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Simple Summary: Breast cancer, especially in Asia, is on the rise. With improvements in tailored treatment, needs for more individualized subtyping are increasing. This retrospective study aimed to compare human epidermal growth factor receptor 2 (HER2)-low and HER2-0 breast cancers in hormone receptor (HR)-positive patients and investigate how it affect patients. We reviewed over 10,000 breast cancer cases, focusing on strong HR-positive subtypes. HER2-low breast cancer patients tended to have better oncologic outcomes compared to HER2-0 patients. Importantly, this difference was more pronounced in postmenopausal patients. This research highlights the need for reevaluating how we classify breast cancer subtypes. Understanding these distinctions could potentially lead to more tailored treatments for patients with HER2-low breast cancer in the future. Breast cancer is a prevalent malignancy with increasing incidence, particularly in Asian countries. Classification based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is pivotal in determining treatment. Recent advances have challenged the traditional dichotomy in HER2 classification, prompting investigation into the HER2-low subtype's characteristics and outcomes. This retrospective study analyzed 10,186 non-metastatic hormone receptor (HR)-positive, HER2-negative breast cancer cases treated from 2008 to 2020. Data encompassed clinical, pathological, and treatment information. Oncologic outcomes included disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS). In total, 56.5% were HER2-low cases. Differences in patient characteristics were noted, with more BRCA1/2 mutations and higher mastectomy rates in the HER2-low group (p = 0.002, p < 0.001, respectively). Fewer received adjuvant chemotherapy or radiation therapy, and fewer histologic and nuclear grade 1 tumors were identified (all p < 0.001). With a median follow-up of 64 months (range: 13–174), HER2-low cases exhibited better DFS, OS, and BCSS than HER2-0 cases (p = 0.012, p = 0.013, and p = 0.013, respectively). Notably, the prognosis differed between premenopausal and postmenopausal subgroups, with BCSS benefitting premenopausal patients (p = 0.047) and DFS and OS benefitting postmenopausal patients in the HER2-low group (p = 0.004, p = 0.009, respectively). Multivariate analysis confirmed HER2 status as an independent predictor of these outcomes (p = 0.010, p = 0.008, and p = 0.014, respectively). This extensive single-center study elucidates the favorable prognosis associated with HER2-low status in HR-positive breast cancer. However, this effect differs among premenopausal and postmenopausal patients, necessitating further research into the underlying tumor biology. [ABSTRACT FROM AUTHOR]

Breast cancers include a heterogeneous group of diseases with clinical behaviors that may vary according to the hormonal receptor status. However, limited knowledge is available on the role of breast cancer environmental and occupational risk factors in the onset of specific molecular disease phenotypes. Therefore, the aim of this review was to provide an overview on the possible correlation between occupational chemical exposures and breast cancers with a specific receptor pattern. Pubmed, Scopus, and ISI Web of Science databases were systematically reviewed to identify all the studies addressing chemical exposure in workplaces and risk of breast cancer classified according to the presence of estrogen and/or progesterone receptors. Some positive associations were reported between solvent, polycyclic aromatic hydrocarbon, organophosphoric insecticide, and synthetic fiber exposure and estrogen receptor-positive cases, while other investigations demonstrated a relationship with receptor-negative tumors or failed to detect any significant effect. Overall, further investigation should overcome limitations due to the self-reported information on work histories, the chemical classification in general categories, and the lack of environmental or biological monitoring exposure data. This may support the development of suitable and individually "tailored" occupational risk assessment and management strategies to protect the health of exposed workers, particularly those with hypersusceptibility conditions. [ABSTRACT FROM AUTHOR]