Breast biopsy markers—often called breast clips—have become a routine part of breast imaging and biopsy procedures. These very small markers made of metal and polymers or other bioabsorbable materials are placed into the breast after a biopsy with the intent to identify the location of a sampled abnormality so that it can be found again on future mammograms, ultrasound, MRI, or during surgery.

If an abnormality becomes difficult to see after biopsy, responds to treatment, or needs to be surgically removed later, the metal marker provides a reference point for the original area of concern. Radiologists overall prefer use of breast biopsy markers as it helps them for follow-up imaging and surgical localization.

However, an important question remains that has not received appropriate attention :

What happens to the breast tissue surrounding a biopsy site and retained marker over time?

Breast Tissue Does React After Biopsy and Marker Placement

It is sometimes assumed that after the initial biopsy heals, the surrounding breast tissue simply returns to its previous state. Histologic studies—studies in which the actual tissue is examined under a microscope—show that this is not the case.

Researchers have documented changes around breast biopsy sites that include:

• Local inflammation
• Foreign-body reactions
• Macrophage and multinucleated giant-cell accumulation
• Granulation tissue
• Fibrosis and scar formation
• Fat necrosis
• Hemorrhage and hemosiderin deposition
• Fibrovascular tissue and new blood vessel formation
• Persistent foreign material associated with some biopsy-marker carriers

These findings do not automatically mean that the marker itself is dangerous, nor do they establish that the marker is responsible for all of these changes. A needle biopsy itself creates tissue injury and initiates a wound-healing response. But the findings raise worthwhile questions about how long these changes persist and how much of the response may be related to the biopsy versus the retained marker and its surrounding materials.

A Study Looking Directly at Breast Tissue After Needle Biopsy

One particularly interesting study, published in Pathobiology and indexed in PubMed, examined surgically removed breast tumors from 73 women who had previously undergone image-guided needle biopsy.

Researchers specifically examined tissue surrounding the visible biopsy tract.

Their findings were striking.

Foreign-body giant-cell reactions with macrophage accumulation were identified in 53.4% of cases.

Organized granulation tissue containing fibroblasts along with chronic inflammation was present in 20.5%.

Another 20.5% demonstrated vascular-rich granulation tissue with extensive angiogenesis—the development of new blood vessels.

Fat necrosis occurred in 18% of specimens, and hemosiderin deposition was identified in 2.7%.

Perhaps particularly relevant to the discussion of breast markers, material believed to represent residual carrier material from the biopsy marker was visible in 60.2% of cases.

The researchers also found an association between visible biopsy-marker carrier material and inflammatory cells including neutrophils, eosinophils, and plasma cells. They proposed that this could represent a foreign-body response to the marker material.

It Isn’t Necessarily Just the Metal Clip

When we talk about a “breast clip,” it is easy to imagine that a tiny piece of titanium or stainless steel is the only material being introduced.

That isn’t the case.

Modern biopsy markers vary considerably in composition and design. Some incorporate materials intended to improve ultrasound visibility or help stabilize the marker at the biopsy site. Published reviews describe markers and carriers incorporating materials such as titanium, stainless steel, nitinol and various polymers, hydrogels, collagen and other bioabsorbable materials.

This matters because the tissue response may depend not only upon the metallic marker but also upon the material surrounding it.

The Nature/Modern Pathology Findings

Another fascinating study published in Modern Pathology, a Nature journal, specifically examined tissue surrounding hygroscopic, ultrasound-visible biopsy markers.

The authors noted that biopsy tracts, wires and clips can produce histologic findings including:

local inflammation, foreign-body reaction, fat necrosis, fibrosis and hemosiderin deposition.

They also described inflammation, fibrosis, giant-cell reactions and accumulation of fibrinous material associated with certain marker materials.

Most interestingly, the researchers identified a distinctive response surrounding the hygroscopic markers: formation of pseudocyst-like structures lined by epithelioid histiocytes, a type of immune cell involved in foreign-body and inflammatory responses.

The authors pointed out that tissue responses to breast biopsy marking devices can vary depending upon the type of device being used.

That is an important distinction.

There isn’t one universal “breast clip.” There are numerous commercially available markers with different metals, shapes, coatings and carrier materials. A review from Memorial Sloan Kettering identified 38 different marker shapes from six manufacturers and documented considerable variation in marker composition and carrier properties.

Is It the Biopsy or the Marker?

This is probably the most important unanswered question.

A core or vacuum-assisted breast biopsy is itself a physical injury. Tissue is removed with a relatively large needle, bleeding occurs, and the body initiates normal wound healing.

Inflammation, macrophage recruitment, fibroblast activity, new blood vessel formation and eventually scar tissue can all be components of normal wound repair.

Therefore, finding inflammation or fibrosis around a clipped biopsy site does not prove that the clip caused it.

At the same time, the presence of foreign-body giant-cell reactions and inflammatory cells associated with visible marker carrier material suggests that the marker system itself may contribute to the local response.

Separating those two effects would require studies comparing similar biopsy procedures with versus without retained markers, ideally with longitudinal imaging and, where available, pathology.

Unfortunately, this specific question has not been studied nearly as thoroughly as other aspects of breast-marker safety.

“Safe” Can Mean Different Things

There are many studies involving breast markers, but they only study migration, visibility, localization accuracy, deployment, MRI artifact, surgical retrieval, or feasibility.  These ARE NOT SAFETY STUDIES for women. There is only one published “long term safety study”  of breast biopsy markers placed in women, and this study was conducted by authors affiliated with the medical device manufacturer, representing an important conflict of interest.  This retrospective study (retrospective means they went back and reviewed medical charts) evaluating 768 breast and axillary biopsy markers reported only three device-related events and no serious adverse events, concluding that the markers demonstrated favorable long-term safety. This is another important limitation: what did the researchers actually define as an adverse event?   Studies, like this one, meant to  evaluate the “safety” of biopsy markers commonly focus on outcomes such as serious adverse events, device malfunction, deployment problems, migration, inability to locate the marker, or complications affecting subsequent surgery.

Those endpoints do not answer a different and important question all women deserve to know:

Does the breast tissue surrounding a retained biopsy marker remain structurally and biologically unchanged over time?

The limited pathology literature demonstrates that it does not remain unchanged. Researchers have documented local inflammation, foreign-body giant-cell reactions, fibrosis, fat necrosis, granulation tissue and hemosiderin deposition at breast biopsy and marker sites.

This does not establish that the marker itself caused every one of these findings—the biopsy procedure is an important confounding factor—but it highlights a significant distinction between “no serious device-related adverse event was reported” and “the implanted material produces no persistent local tissue response.”

Both questions matter, and they should not be treated as though they are the same question.

Why More Research Is Needed

In clinical practice, I have personally observed tissue changes surrounding breast biopsy-marker sites repeatedly over many years and in well over 100 women.

Clinical observation alone cannot establish causation. There are several potential explanations for what we observe—including the original abnormality, biopsy trauma, hematoma formation, subsequent fibrosis, the body’s response to retained material, and even imaging artifact.

But repeated clinical observations can—and historically often do—generate important research questions.

The published pathology findings make this particular observation worth investigating rather than dismissing.

A valuable study would follow women prospectively before biopsy and after biopsy-marker placement, documenting the tissue at baseline and at defined intervals afterward. Ideally, researchers would compare biopsy sites with and without retained markers and evaluate different marker compositions.

Such a study could examine ultrasound architecture, mammographic changes, MRI findings, fibrosis, vascularity, elastography, symptoms and—when tissue is eventually removed—histopathology.

It could also determine whether particular marker materials produce greater or lesser tissue responses.

What Should Women Do With This Information?

This information is not a recommendation to refuse a breast biopsy.

Breast biopsy can provide critically important diagnostic information, and marker placement may be useful when an abnormality needs to be located again.

Rather, we should be avidly researching and working to make them as safe as possible. Women should be able to participate in an informed discussion about what is being placed in their bodies and not dismissed when questioning the safety of a procedure that clearly deserves more research and true, unbiased safety standards.  In my observation, this simply does not currently exist.

The Bottom Line

Breast biopsy markers have become an established norm in modern standard of care breast imaging. Available clinical safety studies focus on major adverse effects and migration, but are lacking in the realm of local tissue changes and potential harm to surrounding tissue and malignant processes.

Published pathology demonstrates that breast biopsy sites can exhibit persistent inflammation, foreign-body giant-cell reactions, granulation tissue, fibrosis, fat necrosis and hemosiderin deposition, and some studies have directly identified residual marker carrier material within these areas.

What we do not yet know well enough is how much of that response is caused by the biopsy itself versus the retained marker, how frequently clinically meaningful changes persist long term, whether certain marker materials produce greater reactions than others, and whether those changes have any implications beyond making the tissue look or feel different, especially important in the realm of cancer. 

These are reasonable questions and in my opinion, they should have been answered properly before this practice became widely accepted standard of care.

More than one million American women undergo breast biopsy every year, and biopsy-marker placement has become a routine component of image-guided breast biopsy. Despite this very large population potentially exposed to retained breast markers, surprisingly little to no research has specifically examined their long-term biological effects on surrounding breast tissue. Women deserve better.

References

Sustained Inflammation of Breast Tumors after Needle Biopsy. Pathobiology. Histologic evaluation of 73 breast cancer cases demonstrated persistent inflammatory and wound-healing changes adjacent to biopsy tracts, including foreign-body giant-cell reactions, granulation tissue, angiogenesis, fat necrosis, hemosiderin and residual biopsy-marker carrier material.

Hygroscopic sonographically detectable clips form characteristic breast and lymph node pseudocysts. Modern Pathology. This study describes histologic responses surrounding breast biopsy markers, including local inflammation, foreign-body reaction, fat necrosis, fibrosis, hemosiderin deposition and distinctive pseudocyst formation associated with hygroscopic markers.

Current status of biopsy markers for the breast in clinical settings. Expert Review of Medical Devices. Review of breast-marker composition, properties, applications and limitations.

Advantages and Challenges of Using Breast Biopsy Markers. Journal of Breast Imaging. Review of the clinical indications, advantages and challenges associated with breast biopsy markers.