Advances and controversies in new techniques of breast pathology

The development of breast pathology technology provides basic support for precise typing and individualized treatment of breast cancer. Precision in breast cancer diagnosis and management is evolving as a fundamental trend, with the advent of novel therapeutic agents necessitating enhanced accuracy in pathological diagnostic evaluations. The application of trastuzumab deruxtecan (T-DXd) has offered new therapies for breast cancer patients with human epidermal growth factor receptor 2 (HER2)-low and HER2-ultra low status. With the refinement of the classification for HER2 expression status, as a traditional detection method, the efficacy of immunohistochemistry (IHC) has been challenged. In addition, HER2-low has poor interpretation consistency, with spatial and temporal heterogeneity, which is affected by the storage time of the blank slides. Nowadays, finding auxiliary methods that can effectively improve the testing efficiency and interpretation accuracy of IHC as well as new accessible HER2 detection methods are important exploration directions. Whether HER2-low can be considered an independent molecular type of breast cancer has become an important issue with the update of treatments and the progress of new drugs. However, the answer is no at this time due to the absence of distinct and stable biological and pathological features and the lack of specific therapeutic benefit and prognostic relevance. With the widespread adoption and advancement of genomic profiling technologies, multiple causative genetic mutations associated with breast cancer have been identified. The development and clinical application of targeted drugs have elevated genomic profiling to an increasingly pivotal role in clinical decision-making for breast cancer treatment. In recent years, multiple inhibitors targeting the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) have demonstrated promising therapeutic efficacy in hormone receptor (HR) positive/HER2-negative breast cancer. The clinical prioritization of PIK3CA/AKT1/PTEN molecular profiling has been intensified, and the trend is to move forward the time of the initial test. Tumor tissue samples are preferred for testing, and plasma samples can be used as a necessary supplement. Samples from primary or recurrent tumors are considered to have similar testing efficacy and can be selected as appropriate. BRCA mutation is one of the common types of genetic mutations in breast cancer. While current guidelines vary in specifics regarding target populations, they universally prioritize clinical parameters including diagnostic age, family history, and treatment response to identify patients who have elevated BRCA mutation risks and may benefit from poly (ADP-ribose) polymerase (PARP) inhibitor therapy. This article summarized the latest advances and controversies in breast pathology techniques, focusing on the diagnostic criteria and methodological limitations in detecting HER2-low and HER2-ultra low breast cancers, therapeutic progress in PAM pathway-aberrant breast cancer, and the target population for detecting BRCA gene mutations.