Chii-Ming Chen

Locoregional failure of postmastectomy patients with 1–3 positive axillary lymph nodes without adjuvant radiotherapy

PURPOSE To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT). MATERIALS AND METHODS Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1-3 positive axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months. RESULTS Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04), tumor size >==3 cm (p = 0.002), negative estrogen receptor protein status (p = 0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size (p = 0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor >==3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of 66.7% (95% CI 42.8-90.5%) compared with 7.8% (95% CI 2.2-13.3%) for the low-risk group (with 0-2 factors; p = 0.0001). For the 110 patients who received no adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9 of 17, 95% CI 24.6-73.4%). For patients without LRR, it was 13.3% (15 of 93, 95% CI 6.3-20.3%; p = 0.0001). The 4-year survival rate for patients with and without LRR was 75.1% (95% CI 53.8-96.4%) and 88.7% (95% CI 82.1-95.4%; p = 0.049), respectively. LRR was independently associated with a higher risk of distant metastasis and worse survival in multivariate analysis. CONCLUSION LRR after mastectomy is not only a substantial clinical problem, but has a significant impact on the outcome of patients with T1 or T2 primary tumor and 1-3 positive axillary nodes. Patients with risk factors for LRR may need adjuvant RT. Randomized trials are warranted to determine the potential benefit of postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1-3 positive nodes.

Adherence to Quality Indicators and Survival in Patients With Breast Cancer

Background:International initiatives increasingly advocate physician adherence to clinical protocols that have been shown to improve outcomes, yet the process-outcome relationship for adhering to breast cancer care protocol is unknown. Objective:This study explores whether 100% adherence to a set of quality indicators applied to individuals with breast cancer is associated with better survival. Research Design and Subjects:Ten quality indicators (4 diagnosis-related and 6 treatment-related indicators) were used to measure the quality of care in 1378 breast cancer patients treated from 1995 to 2001. Adherence to each indicator was based on the number of procedures performed divided by the number of patients eligible for that procedure. The main analysis of adherence was dichotomous (ie, 100% adherence vs. <100% adherence). Measures:The outcome measures studied were 5-year overall survival and progression-free survival, calculated using the Kaplan-Meier method. The Coxs proportional hazard regression model was used for univariate and multivariate analyses. Results:Most patients received care that demonstrated good adherence to the quality indicators. Multivariate analysis revealed that 100% adherence to entire set of quality indicators was significantly associated with better overall survival [hazard ratio (HR): 0.46; 95% confidence interval (CI): 0.33–0.63] and progression-free survival (HR 0.51; 95% CI, 0.39–0.67). One hundred percent adherence to treatment indicators alone was also associated with statistically significant improvements in overall and progression-free survivals. Conclusions:Our study strongly supports that 100% adherence to evidence supported quality-of-care indicators is associated with better survival rates for breast cancer patients and should be a priority for practitioners.

Treating high-mercury-containing lamps using full-scale thermal desorption technology.

The mercury content in high-mercury-containing lamps are always between 400 mg/kg and 200,000 mg/kg. This concentration is much higher than the 260 mg/kg lower boundary recommended for the thermal desorption process suggested by the US Resource Conservation and Recovery Act. According to a Taiwan EPA survey, about 4,833,000 cold cathode fluorescent lamps (CCFLs), 486,000 ultraviolet lamps and 25,000 super high pressure mercury lamps (SHPs) have been disposed of in the industrial waste treatment system, producing 80, 92 and 9 kg-mercury/year through domestic treatment, offshore treatment and air emissions, respectively. To deal with this problem we set up a full-scale thermal desorption process to treat and recover the mercury from SHPs, fluorescent tube tailpipes, fluorescent tubes containing mercury-fluorescent powder, and CCFLs containing mercury-fluorescent powder and monitor the use of different pre-heating temperatures and desorption times. The experimental results reveal that the average thermal desorption efficiency of SHPs and fluorescent tube tailpipe were both 99.95%, while the average thermal desorption efficiencies of fluorescent tubes containing mercury-fluorescent powder were between 97% and 99%. In addition, a thermal desorption efficiency of only 69.37-93.39% was obtained after treating the CCFLs containing mercury-fluorescent powder. These differences in thermal desorption efficiency might be due to the complexity of the mercury compounds contained in the lamps. In general, the thermal desorption efficiency of lamps containing mercury-complex compounds increased with higher temperatures.

Chromosomal comparative genomic hybridization abnormalities in early- and late-onset human breast cancers: correlation with disease progression and TP53 mutations

Nearly 30% of the breast cancer patients in the Taiwanese community have their diseases diagnosed before the age of 40. Their 5-year survival rate is poorer than that of their late-onset breast cancer counterparts. Genomic abnormalities between these two breast cancer age groups were compared using comparative genomic hybridization (CGH) analyses. The sample set was made up of 44 early-onset (<35 years old) and 54 late-onset cases (>63 years old). Frequent CGH changes were noted, such as gains on 8q, 1q, and 17q and losses on 16q, 17p, and 8p. These were very similar for the two age groups, as well as for Taiwanese women and other ethnic populations. In contrast, several less common lesions, such as gains on 16p and 8p and losses on 11q and 9p, were significantly different between the early- and late-onset breast tumors. In addition, more profound chromosomal changes were consistently associated with the more advanced-stage tumors, and less expression of the estrogen and the progesterone receptors, and of HER-2/neu. About 19% of the breast cancers examined carried a TP53 mutation in exons 4-9. Of these, 88% (15/17) were missense point mutations and these were distributed randomly along the tested gene fragments without apparent clustering, as has been shown in certain other ethnic or regional studies. On average, patients carrying these TP53 mutations had 9.5 CGH lesions per case, compared to only 2.8 changes in samples that had no TP53 mutation. Our results indicate that certain genomic lesions, especially 11q loss, may play a role in early-onset breast tumor formation, and that combined use of genomic patterns and molecular targets may provide a useful tool for diagnostic, therapeutic, and prognostic purposes.

SONOGRAPHIC ELASTOGRAPHY IMPROVES THE SENSITIVITY AND SPECIFICITY OF AXILLA SAMPLING IN BREAST CANCER: A PROSPECTIVE STUDY

We describe a study to determine whether elastography of axillary lymph nodes (LNs) combined with B-mode ultrasound (US) is capable of differentiating the benign from the metastatic state in patients with breast cancer. B-mode US, elastography and fine-needle aspiration of 90 axillary lymph nodes from 89 female patients with breast cancer are described in this report. Five elastographic patterns were observed as defined by the percentages of high elasticity according to pattern of distribution and degree of hardness of the target LNs. B-mode US and elastography scores were combined to give the final scores. Sensitivity and specificity were 80% and 88%, respectively, for B-mode US alone, 86% and 90% for elastography alone and 84% and 98% for the combined assessment to differentiate the benign from the malignant state. The combination of B-mode US and elastography is capable of identifying metastatic axillary LNs from benign enlargement in patients with breast cancer.

The Benefit and Risk of Postmastectomy Radiation Therapy in Patients with High-risk Breast Cancer

To evaluate the efficacy of postmastectomy radiation therapy (PMRT) for prophylaxis against locoregional recurrence in high-risk breast cancer patients, and the rate of complication associated with such treatment, we retrospectively reviewed 79 breast cancers in 78 patients, who were given therapy (PMRT) between April 1990 and March 1995. Radiation doses were 46-50 Gy in 2-Gy fractions. High-risk factors included primary tumor (> or = 5 cm) in 19 (24.1%) patients, positive axillary lymph nodes (> or = 4) in 56 (70.9%) patients, positive or close (< or = 2 mm) surgical margins in 14 (17.7%) patients, and central or inner quadrant tumor with positive axillary nodes and lymphovascular invasion in seven (8.9%) patients. Adjuvant chemotherapy was also given to 69 of 78 (88.5%), patients and hormonal therapy to 41 of 78 (53.7%) patients. The median follow-up time was 25 months (range, 7-66 months) after mastectomy. Our study revealed that locoregional failure as the first site of failure occurred in only one of 78 (1.3%) patients. Relapse-free survival at 3 years was 67.7% [95% confidence interval (CI), 52.0-81.3], and overall survival was 76.9% (95% CI, 63.3-90.6). The incidence of radiological evidence of lung fibrosis increased significantly in patients whose internal mammary chain was included in the radiation field. The occurrence of lung fibrosis can be reduced by changing radiation treatment technique and keeping central lung distance (CLD) of tangential field to < or = 2.8 cm in tangential field technique or < or = 1.4 cm in tangential with a separate internal mammary field technique. We concluded that the risk of locoregional recurrence in high-risk breast cancer patients can be much reduced by PMRT. With careful selection of radiation treatment fields, radiotherapy technique, and limitation of CLD to < or = 2.8 cm in tangential technique or < or = 1.4 cm in separate technique, the risk of symptomatic radiation pneumonitis is minimal. PMRT should be recommended for breast cancer patients who are at high risk for locoregional recurrence.

The effect on improvement of recovery and pain scores of paravertebral block immediately before breast surgery

OBJECTIVES Paravertebral block (PVB) has the potential to reduce postoperative pain after breast surgery. The aim of the study was to investigate whether PVB performed immediately before surgery could affect the postoperative morbidities in terms of pain and emesis, and improve the quality of recovery (QoR) in patients after surgery for breast cancer. METHODS Postoperative data were collected prospectively from two groups of patients undergoing unilateral breast surgery during the study period of 1 month. Forty consecutive patients received either solely general anesthesia (GA group, n=25) or GA plus ultrasound-guided PVB (GA+PVB group, n=15) for the surgery. Pain scores and areal distribution of pain were compared between the two groups 1 hour and 6 hours postoperatively and on the midmorning of postoperative Day 1 (POD1). The QoR scores were compared between the two groups 6 hours postoperatively and on the midmorning of POD1. Incidence of postoperative nausea and vomiting and doses of analgesics and narcotics given were also compared. RESULTS Pain scores at rest were significantly lower in the GA+PVB group at all designated time points [1 hour (p<0.0001), 6 hours (p<0.0001), and on midmorning of POD1 (p=0.041)]. Pain scores with movements was also significantly lower at all time points in the GA+PVB group (1 hour, p<0.0001; 6 hours, p<0.0001; midmorning of POD1, p=0.0012). Areal distribution of pain at rest and with movement was wider in the GA group 1 hour and 6 hours postoperately but was identical to that of GA+ PVB group on the mid-morning of POD1 [1 hour postoperatively at rest (p<0.0001), with movement (p<0.0001); 6 hours postoperatively at rest (p=0.0018), with movement (p=0.0048)]. The QoR scores were significantly higher in the GA+PVB group at 6 hours (p<0.0001) and on midmorning of POD1 (p=0.0079). The incidences of postoperative nausea and vomiting were significantly lower in the GA+PVB group (p=0.0004). Doses of postoperative analgesics and narcotics were significantly less in the GA+PVB group (p<0.0001 and p=0.001, respectively). Time to first request for analgesics was significantly longer in the GA+PVB group (p=0.0002). CONCLUSIONS PVB given before surgery in combination with GA could provide better postoperative analgesia and better QoR than did GA alone in patients undergoing surgery for unilateral breast cancer.

Breast mass due to alveolar soft part sarcoma of the pectoris major muscle

We present a case of alveolar soft part sarcoma (ASPS) of the pectoris major muscle in a 20-year-old female. She felt a mass in her right side breast for 7 years. The lesion was almost the same size with occasional throbbing pain and tenderness. Fine needle aspiration of the tumor was performed in the OPD and suspicious abnormal cells were reported. Ultrasound (US) examination of the breast revealed a large heterogeneously hypoechoic lesion contiguous to the pectoris major muscle. Profound color flow signals were evident in both central and peripheral regions of the mass. Spectral Doppler US showed high flow velocity in the tumor vessels with resistivity index of 0.73. Surgical intervention was performed and the histological examination yielded a diagnosis of ASPS.

Adjuvant sequential chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil (ACMF) with concurrent radiotherapy in resectable advanced breast cancer.

Doxorubicin (Adriamycin) is an anthracycline effective in breast cancer. Despite a worldwide acceptance of Adriamycin in the adjuvant chemotherapy to maximize the survival benefit in the higher risk patients with breast cancer with promising results, oncologists in general do not favorably consider anthracyclines in the adjuvant treatment setting because of concern about the acute and chronic drug-related toxicity. For high-risk patients with breast cancer with more than three positive axillary lymph nodes, this series adopted a modified sequential regimen of ACMF first with Adriamycin (A) as a single agent in 3-weekly administration for three courses, and then a combination of cyclophosphamide, methotrexate, fluorouracil (CMF) every 3 to 4 weeks for six courses given in an outpatient setting concurrent with radiation therapy as an adjuvant treatment. A total of 56 patients underwent modified radical mastectomy and 3 others breast conservation surgery for their invasive breast cancer. Forty-seven (84%) patients completed the intended adjuvant treatment and 1 patient died of infection from treatment-related neutropenia. As a whole, the 3-year overall survival and disease-free survival rates of 56 patients analyzed were 82.3% and 64.4%, respectively. In this high-risk group, patients with four to nine positive nodes showed a slightly better trend of survival than those with 10 or more positive nodes without reaching statistically significant difference (36-month overall survival: 90.9% vs. 72.5%, p = 0.06; disease-free survival: 78.7% vs. 47.8%, p = 0.38). In this entire group of patients, locoregional recurrence was absent. A total of 55 episodes of grade III and IV hematologic toxicity were observed, with only one death from neutropenic sepsis. This modified ACMF regimen offers a good survival rate in breast cancer patients with more than three positive axillary lymph nodes. When these patients are carefully managed, the morbidity and mortality related to the treatment are low.

B1 Field Correction of T1 Estimation Should Be Considered for Breast Dynamic Contrast-enhanced MR Imaging Even at 1.5 T

Purpose To prospectively quantify the effect of T1 estimation in fat by B1 correction in breast magnetic resonance (MR) imaging at 1.5 T and to examine the subsequent quantitative dynamic contrast material-enhanced parameters in breast cancer with and without B1 correction. Materials and Methods This study had institutional review board approval, and informed consent was obtained from 72 patients with breast cancer before breast MR imaging studies were performed between January and July 2015. B1+ field and variable flip angle (FA) mapping were included in the dynamic contrast-enhanced breast MR imaging protocol with a 1.5-T MR imaging system. Precontrast T1 relaxation in fat and breast tumors was computed with and without B1 correction. The pharmacokinetic parameters of breast cancer were calculated by using the Tofts model with T1 values before and after B1 correction. The Mann-Whitney U test and linear regression model were used for statistical analysis. Results The FA was 19% higher in the left breast and 3% lower in the right breast than the prescribed value. This 22% average FA difference created a 43% T1 estimation bias in fat between the breasts. The T1 variation in fat was reduced to 0.96% after B1 correction. There was a 50% overestimation and a 7% underestimation of tumor T1 in the left breast and the right, respectively, associated with B1 error. Assuming T1 after B1 correction represents the true tumor T1, 41% underestimation in the left breast and 10% overestimation in the right without B1 correction were seen in the dynamic contrast-enhanced parameters (including the volume transfer constant, or Ktrans, fraction of extracellular extravascular space, or ve, and blood normalized initial area under the gadolinium concentration curve to 90 seconds, or IAUGCBN90). Conclusion B1 correction for more accurate T1 values should be considered for quantitative dynamic contrast-enhanced breast MR imaging, even at 1.5 T, to offset significant systemic error.