Breast cancer is in the headlines: Angelina Jolie had a double mastectomy when she learned that she carries a gene that puts her at high risk for the disease. We spoke to experts Powel H. Brown and Marisa Weiss to learn more about the genetics of breast cancer.
What made scientists begin looking for a breast cancer gene?
The search started 20 years ago or so and was begun when it was noted that breast cancer can run in families. Some families have a very striking inheritance pattern where somebody's mother had breast cancer and their grandmother had breast cancer and two of their aunts had breast cancer and then another aunt had ovarian cancer—that's the kind of family history that suggests a cancer-causing gene mutation in the family.
This is called a cancer susceptibility syndrome. Another hallmark is having cancer at a very early age. So if you have a family history of a mother who got breast cancer at the age of 42, and a sister who got breast cancer at the age of 38, that's very unusual. In this country most breast cancer occurs on average after the age of 50.
But not every breast cancer is due to a gene?
There are two kinds of breast cancer: the common kind, which is called a sporadic kind, which most people get. It usually occurs over the age of 50. And the strongly inherited kind.
How many cancer-causing genes are there?
There are about 10 genes that can put you at risk for breast cancer. The two most common and famous are the BRCA genes: 1 and 2. They put you at risk for breast and ovarian cancer and for other cancers: BRCA2 carriers are at risk for pancreatic cancer, [and both] 1 and 2 have a slightly higher risk of melanoma.
Are other cancers genetically linked as well?
An inherited p53 gene mutation puts people at risk for breast cancer and also lung cancer, bone cancer, leukemia, and brain tumors. It shows up as extremely young breast cancer at the age of 21 or 23, leukemia and brain tumors and lung cancer in family members. That would point somebody to do genetic testing.
And what percentage of breast cancers are linked to a gene?
It's only about 5 to 10 percent—and probably 3 to 5 percent [are] BRCA1 or 2 associated.
Angelina Jolie had a double mastectomy to reduce her risk. But I understand there is still some risk that remains.
The bilateral mastectomy reduces the risk by 90 percent. Interestingly, it does not reduce the risk by 100 percent. Surgeons can't get every last breast cell. They try to remove everything, but there's a potential that a cell has been left behind. And it can turn into cancer. The other way it's possible [to have cancer after a double mastectomy] is if there is an undetectable breast cancer in the breast tissue that was removed—and it may already have spread.
The same is true for [removing] the ovaries. It reduces risk by 90 percent, not 100 percent. They can get all of the ovary cells, but the lining of the abdomen can turn into cancer and that looks like the same kind of cancer as ovarian cancer. But 90 percent risk reduction is the best we can do, and so many people choose that.
How do you screen for cancer in women who have had a double mastectomy or had ovaries removed?
They don't get screened with imaging tests, they get screened with a physical exam of their chest wall and their lymph glands. For the ovarian risk we use the CA 125 blood test to monitor them.
Even though only a small percentage of women carry the gene, every woman is at risk for breast cancer. Any advice?
Everyone should be aware of their risk and work with their health care professionals to come up with a plan to reduce their risk. For the average-risk person, breast cancer occurs something on the order of one in seven or one in eight women in this country. The average-risk person should have a healthy lifestyle with a healthy diet, low in red meat, high in chicken, fruit, fish, and vegetables. Alcohol also puts you at risk: As little as three glasses per week increases your risk of breast cancer.
Do we know how alcohol increases risk?
Alcohol clearly is a carcinogen. [Its connection] is much more clear with esophageal cancer. With breast cancer, I don't think we know.
Marisa Weiss is a breast cancer oncologist and founder and director of breastcancer.org. She is the author of Living Beyond Breast Cancer and Living Well Beyond Breast Cancer, co-authored with her mother, Ellen Weiss; Taking Care of Your "Girls": A Breast Health Guide for Girls, Teens, and In-Betweens, co-authored with her daughter, Isabel Friedman (2008); and 7 Minutes!: How to Get the Most From Your Doctor Visit (2007).
How are people responding to the news that Angelina Jolie was at risk for breast cancer?
I think it really shocked people. I think people expect that someone who looks so sexual and beautiful and young and fancy and with so much celebrity is immune or has some free pass.
It's also shocking to think she had a double mastectomy and reconstruction.
It's disturbing to think she had to go through this surgery. But saying she feels just as good, just as feminine, is encouraging to women. The fact is that reconstruction has come so far that a lot of women have an excellent result. They feel whole again. She's saying this gene abnormality is not going to define her. That's all positive.
How does a woman know if she is at risk for carrying one of the breast cancer genes?
[The risk is] based on personal and family history of breast and other related cancers. It depends on the pattern of the story that family history tells.
Does insurance cover genetic testing?
Usually you come in and give your family history [to a genetic counselor], which means the history of cancer on both mother's and father's side and age of diagnosis. If the family history sounds like there are multiple affected relatives at a young age or more than one cancer, that means higher risk. If there's a male with breast cancer in the family, that goes along with higher risk.
If your family history adds up like that, starts smelling like an inherited pattern, then you would qualify for genetic testing and the insurance company is likely to pay for it. But if the genetic counselor tells you it's a low risk, the counselor is not going to recommend testing.
Angelina Jolie had the BRCA1 gene.
Women with BRCA1 gene are more likely to have triple-negative breast cancer, which is a harder cancer to treat. If you're looking at an up to 87 percent risk, a mastectomy is not so radical. It makes a lot of sense. If you had a BRCA2 type of gene, you're more likely to have a hormone-receptor-positive breast cancer, a more treatable kind of malignancy. Not all those women choose mastectomy.
How do patients make the decision about treatment once they know they have a gene that puts them at risk?
It happens in steps. Genetic counseling takes time. And so people get used to the information over time, consider pros and cons of each option, and the genetic counselor and doctor will talk about a combination of strategies to lower risk.
Would a mastectomy to prevent cancer ever be appropriate if there isn't a genetic risk?
What I do is I always evaluate an individual person's risk. Sometimes there's a strong family history and no clear genetic abnormality. In that case, family history trumps genetics. What I mean by that is if you're looking at a family with a lot of cancer in it, and you can't find a gene to explain all the cancer, it may just be because you don't know the name of the gene and can't test for it. But something's going on.
And what do people then do if they are at risk by family history or genetics?
Some women come to you and say, "I'm a watch-and-wait kind of girl. I'm confident you'll have new discoveries sooner [rather] than later. I don't need to sacrifice my breasts right now. I'm prepared to be followed very carefully over time. I'll make changes in my life [to reduce risk]: diet, exercise, reproductive choices." But somebody else might say, "I'm a mother with young kids. I've got to be around for the long run. I am prepared to move ahead with any option likely to maximize my chances of never seeing cancer."
Could the women already have cancer and not know it?
For women who find out they have the breast cancer gene and who have what they believe to be a prophylactic mastectomy, about 10 to 15 percent of the time they find cancer in [the breast tissue] they didn't expect.
Editor's Note: Marc Silver is the author of Breast Cancer Husband: How to Help Your Wife (And Yourself) Through Diagnosis, Treatment, and Beyond and co-author of the new book My Parent Has Cancer and It Really Sucks: Real-Life Advice from Real-LIfe Teens.