PurposeThis study aimed to determine the effect of neoadjuvant chemotherapy (NAC) on circulating levels of reproductive hormones and evaluate the correlation of hormone changes after NAC with hormone receptors expression alterations and relapse-free survival (RFS) outcomes in breast cancer.MethodsInformation from 181 breast cancer patients who received NAC was retrospectively analyzed. For hormones parameters, the median and interquartile range (IQR) were provided at baseline and the end of NAC then was compared by Wilcoxon signed-rank test. Categorical variables were represented as numbers and percentages and were compared via two-sided chi-square and Fisher's tests. The RFS outcomes were compared between patients according to hormone changes using the log-rank test. Univariate and multivariate survival analyses with hazard ratios (HR) and 95% confidence intervals (95% CI) were carried out using Cox regression.ResultsSex steroids including estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels decreased significantly after NAC among both premenopausal and postmenopausal patients (all P < 0.05). Decreased estradiol levels were associated with reduced progesterone receptor (PR) expression (P = 0.030). In multivariate survival analysis, the non-decreased progesterone level was strongly associated with worse RFS (non-decreased vs. decreased, HR = 7.178, 95% CI 2.340–22.019, P = 0.001). Patients with decreased progesterone levels exhibited better 3-year RFS compared with those with non-decreased (87.6% vs. 58.3%, log-rank, P = 0.001).ConclusionMultiple reproductive hormone levels were influenced by NAC. The change in estradiol level had a positive connection with PR expression alteration. Furthermore, an inverse association between the change in progesterone level and RFS outcomes was found. These findings may provide a theoretical basis for pre-operative endocrine therapy combined with NAC in breast cancer patients.

Propose Neoadjuvant chemotherapy has been widely used in locally advanced and inflammatory breast cancer. Generally, complete pathological response after neoadjuvant chemotherapy treatment predicts survival. Studies have shown that patient-derived organoids can be used in cancer research and drug development. Therefore, we aimed to generate a living organoid biobank from biopsy samples to predict the response of patients to neoadjuvant chemotherapy. Method We generated a living organoid biobank from locally advanced breast cancer patients receiving neoadjuvant chemotherapy. When the patient received neoadjuvant chemotherapy, the organoids were treated with similar drugs, thereby simulating the situation of the patient receiving treatment. Result We successfully constructed organoids from breast cancer biopsies, demonstrating that organoids can be generated from a small sample of tissue. The phenotype of breast cancer organoid often agreed with the original breast cancer according to the blinded histopathological analysis of H&E stain tissue and organoid sections. In addition, our data confirm that the patient's response to chemotherapy closely matches the organoids' response to drugs. Conclusion Our data indicate that patient-derived organoids can be used to predict the clinical response of breast cancer patients to neoadjuvant chemotherapy in vitro and to screen drugs that have different effects on different patients. Key message Complete pathological response (pCR) after adjuvant chemotherapy can predict, survival, therefore, predicting patient response to neoadjuvant chemotherapy is critical. Patient-derived organoids (PDOs) matched the original tumour in terms of histopathology, hormone receptor levels and HER2 receptor status. Patient-derived organoids can predict the responsiveness of patient to neoadjuvant chemotherapy.

This study aimed to evaluate the correlation of pre-treatment circulating reproductive hormones levels with pathological and survival outcomes in breast cancer patients received neoadjuvant chemotherapy (NAC). Information from 196 premenopausal and 137 postmenopausal breast cancer patients who received NAC were retrospectively analyzed. Treatment response to NAC, with odds ratios (OR) and 95% confidence intervals (95% CI) was estimated using logistic regression adjusted for key confounders. Survival outcomes with hazard ratios (HR) and 95% CI were estimated using Cox regression adjusted for key confounders. The Kaplan–Meier method was applied in the survival analysis. Premenopausal patients with lower testosterone levels (OR = 0.996, 95% CI 0.992–0.999, P = 0.026), and postmenopausal patients with higher follicle-stimulating hormone (FSH) levels (OR = 1.045, 95% CI 1.014–1.077, P = 0.005) were likely to achieve pathological complete response (pCR). In multivariate survival analysis, the lowest tertile (T) progesterone was associated with worse overall survival (OS) in premenopausal patients (T2 vs T1, HR = 0.113, 95% CI 0.013–0.953, P = 0.045; T3 vs T1, HR = 0.109, 95% CI 0.013–0.916, P = 0.041). Premenopausal patients with the lowest tertile progesterone exhibited worse 3-year OS compared with those with higher tertiles (72.9% vs 97.4%, log-rank, P = 0.007). Pre-treatment testosterone and FSH are significant independent predictors for pCR to NAC in premenopausal and postmenopausal patients, respectively. Low progesterone levels are correlated with worse OS in premenopausal patients. These findings may provide a theoretical basis for pre-operative endocrine therapy combined with NAC in breast cancer.

Placenta accreta spectrum (PAS) is an umbrella term for a variety of pregnancy complications due to abnormal placental implantation, including placenta accreta, placenta increta and placenta percreta. During the past several decades, the prevalence of PAS has been increasing, and the clinical importance of this disease is significant because of the severe complications. In this review, we summarized the available evidence-based data for PAS in various aspects: prevalence, risk factors, pathogenesis, clinical presentation and prenatal screening, and clinical management. Meanwhile, we provided a series of prospects in each section for further studies on PAS. Moreover, we first present a visualized workflow for the management of PAS from three steps: predelivery, during delivery and postdelivery.

Abstract Background The aim of this study was to evaluate the relationship between pre-treatment plasma fibrinogen (Fib) level and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and to assess the role of plasma Fib as a predictive factor. Methods Data from 1004 consecutive patients with invasive breast cancer who received NAC and subsequent surgery were retrospectively analysed. Both univariate and multivariate analyses based on logistic regression model were performed to identify clinicopathological factors associated with pCR to NAC. Cox regression model was used to determine the correlation between clinical or pathological parameters and recurrence-free survival (RFS). The Kaplan-Meier method and the log-rank test were applied in the survival analysis. Results The median value of Fib, rather than other plasma coagulation parameters, was significantly increased in non-pCR patients compared with pCR patients (P = 0.002). Based on the cut-off value estimated by the receiver operating characteristic (ROC) curve analysis, patients were divided into low or high Fib groups (Fib < 3.435 g/L or ≥ 3.435 g/L). Low Fib levels were significantly associated with premenopausal or perimenopausal status (P < 0.001), tumour size ≤5 cm (P = 0.002), and positive hormone receptor status (P = 0.002). After adjusted for other clinicopathological factors in the multivariate logistic regression model, low Fib status was strongly associated with pCR to NAC (OR = 3.038, 95% CI 1.667–5.537, P < 0.001). Survival analysis showed that patients with low Fib levels exhibited better 3-year RFS compared with patients with high Fib levels in the tumour size>5 cm group (77.5% vs 58.4%, log-rank, P = 0.0168). Conclusions This study demonstrates that low pre-treatment plasma Fib (Fib < 3.435 g/L) is an independent predictive factor for pCR to NAC in breast cancer patients. Moreover, T3-featured breast cancer patients with lower Fib level exhibit better RFS outcomes after NAC compared with high Fib status.

PurposeThe aim of this study was to assess the prognostic influence of Ki67 index changes in patients with primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), and to evaluate whether the combination of Ki67 index changes and residual disease (RD) tumor-infiltrating lymphocytes (TILs) provides additional prognostic information for this group.Materials and MethodsData from 109 patients with primary TNBC and RD after NAC were analyzed retrospectively. Ki67 changes and RD TIL levels were investigated for associations with recurrence-free survival (RFS) and overall survival (OS) using Kaplan–Meier and Cox analyses.ResultsKi67 index decreased after NAC in 53 patients (48.6%) and high RD TIL levels (≥30%) were observed in 54 patients (49.5%). In multivariate Cox analyses, no Ki67 decrease status and low RD TIL levels were significantly associated with reduced RFS (hazard ratio (HR): 2.038, 95% confidence interval (CI): 1.135–3.658, P = 0.017; HR: 2.493, 95% CI: 1.335–4.653, P = 0.004), and OS (HR: 2.187, 95% CI: 1.173–4.077, P = 0.014; HR: 2.499, 95% CI: 1.285–4.858, P = 0.007), respectively. Notably, low RD TIL levels were significantly associated with reduced RFS (HR: 3.567, 95% CI: 1.475–8.624, P = 0.005) and reduced OS (HR: 3.873, 95% CI: 1.512–9.918, P = 0.005) in only the no Ki67 decrease group. The differences in 3-year RFS and OS between patients with no Ki67 decrease and low or high RD TIL levels were 24.4% vs 79.1% (P = 0.0001) and 33.1% vs 87.5% (P = 0.0001), respectively.ConclusionKi67 index changes and RD TIL levels were associated with the prognosis of patients with primary TNBC with RD after NAC. RD TIL levels had greater prognostic significance in the no Ki67 decrease group.

BACKGROUND:Excellent response of the primary tumor after neoadjuvant therapy may indicate a better axillary status in breast cancer. However, this treatment response correlation has not been investigated in Chinese breast cancer patients.METHODS:Patients diagnosed with breast cancer and treated with neoadjuvant therapy were included in this retrospective study, conducted at a comprehensive breast cancer institution in China. Clinicopathological factors at baseline were analyzed by univariate and multivariate analyses. Furthermore, association rules analyses were used to investigate the correlation between the pathologic response of the primary tumor and that of the axillary lymph nodes based on such factors.RESULTS:Multivariate logistic regression analysis showed that breast pathologic response was influenced by tumor size, classification of regional lymph nodes, histological grade, progesterone receptor status, and Ki67 expression. The potential influencing factor for the pathologic response of the axilla was found to be regional lymph node classification. The findings from association rules analyses demonstrated that when a pathologic complete response (pCR) in the breast was achieved among patients with cT2N0 and hormone receptor-negative disease, the axilla response in these patients was also highly likely to be pCR (the likelihood for axilla pCR was more than 90%). However, cT3N1-2 patients hardly achieved pCR for both the primary tumor and axillary lymph nodes (mean confidence, 0.9637). The clinicopathological factors accounting for the inconsistent response between the breast and the axilla were found to be hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, and low Ki67 expression.CONCLUSIONS:Our findings suggest a strong correlation between breast pCR and axilla pCR among patients with specific characteristics. These findings provide a basis for the selection of candidates for clinical trials on the omission of axillary surgery.

Background: The correlation between programmed cell death-ligand 1 (PD-L1) which may affect T cell to form the immune tolerance and breast cancer (BC) still maintains to be uncovered. This meta-analysis was about to explore PD-L1 expression as well as its prognostic role in BC. Methods: First of all, we performed 3 databases: PubMed, Embase, and Web of Science to explore publications between January of 2015 and January of 2020. Strict inclusion and exclusion criteria were conducted: immunohistochemistry shall be used to detect target molecule expression and at least 1 survival indicator and related data we need should be included. The hazard ratio and 95% confidence interval were pooled related with survival as well as clinicopathological parameters. The effects of PD-L1 in differed aspects like sample size and age of each cohort were demonstrated by subgroup analyses as well as sensitivity analyses which may complain the potential source of heterogeneity. P Results: We identified 12 studies containing a blanket of 4336 patients with BC for whom PD-L1 positive tumor cells were related with higher tumor stage, lymph node metastasis, estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, luminal B and triple negative BC molecular subtype and high nuclear-associated antigen Ki- 67 expression. Meanwhile, compared to patients with PD-L1 negative expression, PD-L1 positivity associated with worse overall survival (Hazard ratio [HR]:1.43; 95% CI:0.98-2.10; P < .001) and might have no obvious tight connection with disease free survival (HR:1.40; 95% CI:1.11-1.78; P = .101) and recurrence free survival (HR:2.36; 95% CI:1.04-5.34; P = .145). The outcome of the meta-analysis was confirmed to be credible by sensitivity analysis. Publication bias was not existed indicated (P = .640). Conclusion: Positive PD-L1 expression has a worse clinical outcome in patients with BC demonstrated by our meta-analysis. Being urgent to catch attention to the role of PD-L1 in BC, it may be considered as prognostic marker of immune microenvironment for improving therapy efficacy.

Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade fibroblastic mesenchymal tumor derived from the dermis. The aim of this retrospective analysis was to summarize the clinicopathological data from our cases and published cases to offer more evidence for the recognition of dermatofibrosarcoma protuberans (DFSP). A total of 6 breast DFSP patients who had received treatment in our hospital were retrospectively enrolled, and detailed clinicopathological data were gathered for analysis. The median age was 29.5 years (ranging from 17 to 42 years). Most cases presented a red or brown-red, mobile, well-circumscribed, protruding, breast mass (ranging from 1 to 3 cm). For histopathology, all cases (6/6) showed a storiform pattern of spindle cells that were positive for CD34 (6/6) and Vimentin (5/6) and negative for smooth muscle actin (0/6) and S-100 protein (0/6). The majority of patients (5/6) underwent wide local excision, with 2 cases treated with radiotherapy. With a median follow-up of 36 months, all 6 patients survived without recurrence or metastasis. The PubMed database was used to search for similar cases. Eventually, 36 cases were included in this review, while cases without detailed clinical information or not reported in English were excluded from the analysis. To summarize, DFSP of the breast is an extremely rare malignancy characterized by spindle tumor cells arranged in a storiform pattern and positivity for CD34. The core needle biopsy is one of the crucial methods for its preoperative diagnosis. Management of DFSP is mainly based on surgical excision. It is prone to local recurrence, so long-term follow-up is required.

Background: The aim of this study was to evaluate the relationship between pre-treatment plasma fibrinogen (Fib) level and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and to assess the role of plasma Fib as a predictive factor.Methods: Data from 1035 consecutive patients with invasive breast cancer who received NAC and subsequent surgery were retrospectively analysed. Both univariate and multivariate analyses were performed to identify clinicopathological factors associated with pCR to NAC.Results: The median value of Fib, rather than other plasma coagulation parameters, was significantly increased in non-pCR patients compared with pCR patients (P = 0.008). Based on the cut-off value estimated by the ROC curve analysis, samples were divided into low or high Fib groups (Fib < 3.145 g/L or ≥ 3.145 g/L). Low Fib status was significantly associated with premenopausal or perimenopausal status (P < 0.001), ≤ 5cm tumour size (P = 0.001), positive hormone receptor status (P = 0.003) and > 14% Ki67 index (P = 0.028). Adjusted for other clinicopathologic factors in the multivariate logistic regression model, low Fib status was strongly associated with pCR to NAC (OR = 2.365, 95% CI = 1.354-4.133, P = 0.002).Conclusions: This study demonstrates that low pre-treatment plasma Fib (Fib < 3.145 g/L) is an independent predictive factor for pCR to NAC in breast cancer patients.