Differentiating between benign and malignant breast lesions using dual-energy CT-based model: development and validation.

OBJECTIVES: To develop and validate a dual-energy CT (DECT)-based model for noninvasively differentiating between benign and malignant breast lesions detected on DECT. MATERIALS AND METHODS: This study prospectively enrolled patients with suspected breast cancer who underwent dual-phase contrast-enhanced DECT from July 2022 to July 2023. Breast lesions were randomly divided into the training and test cohorts at a ratio of 7:3. Clinical characteristics, DECT-based morphological features, and DECT quantitative parameters were collected. Univariate analyses and multivariate logistic regression were performed to determine independent predictors of benign and malignant breast lesions. An individualized model was constructed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic ability of the model, whose calibration and clinical usefulness were assessed by calibration curve and decision curve analysis. RESULTS: This study included 200 patients (mean age, 49.9 ± 11.9 years; age range, 22-83 years) with 222 breast lesions. Age, lesion shape, and the effective atomic number (Zeff) in the venous phase were significant independent predictors of breast lesions (all p < 0.05). The discriminative power of the model incorporating these three factors was high, with AUCs of 0.844 (95%CI 0.764-0.925) and 0.791 (95% CI 0.647-0.935) in the training and test cohorts, respectively. The constructed model showed a preferable fitting (all p > 0.05 by the Hosmer-Lemeshow test) and provided enhanced net benefits than simple default strategies within a wide range of threshold probabilities in both cohorts. CONCLUSION: The DECT-based model showed a favorable diagnostic performance for noninvasive differentiation between benign and malignant breast lesions detected on DECT. CRITICAL RELEVANCE STATEMENT: The combination of clinical and morphological characteristics and DECT-derived parameter have the potential to identify benign and malignant breast lesions and it may be useful for incidental breast lesions on DECT to decide if further work-up is needed. KEY POINTS: It is important to characterize incidental breast lesions on DECT for patient management. DECT-based model can differentiate benign and malignant breast lesions with good performance. DECT-based model is a potential tool for distinguishing breast lesions detected on DECT.

Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial.

BACKGROUND: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer. METHODS: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m2, intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKTmut and MES-PI3K/AKTmut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKTWT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989). FINDINGS: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group. INTERPRETATION: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway. FUNDING: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial.

Triple-negative breast cancer (TNBC) is a heterogeneous disease and lacks effective treatment. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we report the final results of FUTURE, a phase II umbrella trial designed to explore whether the subtyping-based strategy may improve the outcomes in metastatic TNBC patients. A total of 141 patients with a median of three previous lines of therapies in the metastatic setting were enrolled in seven parallel arms. Confirmed objective responses were achieved in 42 patients (29.8%; 95% confidence interval [CI], 22.4-38.1). The median values of progression-free survival and overall survival were 3.4 (95% CI: 2.7-4.2) and 10.7 (95% CI: 9.1-12.3) months, respectively. Given Bayesian predictive probability, efficacy boundaries were achieved in four arms. Furthermore, integrated genomic and clinicopathological profiling illustrated associations of clinical and genomic parameters with treatment efficacy, and the efficacy of novel antibody-drug conjugates was explored in preclinical TNBC models of subtypes for which treatment was futile. In general, the FUTURE strategy recruits patients efficiently and provides promising efficacy with manageable toxicities, outlining a direction for further clinical exploration.

Omission of axillary surgery for ipsilateral breast tumor recurrence with negative nodes after previous breast-conserving surgery: is it oncologically safe?

PURPOSE: Salvage mastectomy is traditionally recommended for patients who developed ipsilateral breast tumor recurrence (IBTR) in light of previous breast irradiation. However, it remains controversial whether surgical axillary staging (SAS) is necessary for IBTR patients with negative nodes. This study aimed to evaluate the oncologic safety of omitting SAS for IBTR. METHODS: We retrospectively identified patients who developed invasive IBTR with negative nodes after undergoing breast-conserving surgery (BCS) from 2010 to 2018. Patterns of care in nodal staging were analyzed based on prior axillary staging status. Clinicopathologic characteristics and adjuvant treatment of the initial tumor, as well as the IBTR, were compared between the SAS and no SAS groups. Kaplan-Meier method and Cox regression model were utilized to compare the locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates after IBTR removal between the two groups. RESULTS: A total of 154 IBTR patients were eligible for final analysis. Compared to the no SAS group, SAS group was less likely to undergo ALND (15.1 vs 73.3%, p < 0.001) at initial BCS, had a longer recurrence interval (2.8 vs 2.1 years, p = 0.03), and were more likely to have discordant molecular subtype (35.8 vs 12.9%, p = 0.001) and different quadrant location (37.7 vs 19.8%, p = 0.02) with primary tumor. However, the extent of axillary staging did not affect systemic or radiation recommendations. In the subgroup of patients without previous ALND, the clinicopathologic characteristics were roughly comparable. No significant differences were observed in LRRFS, DMFS or OS between the two groups. CONCLUSION: For node-negative IBTR patients, we observed selection bias on the basis of prior ALND, shorter recurrence interval, and concordant molecular subtype favoring no SAS but comparable LRRFS, DMFS, and OS. These results support a wider consideration of sparing SAS in the management of IBTR, especially in patients without previous ALND.

Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.

PURPOSE: Camrelizumab, an mAb against programmed cell death protein 1 (PD-1), plus nab-paclitaxel exhibited promising antitumor activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC). Famitinib is a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit. We aimed to assess the efficacy and safety of a novel combination of famitinib, camrelizumab, and nab-paclitaxel in advanced immunomodulatory TNBC. PATIENTS AND METHODS: This open-label, single-arm, phase II study enrolled patients with previously untreated, advanced, immunomodulatory TNBC (CD8 IHC staining ≥10%). Eligible patients received 20 mg of oral famitinib on days 1 to 28, 200 mg of i.v. camrelizumab on days 1 and 15, and i.v. nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by investigators per RECIST v1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and exploratory biomarkers. RESULTS: Forty-eight patients were enrolled and treated. Median follow-up was 17.0 months (range, 8.7-24.3). Confirmed ORR was 81.3% [95% confidence interval (CI), 70.2-92.3], with five complete and 34 partial responses. Median PFS was 13.6 months (95% CI, 8.4-18.8), and median DOR was 14.9 months [95% CI, not estimable (NE)-NE]. Median OS was not reached. No treatment-related deaths were reported. Among 30 patients with IHC, 13 (43.3%) were programmed death-ligand 1 (PD-L1)-negative, and PD-L1 was associated with favorable response. PKD1 and KAT6A somatic mutations were associated with therapy response. CONCLUSIONS: The triplet regimen was efficacious and well tolerated in previously untreated, advanced, immunomodulatory TNBC. The randomized controlled FUTURE-SUPER trial is under way to validate our findings. See related commentary by Salgado and Loi, p. 2728.

Breast-conserving in centrally located breast cancer patients confirmed safe by SEER based study.

BACKGROUND: Due to the lack of high-level data, there is still controversy over the oncological safety of breast conservation in patients with centrally located breast cancer. This study aimed to assess the safety of breast-conserving surgery in patients with centrally located breast cancer based on the data from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We collected data for all cases diagnosed with breast cancer who underwent breast-conserving surgery from 2012-2014 in the SEER database. The primary outcome of our study was disease-specific survival (DSS) and overall survival (OS). The PSM was used to eliminate the effects of non-random statistics. Chi-square test, Kaplan-Meier method and Cox proportional hazards regression model on univariate and multivariate analysis were used to analyze the data. RESULTS: Data from 79,214 patients who had undergone breast-conserving surgery were analyzed in this study, including those with breast cancer in the central region (n=3,128) and outside the central region (n=76,086). The DSS of central breast cancer patients and outside the central breast cancer patients was 58.1 months versus 58.0 months (P>0.05), respectively, while the OS of the 2 groups was 58.0 months versus 58.0 months (P>0.05), respectively. CONCLUSIONS: Breast cancer in the central region should not be contraindicated for breast conserving surgery and breast-conserving surgery can benefit a wider range of patients.

A Retrospective Cohort Study Comparing Traditional Breast Conservation With Oncoplastic Surgery in Breast Cancer Patients After Neoadjuvant Chemotherapy.

BACKGROUND: To better understand the difference between traditional breast-conserving surgery (BCS) and oncoplastic surgery (OPS), we conducted a retrospective cohort study involving breast cancer patients who received neoadjuvant chemotherapy (NAC) and then underwent breast conservation at the Fudan University Shanghai Cancer Center. METHODS: A retrospective chart review was conducted. All breast cancer patients who received NAC and then underwent traditional BCS or OPS at the Fudan University Shanghai Cancer Center from January 1, 2008, to December 31, 2019, were included. RESULTS: Three hundred ninety-nine breast cancer patients received NAC and underwent traditional BCS, and 99 patients underwent OPS. The average age of the patients in the OPS group was younger than that in the BCS group (43 vs 48 years, P = 0.017). The size of the tumor assessed by ultrasonography at baseline in the OPS group was larger than that in the BCS group (31.3 vs 28.1 mm, P = 0.013). The same trend was observed in the clinical T stage and overall staging assessments before the administration of NAC in these 2 groups. Oncoplastic techniques were more frequently applied when tumors were located in areas with relatively few glands, such as the upper inner quadrant. There were no significant differences in the margins and distributions of pathological types and molecular subtypes between these 2 groups. The rates of pathological complete response were similar in the traditional BCS and OPS groups. CONCLUSIONS: Unlike traditional BCS, in breast cancer patients after NAC, the adoption of oncoplastic techniques makes breast conservation feasible, even in patients with large tumors, late stages, and unfavorable tumor locations.

Spatiotemporal Patterns of Loco-Regional Recurrence After Breast-Conserving Surgery.

BACKGROUND: Loco-regional recurrences (LRR) following breast-conserving surgery (BCS) remain a heterogeneous class of disease that has significant variation in its biological behavior and prognosis. METHODS: To delineate the spatiotemporal patterns of LRR after BCS, we analyzed the data of 4325 patients treated with BCS from 2006 to 2016. Clinico-pathological and treatment specific factors were analyzed using the Cox proportional hazards model to identify factors predictive for LRR events. Recurrence patterns were scrutinized based on recurrence type and recurrence-free interval (RFI). Annual recurrence rates (ARR) were compared according to recurrence type and molecular subtype. RESULTS: With a median follow-up of 66 months, 120 (2.8%) LRRs were recorded as the first site of failure. Age, pathologic stage, and molecular subtype were identified as predictors of LRR. The major recurrence type was ipsilateral breast tumor recurrence, which mainly (83.6%) occurred ≤5y post surgery. In the overall population, ARR curves showed that relapse peaked in the first 2.5 years. Patients with regional nodal recurrence, shorter RFI, and synchronous distant metastasis were associated with a poorer prognosis. HER2-positive disease had a higher rate of LRR events, more likely to have in-breast recurrence, and had an earlier relapse peak in the first 2 years after surgery. CONCLUSIONS: LRR risk following BCS is generally low in Chinese ethnicity. Different recurrence patterns after BCS were related to distinct clinical outcomes. Management of LRR should be largely individualized and tailored to the extent of disease, the molecular profile of the recurrence, and to baseline clinical variables.

A predictor of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients with the DNA repair genes.

BACKGROUND: We conducted this study to investigate the prevalence of potential chemo-response-related gene mutations in triple-negative breast cancer (TNBC) patients and to evaluate the potential relationship between these gene mutations and neoadjuvant chemotherapy response in TNBC patients. METHODS: One hundred sixty-two TNBC patients in Fudan University Shanghai Cancer Center who received NAC with 4 cycles of paclitaxel and carboplatin were enrolled in this study. Fifty-six pathological complete response (pCR) patients and 56 non-pCR patients were enrolled in this retrospective study for the training set. Clinical assessments of postoperative residual tumors were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Forty chemo-response-related genes were screened in each tumor specimen by second-generation sequencing analysis. Fifty TNBC patients who received neoadjuvant chemotherapy with paclitaxel and carboplatin were enrolled in the validation group. RESULTS: Fifty-seven of 112 (50.9%) TNBCs contained at least one detected somatic mutation. As expected, TP53 mutation was the most common alteration, which was observed in 21.4% of patients. BRCA1, BRCA2, RET, PI3KCA, and PTEN mutations were each observed in 11.6%, 4.5%, 5.4%, 2.7% and 3.6% of all cases, respectively. No significant differences in any gene mutation frequency between pCR and non-pCR groups were identified. We found that the mutation status of 10 DNA repair genes involved in homologous recombination (HR) pathway successfully discriminated between responding and nonresponding tumors in the training group. Up to 18 patients who were mutation-positive experienced pCR compared to only 6 in the non-pCR group (P=0.006), and 75% the HR related gene mutation patients achieved pCR. In the validation group, TNBC patients with DNA repair gene mutations achieved 77.8% pCR. CONCLUSIONS: A subset of TNBC patients carry deleterious somatic mutations in 10 HR-related genes. The mutation status of this expanded gene panel is likely to effectively predict respond rate to neoadjuvant chemotherapy based on paclitaxel and carboplatin. Our findings need to be validated through follow-up studies in this and additional cohorts.

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

BACKGROUND: Hereditary factors contributed to breast cancer susceptibility. Low BRCA mutation prevalence was demonstrated in previous BRCA mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in. BRCA: negative breast cancers. METHODS: A total of 384 Chinese subjects with any two of high-risk factors were recruited and screened by next-generation sequencing (NGS) for 30 cancer susceptible genes. Variants with a truncating, initiation codon or splice donor/acceptor effect, or with pathogenicity demonstrated in published literature were classified into pathogenic/likely-pathogenic mutations. RESULTS: In total, we acquired 39 (10.2%) patients with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11, 2.9%), PTCH1 (n=7, 1.8%), RET (n=6, 1.6%) and PALB2 (n=5, 1.3%). Other mutant genes included TP53 (n=3, 0.8%), RAD51D (n=2, 0.5%), CHEK2 (n=1, 0.3%), BRIP1 (n=1, 0.3%), CDH1 (n=1, 0.3%), MRE11 (n=1, 0.3%), RAD50 (n=1, 0.3%) and PALLD (n=1, 0.3%). A splicing germline mutation, MUTYH c.934-2A>G, was a hotspot (9/384, 2.3%) in Chinese breast cancer. CONCLUSIONS: Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Multigene testing contributes to understand genetic background of BRCA-negative breast cancer patients with high hereditary risk.

Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing.

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

Concordance of Hormone Receptor Status and BRCA1/2 Mutation Among Women With Synchronous Bilateral Breast Cancer.

Goals: BRCA1/2 mutations are associated with bilateral breast cancer. The extent of concordance between synchronous bilateral breast cancer (SBBC) tumors with respect to hormone receptor expression and BRCA1/2 mutations is unknown. We investigated the distribution of BRCA1/2 mutations and bilateral estrogen receptor (ER) status in SBBC. Methods: A retrospective analysis was performed on 15,337 patients with primary breast cancer who underwent surgical treatment at the Fudan University Shanghai Cancer Center between 2007 and 2014. We included 163 patients with synchronous bilateral breast cancer who had germline BRCA1/2 mutations testing. BRCA1/2 pathogenic/likely pathogenic mutations and other clinicopathological characteristics were studied in further analyses. Results: Patients with SBBC developed breast cancer at an older age and had a higher rate of ER positivity than patients with UBC (p < 0.001, separately). In contrast, 14.1% of SBBC patients had carcinomas with a lobular component in either breast based on pathological reports (p < 0.001). Twelve patients had BRCA1 mutations, and 14 patients had BRCA2 mutations, while no patients had mutations in both genes. The BRCA1/2 mutation rate was higher in younger patients (23.4 vs. 11.1%, p = 0.036). SBBC patients with a family history of breast cancer or bilateral ER-negative disease had a higher frequency of BRCA1/2 mutations than the cohort without a history of these conditions. SBBC with a bilateral ER-discordant status had a very low frequency of BRCA1/2 mutations (5.6%). Patients with an ER-positive (concordant or discordant) status had better 3-year disease-free survival than patients with a concordant ER-negative status (HR = 0.324, 95% CI: 0.126-0.837, P = 0.020). However, the outcomes were similar during long-term follow-up. Pathological lymph node stage was the only prognostic factor for SBBC in both univariate and multivariate Cox analyses. Conclusions: Our study shows that Chinese women with SBBC have different characteristics from their UBC counterparts. SBBC patients with a younger age, family history of breast cancer, or bilateral ER-negative disease are more likely to have BRCA1/2 mutations. SBBC patients with a concordant ER-negative status had worse early outcomes. Our results suggest that there may be additional factors underlying the tumor biology and genetics of SBBC.

Outcomes and risk of subsequent breast events in breast-conserving surgery patients with BRCA1 and BRCA2 mutation.

PURPOSE: Previous studies provide inconsistent interpretations of the effect of inherited genetic factors on the survival and prognosis of patients with breast cancer. The aim of this study was to examine the effect of germline BRCA1 and BRCA2 mutation on survival and subsequent breast events in Chinese women who underwent breast-conserving surgery. METHODS: A retrospective review of the clinical and pathological records was performed in patients diagnosed with primary invasive breast cancer between 2005 and 2018 in the cancer registry database. Clinicopathological data and data regarding treatment and outcomes, including date and site of disease progression, were collected. The survival outcomes and independent risk factors were conducted using SPSS. RESULTS: Overall, a total of 501 patients who underwent breast-conserving surgery were identified and subjected to analyses, of which 63 cases with BRCA1 or BRCA2 mutation. The median age at diagnosis was 41 (range, 24-74) for carriers and 37 (range, 17-84) for noncarriers. After a median follow-up time of 61 months (range, 8-161) and 70 months (range, 0-153), respectively, in carriers and noncarriers, the overall survival (P = .173) and disease-free survival (P = .424) were not significantly different. Analogously, there was no significant difference between the two groups about the outcomes of ipsilateral breast tumor recurrence (P = .348), yet the contralateral breast cancer (CBC) was overt worse than noncarriers (P < .001). When adjusted to confounding factors, BRCA mutation was the only independent risk factors to CBC (HR = 7.89, P = .01). CONCLUSION: In this study, BRCA mutation carriers have higher risk of CBC. And, BRCA mutation is the only independent risk factor to CBC. Therefore, intensive surveillance and follow-up as well as more effective individual prevention are urgent. Decisions on alternatively effective prevention, especially the prevention of CBC, are urgent and should take into account patient prognosis and preferences.

Insights Into the Impacts of BRCA Mutations on Clinicopathology and Management of Early-Onset Triple-Negative Breast Cancer.

BACKGROUND: Little is known regarding the clinicopathologic characteristics, oncologic outcomes, and treatment strategies that could be ascribed to BRCA mutation in early-onset triple-negative breast cancer (eTNBC). METHODS: eTNBC patients who underwent BRCA genetic testing were derived from our clinical database between 2012 and 2018. Differences in clinical features and pathologic characteristics were examined in groups divided by BRCA mutation status, and the contribution of germline mutations in conjunction with treatment modalities to survival outcomes was determined. RESULTS: Of the 355 qualifying eTNBC patients, 67 (18.87%) were BRCA mutated and 288 (81.13%) were BRCA wild. Overall, median age at diagnosis was 34 years (range, 24-40 years) in the BRCA mutated subgroup and 35 years (range, 21-40 years) in BRCA wild. The majority of clinicopathologic parameters were parallel; however, tumor size (P = 0.07) and nuclear grade (P =0.08) tend to be more aggressive in the BRCA mutated subgroup. Compared with BRCA wild patients, BRCA mutated patients had a higher likelihood of receiving anthracyclines and taxane-based combination chemotherapy (P = 0.04) and tend to be lower tumor burden (P =0.01). After approximately 5-year median follow-up, the overall survival (OS) (P = 0.021) and breast cancer-specific survival (BCSS) (P = 0.004) in BRCA mutated patients were superior to those in their BRCA wild counterparts. Intriguingly, the clinical outcomes were comparable in patients with breast conserving surgery (BCS) regardless of BRCA mutations and in patients with BRCA mutations in spite of surgical schedules. CONCLUSIONS: These results suggest that eTNBC patients with BRCA mutations are prone to better OS and BCSS, which might be largely attributed to more benefit from anthracyclines and taxane-based chemotherapy. The BCS procedure could be a safe alternative surgical option for eTNBC patients with BRCA mutations. Future studies with substantial numbers of participants are urgently needed to validate whether BRCA mutation eTNBC patients are more sensitive to chemotherapy.

Current practice and barriers of mesh-assisted implant-based breast reconstruction in China: A nationwide cross-sectional survey of 110 hospitals.

BACKGROUND: The current National Practice Questionnaire of implant-based breast reconstruction (IBBR) (NPQi) was to assess the clinical practice of mesh-assisted IBBR in China. METHODS: A questionnaire was mailed to 110 hospitals in China, which have more than 200 breast cancer operations performed in 2017. The survey mainly included questions on the type and timing of IBBR, questions about the use of TiLOOP® Bra and acellular dermal matrix (ADM) and the complications of IBBR. RESULTS: IBBR was routinely carried out in 86.36% (95/110) hospitals. IBBR was the most frequently-used (65.7%, 4,296/6,534) BR after mastectomy with a median of 24 cases (IQR 7.5-65) in each hospital. TiLOOP® Bra and ADM were available in 49.5% and 33.7% hospitals, respectively. Hospitals with ADM offered were more likely to located in economically developed regions (65.6%), when compared with hospitals without any mesh offered (14/35, 40.0%, P = 0.036) and with only TiLOOP® Bra offered (16/28, 57.1%, P = 0.032). The surgery volume was largely variated from hospitals without any mesh offered (median 380 cases, IQR 304-550), with only TiLOOP® Bra offered (median 790 cases, IQR 439-1096, P = 0.001) and with ADM offered (median 797 cases, IQR 497-1528, P < 0.001). Higher proportion of one-stage mesh-augmented direct-to-implant BR and lower proportion of autologous BR were observed in hospitals with mesh offered. The reported major complications were similar between hospitals with or without mesh offered. CONCLUSIONS: The NPQi has provided a valuable insight into the current practice of IBBR and mesh used in China. The introduction of mesh-assisted techniques has revolutionized the clinical practice.

Insights Into Breast Cancer in the East vs the West: A Review.

IMPORTANCE: During the past few decades, the incidence of breast cancer (BC) has been increasing rapidly in East Asia, and BC is currently the most common cancer in several countries. The rising incidence is likely related to changing lifestyle and environmental factors in addition to the increase in early diagnosis with BC awareness and screening. The understanding and management of BC are generally based on research and data from the West. However, emerging differences in BC epidemiology and tumor and host biology in Asian populations may be clinically relevant. OBSERVATIONS: A higher proportion of premenopausal BCs occur in Asia, although this factor is possibly an age-cohort effect. Although the relative frequencies of different immunohistochemical subtypes of BC may be similar between the East and West, the higher prevalence of luminal B subtypes with more frequent mutations in TP53 may be confounded by disparities in early detection. In addition, Asian BCs appear to harbor a more immune-active microenvironment than BCs in the West. The spectra of germline mutations in BC predisposition genes and single-nucleotide polymorphisms contributing to BC risk vary with ethnicity as well. Differences in tolerability of certain cytotoxic and targeted agents used in BC treatment may be associated with pharmacogenomic factors, whereas the lower body mass of the average woman in East Asia may contribute to higher toxicities from drugs administered at fixed doses. Phenotypic characteristics, such as lower breast volume, may influence the type of surgery performed in East Asian women. On the other hand, increased breast density may affect the sensitivity of mammography in detecting BCs, limiting the benefits of screening mammography. CONCLUSIONS AND RELEVANCE: Breast cancer has become a major health problem in Asia. The inclusion of more women from Asia in clinical trials and epidemiologic and translational studies may help unravel the interethnic heterogeneity of BCs and elucidate the complex interplay between environmental and intrinsic factors in its pathogenesis. These insights may help to refine prevention, diagnosis, and management strategies for BC in the setting of ethnic diversity.

The Preventive Intervention of Hereditary Breast Cancer.

Approximately 5-10% of breast cancer is considered to be hereditary. Familial breast cancers exhibit a dominant hereditary pattern, which typically have an early age of onset and are accompanied by symptoms of ovarian cancer, bilateral breast cancer, or male breast cancer. BRCA gene mutation carriers should be regarded as high-risk groups for breast cancer, which necessitates early examination of breast cancer. Studies have built up kinds of predictive models and recommended that female BRCA mutation carriers should receive breast self-test training and take monthly breast self-examination. Familial or hereditary breast cancer family members are high-risk groups, and their risks of breast cancer can be reduced by chemoprevention, including dietary composition adjustment and application of endocrine drugs. In recent years, large-scale clinical trials have shown the important role of chemoprevention in reducing the occurrence of hereditary breast cancer. Prophylactic mastectomy is also suitable for healthy women with high breast cancer risk factors. It can reduce the incidence rate of breast cancer in high-risk women by 90% and decrease the breast cancer mortality rate in medium-risk and high-risk women by 100% and 81%, respectively.

The spectrum of BRCA mutations and characteristics of BRCA-associated breast cancers in China: Screening of 2,991 patients and 1,043 controls by next-generation sequencing.

To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA mutations using next-generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS-based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6-100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease-free survival among HER2- or hormone receptor-positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132-3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS-based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier- and moderate-grade risks receive BRCA1/2 mutations testing in China.

Health-related quality of life of postmenopausal Chinese women with hormone receptor-positive early breast cancer during treatment with adjuvant aromatase inhibitors: a prospective, multicenter, non-interventional study.

BACKGROUND: Estimating quality of life (QoL) in patients with breast cancer is of importance in assessing treatment outcomes. Adjuvant endocrine therapy is widely used for hormone receptor-positive (HR+) early-stage breast cancer (EBC), and evidence suggests that aromatase inhibitors (AIs) may improve QoL for these patients. This study evaluated QoL in postmenopausal Chinese patients with HR+ EBC taking AIs. METHODS: This was a prospective, multicenter, and observational study that had no intent to intervene in the current treatment of recruited patients. Eligible patients were recruited within 7 days of beginning adjuvant treatment with AIs. The Functional Assessment of Cancer Therapy-Breast (FACT-B) scale was used to evaluate the patients' QoL. Data were collected at baseline and at 6, 12, 18, and 24 months. RESULTS: From June 2010 to October 2013, a total of 494 patients with HR+ EBC were recruited from 21 centers. There was a 7.51-point increase in the patients' mean FACT-B trial outcome index (TOI), from 90.69 at baseline to 98.72 at 24 months (P < .0001). The mean TOI scores at baseline, 6, 12, and 18 months were 90.69, 94.36, 97.71, and 96.75, respectively (P < .0001, for all). The mean (FACT-B) emotional well-being subscale scores at baseline, 6, 12, 18, and 24 months were 16.32, 16.55, 17.34 (P < .0001), 17.47 (P < .0001), and 17.85 (P < .0001), respectively, and social well-being scores were 18.61, 19.14 (P < .04), 19.35 (P < .008), 18.32, and 18.40, respectively. In the mixed model, baseline TOI, clinical visits, prior chemotherapies, age group, and axillary lymph-node dissection presented statistically significant effects on the change of FACT-B TOI and FACT-B SWB, whereas only baseline TOI, clinical visits, and prior chemotherapies presented statistically significant effects on the change of FACT-B EWB. FACT-B TOI, being the most pertinent and precise indicator of patient-reported QoL, demonstrated significant changes reflecting clinical benefit of adjuvant AIs endocrine therapy in the QoL of HR + EBC patients. CONCLUSIONS: The study demonstrated significant improvements in the long-term QoL of postmenopausal Chinese patients with HR+ EBC at 6, 12, 18, and 24 months after starting treatment with AIs. The current study indicates improved long-term QoL with AI adjuvant treatment, which will aid clinicians in optimizing treatment to yield effective healthcare outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01144572.

Epidural Combined with General Anesthesia versus General Anesthesia Alone in Patients Undergoing Free Flap Breast Reconstruction.

BACKGROUND: Addition of epidural anesthesia may have several benefits. The purpose of this study was to investigate the effectiveness and safety of epidural anesthesia combined with general anesthesia in patients undergoing free flap breast reconstruction. METHODS: A retrospective chart review identified 99 patients who underwent free flap breast reconstruction under general anesthesia alone (46 patients) or general anesthesia plus epidural anesthesia (53 patients) between 2011 and 2014. Mean arterial blood pressure was measured before induction, after flap elevation but before flap transfer, 15 minutes after flap revascularization, and at the end of surgery. Postoperative pain was assessed using a visual analogue scale. RESULTS: The incidence of flap thrombosis was 3.8 percent in the epidural anesthesia/general anesthesia group versus 4.3 percent in the general anesthesia group (p = 1). Flap failure was 0 percent in the epidural anesthesia/general anesthesia group versus 4.3 percent in the general anesthesia group (p = 0.213). Patients in the epidural anesthesia/general anesthesia group had lower visual analogue scale scores at 2 hours (0.76 ± 0.62 versus 2.58 ± 0.99; p < 0.001), 6 hours (1.94 ± 1.19 versus 4.04 ± 1.46; p < 0.001), and 24 hours (0.74 ± 0.69 versus 1.56 ± 1.01; p < 0.001) postoperatively. Mean arterial blood pressure was lower in the epidural anesthesia/general anesthesia group after flap elevation but before flap transfer, 15 minutes after flap revascularization, and at the end of surgery. CONCLUSION: Epidural anesthesia/general anesthesia combination improves postoperative pain and side effects without increasing the risk of flap thrombosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.