Breast Cancer Basics: Reduce The Risk Of Cancer Metastases After Surgery or Biopsy (Controversial)

Can cancer surgery or biopsies cause tumor cells to metastasize or become more aggressive? Yes. But before you say to yourself that I won’t have these done, it’s VERY important to know that:

  1. Surgery on tumors that have not spread distantly can be curative (in some circumstances of limited metastatic disease, surgery on the primary and metastatic sites can be part of a curative approach), and
  2. Without a biopsy to get crucial information about the tissue of interest we may not be able to make the best decisions on your management.

Let’s discuss the concerns and what approaches might be able to be done to mitigate them.

Local Tumor Spread:

The seeding of cancer cells in the surgical bed, body cavities, surgical wound scars, laparoscopic port sites and biopsy tracts are well-known risks of any interventional procedure in which cancer is being poked with a needle or cut into with a knife.

Fortunately, these are not common events but when they occur tumors can develop in these violated tissues if the conditions for the seeded cancer cells are just right.

What are those conditions? In a word, it’s “trauma.”

  • Tissue trauma from interventional procedures (biopsy, surgery, etc.) activates the body’s natural wound healing mechanisms, a complex cascade of events that involves epithelial, endothelial, inflammatory cells, platelets and fibroblasts.
  • These cells release numerous proteins (i.e. growth factors, chemokines, and cytokines) into the locally damaged tissues to stimulate growth and repair of blood vessels and and other critical stromal elements.
  • These proteins also get released into the circulation and can cause:
    • Systemic stress
    • Inflammation
    • Immune suppression
    • And other effects (see images, below.)
  • Studies have shown that if there are dormant cancer cells or cancer stem cells in the wound, they can be stimulated to grow into tumors by the same wound healing proteins coupled with perioperative immunosuppression, inflammation, stress and other cancer-promoting pathophysiological processes.

Trauma And Other Perioperative Factors That Promote Cancer Growth

The schematics (below) demonstrate perioperative risk factors that can fuel established cancer cells to grow and metastasize, and awaken dormant cancer cells and stem cells throughout the body. These effects affect cancer cells by directly interacting with them and/or through impacting their surrounding microenvironment.

Distant Metastases:

How does surgery impact the risk of developing distant metastatic disease?

  • We know that cancer cells can gain access into the circulation during cancer surgery, as there is a measurable rise in circulating tumor cells (CTCs) in the blood in the days-to-weeks after surgery.
  • We also know that cancer cells metastasize very early in the development of a malignant tumor. In fact, tumors (with or without surgery) shed thousands of cancer cells into the circulation daily.

Fortunately, very few of these will be able to set-up shop in distant places around the body and successfully grow into metastatic tumors. If they do find a new home in a distant site and don’t get killed by the immune system, many of these metastatic cancer cells can remain dormant for years until their microenvironment becomes conducive to growth.

Mounting evidence from numerous studies has found that after any tissue trauma (i.e. surgery), the same effects that can cause growth of seeded cancer cells in the wound site can also stimulate the awakening and growth of dormant metastatic cancer cells anywhere in the body.

This is not new information. In 1889, the English surgeon, Dr. Stephen Paget, noted that metastatic growth can only be supported in the presence of a favorable microenvironment.

Opioid Medications Are Immunosuppressant:

Many studies report that the use of opioids can suppress the immune system through activation of the sympathetic nervous system and the subsequent release of stress hormones. How is this related to worsening cancer outcomes?

  1. Stress hormone receptors are located on most cancer cells, and are able to promote growth when they are stimulated.
  2. Stress hormones can suppress the function of white blood cells in their ability to both identify cancer cells and destroy them.
  3. Opioids activate opioid receptors located on vascular endothelial cells, stimulating angiogenesis.

While the use of opioids has been shown in many studies to be associated with a greater risk of cancer recurrence and metastases, the data is not always consistent in these findings. Much more research is needed to more clearly define the risk.

Recent studies have reported that the immunosuppression from opioids also increases the risk of infections.

Alternatives to using systemic opioids can include: anticonvulsants, antidepressants, regional pain blocks, neuromodulation, intrathecal drug delivery, cannabinoids and numerous complementary therapies (i.e. acupuncture, aromatherapy, etc.)

While these data and alternative pain management approaches should be considered, it’s important that your pain is adequately controlled. Uncontrolled pain leads to systemic stress and inflammation (both driving factors for cancer progression.) Don’t refuse opioids if they are the most effective therapies for managing your pain.

Strategies To Reduce Metastatic Disease:

Studies show that by reducing the systemic wide effects caused by tissue trauma and the subsequent wound healing process, the awakening of dormant cancer cells (locally and distantly) can be reduced.

  • Decrease inflammation using anti-inflammatory compounds (before and after surgery).
    • Studies report decreased metastases when NSAIDs are given perioperatively.
    • Preclinical study that supports the efficacy of this approach.

  • Decrease stress hormone induced immune suppression and cancer cell stimulation using beta-blocker drugs, supplements or stress reduction interventions (before and after surgery)
    • Studies report lower rates of metastatic disease and death in patients taking beta-blockers perioperatively.
  • Minimize the use of systemic opioid pain medications, which can cause immune suppression and angiogenesis (before and after surgery)
    • Studies have found higher rates of cancer recurrence and death in patients using opioids perioperatively.
  • Minimize tissue trauma, which stimulates wound healing and cancer progression (during surgery)
    • The preponderance of data finds that invasive procedures (i.e. biopsies and surgeries) which necessarily cause tissue trauma, lead to local and distant tumor growth stimulating effects.
    • As an example: Robot-assisted laparoscopic surgery decreases tissue trauma in several ways. First, the use of laparoscopic instruments allows for small keyhole incisions opposed to a larger incision needed for open surgery. Additionally, the advancement of the robotic tools over traditional laparoscopic instruments allows the surgeon greater range of motion allowing for a more delicate and deliberate dissection and decreased injury to surrounding tissue. The camera used in robotic-assisted surgery also decreases damage to neighboring tissue as it generates a 3-dimensional highly magnified image of the surgical field.  The improved visualization allows for increased accuracy of  surgical movements. Overall, the decreased tissue trauma translates into decreased recovery time and blood loss.
  • Use a multi-pronged approach to blocking cancer cell metabolic pathways to reduce the fuels that support cancer growth. See my article “Blocking Cancer With Combinations of Supplements and Off-Label Drugs.”

Ask Your Physicians If They Will Allow You To Take Anti-Inflammatories and Beta-Blocker Drugs Before and After Surgery or Biopsy:

  • There are numerous studies that suggest that this may be an efficacious approach to reduce your risk of cancer recurrence after surgery.
  • By extrapolation, one could also consider taking both an anti-inflammatory (NSAID) and beta-blocker (or stress reducing complementary therapies: meditation, breathing exercises, cognitive behavioral therapy, exercise, prayer, aromatherapy, message, acupuncture, stress-reducing botanicals, etc.) before and after any cancer biopsy.
  • One recently reported study found that the use of perioperative beta-blockers and NSAIDs was safe and reduced biomarkers for metastatic cancer.

Here are two clinical trials that are currently enrolling patients to study the efficacy of this approach:

Pre- and Post-Cancer Surgery Protocol #1:

Both study medications will be given orally for an intervention phase of 20 days as follows: 5 days prior to surgery, on the day of surgery, and 14 days postoperatively.

  • Etodolac: 800 mg 2 x/day for the entire intervention period
  • Propranolol: 20 mg 2 x/day for 5 preoperative days, 80 mg 2 x/day on the day of surgery, 40 mg 2 x/day for the first postoperative week, 20 mg 2 x/day for the second postoperative week
  • Clinical trial reference:

Pre- and Post-Cancer Surgery Protocol #2:

Six total days of treatment: starting 3 days before surgery and until 2 days after surgery