Skye Hung-Chun Cheng

Gene expression profiling in prognosis of distant recurrence in HR-positive and HER2-negative breast cancer patients

There had been several studies using gene-expression profiling in predicting distant recurrence in breast cancer. In this study, we developed an 18-gene classifier (18-GC) to predict distant recurrence of breast cancer and compared it with the 21-gene panel (Oncotype DX®, ODx) in performance. Included were 224 breast cancer patients with positive hormonal receptor (HR+) and negative human epidermal growth factor receptor 2 (HER2-). We compared the demographic, clinical, and survival information of the patients, and further compared the prediction of recurrence risk obtained by using the 18-GC with that by ODx. To have the best combined sensitivity and specificity, receiver operating characteristics (ROC) curve analysis was performed to determine the cutoff values for several breakpoint scores. For the new 18-GC, a breakpoint score of 21 was adopted to produce a combined highest sensitivity (95%) and specificity (39%) in detecting distant recurrence. At this breakpoint score, 164 of the 224 patients were classified by the 18-GC in the same risk level as by ODx, giving a concordance rate of 73%. Along with patient age and tumor stage, this 18-GC was found to be an independent significant prognostic factor of distant metastasis of breast cancer. We have thus created a new gene panel assay for prediction of distant recurrence in HR+ and HER2- breast cancer patients. With a high concordance rate with ODx, this new assay may serve as a good tool for individual breast cancer patients to make an informed decision on whether adjuvant chemotherapy should be performed post-surgery.

From microarray to RT-qPCR for a multigene panel to predict the risk of breast cancer recurrence.

e24249Background: A new 28-gene panel is composed of three parts (1) an 18-gene classifier, which has proven as an independent prognostic factor of local/regional recurrence (LRR) and distant recur...

Survival without adjuvant chemotherapy for selected patients with stage II and III nasopharyngeal carcinoma after concurrent chemoradiotherapy alone

The role of adjuvant chemotherapy after concurrent chemoradiotherapy (CRT) for nasopharyngeal carcinoma (NPC) is controversial. We report our phase II prospective study of withholding adjuvant chemotherapy in a subgroup of patients with American Joint Committee on Cancer (AJCC) stage II and III NPC with low risk for metastasis.

Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%–98.8%) and 80.9% (74.6%–81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%–98.5%), and 90.9% (50.8%–98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8–14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%–100%) and 80.3% (70.7%–89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%–94.1%) and 73.6% (67.2%–79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

Neoadjuvant Trastuzumab Concurrent with Nonanthracycline-based Regimens for HER2-positive Locally Advanced Breast Cancer

Trastuzumab, a humanized monoclonal antibody directed against the external domain of the HER-2 protein, has shown remarkable activity against HER-2 positive breast cancer. Consequently, the use of adjuvant trastuzumab plus chemotherapy in patients with HER2-positive stage breast cancer (stage I to III) has become the standard treatment option. However, the role of trastuzumab in neoadjuvant treatment therapy is still uncertain. An increasing number of clinical trials and inadequate analysis show the benefit of adding trastuzumab to chemotherapy in the neoadjuvant setting. We report a case of HER2-positive locally advanced breast cancer in a patient who received cytotoxic agents concomitant with trastuzumab as neoadjuvant therapy, and also review the published literature. The patient achieved pathological complete response, and remained disease-free for more than 5 years.

Late Recurrences in Luminal-Like Breast Cancer

Purpose: The intention of this study is to both examine the disease entity and late recurrences of luminal-like (hormonal receptor positive and HER2-negative) breast cancer, and identify the prognostic factors associated with disease recurrences. Materials and Methods: We selected for this study breast cancer patients initially treated with primary surgeries in our institution between 1990 and 2007, who also fit the following criteria: 1) pathology stage I-III, 2) hormonal receptor-positive, and 3) HER2/neu-negative. Out of the total 1763 eligible patients, 1275 (72%) received adjuvant chemotherapy, 937 (53%) underwent radiotherapy, and 1629 (92%) had hormonal therapy. Cox proportional hazards regression models were used to assess the prognostic significance of the risk factors related to disease recurrences. Results: The five- and ten-year disease-free survival rates were 96% and 91% for stage I patients, 90% and 81% for stage II, and 79% and 65% for stage III patients, respectively. The incidence of recurrence at each stage in the first 5 years was almost equal to that in the second 5 years. The independent risk factors, according to the multivariate analysis, were: age ≤ 40 (hazard ratio [HR] 1.8, 95% confidence interval [CI], 1.4-2.5); tumor ＞ 2cm (HR 1.6, 95% CI, 1.1-2.1); axillary lymph node positive (HR 1.9/2.0/3.9, 95% CI, 1.3-2.8/1.2-3.4/2.2-6.8 for node positive 1-3/4-9/≥10, respectively); nuclear grade III (HR 1.4, 95% CI, 1.1-1.9); the presence of ECS (HR 1.6, 95% CI, 1.1-2.30); and adjuvant hormonal therapy (HR 0.48, 95% CI, 0.30-0.76). Conclusions: Luminal-like (hormonal receptor positive and HER2-negative) breast cancer has excellent long-term outcomes, but also has a considerable frequency of late recurrences. The risk of breast cancer recurrence is relatively high for patients ≤ 40 years of age, with tumor size greater than 2cm, with axillary LN metastasis, status of nuclear grade III, or with ECS involvement. Clinical trials should be considered for these high-risk breast cancer patients, especially for patients who are diagnosed at 40 years of age or younger.

Risk Factors for Ipisilateral Breast Tumor Recurrence in Patients with Ductal Carcinoma in Situ Undergoing Wide Excision Alone

Purpose: We review our experience of treating ductal carcinoma in situ (DCIS) patients with wide excision alone and examine risk factors that are associated with ipsilateral breast tumor recurrence (IBTR). Materials and Methods: Between January 1990 and December 2002, 47 out of 257 DCIS patients who were treated with wide excision alone were included in this study. The primary end point of this study was IBTR. Local control rate was calculated by Kaplan-Meier method. Variables including tumor size, nuclear grade, margin status, necrosis, mitosis, multifocal disease, ER/PR status, patients age, microcalcification, re-excision, contralateral invasive carcinoma, and Van Nuys prognostic index (VNPI) were enrolled for analysis Result: With a median follow-up interval of 5.94 years, IBTR developed in 6 patients (12.5%), with 3 invasive carcinomas, and 3 DCIS. Necrosis was the only significant prognostic factor for IBTR (p= 0.0249) by Fishers exact test. Nuclear grade, VNPI ≥ 6, and mitosis were marginal significant (p= 0.0586, p= 0.0718, and p= 0.0684, respectively). Multivariate analysis failed to identify any significant risk factors. Conclusion: Necrosis is a significant risk factor for IBRT in patients with DCIS undergoing wide excision alone.