Angelina no longer has them. Does that mean I should get rid of them too?

We love them and yet we hate them. They get censored, augmented, reduced, replaced, covered, exposed. They get grilled, occasionally, but those are not the ones I'm talking about. We want to see them and yet we pretend we don't. We criticize them and yet we forget what they are made for, the most beautiful thing of all: nourish a new life.

Yes, I'm talking about breasts.

Angelina Jolie's breasts have been extensively discussed this week, more now that they are reportedly gone than when they were around. Sort of ironic, if you thin about it. Angelina did the unthinkable: she had both her healthy breasts removed to prevent cancer. In a second phase of her preventive plan, she will have her ovaries removed, too. The tabloids will no longer be able to speculate on her possible new pregnancies, but they will have plenty to discuss on and around her missing body parts.

Somehow the news left me a little puzzled, unable to share the views of those who praised Angelina for her bravery. Yes, it takes guts to do what she did. At the same time, the huge resonance she's been given seems blown out of proportion. Just another Hollywood thing. It reminds me of back when our mothers were told that formula was way better than breast milk. Are we facing a new era where silicon is better than milk ducts? Are they trying to convince us that fake is healthier than real? Well, of course it is. It's fake!

So, before we go around demonizing breasts and invoking chopping off body parts in the name of longevity, I wanted to get some facts straight.

First of all, I read over and over again, "Angelina Jolie carries the gene BRCA1 ..." Turns out, we all carry the gene. What makes us different is that there are distinct copies of this gene across individuals, and some copies (but not all) do raise the risk of breast and ovarian cancer.

BRCA1 and BRCA2 are part of the so called tumor suppressor genes, genes that code for proteins that are in charge of repairing damaged DNA. Our cells undergo numerous cellular divisions during our lifespan, and every cell division carries a certain chance of damaging the DNA. Though rare, mutations can be introduced, which can either be lethal or create a cancerous cell. Tumor suppressor proteins make a first attempt to repair the damaged DNA. If the DNA cannot be repaired, they promote apoptosis, or cell death. Another example of tumor suppressor gene is TP53, which encodes the protein p53.

The first link between BRCA1 and breast cancer was discovered in 1990 by Hall et al. [1]. BRCA1 and BRCA2 are expressed mostly in breast tissue. Some mutations in these genes cause them to code proteins that are not fully functional. When this happens, a cell with damaged DNA has a higher chance to escape the "screening" and start dividing instead of undergoing apoptosis. Because BRCA1 and BRCA2 are expressed mostly in the breast tissue, by removing the breast tissue one gets rid of the majority of cells expressing the defective genes, which in turns significantly lowers the chance of developing breast cancer.

While hundreds of mutations/variations in the BRCA1 and BRCA2 genes have been found, not all are linked to breast cancer, and the ones that are don't increase the risk in the same amount. Furthermore, the majority of breast cancers are not linked to mutations in these two genes. In other words, having the mutations raises the risk, but not having them does not lower it.

So, let's get some numbers straight. According to the American Cancer Society about 15% of women diagnosed with breast cancer have a family member diagnosed with it. That leaves the majority of breast cancers unrelated to family history:

"About 85% of breast cancers occur in women who have no family history of breast cancer. These occur due to genetic mutations that happen as a result of the aging process and life in general, rather than inherited mutations."

It's a puzzle I've discussed before, the missing herediatbility. On the one hand we know genes play a large role in cancer and we spend all this research money into looking for genetic causes. Yet, the vast majority of cancers are non-hereditary.

While women with certain mutations in either the BRCA1 or BRCA2 genes have up to 80% (the exact chance varies depending on the type of mutation they carry) increased risk of developing breast cancer, only between 5% and 10% of breast cancers are linked to deleterious mutations in the BRCA1 or BRCA2 genes. So, yes, get tested. But chances are, your copy of BRCA1 and BRCA2 are fine.

So, what makes BRCA1 and bRCA2 so scary?

The American Cancer Society reports that approximately 60% of women with one of the harmful mutations in BRCA1 or BRCA2 develop breast cancer during their lifetime, versus the 12% of women in the general population. Remember, though: these genes are not the only ones playing a role in cancer. Things like epistasis with other loci in the genome can deeply affect such risks and, unfortunately, we still don't know enough to quantify them. High levels of IGF-1, the insulin-like growth factor have also been linked to breast cancer. So while having those mutations raises the risk, it does not mean that the individual will develop breast cancer for sure as other factors are still unknown. Careful considerations should be made before making a drastic choice like Angelina's. These considerations should also include risks associated to a double mastectomy (infection, necrosis, etc.) and reconstruction surgery, neither one free of complications. I'm somehow reluctant to consider implants healthier than normal breasts, whether or not those breasts were expressing faulty genes.

What about those 85% of breast cancers that are not linked to BRCA1 or BRCA2 mutations? Can we do anything to prevent those?

When you look at the global population, the most common risk factors for breast cancer are not the mutations in BRCA1 and BRCA2, rather, as Bernstein reports in a 2009 review [2]:

"The most consistently acknowledged risk factors for breast cancer other than gender and race/ethnicity are age, family history of breast cancer, early menarche, late age at first birth, nulliparity, late age at menopause, high postmenopausal weight or substantial weight gain as an adult, exposure to high levels of ionizing radiation and a history of benign proliferative breast disease [2]."

All these risk factors point at one common etiology, ovarian hormones (estradiol and progesterone), because they

"promote cellular proliferation in the breast, providing greater opportunity for the accumulation of random errors, which may lead to tumor development [2]."

Body weight and exercise can be linked to different levels of estradiol in the blood (high body weight is associated with higher levels, exercise is associated with lower levels), hence their correlation to breast cancer risk. Some studies found up to 40% reduction in risk in women who exercised in particular in their adolescence. Of all risk factors, these two, body weight and exercise, are the ones we can actually take control over and actively lower our risk of developing breast cancer. A diet rich in antioxidants may lower the risk of DNA damage during cellular division.

Things we have less control over is the woman's age at the first pregnancy. One of my grad school professors used to say, "Having a baby as a teen may ruin your life, but it sure lowers your risk of developing breast cancer later in life." The risk keeps lowering for every additional pregnancy, though not as significantly as with the first one.

What's not clear is the extent to which breastfeeding can lower the risk of breast cancer, as the American Cancer Society reports:

"Research suggests that breastfeeding has only a slight effect on breast cancer risk and that effect is only among women who have breastfed for a long time. They also concluded that breastfeeding seems to be more protective against the most aggressive types of breast cancer, including tumors in women with mutations in the BRCA1 gene, basal-like cancers, hormone-receptor negative, and possibly triple negative tumors."

And while we do the things that we can to lower our risks, I am hopeful that one day gene therapy will be perfected to the point that it will offer a better options than what, in gross terms, amounts to amputation.

Thoughts?

[1] Hall, J., Lee, M., Newman, B., Morrow, J., Anderson, L., Huey, B., & King, M. (1990). Linkage of early-onset familial breast cancer to chromosome 17q21 Science, 250 (4988), 1684-1689 DOI: 10.1126/science.2270482

[2] Bernstein, L. (2008). Identifying population-based approaches to lower breast cancer risk Oncogene, 27 DOI: 10.1038/onc.2009.348