Williams Cancer Institute

Breast Biopsy And Possible Increased Risk Of Metastasis

Breast Biopsy And Possible Increased Risk Of Metastasis

First, I want to state that biopsy is very important in cancer diagnosis and treatment. This is not to condemn biopsy, but to have discussions on how we can lower risk. The article titled “Needle Biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay” is a needed publication to discuss this topic of increased risk associated with a biopsy. In reality, this goes beyond just breast cancer. For over 14 years now I have used injection of NSAIDS at the biopsy site, which as suggested in this article may be a good option. The other is that once a biopsy has been done, the clock is ticking to have a more definitive treatment, such as surgery. There clearly is room for improvement. However adjustments in practice can be made and certainly use of NSAIDS at biopsy, and rapid treatment after biopsy should be evaluted more and could become the standard of care in the future. Preventing metastasis upfront at the biopsy could potentially save many lives.

Jason R. Williams, MD, DABR, author of “The Immunotherapy Revolution.”

This article discusses the impact of the interval between diagnostic biopsy and surgery on the mortality risk in early-stage breast cancer (BC) patients. The study suggests that a prolonged biopsy-to-surgery interval is associated with an increased risk of mortality and accelerated disease progression. The research focuses on the pro-metastatic effects induced by needle biopsy, revealing that it creates a wound stroma rich in pro-metastatic factors, particularly in estrogen-receptor-positive (ER+) BC.

Key points and findings:

Increased Mortality Risk: The study, based on a large BC cohort, shows a delayed onset of significantly increased mortality risk when the surgery is performed ≥53 days after biopsy. The mortality risk rises exponentially with a longer biopsy-to-surgery interval.

Biopsy-Induced Pro-Metastatic Effects: Needle biopsy induces changes in the tumor microenvironment, leading to the dominance of pro-metastatic macrophages (Mφ) and the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). These changes stimulate angiogenesis, epithelial-to-mesenchymal transition (EMT), and systemic dissemination of cancer cells.

Biphasic Trajectory of Mortality Risk: The analysis reveals a biphasic trajectory, with an initial lag phase of 43 days without a detectable increase in mortality risk, followed by a significant increase after 53 days. This suggests that early-stage BC undergoes accelerated disease progression after diagnosis, emphasizing the critical safety window of the first 53 days post-biopsy.

COX-2/PGE2/EP2 Feedforward Loop: The study identifies a feedforward loop involving COX-2, PGE2, and the EP2 receptor, contributing to M2-like macrophage dominance, EMT, and metastasis. Inhibiting this loop with selective inhibitors for COX-2 or EP2 disrupts biopsy-induced metastasis in preclinical models.

Clinical Implications and Recommendations: The findings support the recommendation to keep the diagnosis-to-surgery time within 60 days or fewer. The study proposes a pharmacologic strategy using selective NSAIDs to inhibit the COX-2/PGE2/EP2 feedforward loop in cases where surgery delay is unavoidable.

Limitations: The study acknowledges limitations, including the need for further investigation into the association between biopsy-associated histologic changes and recurrence or mortality in larger patient cohorts.

In conclusion, the research suggests that needle biopsy in early-stage ER+ BC may initiate rapid pro-metastatic progression, contributing to increased mortality risk. The findings provide insights into the importance of minimizing the biopsy-to-surgery interval and offer a potential pharmacologic strategy to mitigate pro-metastatic effects.

Reference: Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John F. Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka, 19 December 2023, Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay, https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00547-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379123005475%3Fshowall%3Dtrue

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