Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

PURPOSE: To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy. METHODS: A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present. Clinical and radiological responses after NACT were also evaluated. Univariate and multivariate analyses by logistic regression were performed. Distant disease-free survival (DDFS) was calculated in relation to the status of the axillary lymph nodes after NACT. RESULTS: After NACT, 89 patients (40.3%) had axillary pathologic complete response (pCR) (ypN0) and 132 (59.7%) had residual axillary disease (ypN+). Molecular surrogate subtype, Ki-67 expression, and the clinical and radiological responses to NACT were the only independent factors associated with ypN0. Axillary pCR was observed more often in HER2-positive and triple-negative tumours than in luminal ones (OR 7.5 and 3.6, respectively). DDFS was 88.7% (95% CI 80.7-96.7%) for ypN0 and 56.2% (95% CI 32.1-80.3%) for ypN+ (p = 0.09). CONCLUSIONS: In HER2-positive and triple-negative breast cancer patients staged as cN2 or with high axillary burden before NACT, a sentinel lymph node biopsy after NACT could be recommended if there is a clinical and radiological response.

Assessment of outcomes and novel immune biomarkers in metaplastic breast cancer: a single institution retrospective study.

BACKGROUND: Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear. METHODS: We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples. RESULTS: Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1-19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02). CONCLUSIONS: Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

Early breast cancer patients benefit more from longer course chemotherapy: a matched-pair analysis.

Aim: Benefit of longer course of taxane-anthracycline-based adjuvant chemotherapy is yet to be identified. Patients & methods: We conducted a retrospectively matched-pair analysis to compare four cycles of fluorouracil, epirubicin and cyclophosphamide followed by four cycles of docetaxel (4FEC-4T) with three cycles of FEC followed by three cycles of docetaxel (3FEC-3T) as adjuvant chemotherapy for early-stage breast cancer. One hundred and thirty-seven patients treated with 4FEC-4T were matched to 411 in 3FEC-3T. The primary end point was event-free survival (EFS). The secondary end point was distant disease-free survival (DDFS). Results: The 4FEC-4T resulted in significantly longer EFS than matched 3FEC-3T (p = 0.020). Furthermore, DDFS was superior in the 4FEC-4T to that in the 3FEC-3T (p = 0.046). Conclusion: Extending taxane-anthracycline-based regimens with identical schedules significantly improves EFS and DDFS for early-stage breast cancer.

Survival Outcomes of Breast Cancer Patients in South India Over 20 Years.

OBJECTIVE: The study aimed to investigate the distribution and clinicopathologic features of breast cancer patients in South India, while also examining the overall survival (OS) and identifying predictive factors affecting it. Additionally, we aimed to assess the influence of risk factors on Disease Free Survival (DFS) and Distant Disease-Free Survival (DDFS). METHODS: This retrospective cohort study on breast cancer trends used comprehensive follow-up including regular patient contact, medical record review and collaboration with healthcare providers. Patients without follow-up information for more than 12 months were contacted by telephone, while those with no follow-up after 2 years were labelled as lost to follow-up. RESULTS: A total of 3256 patients were identified from a single cancer institute in India. The median follow-up time was 8.1 years. The 5-year survival rates were 89%, 84%, 85%, 88% and 10-year were 82%, 78%, 79%, 83% for luminal cancers, Triple Negative Breast Cancers, HER2 enriched and luminal with HER2 enriched respectively. CONCLUSION: Poorer survival rates were seen among those with pT3/4 tumors, nodal involvement at diagnosis, Estrogen receptor negative status, high Ki67 proliferative index and higher TNM stage at diagnosis of the disease. Although our patients were younger and had more aggressive types of cancer, their DFS, DDFS and overall survival were comparable to other developed nations.

Development and validation of novel risk prediction models of breast cancer based on stanniocalcin-1 level.

PURPOSE: The function of stanniocalcin-1 (STC-1) in the oncogenesis and progression of tumors has been extensively studied. The purpose of this study was to investigate the relationship between secreted STC-1 and prognosis in patients with breast cancer (BC) and to determine whether STC-1 could be a key prognostic factor in BC. METHODS: The STC-1 level was measured by ELISA and clinical data from 1210 female patients with BC were used to develop and validate nomograms. We then verified the models through the plotting of ROC curves and calibration curves, calculating the C-index, and performing decision curve analyses (DCA). RESULTS: The level of STC-1 in the peripheral plasma was significantly correlated with the T stage, N stage, clinical stage, grade, hormone receptors, HER-2 status, and tumor subtype. Cox regression analyses revealed that estrogen receptor(ER) status, N stage, and STC-1 level were risk factors for overall survival (OS), whereas T stage, N stage, and STC-1 level were independent prognostic factors for distant disease-free survival (DDFS) and disease-free survival (DFS). Both the ROC curve and the C-index confirmed the high resolution of these models, while the DCA identified the feasibility of their practical application. In addition, the calibration curves indicated good consistency between the predicted and actual survival rates. CONCLUSION: Nomograms were created based on STC-1 levels for 3-, 5-, and 7-year OS, DDFS, and DFS of patients with BC respectively. As a key prognostic factor for BC, peripheral blood STC-1 level can be used clinically as a liquid biopsy indicator.

Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial.

BACKGROUND: The ExteNET trial demonstrated improved invasive disease-free survival (iDFS) with neratinib, an irreversible pan-HER tyrosine kinase inhibitor, versus placebo in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) early-stage breast cancer (eBC). PATIENTS AND METHODS: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2+ eBC after neoadjuvant/adjuvant trastuzumab-based therapy. Patients were stratified by HR status and randomly assigned 1-year oral neratinib 240 mg/day or placebo. The primary endpoint was iDFS. Descriptive analyses were performed in patients with HR+ eBC who initiated treatment ≤ 1 year (HR+/≤ 1-year) and > 1 year (HR+/> 1-year) post-trastuzumab. RESULTS: HR+/≤ 1-year and HR+/> 1-year populations comprised 1334 (neratinib, n = 670; placebo, n = 664) and 297 (neratinib, n = 146; placebo, n = 151) patients, respectively. Absolute iDFS benefits at 5 years were 5.1% in HR+/≤ 1-year (hazard ratio, 0.58; 95% confidence interval [CI], 0.41-0.82) and 1.3% in HR+/>1-year (hazard ratio, 0.74; 95% CI, 0.29-1.84). In HR+/≤ 1-year, neratinib was associated with a numerical improvement in overall survival (OS) at 8 years (absolute benefit, 2.1%; hazard ratio, 0.79; 95% CI, 0.55-1.13). Of 354 patients in the HR+/≤ 1-year group who received neoadjuvant therapy, 295 had residual disease, and results showed absolute benefits of 7.4% at 5-year iDFS (hazard ratio, 0.60; 95% CI, 0.33-1.07) and 9.1% at 8-year OS (hazard ratio, 0.47; 95% CI, 0.23-0.92). There were fewer central nervous system events with neratinib. Adverse events were similar to those previously reported. CONCLUSION: Neratinib significantly improved iDFS in the HER2+/HR+/≤ 1-year population, and a similar trend was observed in patients with residual disease following neoadjuvant treatment. Numerical improvements in central nervous system events and OS were consistent with iDFS benefits and suggest long-term benefit for neratinib in this population.

Breast-conserving surgery vs. total mastectomy in patients with triple negative breast cancer in early stages: A propensity score analysis.

BACKGROUND: Breast-conserving surgery (BCS) as an alternative to total mastectomy (TM) in patients with early-stage triple-negative breast cancer (TNBC) is not widely spread. OBJECTIVE: We aimed to compare the overall survival (OS) and disease-free survival (DFS) between both surgical approaches in early-stage TNBC patients at 10 years. METHODS: We conducted a retrospective cohort study in TNBC female patients with stage I-IIa, treated at a single-center during the period of 2000-2014. We estimated and compared the survival rates with the Kaplan Meier and Long-rank test. Propensity scores were calculated with the generalized boosted regression model and were used in the multivariate Cox regression analysis with the covariate adjustment method. RESULTS: We included 288 patients, 111 in the BCS vs. 177 in the TM group. The median follow-up was 102 months. Moreover, the patients in the BCS group had superior OS (85% vs. 81%, p = 0.56) and DFS (83% vs. 80%, p = 0.42) at 10 years. In the multivariate Cox analysis, BCS decreased the mortality risk (HR: 0.79, 95% CI: 0.37-1.67, p = 0.538), and the locoregional or distant recurrence risk (HR: 0.67, 95% CI: 0.32-1.41, p = 0.294), albeit with no statistical significance. CONCLUSION: BCS is a safe alternative to TM in Latin-American patients with early-stage TNBC.

Inverse correlation between Ki67 expression as a continuous variable and outcomes in luminal HER2-negative breast cancer.

OBJECTIVES: Few studies to date have investigated the prognostic significance of Ki67 expression as a continuous variable in breast cancer. This study aimed to evaluate the impact of Ki67 expression as a dichotomous or continuous variable on outcomes in estrogen receptor (ER)+ and human epidermal growth factor receptor 2 (HER2)- breast cancer. METHODS: Survival analysis was performed to estimate the likelihood of distant recurrence and death in retrospective data from 794 patients with ER+/HER2- breast cancer. We assessed the relationship between outcomes and two Ki67 cutoffs, 14% and 20%, and the Ki67 labeling index as a continuous variable. RESULTS: In univariate analysis, T stage, lymph node involvement, histological grade, progesterone receptor status, and Ki67 expression at the two cutoffs and as a continuous variable were identified as significant prognostic factors for distant disease-free survival (DDFS) and overall survival (OS). There were no statistical differences in DDFS and OS between women with Ki67 expression of <14% and 14-<20%. Multivariate analysis showed that Ki67 expression ≥20% was an independent prognostic indicator for DDFS. Regarding the risk of distant metastasis, the 20% cutoff was more reliable than 14%. We also found that Ki67 expression as a continuous variable was an independent prognostic factor for DDFS and OS in multivariate analyses. CONCLUSIONS: High Ki67 expression is associated with a survival disadvantage in patients with ER+/HER2- breast cancer, indicating that these patients might have a higher risk of recurrence after primary treatment and might therefore benefit from individualized treatment.

Impact of clinical and pathological factors on local recurrence after breast-conserving treatment: CT-based localization for a tumor bed boost yielded better local control when compared with a surgical scar.

Background: We investigated the effects of risk factors on the incidence of local recurrence (LR) in patients who underwent breast-conserving treatment (BCT) for primary breast cancer at a single institution in China from 1999 to 2011. Methods: Patient outcomes were compared with respect to LR, ipsilateral breast tumor recurrence (IBTR), distant disease-free survival (DDFS), and disease-free survival (DFS). Additionally, the risk factors for relapse after BCT were studied. Results: The 2028 patients with invasive breast cancer included in this study were followed for a median of 95 months, during which the 8-year LR, IBTR, DDFS, and DFS rates were 2.6%, 3.0%, 93.7%, and 91.3%, respectively. Lymph node involvement, the human epidermal growth factor receptor 2 (HER2) status, and the use of computed tomography (CT) information during boost field planning were identified as significant predictors of LR and IBTR. Notably, use of the surgical scar for tumor bed identification during boost field planning was associated with a higher adjusted risk of LR, compared with the use of CT. By contrast, the neoadjuvant chemotherapy (NAC) was not an independent predictor of LR (hazard ratio of no NAC vs. NAC, 0.63; 95% confidence interval, 0.33-1.19; P = 0.157). In a multivariate analysis, the age at diagnosis, tumor diameter, lymph node involvement, HER2-positive status, and use of CT information during boost field planning were identified as significant factors affecting DFS. Conclusions: The use of CT information during boost field planning could reduce the risk of LR among patients undergoing BCT. Neoadjuvant and adjuvant treatments for breast cancer did not show the significant difference in respect to the outcome of LR.

Differences in subtype distribution between screen-detected and symptomatic invasive breast cancer and their impact on survival.

PURPOSE: Stage shift is considered a major reason for more favorable outcomes in patients with screen-detected breast cancer. However, even after adjusting for clinical stage, unresolved issues concerning the reasons for a survival benefit associated with screening programs remain. This study aims to evaluate differences in subtype distribution and outcomes among patients with screen-detected and symptomatic invasive breast cancer and assess whether variations in subtype distribution could explain differences in prognosis. METHODS: Survival analysis was performed to estimate the likelihood of distant recurrence and death in 1132 patients. Subtypes were defined as luminal A [estrogen receptor (ER)+ and/or progesterone receptor (PR)+, human epidermal growth factor receptor 2 (HER2)-, and Ki67 low], luminal B (HER2-) (ER+ and/or PR+, HER2-, and Ki67 high), luminal B (HER2+) (ER+ and/or PR+ and HER2+), HER2 overexpressing (ER-, PR-, and HER2+), and triple negative (ER-, PR-, and HER2-). RESULTS: Screen-detected cancers had favorable clinicopathological characteristics, such as smaller tumor size and a lower frequency of lymph node involvement. Women with screen-detected cancers had a survival advantage. Subtype distribution differed significantly among women with screen-detected and symptomatic cancer. Screen-detected cancers were more likely to be luminal A and less likely to be HER2 overexpressing or triple negative cancer compared with symptomatic cancers (luminal A 61.3 vs. 44.2%, HER2 overexpressing 4.0 vs. 8.0%, triple negative 8.0 vs. 15.9%). Node status, mode of detection, and subtype were independent prognostic factors in the multivariate analysis. CONCLUSIONS: Differences in subtype distribution between screen-detected and symptomatic cancer could partially explain differences in outcomes.

T-box transcription factor 21 expression in breast cancer and its relationship with prognosis.

PURPOSE: T-box transcription factor 21 (T-bet) is a key lineage-defining transcription factor. The purpose of this study was to verify the relationship between expression in primary tumors and prognosis of breast cancer. METHODS: T-protein expression was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. RESULTS: T-bet was expressed in the nuclei and cytoplasm of both tumor cells and tumor-infiltrating lymphocytes. In LOG-RANK analysis, higher density of interstitial T-bet+ interstitial lymphocytes was related with longer distant disease-free survival (DDFS) (P = 0.047); higher tumor nuclei T-bet expression was related with shorter DFS (P = 0.021) and DDFS (P = 0.026). Cox multivariate analysis showed that density of interstitial T-bet+ interstitial lymphocytes was an independent positive prognostic factor for DFS (HR = 0.474, P = 0.051) and DDFS (HR = 0.414, P = 0.030); tumor nuclei CTLA-4 expression was an independent adverse prognostic factor for DFS (HR = 3.007, P = 0.003), DDFS (HR = 2.931, P = 0.005) and OS (HR = 2.352, P = 0.029). CONCLUSIONS: This study found that, high tumor nuclei T-bet expression in primary tumors of breast cancer was correlated with poor prognosis and high density of T-bet+ interstitial lymphocytes in primary tumors of breast cancer were correlated with favorable prognosis.