Xun-Xing Guan

Predictive value of breast cancer molecular subtypes in Chinese patients with four or more positive nodes after postmastectomy radiotherapy.

The molecular subtypes of breast cancer based on status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) expression are associated with markedly different clinical outcomes. We retrospectively analyzed 774 breast cancer patients with four or more positive nodes, who underwent mastectomy between March 1999 and December 2007. Treatment with postmastectomy radiotherapy (PMRT) reduced the rates of locoregional recurrence-free survival (LRFS; 6.7% vs. 26.6%), distant metastasis-free survival (DMFS; 26.9% vs. 50.0%), and mortality (24.4% vs. 45.3%) for luminal-A subtypes (ER+ or PR+, Her2-) and reduced LRFS (12.1% vs. 27.5%) for the luminal-B subtype (ER+ or PR+, Her2+) compared with patients not receiving PMRT. However, PMRT did not affect the endpoints for the Her2-enriched or basal subtypes. Thus, understanding the differences in patterns of relapse between the different subtypes of breast cancer may enable targeted adjuvant therapy and improved surveillance decisions.

Prognostic Value of Metastatic Axillary Lymph Node Ratio for Chinese Breast Cancer Patients

Objective The prevalence of breast cancer varies among countries and regions. This retrospective study investigated the prognostic value of the lymph node ratio (LNR) compared with the number of positive lymph nodes (pN) in Chinese breast cancer patients. Methods The medical records of female breast cancer patients (N = 2591) were retrospectively evaluated. The association of LNR and TMN staging system were compared with respect to overall, disease-free, and distant metastasis-free survival. Results Out of 2591 patients, 2495 underwent modified radical surgery and 96 received breast conserving surgery. All patients had adjuvant chemotherapy following surgery. The median follow up period 66.9 months (range 5–168 months). The 5-year and 10-year overall survival rates were 89.3% and 78.8%, respectively, and 5-year disease-free survival and distant metastasis-free survival rates were 81.6% and 83.5%, respectively. Univariate analysis indicated that in general T, pN, LNR, as well as tumor expression of the estrogen receptor, progesterone receptor, and HER2 were associated with overall, disease-free, and distant metastasis-free survival (all P-values <0.05). Mutlivariate analysis found pN stage and LNR were independent predictors of overall, disease-free, and distant metastasis-free survival (all P-values <0.001). If pN stage and LNR were both included in a multivariate analysis, LNR was still an independent prognostic factor for overall, disease-free, and distant metastasis-free survival (all P-values <0.001). Conclusion Our findings support the use of LNR as a predictor of survival in Chinese patients with breast cancer, and that LNR is superior to pN stage in determining disease prognosis.

Prognostic Value of Ki-67 in Breast Cancer Patients with Positive Axillary Lymph Nodes: A Retrospective Cohort Study

Introduction Ki-67 expression is a biomarker for proliferation. Its prognostic value is recognized in breast cancer (BC) patients with negative axillary nodes, but is less clear in BC patients with positive axillary lymph nodes. Methods We retrospectively reviewed the medical records of 1131 Chinese BC patients treated from January 2002 to June 2007 and 450 patients met the inclusion criteria: positive nodes, adjuvant therapy, and complete biomarker profile (estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki-67). Univariate and multivariate regression analysis were used to correlate biomarkers and tumor characteristics with metastasis free survival (MFS) and overall survival (OS). Results Median follow-up time was 46 months (range 5–76 months). The Ki-67 expression was associated significantly with histological grade, ER, PR, HER2, and P53 status (P<0.05). Tumor stage, nodal stage, and ER status were independent prognostic factors for MFS. Ki-67 status was associated significantly with OS but not MFS. To determine whether the extent of LN involvement in the BC patients influenced the role of Ki-67 in survival rates, we compared these variables in patients with 1–3 positive lymph nodes (N1) to those of patients with ≥4 positive lymph nodes. Ki-67 status was an independent prognostic factor for MFS (Hazard Ratio, 3.27, P = 0.026) and overall survival (HR, 10.64, P = 0.007) in patients with 1–3 positive nodes (N1). Conclusions The possibility that Ki-67 expression together with clinical factors can improve prediction of the prognosis of BC patients with 1∼3 positive axillary lymph nodes warrants further studies.

Accelerated partial breast irradiation: Use of four-dimensional CT for target localization and assessment of intrafractional motion.

The aim of this study was to use four-dimensional CT (4DCT) in the planning of 3D conformational external beam radiation therapy (3DCRT) for patients with early stage breast cancer. A total of nine Chinese women who received breast conservation treatment were included in this study. Target localization and movement (range of motion) during normal respiration were assessed using ultrasound and 4DCT. Plans based on 3DCT and 4DCT scans were developed in accordance to RTOG0319 guidelines and dose delivery comparisons were made between these plans. The mean ranges of motion of the excision cavity volume as determined using 4DCT were 1.03 +/- 0.51, 2.08 +/- 0.92, and 1.27 +/- 0.58 mm in the right-left, anterior-posterior, and superior-interior directions, respectively. There were no significant differences between the mean and maximum PTV-E doses or the volume receiving 95% of the prescribed dose (V95). 4D plan prescribed dose levels were significantly lower (p < 0.05) than 3D plan levels for all of the following: ipsilateral breast V100, ipsilateral lung V30, and contralateral lung V5. Maximum contralateral breast and thyroid doses were also significantly lower with the 4D plan (p < 0.05). This study highlights the usefulness of 4DCT for the planning of 3DCRT in breast cancer patients. Our findings suggest that the use of 4DCT can lead to improvements in target definition and decreases in normal tissues irradiation.

Second-line combination chemotherapy with vinorelbine and capecitabine in patients with advanced breast cancer previously treated with anthracyclines and/or taxanes.

Objective: This phase II study was designed to evaluate the effects of vinorelbine (VRL) and capecitabine (CAP) as second-line combination chemotherapy in patients with advanced breast cancer (ABC) previously treated with anthracyclines and/or taxanes. Methods: Treatment consisted of VRL 25 mg/m2 administered on days 1 and 8 of a 21-day treatment cycle, along with oral CAP 825 mg/m2 twice daily for 14 days, followed by 7 days of rest. Results: 50 patients were enrolled and 48/50 (96.0%) patients were assessable for response. The median time to progression (TTP) and overall survival (OS) of the patients were 5.0 (95% confidence interval, CI, 2.1–7.9 months) and 12.0 months (95% CI, 8.0–16.0 months), respectively. The objective response rate was 26.0% (95% CI, 13.8–38.2%) with 1 confirmed complete response and 12 partial responses. The most frequent hematological adverse event was neutropenia of grade 3 and 4 in 5 (10.4%) and 2 patients (4.2%), respectively. Grade 3 stomatitis, asthenia, and diarrhea were observed in 1 (2.1%), 2 (4.2%) and 3 (6.3%) patients, respectively. Conclusion: The combination of VRL and CAP is feasible as second-line chemotherapy in patients with ABC previously treated with anthracyclines and/or taxanes, with efficacy being comparable to other available combination regimens.

Risk factors for locoregional recurrence after postmastectomy radiotherapy in breast cancer patients with four or more positive axillary lymph nodes

BACKGROUND We investigated risk factors for locoregional recurrence (lrr) in breast cancer patients with 4 or more positive axillary lymph nodes receiving postmastectomy radiotherapy (pmrt). METHODS Medical records (1998-2007) were retrospectively reviewed for the population of interest. The Kaplan-Meier method was used to calculate the survival rate; Cox regression models were used for univariate and multivariate analysis of predictors of breast cancer lrr. RESULTS The study enrolled 439 patients. Median duration of follow-up was 54 months. The 5-year rates of locoregional recurrence-free survival (lrrfs), distant metastasis-free survival (dmfs), and breast cancer-specific survival (bcss) were 87.8%, 59.5%, and 70.7% respectively. In patients with lrr and no concomitant metastasis, and in those without lrr, the 5-year rates of dmfs were 21.1% and 65.7% respectively (p < 0.001), and the 5-year rates of bcss were 34.5% and 76.4% respectively (p < 0.001). Univariate analysis showed that menopausal status (p = 0.041), pN stage (p = 0.006), and positivity for her2 [human epidermal growth factor receptor 2 (p = 0.003)] or the triple-negative disease subtype (p < 0.001) were determinants of lrrfs. Multivariate analysis showed that pN3 stage [hazard ratio (hr): 2.241; 95% confidence interval (ci): 1.270 to 3.957; p = 0.005], her2 positivity (hr: 2.705; 95% ci: 1.371 to 5.335; p = 0.004), and triple-negative disease subtype (hr: 4.617; 95% ci: 2.192 to 9.723; p < 0.001) were independent prognostic factors of lrrfs. CONCLUSIONS In breast cancer patients with 4 or more positive axillary lymph nodes who undergo pmrt for breast cancer, lrr significantly influences survival. Patients who developed lrr carried a high risk for distant metastasis and death. Pathologic stage (pN3), her2 positivity, and the triple-negative disease subtype are risk factors that significantly influence lrrfs.

Prognostic Value of Different Lymph Node Staging Methods in Esophageal Squamous Cell Carcinoma After Esophagectomy

BACKGROUND This study aimed to investigate the prognostic value of number of involved lymph nodes, number of removed lymph nodes, ratio of involved to removed nodes (lymph node ratio), and number of negative lymph nodes in esophageal squamous cell carcinoma (ESCC) patients after esophagectomy. METHODS A retrospective review of 603 patients receiving esophagectomy for ESCC was made. Cox regression analysis was performed to identify significant prognostic factors. RESULTS The median follow-up time was 36.7 months, and the 5-year overall survival (OS) was 43.5%. Patients with negative lymph node count ≥ 14 had better survival (p < 0.001). Univariate Cox analysis showed that the number of involved lymph nodes, number of removed lymph nodes, lymph node ratio, and number of negative lymph nodes influenced OS (p < 0.05 for all). Multivariate Cox analysis indicated that the number of involved lymph nodes and number of negative lymph nodes were independent prognostic factors for OS, and a higher number of negative lymph nodes was associated with lower mortality. The number of removed lymph nodes and lymph node ratio had no significant effect on OS. The number of negative lymph nodes had prognostic value in different lymph node stages and in two-field or three-field lymphadenectomy. CONCLUSIONS For ESCC patients after esophagectomy, the number of involved lymph nodes and the number of negative lymph nodes had a better prognostic value than did the number of removed lymph nodes and lymph node ratio.

Dosimetric comparison of moderate deep inspiration breath-hold and free-breathing intensity-modulated radiotherapy for left-sided breast cancer.

PURPOSE This study determined the dosimetric comparison of moderate deep inspiration breath-hold using active breathing control and free-breathing intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for left-sided breast cancer. PATIENTS AND METHODS Thirty-one patients were enrolled. One free breathe and two moderate deep inspiration breath-hold images were obtained. A field-in-field-IMRT free-breathing plan and two field-in-field-IMRT moderate deep inspiration breath-holding plans were compared in the dosimetry to target volume coverage of the glandular breast tissue and organs at risks for each patient. RESULTS The breath-holding time under moderate deep inspiration extended significantly after breathing training (P<0.05). There was no significant difference between the free-breathing and moderate deep inspiration breath-holding in the target volume coverage. The volume of the ipsilateral lung in the free-breathing technique were significantly smaller than the moderate deep inspiration breath-holding techniques (P<0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans. There were no significant differences in target volume coverage between the three plans for the field-in-field-IMRT (all P>0.05). The dose to ipsilateral lung, coronary artery and heart in the field-in-field-IMRT were significantly lower for the free-breathing plan than for the two moderate deep inspiration breath-holding plans (all P<0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans. CONCLUSION The whole-breast field-in-field-IMRT under moderate deep inspiration breath-hold with active breathing control after breast-conserving surgery in left-sided breast cancer can reduce the irradiation volume and dose to organs at risks. There are no significant differences between various moderate deep inspiration breath-holding states in the dosimetry of irradiation to the field-in-field-IMRT target volume coverage and organs at risks.

Role of Goserelin in Combination with Endocrine Therapy for the Treatment of Advanced Breast Cancer in Premenopausal Women Positive for Hormone Receptor: A Retrospective Matched Case–Control Study

OBJECTIVE This research was to investigate the role of goserelin in combination with endocrine therapy for the treatment of advanced breast cancer in premenopausal women positive for hormone receptors. METHODS We retrospectively analyzed 40 patients as the treatment group with advanced breast cancer who, were positive for hormone receptors, received goserelin in combination with endocrine therapy and 40 patients as the control group received endocrine therapy alone, matched for age, gender, receptor status, and tumor stage. RESULTS The median period of follow-up was 38.9 months. The response status at 6 months, the overall clinical benefit rate was 87.5% and 70.0% in the treatment group and control group, respectively. The mean progression-free survival (PFS) in the treatment group and control group was 27.9 and 16.9 months, respectively. The 1-, 2-, and 3-year PFS rates were 87.5%, 66.2%, and 49.7%, respectively, in the treatment group and 59.2%, 38.8%, and 35.3%, respectively, in the control group (p=0.076). The 1-, 2-, and 3-year overall survival (OS) rates were 100%, 87.2%, and 76.6%, respectively, in the treatment group and 90.0%, 74.2%, and 55.8%, respectively, in the control group (p=0.048). For the treatment group with age <40 years, PFS (p=0.036) and OS (p=0.014) were significantly longer than the control group, but it was no effect on the prognosis with the patients aged ≥40 years. Continued use of goserelin after disease progress again in the median survival time was significantly longer than nonusers (28.2 months vs. 7.0 months), and there is the potential benefit of OS (p=0.070). CONCLUSIONS For premenopausal hormone receptor-positive advanced breast cancer, goserelin-combined endocrine therapy can be used for those <40 years, the standard endocrine treatment for patients, we recommend continued use of goserelin for patients with disease progress again.

Accelerated partial breast irradiation with intensity-modulated radiotherapy is feasible for chinese breast cancer patients.

Purpose Several accelerated partial breast irradiation (APBI) techniques are being investigated in patients with early-stage breast cancer. The present study evaluated the feasibility, early toxicity, initial efficacy, and cosmetic outcomes of accelerated partial breast intensity-modulated radiotherapy (IMRT) for Chinese female patients with early-stage breast cancer after breast-conserving surgery. Methods A total of 38 patients met the inclusion criteria and an accelerated partial breast intensity-modulated radiotherapy (APBI-IMRT) plan was designed for each patient. The prescription dose was 34 Gy in 10 fractions, 3.4 Gy per fraction, twice a day, in intervals of more than 6 hours. Results Of the 38 patients, six patients did not meet the planning criteria. The remaining 32 patients received APBI-IMRT with a mean target volume conformity index of 0.67 and a dose homogeneity index of 1.06. The median follow-up time was 53 months and no local recurrence or distant metastasis was detected. The most common acute toxicities observed within 3 months after radiotherapy were erythema, breast edema, pigmentation, and pain in the irradiated location, among which 43.8%, 12.5%, 31.3%, and 28.1% were grade 1 toxicities, respectively. The most common late toxicities occurring after 3 months until the end of the follow-up period were breast edema, pigmentation, pain in the irradiated location, and subcutaneous fibrosis, among which 6.2%, 28.1%, 21.9%, and 37.5% were grade 1 toxicities, respectively. Thirty-one patients (96.8%) had fine or excellent cosmetic outcomes, and only one patient had a poor cosmetic outcome. Conclusion It is feasible for Chinese females to receive APBI-IMRT after breast conserving surgery. The radiotherapeutic toxicity is acceptable, and both the initial efficacy and cosmetic outcomes are good.