All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits.

BACKGROUND: The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA). METHODS: We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2. RESULTS: Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively. DISCUSSION: By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.

Predicting Non-sentinel Lymph Node Metastasis in a Chinese Breast Cancer Population with 1-2 Positive Sentinel Nodes: Development and Assessment of a New Predictive Nomogram.

BACKGROUND: We have developed a new nomogram to predict the probability of a patient with 1-2 metastatic sentinel lymph nodes (SLNs) to present further axillary disease. METHODS: Data were collected from 480 patients who were diagnosed with 1-2 positive lymph nodes and thus underwent axillary lymph node dissection between March 2005 and June 2011. Clinical and pathological features of the patients were assessed with multivariable logistic regression. The Shanghai Cancer Center Non-SLN nomogram (SCC-NSLN) was created from the logistic regression model. This new model was subsequently applied to 481 patients from July 2011 to December 2013. The predictive accuracy of the SCC-NSLN nomogram was measured by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: Based on the results of the univariate analysis, the variables that were significantly associated with the incidence of non-SLN metastasis in an SLN-positive patient included lymphovascular invasion, neural invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis (P < 0.05). Using multivariate analysis, lymphovascular invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis were identified as independent predictors of non-SLN metastasis. The SCC-NSLN nomogram was then developed using these four variables. The new model was accurate and discriminating on both the modeling and validation groups (AUC: 0.7788 vs 0.7953). The false-negative rates of the SCC-NSLN nomogram were 3.54 and 9.29 % for the predicted probability cut-off points of 10 and 15 % when applied to patients who have 1-2 positive SLNs. CONCLUSION: The SCC-NSLN nomogram could serve as an acceptable clinical tool in clinical discussions with patients. The omission of ALND might be possible if the probability of non-SLN involvement is <10 and <15 % in accordance with the acceptable risk determined by medical staff and patients.

Predicting sentinel lymph node metastasis in a Chinese breast cancer population: assessment of an existing nomogram and a new predictive nomogram.

We assessed the MSKCC nomogram performance in predicting SLN metastases in a Chinese breast cancer population. A new model (the SCH nomogram) was developed with clinically relevant variables and possible advantages. Data were collected from 1,545 patients who had a successful SLN biopsy between March 2005 and November 2011. We validated the MSKCC nomogram in the modeling and validation group. Clinical and pathologic features of SLN biopsy in modeling group of 1,000 patients were assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The SCH nomogram was created from the logistic regression model and subsequently applied to 545 consecutive SLN biopsies. By multivariate analysis, age, tumor size, tumor location, tumor type, and lymphovascular invasion were identified as independent predictors of SLN metastasis. The SCH nomogram was then developed using the five variables. The new model was accurate and discriminating (with an AUC of 0.7649 in the modeling group) compared to the MSKCC nomogram (with an AUC of 0.7105 in the modeling group). The area under the ROC curve for the SCH nomogram in the validation population is 0.7587. The actual probability trends for the various deciles were comparable to the predicted probabilities. The false-negative rates of the SCH nomogram were 1.67, 3.54, and 8.20 % for the predicted probability cut-off points of 5, 10, and 15 %, respectively. Compared with the MSKCC nomogram, the SCH nomogram has a better AUC with fewer variables and has lower false-negative rates for the low-probability subgroups. The SCH nomogram could serve as a more acceptable clinical tool in preoperative discussions with patients, especially very-low-risk patients. When applied to these patients, the SCH nomogram could be used to safely avoid a SLN procedure. The nomogram should be validated in various patient populations to demonstrate its reproducibility.

Breast cancer in a transitional society over 18 years: trends and present status in Shanghai, China.

As a metropolis with rapid social and economic development over the past three decades, Shanghai has a breast cancer incidence that surpasses all other cancer registries in China. In order to estimate the regular changing patterns of female breast cancer in urban Shanghai, population-based incidence data from 1975 to 2004 were studied. In addition, a one-hospital-based in-patient database of 7,443 female breast cancer patients treated surgically between January-1990 and July-2007 were reviewed, retrospectively. We observed that breast cancer incidence increased dramatically over the past 30 years and documented a peak incidence represented by the middle-age group (45-59 years), which emerged in the last 20 years. The incidence peak moved from the 40-44 year group in the previous two decades to the 50-54 year group in the most recent decade. Median age at diagnosis was earlier in Shanghai than in the western countries, although it increased from 47.5-year in 1990 to 50-year in 2007. Considerably higher exposure to reproductive risk factors and relatively fewer hormone-dependent cases were observed. The proportion of asymptomatic cases detected by screening gradually increased, as well as that of early-stage cases (from 78.6% in 1990 to 93.3% in 2007) and carcinoma in situ (14.7% in 2007). Analysis of surgical treatment patterns suggested a trend of less-invasive options. Both age of peak incidence and median age at diagnosis increase with time, which suggests that increased incidence trending along with increasing age, will be observed in the future. Consequently, specific screening protocol should be refined to consider birth cohorts.