Search

Purpose: A center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients. Patients and methods: Luminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status. Results: Among 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P =0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P =0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P <0.05). Compared to non-overweight patients, obese ones presented significantly higher ER , PR , CEGP1 , Ki67 , CCNB1 and GSTM1 (all P <0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P =0.001). RS was associated with DFS in non-overweight (P =0.046), but not in overweight (P =0.558) or obese (P =0.114) population. Conclusions: RS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS.Methods: We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models.Results: A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772-0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781-0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685-0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804-0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. CONCLUSIONS: We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing. [ABSTRACT FROM AUTHOR]

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22–0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17–0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab. • ER+/HER2+ early breast cancer patients treated with trastuzumab-based chemotherapy had superior prognosis. • ER+/HER2+ early breast cancer patients had distinct patterns of relapse or death from those of ER+/HER2-patients. • HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown. Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups. Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS <18, 18–30, and ≥ 31 groups, respectively. Recurrent patients with RS ≥ 31 were more likely to receive chemotherapy as their first-line treatment compared to those with RS <31 (P = 0.025). Compared to those with RS <31, patients with RS ≥ 31 had significantly worse OS (P = 0.025), worse PR-OS (P = 0.026), and a trend of inferior PR-PFS (P = 0.106). Multivariate analysis demonstrated that primary ER expression level (OS: P = 0.009; PR-OS: P = 0.017) and histological grade (OS: P = 0.003; PR-OS: P = 0.009), but not primary 21-gene RS (OS: P = 0.706; PR-OS: P = 0.120), were independently associated with worse OS and PR-OS. Conclusions: High primary 21-gene RS tended to be associated with worse disease outcome in loco-regional and distant recurrent breast cancer patients, which could influence the first-line systemic treatment after relapse, warranting further clinical evaluation. [ABSTRACT FROM AUTHOR]

Purpose: Hormone receptor (HR)-positive breast cancer patients with tumor size ≤1.0 cm and negative node have favorable outcomes. The 21-gene Recurrence Score (RS) could predict response to chemotherapy for HR+ breast cancer, but its role in T1bN0 disease is challenging. Methods: T1bN0 breast cancer patients diagnosed between January 2014 and June 2019 with RS results were included and categorized as Low- (RS < 18), Intermediate- (RS 18–30), or High-risk (RS > 30) groups. Univariate and multivariate analysis were used to assess factors associated with RS distribution and chemotherapy recommendation. Chemotherapy decisions change and patient adherence after 21-gene RS testing were also evaluated. Results: Among 237 patients with T1bN0 tumors, proportions of Low-, Intermediate-, and High-risk RS were 19.8, 63.3, and 16.9%, respectively. Multivariate analysis found that ER expression (P = 0.011), PR expression (P < 0.001), and Ki-67 index (P = 0.001) were independently associated with RS distribution. Adjuvant chemotherapy was recommended for 31.6% of patients, which was more frequently given to patients with higher tumor grade [Odds ratio (OR) = 2.99 for grade II, OR = 59.19 for grade III, P = 0.006], lymph vascular invasion (OR = 8.22, P = 0.032), Luminal-B subtype (OR = 5.68, P < 0.001), and Intermediate-to High-risk RS (OR = 10.01 for Intermediate-risk, OR = 192.42 for High-risk, P < 0.001). Chemotherapy decision change was found in 18.6% of patients, mainly in those with Intermediate- to High-risk RS tumor with the majority from no-chemotherapy to chemotherapy. The treatment compliance rate after the 21-gene RS testing with MDT was 95.4%. Conclusion: RS category was related to ER, PR, and Ki-67 expression, which was recognized as an independent factor of chemotherapy recommendation in T1bN0 breast cancer. The 21-gene RS testing would lead to a chemotherapy decision change rate of 18.6% as well as a high treatment adherence, which can be applied in T1bN0 patients. [ABSTRACT FROM AUTHOR]

Purpose: Dysmetabolism and high circulating insulin-like growth factor 1 (IGF-1) would increase breast cancer risk, but its association with survival in HER2+ breast cancer patients has not been well-studied. Herein, we aim to evaluate the prognostic value of IGF-1 and metabolic abnormalities in HER2+ population. Patients and Methods: HER2+ breast cancer patients treated in Ruijin Hospital between November 2012 and June 2017 were retrospectively analyzed. Median value of circulating IGF-1 was adopted to classify low or high IGF-1 group. Metabolic syndrome (MetS) was defined using AHA/NHLBI criteria. Overweight was defined by body mass index (BMI) ≥ 24.0 kg/m2 in Chinese population. Results: Overall, 679 patients were included and 209 had synchronous MetS. High IGF-1 level was more common in pre/peri-menopausal women (P < 0.001) and high IGFBP-3 patients (P < 0.001). After a median follow-up of 36 months, 52 patients had disease recurrences. IGF-1 level was not associated with recurrence-free survival (RFS, P = 0.620) in the whole population. However, exploratory subgroup analysis found that BMI and IGF-1 interacted in predicting RFS (P = 0.009). For non-overweight patients, high IGF-1 showed a superior 4-years RFS (91.1 vs. 85.0%; HR 0.53, 95% CI 0.27–1.00, P = 0.049) compared with patients with low IGF-1 level. In contrast, for overweight patients, high IGF-1 was associated with an impaired 4-years RFS (88.3 vs. 95.7%, HR 3.20, 95% CI 1.00–10.21, P = 0.038). Furthermore, high IGF-1 level was independently associated with better OS in the whole (HR 0.26, 95% CI 0.08–0.82, P = 0.044) as well as non-overweight population (HR 0.15, 95% CI 0.03–0.68, P = 0.005). Conclusions: IGF-1 level was not associated with RFS in HER2+ breast cancer patients. However, IGF-1 and BMI had significant interaction in disease outcome prediction in HER2+ patients. High IGF-1 was protective in non-overweight patients, but risk factor for those overweight, which deserves further evaluation. [ABSTRACT FROM AUTHOR]

Anthracycline chemotherapy serves an important role in treating patients with breast cancer but is associated with cardiotoxicity. Although brain natriuretic peptide (BNP) is not the ideal marker for detecting the presence of diseases of the heart, several studies have demonstrated the predictive utility of BNP in the diagnosis of anthracycline-induced cardiotoxicity (AIC). The aim of the present study was to evaluate the role of BNP as a marker for the early prediction of AIC in patients with breast cancer. In the present study, a total of 149 patients with breast cancer who received anthracycline therapy were evaluated. The levels of BNP and echocardiography were detected during the anthracycline-based chemotherapy and patients were followed up after chemotherapy to determine the cardiotoxicity-free survival times. In the patients who received chemotherapy, an increase in the levels of BNP was observed. The concentration of BNP was significantly higher in the cardiotoxicity group during anthracycline chemotherapy (P=0.022) compared with the non-cardiotoxicity group and it was an independent predictor of cardiotoxicity (P=0.028). The optimal diagnostic threshold of BNP after the last anthracycline chemotherapy treatment was 107.9 pg/ml, the diagnostic sensitivity was 0.538, the specificity was 0.794, the Youden index was 0.332, the positive predictive value was 0.583 and the negative predictive value was 0.762. Based on the BNP threshold, a log-rank test was performed and it was determined that the cardiotoxicity-free survival rate of the group with higher levels of BNP was always lower compared with the group with lower levels of BNP. BNP elevation was associated with cardiotoxicity during the anthracycline chemotherapy. Detecting BNP after the final treatment of anthracycline chemotherapy may contribute to the early detection of cardiotoxicity. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is associated with high pathological complete remission (pCR) rate in neoadjuvant treatment (NAT). TNBC patients who achieve pCR have superior outcome than those without pCR. A meta-analysis was done to evaluate whether integrating novel approaches into NAT can improve the pCR rate in TNBC. Medical subject heading terms (Breast Neoplasm) and key words (triple negative OR estrogen receptor (ER) negative OR HER2 negative) AND (primary systemic OR neoadjuvant OR preoperative) were used to select eligible studies. Experimental arm in each study was considered as the testing regimen, and control arm was defined as the standard regimen in this meta-analysis. A total of 11 studies with 14 paired regimens were included in the final analysis. Aggregate pCR rate was 37.3% and 44.6% in the standard and testing group, respectively. Novel approaches in the testing regimen significantly improved the pCR rate in NAT of TNBC patients compared with the standard regimen, with an odds ratio (OR) of 1.34 (95% confidence interval (CI) 1.11–1.62, P = 0.002). Considering specific regimens, we demonstrated the pCR rate to be much higher in the carboplatin-containing (OR = 1.80, 95% CI 1.39–2.32, P<0.001) or bevacizumab-containing regimens (OR = 1.36, 95% CI 1.11–1.66, P = 0.003) than in the control regimens. The addition of carboplatin in NAT had a pCR rate as high as 51.2% in TNBC patients, with an absolute pCR difference of 13.8% as compared with control regimens. No significant heterogeneity was identified among studies evaluating the addition of carboplatin or bevacizumab efficacy in NAT. This meta-analysis indicates that these novel NAT regimens have achieved a significant pCR improvement in TNBC patients, especially among patients treated with carboplatin-containing or bevacizumab-containing regimen. This can help us design appropriate trials in the adjuvant setting and guide clinical practice. [ABSTRACT FROM AUTHOR]