Friday, 24 January 2014

Does removing breast cancer affect survival?

Allow me to make an assertion: breast cancer survival is not influenced by surgical excision of the primary tumour. This goes against the prevailing wisdom that cancer is cured by removing it, but that kind of thinking is simplistic and at odds with much of the evidence. Lets walk through that evidence.

There is a theory that breast cancer is a systemic, rather than a local disease, and that local control (by surgery) does not influence the course of the disease regarding its ability to cause death. The common thinking about breast cancer is that it starts in the breast and spreads such that if you remove it early, and completely, you can be cured. This is the basis of breast cancer screening, but as I have discussed before, there is debate about whether screening reduces one’s risk of dying.

Note that I am referring to overall or all cause mortality, rather than disease-specific mortality. For more on the important difference between these, see my blog on how you die versus if you die.

The counter argument to the prevailing wisdom is that breast cancer comes in different grades: low grade cancers that are unlikely to se death (with or without surgery) and high grade cancers are likely to have spread before they are even diagnosed, and are likely to cause death with or without surgery.

If survival after breast cancer is influenced by local excision (surgery), then the following statements should be true:

1. “The wider the margin, the better the cure rate”
We already know the folly of the "more-is-better" radical mastectomy (see my previous post). These days, the arguments are about much smaller ‘margins’ (how close to the tumour is to the surface of the excised lump) and usually refer to local recurrence, where the prevailing wisdom is that wider margins make local recurrence less likely. Avoiding local recurrence is desirable, but it is a different thing to all-cause mortality (overall survival). But even if you are talking about local recurrence, it appears that margins of 10mm, 5mm, 3, 2, and even down to 1mm all have similar recurrence rates (discussion here). Regarding excision of the associated (axillary) lymph nodes, overall survival is not improved by excising the lymph nodes when they are not involved (no cancer found in them). Other studies (here and here) show that even when patients have cancer in the lymph nodes, excising the axillary lymph nodes does not improve overall survival (but it does result in more complications). Interestingly, in both these studies the survival was a little better in patients who did not have the cancerous lymph nodes excised. Therefore, the statement above cannot be supported.

2. “Incomplete excision will adversely affect survival”
Similar to the case with cancerous lymph nodes, having a complete excision of the tumour or leaving some behind makes no difference to the overall survival (here, here, and here). And although the measurement of margins is not all that exact, it does appear that they are an accurate measure of the amount of tumour left behind (here). Therefore, the statement above cannot be supported.

3. “Other forms of local control will influence survival”
Twenty-year follow up of lumpectomy alone versus lumpectomy with radiotherapy showed no difference in overall survival (here). In fact, having radiotherapy did lower the chance of dying from breast cancer, but this was offset by a corresponding increase in the chance of dying from other causes. This review from 2003 noted that: “There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival.” And this Cochrane review of radiotherapy for low grade breast cancer (DCIS) showed no difference in overall survival with radiotherapy. Again, the statement cannot be supported.

4. “Non-operative treatment will have a higher mortality rate than surgical excision”
Unfortunately, there is no randomised comparative study to report, but there are some interesting studies out there, like this one, that estimated that most breast cancers, including invasive cancers, would regress if left alone.
In older patients (over 74), non-operative treatment has been tried, and most patients die with their breast cancer than of their breast cancer (here).
This study looked at patients that refused surgery for their breast cancer. 41% were still alive after 5 years, compared to 61% in a similar group who had surgery. The two groups being compared, however, were not otherwise equal. For example, patients who refused surgery, had almost no other treatment (apart from Tamoxifen), whereas at least half of the “similar group” who had surgery, also had other treatments such as radiotherapy and chemotherapy. Also, most people who refused surgery did so because they thought they were too sick to withstand the surgery or because of other health problems, so I could make an argument that the background mortality for this group would be higher than the “similar group” who thought they were well enough for surgery. There may be other factors in this non-randomised study that explain the (surprisingly small) difference in survival; people who refuse surgery might do other things that are not good for their health (like not taking their heart pills, for example). The figure below is taken from this study. It does not convince me that surgery was responsible for the difference between the two lines on the graph.



The bottom line

The argument for overall survival being influenced by local (surgical) excision of breast cancer is not strongly supported. For most of the comparisons provided above, although there was no difference in overall survival between the treatment groups, those with more local treatment (like having complete margins or adding radiotherapy) had less local recurrence. This means that local treatment, like surgery, does something (it provides local control), but that “something may not extend to reducing the risk of death.

8 comments:

  1. Hi Dr Skepitc
    Interesting and brave assessment. No doubts your research will cause alot of controversy if seen by a bigger audience. Thanks for the insight.
    Warm Regards
    Dr Post

    ReplyDelete
    Replies
    1. "if seen by a bigger audience"? I am offended. This has been picked up widely in the Twitterverse and had strong numbers here on the blog.

      I had the same thought, but interestingly no one with a counter-argument so far.

      Delete
  2. What is strongly supported by good scientific data is that "local (surgical) excision of breast cancer" increases total mortality, primarily because the invasive intervention leads to a significantly increased risk of secondary cancers, many of which are metastatic (discussed in "The Mammogram Myth" by Rolf Hefti). Local treatment does something very specific: more damage.

    ReplyDelete
    Replies
    1. Thanks. I am aware of the theory that surgical handling of the tumour amy increase the risk of metastasis, and of the theory that removing the primary tumour reduces the drive on the body's immunity to fight the cancer, therefore increasing cancer growth elsewhere. But like alternative theories that support tumour removal, they require supporting evidence that tumour removal causes harm (beyond the direct harm of the surgery).
      As many readers know, I am less concerned with biological explanations, and more concerned with clinical evidence to support or refute hypotheses. My question is simply: does removing the primary tumour lead to a reduction in the risk of dying over the following 5 - 10 years? You argue that removing the tumour may increase that risk, but I am not aware of any evidence that supports that contention, just as I am not convinced by the evidence that it reduces the risk.

      Delete
  3. Mechanical view dominates the thinking of patients and, unfortunately, most doctors, and the idea of meaningful outcome is difficult to get across to both. Once, when I questioned the value of coronary stents a colleague of mine exclaimed: "So what, if you get an MI you're going to refuse a stent?" When I said that probably yes, as there is no evidence a stent would make me live longer he turned to other doctors in the tea room and declared that I am mad. The rest of the room seemed to agree with him.

    The question of benefits of removing small breast cancer once came up in a conversation with another friend of mine, a GP. Her argument for removal was that "it is a bad thing that should not be there, so it should be removed". Emotional response is stronger than thinking in probabilities.

    Good article. I hope to see more of our colleagues thinking critically.

    ReplyDelete
    Replies
    1. Thanks for your support and I agree with you. You are highlighting the fact that it is easier just to go along with things than to question them, and the simplistic thinking about cancers. This is why it is hard to treat prostate cancer non-operatively. It is hard to sleep knowing the cancer is inside you; as you say, emotion trumps logic every time.

      Delete


  4. My name is Mrs Marian am from Philippine.I have been suffering hardship from Breast Cancer since 7yrs now, and i happen to have 2 kids for my husband, and now we cannot proceed to have another kids all because of my disease and now i have do all what a human like i and my husband can do just to get my disease healed, i have went to several places to seek for help not even one person could ever help, until i melt a comment on the daily news paper that was commented by Desmond about how this powerful traditional doctor help him get cured of the disease (Breast Cancer) " my fellow beloved" i firstly taught having a help from a spiritual traditional healer was a wrong idea, but i think of these, will i continue to stress on these disease all day when i have someone to help me save my life?" so i gather all my faiths and put in all interest to contact him through his Email address at drehohospiritualtemple@gmail.com , so after i have mailed him of helping get my disease cured, he respond to me fast as possible that i should not be afraid, that he is a truthful and powerful doctor which i firstly claimed him to be. So after all set has been done, he promise me that i will be healed but on a condition that i provide him some items and obeyed all his oracle said. I did all by accepting his oracles fact and only to see that after some weeks of taking his herbal medicine i notice some changes in my body system and i went for check up the day he ask me to go for check up to confirm if the sickness was still there,to my greatest surprise i could not find any sickness in my body i was first shocked and later arise to be the happiest woman on earth after i have concluded my final test on the hospital by my doctor that i am now Breast Cancer- Negative. My papers for check are with me and now i am happy and glad for his miraculous help and power.With these i must tell everyone who might seek for any help, either for Breast Cancer cure or much more to contact him now at these following email now,Email: drehohospiritualtemple@gmail.com or call +2347058747764" sir thank you so much for your immediate cure of my disease, i must say a big thanks for curing my disease, i owe you in return. Thanks and be blessed sir.
    Mrs Marian

    ReplyDelete
    Replies
    1. I did not mark this comment as spam in order to make a point, but first I need to make another point.
      Firstly, I advise against contacting this, or any other traditional doctor about this, or any other condition.
      My main point is that I spend a lot of time looking for biases and flaws in the scientific support of traditional medicine, and this may create an impression that medicine, or the science behind it, is fundamentally flawed - that it is wrong. This is not the case.
      I fully support the scientific method, and medicine's foundation in science. It is the proper use of the scientific method that has guided improvements in treatments over time - it has told us what works and what doesn't.
      My argument is not against science, it is for a more rigorous use of science. Sloppy methods, and the inability of readers to properly appraise those methods is the problem, and my contention is that this 'problem' produces a biased assessment that overestimates the net benefit of modern medicine.

      Delete