The puzzle of breast cancer


Next to heart disease, cancers are the leading cause of death in the US. But Richard Stevens writes that unlike with most other cancers where the major causes are known, identifying what primarily causes breast cancer remains stubbornly elusive.

For most of the common cancers, a major cause has been identified: smoking causes 90% of lung cancer worldwide, hepatitis viruses cause most liver cancer, H pylori bacteria causes stomach cancer, Human papillomavirus causes almost all cases of cervical cancer, colon cancer is largely explained by physical activity, diet and family history.

But for breast cancer, there is no smoking gun. It is almost unique among the common cancers of the world in that there is not a known major cause; there is no consensus among experts that proof of a major cause has been identified.

One of the problems has been that the geographical pattern has been changing rapidly. Women in North America and Northern Europe used to have five times the risk of women in Asia and Africa but rates in the latter continents have been rising rapidly. Also, the children of Asian immigrants to the US have elevated risk rates, comparable to those who were the descendants of people who had been here for many generations, suggesting that genetic factors may not be that significant.

It used to be thought that diet, especially the amount of fat intake, may be a significant cause but the evidence for that has weakened, and now there seems to be no correlation at all, so the search has shifted to possible other causes.

The factors shown to affect a woman’s risk for developing breast cancer fall into two categories. First, those that cannot be easily modified: age at menarche, age at birth of first child, family history, genes like BRCA1. And second, those that are modifiable: exercise, body weight, alcohol intake, night-work jobs.

The role of environmental pollution is controversial and also difficult to study. The concern about chemicals, particularly endocrine disruptors, started after the realization that such chemicals could affect cancer risk in rodent models. But in human studies the evidence is mixed.

Researchers are also looking at the effect of electric light, that disrupting circadian rhythms may upset the production of hormones that influence breast cancer. There is some evidence for this hypothesis but not overwhelming.

The worst possible outcome may be that breast cancer is caused by the influence of many independent factors, the contribution of each being so small as to be not only difficult to tease out but also difficult to target to combat.

Comments

  1. DonDueed says

    I wonder whether the number of pregnancies could be involved. That number would have fallen some time ago in the developed world, and is falling now in the developing world, which seems like a fair fit to the pattern of incidence.

  2. says

    There is a wonderful book “The Emperor of All Maladies: A Biography of Cancer” by Siddhartha Mukherjee. It earned a Pulitzer (I hesitate to say that, after all the kerfluffle surrounding the Hugos) I highly recommend it. It’s fascinating.

  3. Heidi Nemeth says

    Breast-feeding for 6 years brings a woman’s risk for breast cancer down to a negligible likelihood. Unfortunately, the modern Westernized world discourages exclusive breast-feeding for the first 6 months, which makes continued breast feeding difficult. Perhaps low breast-feeding rates, short duration of breast feeding, and few births per woman are one reason why breast cancer is on the rise.

  4. tbrandt says

    Didn’t this paper recently show that most cancers can be explained by stochastic replication errors in stem cell division? I’m not sure that the search for causes for all of these things will turn up anything. We have stochastic errors in replication, damage from cosmic rays and other natural radiation, and other things we can’t do anything about. Environmental factors generally don’t seem that important for cancer. Sure, there are a few, like smoking and a few others like asbestos and a handful of infectious diseases, but the evidence is that most cancers are not explained by this.

    As for breast cancer and breastfeeding, the studies are not so clear-cut as Heidi (at 3) implies. The major study, according to the cancer society, gives a 4% risk reduction per year of breastfeeding. Extrapolating this to six years (a very dicey proposition), you would get a 1-0.96^6 = 22% risk reduction. I would add that this is one study and that the 4% number comes with an error bar.

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