Feng Mao

To comprehensively characterize the evolution of racial disparities in U.S. female breast cancer mortality between non-Hispanic Black and White women from 1999 to 2023 across age, geography, and urbanization levels. We analyzed nationwide mortality data from the CDC WONDER database for women aged ≥ 25 years. We calculated age-adjusted mortality rates (AAMRs), absolute rate differences (ARD), and age-standardized rate ratios (ASRR). Joinpoint regression was employed to quantify temporal trends and identify significant changes over the 25-year period. Between 1999 and 2023, AAMRs declined for both Black (Average Annual Percent Change [AAPC] = -1.38, 95% CI -1.45 - -1.30) and White (AAPC = -1.46, 95% CI -1.56 - -1.35) women; however, Black women consistently experienced higher mortality. Disparity trends exhibited significant heterogeneity. While the mortality gap narrowed for women aged ≥ 55, the relative disparity for younger women (< 55 years) remained stagnant (ASRR ~ 1.88) despite absolute rate declines. Geographically, the Midwest achieved the most significant reduction in ARD. In contrast, the Northeast showed widening relative disparities. Notably, Massachusetts experienced a "disparity reversal," shifting from a Black survival advantage in 1999 to a significant mortality disadvantage by 2023. Additionally, disparities worsened in Large Fringe Metro areas compared to other urbanization levels. Despite national progress in reducing breast cancer mortality, racial equity remains elusive. The persistent gap among younger women and the widening disparities in specific "hotspot" regions and traditionally affluent states challenge the assumption that general healthcare improvements benefit all populations equitably, underscoring the urgent need for targeted, precision-based public health interventions.

Background: Given the limited access to breast cancer (BC) screening, the authors developed and validated a mobile phone-artificial intelligence-based infrared thermography (AI-IRT) system for BC screening. Materials and methods: This large prospective clinical trial assessed the diagnostic performance of the AI-IRT system. The authors constructed two datasets and two models, performed internal and external validation, and compared the diagnostic accuracy of the AI models and clinicians. Dataset A included 2100 patients recruited from 19 medical centres in nine regions of China. Dataset B was used for independent external validation and included 102 patients recruited from Langfang People’s Hospital. Results: The area under the receiver operating characteristic curve of the binary model for identifying low-risk and intermediate/high-risk patients was 0.9487 (95% CI: 0.9231–0.9744) internally and 0.9120 (95% CI: 0.8460–0.9790) externally. The accuracy of the binary model was higher than that of human readers (0.8627 vs. 0.8088, respectively). In addition, the binary model was better than the multinomial model and used different diagnostic thresholds based on BC risk to achieve specific goals. Conclusions: The accuracy of AI-IRT was high across populations with different demographic characteristics and less reliant on manual interpretations, demonstrating that this model can improve pre-clinical screening and increase screening rates.

Background: The objective was to explore the discordance in the expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 between primary and recurrent/metastatic lesions in patients with early stage breast cancer as well as the prognostic impact.Method: Patients with early-stage primary breast cancer and confirmed recurrence/metastasis at Peking Union Medical College Hospital between January 2005 and August 2018 were screened. The details of discordance in each parameter between primary and recurrent/metastatic lesions and progression were recorded. Regression and survival analysis were applied to determine the association and clinical impact of the discordance.Results: We evaluated 75 patients. The discordance rate of ER, PR, HER2, and Ki-67 expression was 9.3, 14.7, 14.7, and 21.5%, respectively. Additionally, 66.7, 11.8, 14.3, and 0% of patients with Luminal A, Luminal B, HER2, and triple-negative primary tumors presented with a different subtype for the recurrent/metastatic tumors, respectively. No statistical difference in progression-free survival was observed according to the subtype of the recurrent or metastatic breast cancer (p > 0.05). Among 69 patients for whom treatment was adjusted after recurrence or metastasis, 66 patients remained recurrence-free during the follow-up period.Conclusion: For patients with early-stage breast cancer, the ER, PR, HER2, and Ki-67 expression profile for recurrent/metastatic tumors does not always match that of the primary tumor. After adjusting treatment according to the receptor expression in recurrent/metastatic lesions, most patients remained progression-free during the follow-up period.

In this study we applied a strategy to identify sentinel lymph node (SLN) metastasis by combining 68Ga-NOTA-Evans Blue (68Ga-NEB) for SLN mapping and 68Ga-NOTA-RM26 for LN metastasis detection in breast cancer patients. A total of 24 female patients with breast cancer diagnosed by core biopsy or suspected by mammography or ultrasonography were recruited and provided informed consent. All patients underwent 68Ga-NEB and 68Ga-NOTA-RM26 PET/CT imaging. Visual analysis of 68Ga-NEB PET/CT images was used to determine SLNs, and then compared with the 68Ga-NOTA-RM26 results and histopathological findings. SLNs were visualized in 24 of 24 patients (100.0%) within 4.0–10.0 (5.6±1.4) min. All patients were pathologically diagnosed with breast cancer, and 12 patients had ipsilateral lymph node metastasis. By combining 68Ga-NEB and 68Ga-NOTA-RM26 images, 7/12 (58.3%) patients showed mild to intense uptake of 68Ga-NOTA-RM26 in SLNs, 1/12 patient (8.3%) had moderate uptake of 68Ga-NOTA-RM26 in the non-SLNs rather than SLN, indicating possible bypass lymphatic drainage, partially accounting for the false negatives in SLN biopsy during surgery. No false positives were found. The SUVmax of 68Ga-NOTA-RM26 activity in metastatic SLNs was significantly higher than that in nonmetastatic SLNs (2.2 ± 2.3 vs. 0.7 ± 0.1, P = 0.047). This study manifests the value of combination of 68Ga-NEB and 68Ga-NOTA-RM26 dual tracer PET/CT in preoperative evaluation of SLN metastasis in breast cancer patients, especially in those patients with lymphatic obstruction and bypass drainage. In general, positive 68Ga-NOTA-RM26 uptake in either SLN or other lymph nodes can apply lymph node dissection rather than intraoperative SLN biopsy.

Background: This prospective pilot study investigated the value of ⁶⁸Ga-NOTA-RM26, an antagonist targeting gastrin-releasing peptide receptor, in evaluation of breast cancer. Methods: Thirty-five women in suspicion of breast cancer based on mammography or ultrasonography were recruited with informed consent. They underwent PET/CT scans 30 minutes after intravenous injection of ⁶⁸Ga-NOTA-RM26 in a dose of 1.85 MBq (0.05 mCi) per kilogram body weight within 1 week before surgery. The ⁶⁸Ga-NOTA-RM26 uptake was correlated with the pathological and immunohistochemical findings. Results: ⁶⁸Ga-NOTA-RM26 positivity was found correlated with estrogen receptor (ER) expression (P = 0.006) and menstrual status (P = 0.019). In 34 patients diagnosed with breast cancer, the SUVmax was found significantly higher in the ER-positive breast cancer (4.97 ± 1.89) than in the ER-negative breast cancer (2.78 ± 0.65, P < 0.001). ⁶⁸Ga-NOTA-RM26 was also found accumulated in normal breast tissue, with the SUV_max significantly higher in patients at the secretory phase of menstrual cycle (2.27 ± 0.71) than in those at the nonsecretory phase (1.59 ± 0.49, P = 0.017) and postmenopause (1.43 ± 0.44, P = 0.002). If the secretory phase patients were excluded, the sensitivity, specificity, and accuracy for differentiation of breast cancer from breast tissue increased from 85.3%, 86.8%, and 86.1% to 100%, 90.9%, and 95.5%, respectively. Conclusions: This pilot study indicates that the diagnostic accuracy of ⁶⁸Ga-NOTA-RM26 PET/CT in breast cancer may correlate with ER expression and menstrual status of the patient. It may be better to avoid performing this examination during the menstrual secretory phase to reduce physiological uptake in normal breast tissue.

The specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear. 147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated. ALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman’s rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2^{-△△C T} value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001). The ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.