Dr. Amy Nett: I think she’s talking about the BRCA1 and BRCA2 mutations, and there are some recommendations for prophylactic bilateral mastectomy and sometimes prophylactic total abdominal hysterectomy or at least salpingo-oophorectomy.
In terms of talking about genetics and epigenetics, it’s absolutely true that genetics do have an influence on breast and ovarian cancer in particular. The BRCA1 and BRCA2 genes that she’s talking about, those are both human genes that produce tumor suppressor proteins, and we know that the proteins produced from these genes help to repair damaged DNA, so they help to sort of ensure that stability of the genetic material. We know that there are certain mutations in the BRCA1 and BRCA2 mutations that may predispose women to breast and/or ovarian cancer. When you look at breast and ovarian cancer in the general population, we know that breast cancer is probably somewhere about 12 percent in the general population, but in women with certain BRCA1 mutations, it’s about 55 to 65 percent, and with certain BRCA2 mutations, probably 45 percent. Ovarian cancer overall in the general population probably affects about 1.3 percent of women, but you increase that risk up to about 39 percent and 11 percent in women with the BRCA1 and 2 mutations, respectively.
These are population data. Cancer risk in each woman, despite these genes, is also known to be affected by family history of other cancers, the specific mutations inherited, reproductive history, including age of onset at menarche and menopause, oral contraceptives, smoking, alcohol intake—all of these things, the exposome that we talk about, so it’s really difficult to provide individualized predictions about cancer risk, meaning I can provide a patient with the information about the 55 percent likelihood of breast cancer with a BRCA1 mutation, but that doesn’t take into account what her diet looks like, if she smokes, what her alcohol consumption looks like. That’s why it’s difficult to provide the individualized risk and know what a single person’s risk is for developing breast cancer or ovarian cancer.
Based on the current evidence, I’m generally reluctant to advise prophylactic surgery. I might suggest that women think about more aggressive screening. Right now there’s some controversy about the role of mammograms, but breast MRI is potentially useful in women who do have these BRCA1 and BRCA2 mutations and is generally covered by insurance when those mutations are known, so I would consider an annual breast MRI for women with BRCA1/BRCA2 mutations, but I’m, again, reluctant to advise surgery. It’s a very personal decision. Some women do feel strongly about it, in which case I would be supportive. It’s certainly their body, their choice, but I’m not sure that the evidence is there to entirely support that.