2] score 0) and was treated by preoperative chemotherapy with weekly paclitaxel followed by 5-fluorouracil(5-FU) plus epirubicin plus cyclophosphamide regimen(FEC). Partial mastectomy with axillary dissection was performed. The pathological examination disclosed that the tumor was scirrhous carcinoma, and a pathological partial response was achieved by chemotherapy. Multiple bone metastases were detected 18 months after the surgery during treatment with letrozole as adjuvant therapy. Retroperitoneal metastases with hydronephrosis and a lung metastasis were detected 28 months after the surgery, even though exemestane and zoledronate were administrated after detection of the bone metastases. Chemotherapy with capecitabine was started and she recovered from hydronephrosis 4 months after the start of treatment. After 32 months from the first treatment with capecitabine, the patient is presently alive without hydronephrosis due to continued chemotherapy.

Kinesin 18A expression: clinical relevance to colorectal cancer progression.

Kif18A, a member of the kinesin superfamily of molecular motor proteins, is a microtubule depolymerase and a key regulator of chromosome congregation. Kif18A's role in cancer progression has not been well defined. Our hypothesis is that Kif18A has a role in the progression of colorectal cancer (CRC). To investigate this expression of Kif18A, mRNA was assessed by quantitative real-time PCR in 113 operative specimens of primary CRC. Kif18A was overexpressed and significantly (p < 0.0001) higher in CRC than in normal colon tissue. Kif18A overexpression in CRC significantly correlated with clinicopathologic factors such as tumor stage (p < 0.0001), lymphatic invasion (p = 0.001), lymph node metastasis (p = 0.01), venous invasion (p = 0.002) and peritoneal dissemination (p = 0.02), suggesting that it has a key role in CRC progression. In multivariate analysis, high Kif18A expression had independent significance for poorer overall survival after resection of CRC (p = 0.037). To demonstrate Kif18A's role in CRC progression, we performed translational and in situ studies. Using in vitro studies on CRC cell lines, we evaluated Kif18A's role in proliferation, migration and invasion. CRC cells transfected with Kif18A cDNA demonstrated significant enhanced migration (p < 0.01) and invasion (p = 0.018) compared to mock-transfected cells. When Kif18A was targeted with specific small interfering RNA, CRC cells had significantly reduced proliferation (p < 0.01), migration (p < 0.01) and invasion (p < 0.05). The in vitro and translational studies demonstrated that Kif18A expression is related to events of metastasis and is a significant factor for CRC progression.

[A case of scalp metastases from breast cancer successfully treated with letrozole].

A 62-years-old woman visited a dermatology clinic for hard mass at her scalp. Clinicallly, the mass was hard and alopecic. The diameter was 3 cm. A skin biopsy was done and histpathological examination showed adenocarcinoma. Immunehistchemically, estrogen receptor was positive. It was suspected that breast cancer could be metastasized to the scalp, but mammography, ultrasound, and positron emission tomography showed no particular metastases in her breast and other organs. Magnetic resonance imaging showed enhanced lesions in her birateral breast. Needle biopsy was done and pathological findings showed bilateral breast carcinoma and metastases to the scalp. So we started endocrine therapy using letrozole, the mass was shrunk to 1 cm after 6-month. It is rare that breast cancer was metastasized to the scalp. But Conner et al. reported that 84% of metastatic scalp carcinoma was from the breast, so we should examine the breast more carefully.

[A case of breast cancer liver metastases responding to lapatinib and capecitabine therapy].

We report a 55-year-old female with liver metastases from breast cancer who responded to lapatinib and capecitabine combination therapy as third-line. She was diagnosed as invasive ductal carcinoma (T1cN1M0, stage IIA). Biomarker of breast cancer was negative hormone receptor (ER-, PgR-) and overexpression of HER2(HercepTest 3+). We started preoperative chemotherapy with weekly paclitaxel followed by FEC100. Then mastectomy with axillary dissection was performed. Histopathology of the breast and lymph nodes showed complete disappear of invasive cancer cells( pCR, grade 3). We performed her adjuvant therapy with trastuzumab after surgery. The liver metastases developed 5 months after surgery. We treated her in trasutumab combined with vinorelbine, and followed by docetaxel during one year and four months. Because liver metastases re-grew during the combination therapy with trastuzumab, we switched to lapatinib and capecitabine combination therapy. After four months of administration, abdominal CT revealed liver metastases were remarkably reduced in size. The efficacy of chemotherapy lasted for eight months.

Breast cancer screening using digital breast tomosynthesis compared to digital mammography alone for Japanese women.

BACKGROUND: The purpose of this study is to confirm the position of DBT in breast cancer screening in Japan, to assess cancer detection rates, recall rates, positive predictive value (PPV), and to evaluate the type of mammographic findings of cancer with the use of digital mammography alone (2DDM) and combined with digital breast tomosynthesis (DBT). METHODS: 11,894 examinations of the opportunistic breast cancer screening using only 2DDM and 2DDM plus DBT were performed from May 1, 2017 to March 31, 2019. The 11,894 women [3535 women who received DBT in addition to 2DDM (3D group) and 8359 who received 2DDM only (2D group)] participated in this study. The study was approved by the Institute's Ethics Committee and all participants provided written informed consent. RESULTS: The recall rate was 2.6% for the 3D group and 3.6% for the 2D group (p < 0.01). The cancer detection rate was 0.17% in both 3D and 2D groups (p = 0.978). The positive predictive value (PPV) was 6.5% for the 3D group and 4.7% for the 2D group (p = 0.484). The cause of the decrease in recall rate was due to a decrease in the finding of focal asymmetric density (FAD). CONCLUSION: The recall rate was improved by using DBT for breast cancer screening in Japanese women. Cancer detection rates were exactly the same in DBT and 2DDM groups, so only DBT non-inferiority could be verified. We have verified that breast cancer screening combined with DBT is useful even for Japanese women to reduce unnecessary further examination.

[Pilot study of radiofrequency ablation (RFA) therapy in patients with early breast cancer].

A recent breast cancer operation appears to have become more simplified, and we may cure an early stage breast cancer without a surgery in the future. This study was approved by our institutional review board and all patients received the study information. We started a radiofrequency ablation (RFA) in April 2008 for breast cancer patients without extensive ductal spreads and the tumor size of 2 cm or less measured by magnetic resonance imaging (MRI). At first, we performed five patients from a clinical viewpoint of technique and safety. All cases were performed safely. There was no complication such as burns. At the mid observation period of 22 months in average (range 21-24), no local recurrence and distant metastases were occurred after RFA. Cosmetic after RFA was excellent in all cases.

[A case of stage IV breast cancer with bone metastases that responded well for long-term to hormonal therapy].

A case was a 48 years old woman. She was aware of a lump in her left breast and visited our hospital. We diagnosed it as an invasive ductal carcinoma. Immunostaining for both ER and PgR was strongly positive. CT of the initial consultation showed multiple bone metastases (thoracic vertebrae, lumbar vertebrae, and iliac bone). After AC followed by docetaxel and tamoxifen, LH-RH analogue was started. We used anastrozole after menopause. The bisphosphonate has been used from the beginning of the treatment. After the chemotherapy, the clinical response of primary tumor was judged as partial response. For six years, the size of primary tumor has not been changed, and PET-CT has not showed another metastasis. Anastrozole was superior to tamoxifen with respect to TTP (median values of 10.7 and 6.4 months for anastrozole and tamoxifen, respectively) in postmenopausal women with ER and/or PgR receptor positive tumors. Our study indicated that many patients responding to hormonal therapy appear to have been increasing from now on.

[A case of inflammatory breast cancer responding to anastrozole].

A case is 61 years old woman. In February 2008, she was aware of swelling, skin redness and edema in her left breast and visited our hospital. We diagnosed it as inflammatory breast cancer with positive hormone receptor (ER+, PgR+) and unexpression of HER2 (HercepTest 1 +). We started preoperative chemotherapy with weekly paclitaxel followed by FEC100, but we canceled chemotherapy because she developed cerebral infarction when we administered paclitaxel twice. Then, hormonotherapy using anastrozole (Arimidex) was therefore attempted. Three months later, treatment with anastrozole alone reduced the swelling, skin redness and edema in her left breast. After eight months of administration, the breast swelling, skin redness and edema were completely disappeared. MRI revealed the disappearance of the enhanced area. Then mastectomy with auxiliary dissection was performed.