Prognosis and influencing factors of ER-positive, HER2-low breast cancer patients with residual disease after neoadjuvant chemotherapy: a retrospective study.

Previously, we found that patients with estrogen receptor (ER)-positive, HER2-low breast cancer are resistant to neoadjuvant chemotherapy (NACT) and have worse outcomes than those who achieve pathological complete response (pCR) after NACT. This study aimed to investigate the prognosis and influencing factors in these patients. A total of 618 patients with ER-positive breast cancer who received standard thrice-weekly NACT were enrolled, including 411 patients with ER-positive, HER2-low breast cancer. Data on the clinicopathological features of these patients before and after NACT were collected. Univariate and multivariate Cox regression analyses were used to identify the independent factors affecting 5-year disease-free survival (DFS). Among the ER-positive, HER2-low patients, 49 (11.9%) achieved a pCR after NACT. A significant difference in survival was observed between patients with and without residual disease after NACT. Additionally, changes in immunohistochemical markers and tumor stages before and after NACT were found to be significant. According to univariate and multivariate analyses, cN_stage (P = 0.002), ER (P = 0.002) and Ki67 (P = 0.023) expression before NACT were significantly associated with 5-year DFS, while pT_stage (P = 0.015), pN_stage (P = 0.029), ER (P = 0.020) and Ki67 (P < 0.001) levels after NACT were related to 5-year DFS in ER-positive, HER2-low patients with residual disease. Our study suggested that high proliferation, low ER expression and advanced stage before and after NACT are associated with a poor prognosis, providing useful information for developing long-term treatment strategies for ER-positive, HER2-low breast cancer in patients with residual disease in the future.

Clinical significance of multi-genic assay in identifying aggressive papillary thyroid carcinoma.

BACKGROUND: A minority of papillary thyroid carcinoma (PTC) is highly aggressive, with rapid progression and a poor prognosis. This study investigated the ability of multi-genic assay to identify patients with aggressive PTC. PATIENTS AND METHODS: A total of 117 PTC patients treated at The First Affiliated Hospital of Chongqing Medical University with clinicopathological data and multi-genic assay results and 389 patients with complete data from The Cancer Genome Atlas (TCGA) database were included. The chi-square test was used to analyze the relationship between the multi-genic assay results and clinicopathological characteristics. Univariate and multivariate regression analyses were used to analyze the impact of various factors on prognosis. RESULTS: The median follow-up times of the local and TCGA cohorts were 30 months and 34 months, respectively. The results showed that central lymph node metastasis (P = 0.036), lateral lymph node metastasis (P = 0.003) and mutations in genes other than BRAFV600E (P = 0.002) were significantly associated with disease-free survival (DFS) in the local cohort, while the analysis of TCGA data showed that mutations in genes other than BRAFV600E were significantly related to poor prognosis (P = 0.029). According to univariate and multivariate analyses, mutations in genes other than BRAFV600E (P = 0.021) and lateral lymph node metastasis (P = 0.022) were independent factors for postoperative recurrence, as well as, mutations in genes other than BRAFV600E were an independent factor of survival (P = 0.047). CONCLUSIONS: The multi-genic assay was able to identify aggressive PTC, providing an effective biological basis for surgical management and postoperative treatment.

Preoperative and pathological predictive factors of central lymph node metastasis in papillary thyroid microcarcinoma.

OBJECTIVE: The aim of this study was to identify clinical and pathological markers of CLNM in persons with clinical lymph node-negative papillary thyroid microcarcinoma(PTMC). MATERIALS AND METHODS: Retrospective data were analyzed from 804 PTMC clinically negative patients who were receiving thyroid surgery in the First Affiliated Hospital at Chongqing Medical University from January 2017 to December 2018. The CLNM-positive and CLNM-negative groups were categorised according to histological evidence of the central lymph node involvement, statistically, risk variables for CLNM were found. RESULTS: 324 (40.3%) individuals were diagnosed with CLNM. Sex (P=0.001), age at diagnosis (P<0.001), tumour size(P=0.029), microcaccificities presence (P=0.003), capsules discontinuity(P=0.002), multi-focality(P=0.001) and (ETE)extrathyroidal extension (P < 0.001) differed substantially from one positive CLNM group to the next. For multivariate analyses, women (odds ratio [OR] = 0.489), age [OR = 0.540] are the independent protective factors for CLNM; micro-cacification presence (OR = 1.511), discontinuity of capsules (OR= 2.056), multifocality(OR=1.486) and ETE(OR=10.613) are the independent risk factors for CLNM. Feature curves of the receiver were built and the AUC is 0.763. 32.1% percent (80 patients) of the 249 patients who did not have any of the four risk variables got CLNM. This contrasted with the incidence of CLNM in this research, which was as high as 49.1%. CONCLUSIONS: CLNM has been connected with female sex, age - within 45 years, microcacification occurrences, capsule discontinuity, multifocality and extrathyroid expansion. The patients may benefit from the surgical decision of pCLND whether there are risk factors combined.

Exploring the influencing factors of the pathologic complete response in estrogen receptor-positive, HER2-negative breast cancer after neoadjuvant chemotherapy: a retrospective study.

BACKGROUND: Pathological complete response (pCR) is the goal of neoadjuvant chemotherapy (NACT). We aimed to develop a nomogram to predict the probability of achieving pCR in estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer patients. METHODS: A total of 273 ER+, HER2- breast cancer patients who received 4 cycles of thrice-weekly standard NACT in the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to screen the predictive factors to develop the nomograms. The discrimination and calibration abilities were assessed by the C-index, receiver operating characteristic curve (AUC), and calibration plot. RESULTS: There were 28 patients (10.3%) with overall pCR, 38 patients (13.9%) with breast pCR after NACT. ER expression, PgR expression, the neutrophil-to-lymphocyte ratio (NLR) and the Ki-67 index were independent predictive factors for achieving overall pCR. These indicators had good discrimination and calibration ability (AUC 0.843). The nomogram for breast pCR was established based on ER expression, PgR expression, the NLR, and the Ki-67 index and showed great discriminatory ability, with an AUC of 0.810. The calibration curve showed that the predictive ability of the nomogram was a good fit to actual observations. CONCLUSION: The nomograms exhibited a sufficient discriminatory ability for predicting pCR after NACT in ER+, HER2- breast cancer patients. Utilizing these nomograms will enable us to identify patients at high probability for pCR after NACT and provide a reference for preoperative adjuvant therapy.

Efficacy evaluation of neoadjuvant chemotherapy in patients with HER2-low expression breast cancer: A real-world retrospective study.

Background: To characterize the clinicopathological features and evaluate the neoadjuvant chemotherapy (NACT) efficacy of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer. Methods: A total of 905 breast cancer patients who received 4 cycles of thrice-weekly standard NACT in the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled, including 685 cases with HER2-low expression and 220 cases with HER2-negative expression. Clinicopathological features were compared between patients with HER2-negative and HER2-low expression. Univariate and multivariate logistic regression analyses were used to find the independent factors of achieving a pathological complete response (pCR) after NACT. Results: There were significant differences in stage_N (P = 0.014), histological grade (P = 0.001), estrogen receptor (ER) status (P < 0.001), progesterone receptor (PgR) status (P < 0.001), NACT regimens (P = 0.032) and NACT efficacy (P = 0.037) between patients with HER2-negative and HER2-low expression breast cancer. In subgroup analysis, histological grade (P = 0.032), ER (P = 0.002), Ki-67 (P < 0.001) and HER2 status (P = 0.025) were independent predictors of achieving a pCR in ER-positive breast cancer. And the nomogram for pCR in ER-positive breast cancer showed great discriminatory ability with an AUC of 0.795. The calibration curve also showed that the predictive ability of the nomogram was a good fit to actual observations. Then, in the analysis of ER-negative breast cancer, only stage_N (P = 0.001) and Ki-67 (P = 0.018) were independent influencing factors of achieving a pCR in ER-negative breast cancer. Conclusion: HER2-low breast cancer was a different disease from HER2-negative breast cancer in clinicopathological features. Moreover, the NACT efficacy of HER2-low breast cancer patients was poorer.

Risk Factors and a Prediction Model of Lateral Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma Patients With 1-2 Central Lymph Node Metastases.

Background: Papillary thyroid cancer (PTC) in clinically lymph node-negative (cN0) patients is prone toward lymph node metastasis. As a risk factor for tumor persistence and local recurrence, lateral lymph node metastasis (LLNM) is related to the number of central lymph node metastases (CLNMs). Methods: We performed LLNM risk stratification based on the number of CLNMs for cN0 PTC patients who underwent thyroidectomy and lymph node dissection between January 2013 and December 2018. A retrospective analysis was applied to the 274 collected patients with 1-2 CLNMs. We examined the clinicopathological characteristics of the patients and constructed a LASSO model. Results: In the 1-2 CLNM group, tumors >10 mm located in the upper region and nodular goiters were independent risk factors for LLNM. Specifically, tumors >20 mm and located in the upper region contributed to metastasis risk at level II. Hashimoto's thyroiditis reduced this risk (p = 0.045, OR = 0.280). Age ≤ 30 years and calcification (microcalcification within thyroid nodules) correlated with LLNM. The LASSO model divided the population into low- (25.74%) and high-risk (57.25%) groups for LLNM, with an AUC of 0.715. Conclusions: For patients with 1-2 CLNMs, young age, calcification, nodular goiter, tumor >10 mm, and tumor in the upper region should alert clinicians to considering a higher occult LLNM burden. Close follow-up and therapy adjustment may be warranted for high-risk patients.

Prediction Model of Pathologic Central Lymph Node Negativity in cN0 Papillary Thyroid Carcinoma.

BACKGROUND: Most patients with papillary thyroid carcinoma (PTC) have an excellent prognosis. Although central lymph node invasion is frequent, management via central lymph node dissection (CLND) remains controversial. The present study retrospectively investigated independent predictors of pathologic central lymph node negativity (pCLN-) and established a prediction model for pCLN- in clinical lymph node negativity (cN0) PTC. METHODS: A total of 2,687 patients underwent thyroid surgery for cN0 PTC from 2013 to 2018 at the First Affiliated Hospital of Chongqing Medical University, and lobectomy plus ipsilateral CLND was the basic surgical extent. Clinicopathological characteristics were reviewed and analyzed. Univariate and multivariate analyses were performed to identify factors related to pCLN-. A prediction model was established based on the results of multivariate analyses. RESULTS: The pCLN- rate was 51.5% (1,383/2,687). Multivariate analysis revealed that sex, age, thyroid stimulating hormone (TSH), size, location, laterality, unifocality and extrathyroidal extension negativity (ETE-) were independent predictors of pCLN-. The nomogram showed good discriminative ability (C-index: 0.784 and 0.787 in derivation and validation groups, respectively) and was well calibrated. We quantified the clinical usefulness of the nomogram by decision curve analysis. The median length of follow-up was 30 (range 12- 83) months, and 190 cases were lost, with a follow-up rate of 92.9% (2,497/2,687). Of the 2,687 patients included, 21 (0.8%) experienced recurrence. CONCLUSION: This nomogram, which integrates available preoperative clinicopathological features and intraoperative frozen biopsy outcomes, is a reliable tool with high accuracy to predict pCLN- in cN0 PTC.