Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: a study in HER2-positive and HER2-negative breast cancer patients.

BACKGROUND: We aimed to compare the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients. Additionally, the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced cardiotoxicity were determined. METHODS: HER2-positive (n = 37) and HER2-negative (n = 37) breast cancer patients were enrolled. Cardiac function assessment and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at three months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all three-time points was processed for measuring cardiac injury biomarkers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment were also processed for measuring systemic oxidative stress and 85 metabolome levels. RESULTS: Cardiac injury and systolic dysfunction 2 weeks after completion of doxorubicin treatment were comparable between these two groups of patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively. The changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment. CONCLUSIONS: The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, and these changes might serve as severity and prognostic markers of doxorubicin-induced cardiotoxicity. TRIAL REGISTRATION: The study was conducted under ethical approval from the Institutional Review Board of the Faculty of Medicine, Chiang Mai University (Registration number: MED-2563-07001; Date: April 28, 2020). The study also complied with the Declaration of Helsinki.

Integration of breast cancer care in a middle-income country: learning from Suandok Breast Cancer Network (SBCN).

BACKGROUND: Breast cancer incidence in Northern Thailand has shown a continuous increase since records began in 1983. In 2002 the urgency of the situation prompted Maharaj Nakorn Chiang Mai Hospital to initiate the Suandok Breast Cancer Network (SBCN). METHODS: The SBCN is a not-for-profit organization in the university hospital which serves as a training and education center and provides highly specialized medical care for patients in Chiang Mai and in 5 provinces of northern Thailand, with the key mission of improving breast cancer care. The short-term goal was to overcome the barriers to engagement with breast cancer and its treatment and the long-term goal was to increase the overall survival rate of breast cancer patients in our region. RESULTS: We enrolled breast cancer patients treated at Maharaj Nakorn Chiang Mai Hospital between January 2006 and December 2015 and divided into 2 cohorts: 1485 patients who were diagnosed from 2006 to 2009 (cohort 1: early implementation of SBCN) and 2383 patients who were diagnosed from 2010 to 2015 (cohort 2: full implementation of SBCN). Criteria to measure improved cancer waiting time (CWT) would include: time to diagnosis, time to surgery, and time to radiotherapy. The 5-year overall survival (OS) of the cohort 2 was higher than that in cohort 1, at 73.8 (72.0-75.5) compared to 71.5 (69.2-73.7) (p-value = 0.03). CONCLUSIONS: Reasons behind the success of project include the uniformity of care encouragement, service network development and timely access to each step of breast cancer management. The model used in SBCN could be adopted as a learning guide to improve healthcare access and outcome for breast cancer patients in low- to middle-income countries.

Real-world outcomes of different treatments in the management of patients with HER-2 positive breast cancer: a retrospective study.

OBJECTIVE: To investigate the treatment outcome in terms of relapse free survival and overall survival, and explore the determinants of the clinical outcome in HER-2/neu positive breast cancer patients who received or not received adjuvant trastuzumab. MATERIAL AND METHOD: The authors reviewed retrospectively of newly diagnosed non-metastatic breast cancer patients at the Faculty of Medicine, Chiang Mai University between January 2004 and December 2007. Comparisons were made between the two cohorts, women who did not receive adjuvant trastuzumab (100 patients) and women who received adjuvant trastuzumab (14 patients). RESULTS: The median follow-up time was 4.7 years. Four-year relapse-free survival (RFS) and overall survival (OS) in patients receiving trastuzumab was 92.3% and 100%, respectively. In the cohort of HER-2 positive patients who did not receive trastuzumab, the 4-year RFS in this group was 68.2% and 4-year OS was 87.8%. The difference was not statistically significant between the 4-year RFS rates (p = 0.103) and the 4-year OS rates (p = 0.214). By multivariate Cox regression analyses, only nodal status was identified as the independent predictors for superior RFS (hazard ratio 2.93; 95% CI, 1.07 to 5.88; p = 0.034) and none of the clinical parameters were significant predictors for 4-year overall survival. CONCLUSION: A hospital-based analysis of adjuvant Trastuzumab use in our center does not demonstrate the different treatment outcome. However there is a trend of favorable outcome in the group receiving adjuvant trastuzumab.

Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial.

Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies.

Reliability and validity of the Thai translation (Thai PPS Adult Suandok) of the Palliative Performance Scale (PPSv2).

PURPOSE: the Thai PPS Adult Suandok tool was translated from the Palliative Performance Scale (PPSv2) and had been used in Chiang Mai, Thailand for several years. AIM: to test the reliability and validity of the Thai translation of PPSv2. DESIGN: a set of 22 palliative cases were used to determine a PPS score on Time-1, and repeated two weeks later as Time-2. A survey questionnaire was also completed for qualitative analysis. PARTICIPANTS: a total of 70 nurses and physicians from Maharaj Nakorn Hospital in Chiang Mai participated. RESULTS: The Time-1 intraclass correlation coefficient (ICC) for absolute agreement is 0.911 (95% CI 0.86-0.96) and for consistency is 0.92 (95% CI 0.87-0.96). The Time-2 ICC for agreement is 0.905 (95% CI 0.85-0.95) and for consistency is 0.912 (95% CI 0.86-0.96). These findings indicate good agreement among participants and also were somewhat higher in the Time-2 re-test phase. Cohen's kappa score is 0.55, demonstrating a moderate agreement. Thematic analysis from the surveys showed that 91% felt PPS to be a valuable clinical tool overall, with it being 'very useful' or 'useful' in several areas, including care planning (78% and 20%), disease monitoring (69% and 27%) and prognostication (61% and 31%), respectively. Some respondents noted difficulty in determining appropriate scores in paraplegic patients or those with feeding tubes, while others found the instructions long or difficult. CONCLUSION: the Thai PPS Adult Suandok translated tool has good inter- and intra-rater reliability and can be used regularly for clinical care.

Stage-Specific Survival Rate of Breast Cancer Patients in Northern Thailand in Accordance with Two Different Staging Systems.

Objective: This study was attempted to investigate overall survival by stage at diagnosis in female breast cancer patients in Northern Thailand by using 2 different staging systems; namely, American Joint Committee on Cancer (AJCC) Tumor (T), Nodal (N) and Metastatic (M) staging system and Surveillance Epidemiology and End Results (SEER) summary staging system. Methods: We studies female breast cancer patients whose data were registered in Chiang Mai cancer registries between January 2006 and December 2015. Data were recorded in SEER summary staging system. The TNM AJCC staging was searched in the medical records. Results: A total of 3,873 female breast cancer patients were diagnosed from 2006-2015. All data sets were recorded in SEER summary stage 2000. Early stage was the most prevalent stage at the time of diagnosis (58%), followed by loco-regional advanced stage (32%), and metastatic breast cancer (10%). The 5-year overall survival rate of early, loco-regional advanced, and metastatic stages were 85.3%, 66.4%, and 26.2%, respectively. After examining the medical records, we excluded patients who had no data on T, N, and M in their records. Finally, only 3,251 patients were analyzed for AJCC stage-specific survival. The 5-year overall survival rate in stages I, II, III, and IV were 94.4%, 85.0%, 56.6%, and 28.3%, respectively. Conclusion: Comparing to more stable economic countries, the 5-year overall survival rate for a specific stage of breast cancer in Northern Thailand was slightly lower in early stage and stage I-II in accordance with AJCC, but much lower in loco-regional stage and stage III with respect to AJCC. Nevertheless, it was similar in metastatic stage and stage IV according to AJCC.

Preoperative irinotecan/5-FU/leucovorin plus concurrent radiotherapy in rectal cancer.

PURPOSE: To evaluate results of preoperative irinotecan/5-FU/leucovorin plus radiotherapy for locally-advanced rectal cancer. METHODS: Thirty-five patients with locally-advanced rectal cancer were treated with preoperative irradiation 46 Gy plus concurrent chemotherapy(irinotecan 10 mg/m(2)/d d1-d5, d22-d26, 5-FU 350 mg/m(2)/d d1-d5, d22-d26, and leucovorin 20 mg/m(2) d1-d5, d22-d26), followed by radical surgery. RESULTS: There were no treatment-related deaths. Acute toxicity was mainly in neutropenia and diarrhea, with both grade 4 neutropenia and grade 3 diarrhea observed in 4 patients(11%). Radical resectability was performed in 29 patients(83%)with sphincter preservation surgery in 7 patients. Six patients did not undergo the planned surgery due to patient refusal and disease progression. A complete pathological response was observed in 14%(4/29). Pathological T-downstaging was observed in 55%(16/29). CONCLUSIONS: These results suggest that preoperative radiochemotherapy with irinotecan/5-FU/leucovorin is safe and effective in tumor downstaging and allows sphincter-saving resection to be performed in locally-advanced rectal cancer.

Real-life clinical pattern, management, and survival in Thai patients with early-stage or metastatic triple-negative breast cancer.

OBJECTIVES: To characterize the clinical pattern and evaluate real-life practices in the management of patients with triple-negative breast cancer (TNBC) in Thailand. METHODS: In this multicenter, prospective, observational cohort, females (aged ≥18 years) with histologically and immunohistochemically confirmed TNBC were enrolled. Patient data was collected at four study visits-an inclusion visit (for enrollment), and three subsequent follow-up visits at 12±1, 24±1, and 36±1 months after completion of first day of any planned chemotherapy. RESULTS: Of the 293 enrolled patients, 262 (89.4%) had early-stage TNBC (Stage I: 46 patients, Stage II: 151 patients, and Stage III: 65 patients) and 31 (10.6%) had metastatic TNBC (mTNBC). Chemotherapy was prescribed to 95.4% of the early-stage patients and to 100.0% of the mTNBC patients; most commonly as anthracycline-based in combination with cyclophosphamide and other agents. Patients' performance status and consensus guidelines were the major factors affecting choice of treatment. In early-stage patients, median disease-free survival (DFS) and overall survival (OS) had not been reached for Stage I and II patients, and were calculated to be 37.0 months and 40.0 months, respectively, in Stage III patients. In mTNBC patients, progression-free survival (PFS) and OS were found to be 10.0 months and 14.0 months, respectively. In Stage III patients, anthracycline-based regimens were found to be associated with increase in DFS (p = 0.0181) and OS (p = 0.0027) compared to non-anthracycline-based regimens. In mTNBC patients, non-taxane-based regimens were associated with an increase in PFS (p = 0.0025). The 3-year survival rates in early-stage and mTNBC patients were 85.0% and 21.0%, respectively. CONCLUSION: Clinical management of TNBC in Thailand follows the general guidelines for treatment of TNBC. However, prognosis and survival outcomes are suboptimal, especially in progressive disease. This study is the first assessment in the existing practices in which the results could pave to way to improve the treatment outcome of TNBC in Thailand.

Outcome of eribulin as a late treatment line for Thai metastatic breast cancer patients.

BACKGROUND: We report the safety and efficacy of eribulin as a late treatment line in Thai metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: A total of 30 MBC patients treated with eribulin between January 2014 and January 2017 were retrospectively analyzed. The patients were scheduled to receive 1.4 mg/m2 of eribulin on day 1, day 8 and subsequently every 21 days. All patients had previously received at least three chemotherapy regimens including anthracycline and taxane. Response rate and progression-free survival (PFS) were analyzed. RESULTS: The median age was 56 years (range, 40-74 years), with a median follow-up time of 5.7 months (range, 0.2-25 months). The overall response rate was 30% (nine patients): four patients had triple-negative breast cancer, three patients had luminal B breast cancer and two patients had luminal A breast cancer. The median PFS was 2.9 months (range, 0.2-14 months). The median number of previous chemotherapy regimens was 4 (range, 3-9). Univariate analysis showed that the number of regimens (four or fewer) prior to eribulin was statistically associated with superior PFS (P = 0.009). Multivariate analysis also showed similar statistical association between number of prior regimens (four or fewer) and better PFS adjusted by age group (≥50 years; hazard ratio = 1.29; 95% CI: 1.0-1.65; P = 0.046). There were no toxic deaths or grade 4 toxicities. Nine (30%) patients had grade 3 anemia toxicities, and the other common toxicities were leukopenia and neutropenia. Four (13%) patients required dose reduction and 16 (53%) patients required dose delay because of toxicities. CONCLUSION: Eribulin is an effective drug for heavily pretreated MBC patients with tolerable toxicities. The benefit was superior in patients who received fewer than four previous chemotherapy regimens.

Gemcitabine plus cisplatin (GC): a salvage regimen for advanced breast cancer patients who have failed anthracycline and/or taxane therapy.

BACKGROUND: In clinical studies of both heavily and minimally pretreated patients with advanced breast cancer, the combination of Gemcitabine plus cisplatin (GC), given in a variety of schedules and doses, has demonstrated moderate safety and efficacy in both heavily and minimally pretreated advanced breast cancer with response rate from 29-63% (median 46%). METHODS: We evaluated the activity and toxicity of another GC regimen (gemcitabine 1,000 mg/m(2) days 1, 8 plus cisplatin 75 mg/m(2) day 1 every 3 weeks) in 30 breast cancer patients who failed chemotherapy with anthracycline and/or taxanes as adjuvant or neoadjuvant, or primary therapy. RESULTS: We obtained overall response in 15 of 29 evaluable patients (52%), with responses occurring in all subgroups of disease (unresectable locally advanced, locoregional recurrence, and distant metastasis). Toxicity was primarily hematologic, with grade 3/4 neutropenia and thrombocytopenia in 37% and 17% of patients, respectively. The only grade 3/4 non-hematologic toxicity was grade 3 nausea/vomiting in 12% of patients. CONCLUSION: Our data suggest that gemcitabine plus cisplatin appears to be effective and has an acceptable toxicity profile in anthracycline and/or taxane pretreated patients with advanced breast cancer.

"Ruptured" malignant phyllodes tumor of the breast: a case report.

Phyllodes tumor or cystosarcoma phyllodes is a rare disease and is usually seen in middle-aged patients. Ruptured phyllodes tumor is a very rare condition. Our study reports patient presentation, diagnosis method, and treatment of an unusual case. A 58-year-old premenopausal female was diagnosed with a phyllodes tumor and presented with a rapidly growing mass for 2 months that ruptured 1 month later. She underwent simple mastectomy at the left side of her breast and received adjuvant radiotherapy. No recurrence was found 4 months after operation.

A young man with concurrent acute appendicitis and incarcerated right indirect inguinal hernia.

OBJECTIVE: Acute appendicitis and incarcerated hernia rarely present in the same episode. Our study reports patient presentation, diagnosis method, and treatment of an unusual case at the Chiang Mai University Hospital. METHOD: Case report. RESULT: A 20-year-old man visited the Chiang Mai University Hospital with right lower quadrant pain and a right groin mass which could not be reduced. The computerized tomography scan showed acute appendicitis and omentum in the hernia sac. Operative treatment was an appendectomy and herniorrhaphy. The treatment was successful, and the patient was discharged from our hospital without any complications. CONCLUSION: Concurrent acute appendicitis and incarcerated hernia are very rare, but should be kept in mind if a patient presents with right lower quadrant pain and a right groin mass. Further investigation may be helpful if the diagnosis is uncertain. Operative priority treatment depends on each individual case.

Bilateral desmoid tumor of the breast: case seriesand literature review.

BACKGROUND: Desmoid tumor of the breast is very rare and locally aggressive but has no distant metastasis. Bilateral lesions are extremely rare, found in only 4% of patients. Two cases of bilateral desmoid tumor of the breast are reported. The clinical presentation, diagnosis, imaging, treatment, and follow-up outcomes of recurrence as well as a brief literature review are provided. CASE REPORTS: Case 1 is a 31-year-old woman who presented with nipple retraction. An ultrasound revealed BIRAD V in both breasts. She underwent a bilateral excisional biopsy under ultrasound mark with the pathology result of extra-abdominal desmoid tumor in both breasts. The patient had a bilateral mastectomy with silicone implantation due to the involved margins by excision. She remained tumor free after 7-year follow-up. Case 2 is a 28-year-old woman who presented with a lump on her right breast that she had discovered ~2 months earlier. An ultrasound showed a spiculated mass in the right breast and some circumscribed hypoechoic masses in both breasts. A bilateral breast excision was done. The pathology result was an extra-abdominal desmoid tumor. She had recurrence on both sides and underwent a mastectomy and silicone implantation. The tumor has not recurred after 1-year follow-up. CONCLUSION: Imaging cannot distinguish between benign breast lesions and malignancy. Pathology results are helpful in making a definitive diagnosis. Given that the desmoid tumor is locally aggressive, a local excision with clear margins is recommended. Chemotherapy and hormonal treatment are controversial.

Factors affecting local recurrence and distant metastases of invasive breast cancer after breast-conserving surgery in Chiang Mai University Hospital.

BACKGROUND: The purpose of this study was to collect data regarding breast cancer profiles and factors that affect local recurrence and distant metastasis after breast-conserving surgery (BCS) in Chiang Mai University Hospital. MATERIALS AND METHODS: This study was a retrospective review in a single institution of newly diagnosed invasive breast cancer patients who were treated with BCS between April 9, 2001 and December 25, 2011. RESULTS: A total of 185 patients treated with BCS were included in this study, with an average age of 46.83 years. The average recurrence age was 41.1 years and the average nonrecurrence age was 47.48 years, with a recurrence rate of 10.27%. Premenopause was significant in recurrence (P=0.047), as well as non-estrogen-expression patients (P=0.001) and patients who did not receive antihormonal treatment (P=0.011). CONCLUSION: The recurrence rate in our institute was 10.27%. Factors affecting recurrence after BCS included young age, premenopausal status, nonexpression of the estrogen receptor, and patients who had not received antihormonal treatment. The recurrence rate was higher in the first 90 postoperative months.

Capecitabine and weekly paclitaxel as first-line therapy in Thai patients with metastatic breast cancer.

AIM: The combination of a taxane and capecitabine offers synergistic antitumor activity. This study aimed to determine the efficacy and tolerability of a paclitaxel and capecitabine combination in Thai patients with metastatic breast cancer (MBC) not previously treated for metastatic disease. METHODS: This open-label, single-center, non-comparative phase II study was conducted between December 2006 and March 2009. In all 40 MBC patients were treated with oral capecitabine 1000 mg/m(2) twice daily on days 1 to 14, and weekly paclitaxel 80 mg/m(2) in a 3-week cycle for a total of six cycles. RESULTS: After a median follow up of 13.4 months, an overall objective response rate of 80%, with a partial response of 74% and a complete response of 5% were achieved. While 8% of patients achieved stable disease, 13% had progressive disease. Median time to progress was 8 months and median overall survival was 24.4 months. One patient discontinued because of hypersensitivity to paclitaxel. There was no grade 4 toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade 2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3), neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both of which 5% experienced grade 1 severity). CONCLUSION: A first-line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.