Effects of opioids on cancer progression

Looks like you've done some extensive research on the subject. Thanks for sharing. Deanna

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In April of 2009 I had exploratory surgery for a burst appendix and subsequently received IV morphine for 10 days......this was before breast cancer. By August of 2009 I found a lump and after a biopsy and lumpectomy I was diagnosed with IDC stage II. Coincidence? Perhaps. I asked my breast surgeon if she thought I had DCIS that went malignant after the morphine, and she said, "Could be, maybe not, but you will never know." For what ever surgeries I may have in the future I will request that no opioids be involved, just in case.

Here's a paper showing no effect of morphine on cancer progression in mice models:

http://dx.doi.org.udel.idm.oclc.org/10.1097/j.pain...

The discussion section nicely outlines some of the limitations of other studies. Just something to be aware of.

Falls - sorry about that! Here's the abstract:

Author: Doornebal, Chris W. a,b; Vrijland, Kim a; Hau, Cheei-Sing a; Coffelt, Seth B. a; Ciampricotti, Metamia a; Jonkers, Jos c; de Visser, Karin E. a,*; Hollmann, Markus W. b

Institution: (a)Division of Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands

(b)Department of Anesthesiology, Academic Medical Center, Amsterdam, the Netherlands

(c)Division of Molecular Pathology and Cancer Genomics Center, Netherlands Cancer Institute, Amsterdam, the Netherlands

Title:

Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2+ breast cancer.[Article]

Source: Pain. 156(8):1424-1432, August 2015.

Abstract: Morphine and other opioid analgesics are potent pain-relieving agents routinely used for pain management in patients with cancer. However, these drugs have recently been associated with a worse relapse-free survival in patients with surgical cancer, thus suggesting that morphine adversely affects cancer progression and relapse. In this study, we evaluated the impact of morphine on breast cancer progression, metastatic dissemination, and outgrowth of minimal residual disease. Using preclinical mouse models for metastatic invasive lobular and HER2+ breast cancer, we show that analgesic doses of morphine do not affect mammary tumor growth, angiogenesis, and the composition of tumor-infiltrating immune cells. Our studies further demonstrate that morphine, administered in the presence or absence of surgery-induced tissue damage, neither facilitates de novo metastatic dissemination nor promotes outgrowth of minimal residual disease after surgery. Together, these findings indicate that opioid analgesics can be used safely for perioperative pain management in patients with cancer and emphasize that current standards of "good clinical practice" should be maintained.

(My notes here): The difference between this study and others (so they say - I have not looked at the other studies) is that they implanted cancer into the mammary glands of the mice rather than inject into the blood stream as other studies have done. They then surgically removed the cancer with or without morphine, and compared cancer progression to animals that did not go through surgery, with and without morphine. In the end, the use of morphine had no negative effect on the outcome but seemed to have positive effect on the number of lung mets for one mouse model (addition of morphine resulted in lower number of mets). They used two mouse cancer cell lines - lobular and Her2+, so that they could also test to see if the outcome was at all influenced by cancer type, which the was not.

In the discussion, they also mention that mice metabolize morphine differently, and the products of metabolism do not have an analgesic effect, whereas in humans, metabolism produces another compound that is also analgesic - meaning that humans need a smaller dose relative to mice to achieve the same effect. In other studies, the investigators were giving mice the same dose (relative to weight) that humans would get, so did not achieve the same level of pain control in their mice. The authors here hypothesize that the higher level of pain experienced by mice in other studies may have contributed to worse outcome for the mice in these other studies (that is, progression of the disease), and not due to the use of morphine per se.

Of course, all these studies on mice may have no relationship to cancer progression in humans. I understand that there are some clinical trials in progress so we may have an answer soon.

I am going to go back and re-read the paper again to be sure I've summarized everything correctly, so this post may be edited. I also ran across a review paper with a table of all the studies that have been done and how they differed. I'll see if I can find it again and post a link here.

here is a link to the journal with the review article I referenced above. It is open source so should be accessible to anyone:

http://www.ncbi.nlm.nih.gov/pubmed/24467261

the title of the paper is "Comparison and analysis of the animal models used to study the effect of morphine on tumour growth and metastasis" on page 251.

Abstract: The effect of opioids on tumour growth and metastasis has been debated for many years, with recent emphasis on the

possibility that they might influence the rate of disease-free survival after tumour resection when used in the perioperative

pain management of cancer surgery patients. The literature presents conflicting and inconclusive in vitro and in vivo data

about the potential effect of opioids, especially morphine, on tumour growth and metastasis. To inform clinical practice,

appropriate animal models are needed to test whether opioids alter the course of tumour growth and metastasis. Here, we

review the literature on animal-based studies testing the effect of morphine on cancer so far, and analyse differences between

the models used that may explain the discrepancies in published results. Such analysis should elucidate the role of opioids in

cancer and help define ideal pre-clinical models to provide definitive answers.

OK, I just fixed the link in the previous post

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