UNASSIGNED: This study aimed to determine clinical and pathological factors that identify a pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).
UNASSIGNED: A retrospective, single-center study was conducted in women over the age of 18 who had been diagnosed with pathologically confirmed invasive breast cancer and who had received NAC between July 2016 and October 2021. Patient demographics, clinical, radiological, treatment, and pathological data were reviewed from the electronic hospital records. The primary outcome of interest was pCR, defined as the absence of residual invasive breast cancer in both the breast and axillary lymph nodes. Multivariable logistic regression analysis was used to identify factors associated with pCR.
UNASSIGNED: A total of 119 patients were included in the analysis. The distribution of age was 54.5 ± 11.5 years. pCR was observed in 33 (27.7%) patients. pCR for breast tissue was observed in 43 (36.1%) patients. There was no statistically significant relation between the clinical stage and pCR. Age, age at first labor, extent of disease in the breast, NAC completeness, clinical tumor size (cT) stage, clinical lymph node (cN) stage, and molecular subtype were analyzed in a multivariable model. Analysis showed that molecular subtype was the only independent factor related to pCR. pCR rates across molecular subtypes were: 8.7% in luminal-A, 10.8% in luminal-B, 54.5% in human epidermal growth factor receptor 2 (HER-2)-positive, 42.4% in luminal-B (HER-2 positive) and 46.7% in triple-negative. There was no statistically significant difference between luminal-A and luminal-B subgroups (odds ratio 1.15, 95% confidence interval, 0.19-9.35, p= 0.881). Despite the limited number of patients in HER2-positive and triple-negative groups, both demonstrated statistically significant higher odds compared to reference group.
UNASSIGNED: The presented study underscores the relevance of molecular subtypes in determining the response to neoadjuvant chemotherapy in breast cancer patients. Particularly HER2-positive and triple-negative subtypes may demonstrate more favorable response rates.

UNASSIGNED: Male breast cancer is rare, and something different from female breast cancer. The characteristics of molecular subtype in male breast cancer is unclear and lack of large-sample study.
UNASSIGNED: A retrospective study was conducted to investigate the characteristics and prognosis of patients with male breast cancer using the data recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2014. A total of 1,597 cases were enrolled with median age of 66 years. The study endpoint was considered as patient death. The molecular subtype was defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, hormone receptor (HR) positive was defined as ER positive with or without PR positive, including 1,373 cases of HR+/HER2- tumor (86%), 182 cases of HR+/HER2+ tumor (11.4%), 13 cases of HR-/HER2+ tumor (0.8%) and 29 cases with triple negative (TN) tumor (1.8%), respectively.
UNASSIGNED: There were significant differences in distributions of age, race, grade, tumor size and American Joint Committee on Cancer (AJCC) stage between different molecular subtypes. Patients of different molecular subtypes differed significantly in 5 years overall survival and cause-specific survival (CSS). Five-year CSS (5y-CSS) rates of different molecular subtypes was 89.2% (HER2-/HR+), 78.4% (HER2+/HR+), 72.6% (HER2+/HR-) and 43.2% (TN), respectively. According to Cox regression, age ≥65 years [P=0.001, hazard ratio (HR) =2.136 (1.372, 3.324)], ER negative [P=0.02, HR =2.481 (1.159, 5.319)], PR negative [P=0.007, HR =2.294 (1.256, 4.184)], TN subtype [P<0.001, HR =10.676 (4.441, 25.665)], AJCC stage IV [P<0.001, HR =21.222 (10.377, 43.4)], tumor size >5 cm or T4 [P<0.001, HR =2.577 (0.978, 6.792)], Stage M1 [P=0.001, HR =4.519 (1.929, 10.587)] and Black race [P=0.002, HR =2.322 (1.442, 3.74)] were independent prognostic factors for poorer CSS.
UNASSIGNED: Just like female, molecular subtypes also varied in male breast cancer. It could be a predictor for survival and improve the strategy making in clinical practice.

UNASSIGNED: Breast cancer is a complex disease with variability in clinical manifestation, response to current therapy, and biochemical and histological features among various subgroups. Histologic grading and immuno-histochemical evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index play a crucial role in increasing the differential diagnostic value among various types of breast carcinoma. The aim of this study was to determine the histopathological and immuno-histochemical characteristics of breast tumors from a University Laboratory of Pathology in Greece.
UNASSIGNED: The study included female patients over 18 years of age, whose histopathological and immunohistochemical reports were stored in the archives of the First Department of Pathology of National and Kapodistrian University of Athens. The study involved 197 female patients with a median age of 70 years and median tumor size of 2.6 cm.
UNASSIGNED: Most tumors were located at the left breast and ductal carcinoma was the most common histologic type (35.5%). Most tumors had histologic grade 2 (106, 53.8%), and were classified as TNM stage IIA (65, 33%). Most grade 1 and 2 tumors exhibited high expression of PR, whereas most grade 3 tumors had no PR expression. Moreover, patients with triple-negative cancer presented with grades 2 and 3 at a lower percentage compared to patients without a triple-negative phenotype (p=0.001).
UNASSIGNED: The study provided valuable insights into the histopathological and immuno-histochemical characteristics involved in the development and progression of breast cancer.

BACKGROUND: The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) remains controversial, and recent advances in LCNEC molecular subtype classification have provided potential strategies for assisting in treatment decisions. Our study aimed to investigate the impact of treatment regimens, molecular subtypes and their concordance on clinical outcomes of patients diagnosed with LCNEC.
METHODS: All patients diagnosed with advanced pulmonary LCNEC in Peking Union Medical College Hospital (PUMCH) between January 2000 and October 2021 were enrolled in this retrospective study. The tumor samples were collected and sequenced using a tumor-specific gene panel, while clinical information was retrieved from the medical records system. The survival and therapeutic response were analyzed and compared between different subgroups classified by treatment regimen (SCLC or NSCLC-based), molecular subtype (type I or II) or the combination.
RESULTS: In univariate subgroup analysis categorized only by treatment regimen or molecular subtype, there were no differences identified in DCR, ORR, PFS, or OS. Nevertheless, the group with consistent treatment regimen and molecular subtype exhibited significantly longer OS than that of the inconsistent group (median OS 37.7 vs. 8.3 months; p = 0.046). Particularly, the OS of patients with type II LCNEC treated with SCLC-based regimen was significantly prolonged than that of others (median 37.7 vs. 10.5 months; p = 0.039).
CONCLUSIONS: Collectively, our study revealed the clinical outcomes of different treatment regimens for LCNEC patients highly depend on their molecular subtypes, highlighting the need for sequencing-guided therapy.

Based on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge.
From 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).
After post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02).
In patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor\'s hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.

OBJECTIVE: The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women\'s Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50 years of age.
METHODS: Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative).
RESULTS: Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all ptrend ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all ptrend ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18 years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed.
CONCLUSIONS: Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted.

BACKGROUND: Molecular subtypes play an important role in predicting prognosis and guiding treatment for breast cancer. Having a better knowledge of ethnic molecular features is essential.
OBJECTIVE: Determining the distribution of various breast cancer molecular subtypes and investigating the relationship between these subtypes and clinicopathological features.
METHODS: Retrospective data was collected from Hanoi National Cancer Hospital and Bach Mai Hospital that included 274 women diagnosed with invasive breast cancer between January 2017 and June 2019. Patients were categorized into five subtypes according to the 2015 St. Gallen molecular classification. The variables analyzed were molecular subtypes and tumor-related characteristics. To evaluate the relationship between these subtypes and clinicopathological features, a Chi-squared test and Fisher exact test were performed.
RESULTS: The most prominent subtype was Luminal A (33.2%), followed by Luminal B/Her2- (19.7%) and Luminal B/Her2 + (17.5%), then HER2 overexpression (16.4%), whereas triple negative was the least popular subtype (13.1%). Particularly, 33.9% of all patients, including the Luminal B/Her2 + and the HER2 overexpressing groups, were Her2 positive. There was a statistically significant difference between molecular subtypes and histological type (p = 0.01), tumor grade (p < 0.001), but it was independent of age, tumor size, lymph node metastasis, and lymphovascular invasion.
CONCLUSIONS: In contrast to the triple negative variant, the Luminal A variant is the most common among Vietnamese women. The rate of positive tests for HER2 was rather high. These subtypes were closely related to tumor grade and histopathological type. Understanding the molecular subtypes and their relation to clinicopathological features helps clinicians with patient treatment, and prognosis. The application of the 2015 St. Gallen molecular classification should be recommended for use in clinical practice.

Pathogenic germline variants (PGVs) in certain genes are linked to higher lifetime risk of developing breast cancer and can influence preventive surgery decisions and therapy choices. Public health programs offer genetic screening based on criteria designed to assess personal risk and identify individuals more likely to carry PGVs, dividing patients into screened and non-screened groups. How tumor biology and clinicopathological characteristics differ between these groups is understudied and could guide refinement of screening criteria.
Six thousand six hundred sixty breast cancer patients diagnosed in South Sweden during 2010-2018 were included with available clinicopathological and RNA sequencing data, 900 (13.5%) of which had genes screened for PGVs through routine clinical screening programs. We compared characteristics of screened patients and tumors to non-screened patients, as well as between screened patients with (n = 124) and without (n = 776) PGVs.
Broadly, breast tumors in screened patients showed features of a more aggressive disease. However, few differences related to tumor biology or patient outcome remained significant after stratification by clinical subgroups or PAM50 subtypes. Triple-negative breast cancer (TNBC), the subgroup most enriched for PGVs, showed the most differences between screening subpopulations (e.g., higher tumor proliferation in screened cases). Significant differences in PGV prevalence were found between clinical subgroups/molecular subtypes, e.g., TNBC cases were enriched for BRCA1 PGVs. In general, clinicopathological differences between screened and non-screened patients mimicked those between patients with and without PGVs, e.g., younger age at diagnosis for positive cases. However, differences in tumor biology/microenvironment such as immune cell composition were additionally seen within PGV carriers/non-carriers in ER + /HER2 - cases, but not between screening subpopulations in this subgroup.
Characterization of molecular tumor features in patients clinically screened and not screened for PGVs represents a relevant read-out of guideline criteria. The general lack of molecular differences between screened/non-screened patients after stratification by relevant breast cancer subsets questions the ability to improve the identification of screening candidates based on currently used patient and tumor characteristics, pointing us towards universal screening. Nevertheless, while that is not attained, molecular differences identified between PGV carriers/non-carriers suggest the possibility of further refining patient selection within certain patient subsets using RNA-seq through, e.g., gene signatures.
The Sweden Cancerome Analysis Network - Breast (SCAN-B) was prospectively registered at ClinicalTrials.gov under the identifier NCT02306096.

To evaluate multiple parameters in multiple b-value diffusion-weighted imaging (DWI) in characterizing breast lesions and predicting prognostic factors and molecular subtypes.
In total, 504 patients who underwent 3-T magnetic resonance imaging (MRI) with T1-weighted dynamic contrast-enhanced (DCE) sequences, T2-weighted sequences and multiple b-value (7 values, from 0 to 3000 s/mm2) DWI were recruited. The average values of 13 parameters in 6 models were calculated and recorded. The pathological diagnosis of breast lesions was based on the latest World Health Organization (WHO) classification.
Twelve parameters exhibited statistical significance in differentiating benign and malignant lesions. alpha demonstrated the highest sensitivity (89.5%), while sigma demonstrated the highest specificity (77.7%). The stretched-exponential model (SEM) demonstrated the highest sensitivity (90.8%), while the biexponential model demonstrated the highest specificity (80.8%). The highest AUC (0.882, 95% CI, 0.852-0.912) was achieved when all 13 parameters were combined. Prognostic factors were correlated with different parameters, but the correlation was relatively weak. Among the 6 parameters with significant differences among molecular subtypes of breast cancer, the Luminal A group and Luminal B (HER2 negative) group had relatively low values, and the HER2-enriched group and TNBC group had relatively high values.
All 13 parameters, independent or combined, provide valuable information in distinguishing malignant from benign breast lesions. These new parameters have limited meaning for predicting prognostic factors and molecular subtypes of malignant breast tumors.

Neoadjuvant chemotherapy (NAC) is an established treatment option for early breast cancer, potentially downstaging the tumor and increasing the eligibility for breast-conserving surgery (BCS). The primary aim of this study was to assess the rate of BCS after NAC, and the secondary aim was to identify predictors of application of BCS after NAC.
This was an observational prospective cohort study of 226 patients in the SCAN-B (Clinical Trials NCT02306096) neoadjuvant cohort during 2014-2019. Eligibility for BCS was assessed at baseline and after NAC. Uni- and multivariable logistic regression analyses were performed using covariates with clinical relevance and/or those associated with outcome (BCS versus mastectomy), including tumor subtype, by gene expression analysis.
The overall BCS rate was 52%, and this rate increased during the study period (from 37% to 52%). Pathological complete response was achieved in 69 patients (30%). Predictors for BCS were smaller tumor size on mammography, visibility on ultrasound, histological subtype other than lobular, benign axillary status, and a diagnosis of triple-negative or HER2-positive subtype, with a similar trend for gene expression subtypes. Mammographic density was negatively related to BCS in a dose-response pattern. In the multivariable logistic regression model, tumor stage at diagnosis and mammographic density showed the strongest association with BCS.
The rate of BCS after NAC increased during the study period to 52%. With modern treatment options for NAC the potential for tumor response and BCS eligibility might further increase.