Correlation between tumor-associated M 1/M 2 macrophage ratio and NAC response in peripheral blood of patients with breast cancer

Breast cancer remains one of the most common and challenging diseases affecting women worldwide. When doctors treat this disease, they often begin with a course of chemotherapy before surgery, a strategy known as neoadjuvant chemotherapy. The goal is to shrink the tumor, making it easier to remove, and to see how the cancer responds to the drugs. The most successful outcome of this approach is called a pathological complete response, meaning that after the treatment and surgery, no cancer cells can be found in the breast or the nearby lymph nodes. Patients who achieve this result generally live longer and have a better chance of staying cancer-free. However, not every patient responds the same way. Some see their tumors disappear, while others do not, and currently, there is no simple, non-invasive way to predict who will respond well before the treatment is finished. Doctors often have to wait until the end of the chemotherapy course to know if the drugs are working, which can leave patients undergoing ineffective treatment or missing the chance to switch to a better option sooner.

To solve this problem, researchers at Fenyang Hospital in Shanxi Province, China, looked for a new clue hidden within the body's own immune system. They focused on macrophages, a type of white blood cell that acts as a scavenger in the body. Inside a tumor, these cells can take on two very different personalities. One type, often called the M1 type, fights the cancer and helps the immune system attack the tumor. The other type, the M2 type, actually helps the cancer grow and hide from the immune system. The balance between these two types of cells is crucial. The researchers wanted to know if they could track this balance in a patient's blood to predict whether the chemotherapy would work, without needing to perform invasive biopsies of the tumor itself. They also investigated a specific protein called BEST1, which acts like a unique ID tag on certain immune cells, to see if it could help distinguish between normal immune cells and those that have been influenced by the tumor.

The team studied eighty women with breast cancer who were undergoing six rounds of neoadjuvant chemotherapy followed by surgery. They divided the patients into two groups based on the final results of their surgery: those who achieved a complete response with no remaining cancer, and those who still had cancer cells left. Before, during, and after the chemotherapy, the researchers took blood samples from the patients. They also examined tissue samples from the tumors before and after treatment. Using advanced laboratory techniques, they counted the different types of macrophages and measured the levels of the BEST1 protein. They also used computer analysis of existing genetic data to understand how these cells behave at a molecular level.

The study revealed a clear pattern. In the patients who achieved a complete response, the ratio of fighting macrophages to helping macrophages in their blood increased significantly after the chemotherapy started. At the same time, the number of macrophages carrying the BEST1 protein, which the researchers identified as tumor-associated cells, also went up. This change happened early in the treatment process, suggesting that the blood was reflecting what was happening inside the tumor. In contrast, the patients who did not respond well to the chemotherapy showed the opposite trend. Their blood showed a decrease in the fighting macrophages and a drop in the BEST1-positive cells. The researchers found that this shift in the blood matched the changes they saw in the actual tumor tissue, confirming that a simple blood test could mirror the complex environment inside the tumor.

Interestingly, the study found that simply counting the total number of macrophages did not provide useful information. The total count went down in both groups of patients, regardless of whether they were getting better or worse. This ruled out the idea that the sheer number of these cells was the key factor. Instead, the specific type of cell and its behavior were what mattered. The researchers also looked at other factors like the patient's age, the size of the tumor, and the specific genetic type of the cancer. They found that the size of the tumor and whether it had spread to the lymph nodes before treatment started were the only traditional factors that predicted the outcome. Things like the patient's age or the specific molecular subtype of the cancer did not show a strong link to whether the treatment would work in this group of patients.

The findings suggest that the BEST1 protein serves as a reliable marker to identify the specific immune cells that are interacting with the tumor. By tracking the ratio of these cells in the blood, doctors might be able to see early on if a chemotherapy regimen is effective. If the blood shows a shift toward the cancer-fighting type of macrophage, it indicates the treatment is working. If the balance shifts the other way, it suggests the cancer is resisting the drugs. This approach offers a way to monitor treatment progress without the need for repeated, invasive surgeries or biopsies. While the study is a significant step forward, the researchers acknowledge that more work is needed to confirm these results in larger groups of patients and to fully understand the exact role the BEST1 protein plays in this process. Nevertheless, the discovery points toward a future where a simple blood test could guide treatment decisions, helping to spare patients from ineffective therapies and ensuring they receive the right care at the right time.