Hormone Replacement Therapy, Breast Cancer and Causality

It seems a remarkable "coincidence" that they very day after writing about breast cancer screening, we should hear the news about a sudden fall in the rates of breast cancer amongst a certain proportion of the population.

Researchers from the M.D. Anderson Cancer center in Houston presented their data at a meeting of the San Antonio Breast Cancer Symposium. They recorded a 7% drop in new breast cancer cases in the US in 2003, ad an even bigger fall – 12% – in cases of hormone-dependent breast cancer among women aged 50-69. This is the first time that breast can cancer rates have fallen since 1945.

The decrease was most striking for women with so-called estrogen-positive tumors, which account for 70% of all breast cancers. It is the growth of these tumors that may be fueled by estrogen.

The scientists believe that the fall could be linked to the fact that millions of women gave up hormone replacement therapy (HRT) following reports questioning its safety. Around 14,000 fewer US women were diagnosed with breast cancer in 2003, compared with the previous year. The number of American women on HRT had halved by the end of 2002 in the wake of a large study was halted in 2002 after evidence emerged indicating that the therapy was associated with an increased risk of developing breast cancer.

The data are striking, but they need to be confirmed. That being said, there was a different type of study in last month’s issue of the Journal of Clinical Oncology. Researchers found an even larger drop in breast cancers in some parts of the State of California where there had been some of the highest rates of HRT use in the nation.

If the figures are correct – and they will have to confirmed – they could be explained by existing tumors stopping growing, shrinking or disappearing so that they could not be detected.

When I was a full time endocrinologist I saw a great many women who suffered terribly with menopausal symptoms, but I always declined to use HRT because of my take on the research data. I used dozens of alternatives, and if they failed, I had plenty of colleagues who were happy to use HRT, but I was always uneasy about using it.

There is also another important point: epidemiology can never prove causality. We have a plausible link, but no direct proof that a fall in the use of HRT is responsible for the fall in breast cancer.

Let me give you another example. Few people doubt the link between cigarette smoking and lung cancer, but no causality has ever been proven. Typhoid can cause a horrible illness, but all that the epidemiologist can do is to suggest an association between the bug and the pattern of an outbreak. It requires a microbiologist to prove that the bacterium Salmonella Typhi is the cause of the symptoms.

A number of years ago I became involved with the Oxford Causality project. It was fascinating, because not only did we call into question the issue of uni-causality in medicine – one cause for one illness – but some scientists and philosophers – such as Roy Bhaskar and Rom Harre even went so far as to suggest that “laws” of nature are better thought of as “habits” of nature. Clearly there are laws and there is causality. I throw a stone into a pond and there should be a plopping noise and then the ripples spread out. If there were no laws, then atoms could disintegrate. But at the deepest levels of nature, it no longer appears that we live in a clockwork universe in which free will is an illusion.

This is not just of theoretical importance, I recently received some interesting correspondence after I mad some comments about how self-cutting, if ignored, could lead to the development of borderline personality disorder. One correspondent thought that this implied causality, but I do not think so. “Disorders” are best viewed as deviations from a norm and they usually appear in bits and pieces. For example, some people with bipolar disorder may have had problems years before the illness had declared itself. The first signs were there, but they could have evolved along a dozen different pathways. Some people with borderline personality disorder have had varying degrees of distress since childhood, but back then it was impossible to say for sure what was wrong.

It is usually a mistake to try to find one cause for a problem. It is equally a mistake to try and diagnose a problem prematurely. We sometimes need to wait and see how things will evolve.