https://my.clevelandclinic.org/health/diagnostics/24204-breast-biopsy-overview

For a long time, the core value of breast fine-needle aspiration biopsy has been defined as a "diagnostic tool" - to determine the benign or malignant nature of the lesion. However, with the advent of the era of precision medicine, the role of this technology is undergoing a profound transformation. The cell samples obtained by it are no longer merely the "judgment document" for pathological diagnosis; instead, they have become the "key" to unlocking the mysteries of tumor biology and guiding individualized treatment.

From "What is it" to "How is it": Extraction of Molecular Information

Traditional cytological examinations mainly focus on the morphology of cells to determine whether they are cancer cells. However, modern fine-needle aspiration biopsy, through a series of advanced technologies, can extract massive molecular information from a small amount of cell samples.

1. Immunocytochemistry: By conducting immunohistochemical staining on cell slides, we can determine key biomarkers of breast cancer, such as estrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, and proliferation index Ki-67. This information directly determines whether patients can benefit from endocrine therapy or targeted therapy. Studies have confirmed that fine needle aspiration samples and large surgical specimens have a high degree of consistency in the detection of these indicators.
2. Fluorescence in situ hybridization: For cases with uncertain HER2 results, FISH testing can be performed using cells obtained from fine needle aspiration to determine whether there is HER2 gene amplification, thereby accurately screening out patients suitable for anti-HER2 targeted therapy.
3. Gene sequencing: With the maturity of next-generation sequencing technology, even a small amount of cells obtained from fine needle aspiration can successfully extract DNA or RNA for comprehensive genomic analysis. This can detect driver gene mutations such as PIK3CA, ESR1, BRCA1/2, etc., helping patients find potential targeted drugs or clinical trial opportunities. Especially in advanced breast cancer patients, when new tissue samples cannot be obtained, sequencing of fine needle aspiration cell paraffin blocks from the past archived samples becomes an important way to guide subsequent treatment.

The "sentinel" of treatment monitoring: Dynamic assessment of efficacy and drug resistance

During the treatment of breast cancer, especially during neoadjuvant chemotherapy or targeted therapy, the tumor undergoes dynamic changes. Fine needle aspiration, due to its minimally invasive and repeatable characteristics, has become an ideal "real-time monitoring probe".

• Assessing treatment response: After the start of neoadjuvant therapy and before the surgery, sampling of the residual lesions through fine needle aspiration can be conducted to evaluate the degree of pathological remission after the treatment. If it is discovered early on that tumor cells are insensitive to the drugs, the doctor can promptly adjust the treatment plan to avoid ineffective medication.
• Capturing the mechanism of drug resistance: When the patient experiences disease progression, fine needle aspiration of the lesion at the progression site can be performed to analyze whether new gene mutations have occurred in the tumor, thereby leading to drug resistance. For example, during the treatment with aromatase inhibitors, if there is progression, the puncture sample may detect ESR1 mutations, indicating the need to switch to other endocrine treatment drugs.

The "rich mine" of scientific research exploration: Promoting basic and translational research

Apart from its clinical application, breast fine-needle aspiration biopsy also provides valuable resources for scientific research.

• Single-cell analysis: Using the cell suspension obtained through fine needle aspiration, single-cell RNA sequencing can be performed to reveal the heterogeneity within the tumor - that is, the differences in gene expression profiles among different cells within the same tumor. This helps understand which cells are the "seeds" driving tumor growth and which are the "stubborn molecules" resisting treatment.
• Establishing patient-derived organoids: A small amount of tumor cells obtained through puncture are cultured in vitro to form three-dimensional "miniature tumors" (organoids). These organoids retain the genetic characteristics and drug sensitivity of the original tumor and can be used for high-throughput drug screening, helping to find the most effective personalized drug combination for each patient.

Challenges and Future Directions

Although the prospects are promising, the inherent limitations of fine-needle aspiration include the small sample size and the lack of tissue structure information. The future development directions include:

• Cell block technique: After centrifuging and solidifying the cell fragments and tiny tissue blocks obtained through puncture, they are embedded into wax blocks, allowing for the creation of tissue sections similar to small biopsies, providing both cytological and partial histological information.
• Multimodal analysis: Combining fine-needle puncture with imaging biomarker analysis and liquid biopsy (ctDNA) to construct a more comprehensive tumor assessment system.
• Automation and standardization: Developing an automated cell collection and processing platform to reduce human error and improve sample quality and detection throughput.

In summary, in the wave of precision medicine, breast fine-needle aspiration biopsy has gone beyond the simple diagnostic scope. It is evolving into a multifunctional platform that integrates diagnosis, prognosis assessment, discovery of treatment targets, efficacy monitoring, and scientific research exploration. It has become a bridge connecting basic research and clinical practice, and driving the diagnosis and treatment of breast cancer to a higher level.