Risk Modification Strategies for Breast Cancer

Ann H. Partridge, MD, MPH

Ahead of the 2014 American Society of Clinical Oncology (ASCO) Breast Cancer Symposium, held September 4–6 in San Francisco, we spoke with Ann H. Partridge, MD, MPH, an associate professor at Harvard Medical School, the founder and director of the Program for Young Women With Breast Cancer, and the director of the Adult Survivorship Program at the Dana-Farber Cancer Center in Boston. Dr. Partridge will be speaking at the upcoming symposium on non-medicinal approaches to breast cancer risk modifications.

  -Interviewed by Anna Azvolinsky  

Cancer Network: Let’s start with the factors that make some women more susceptible to breast cancer. First, what are the genetic factors that increase the risk of breast cancer?

Dr. Partridge: There are a number of genetic factors that increase the risk of a patient getting breast cancer-both women and men can get breast cancer, although it is much more rare in men. The most common, yet still rare, genetic predispositions that we know about are individuals who carry a BRCA1 or BRCA2 mutation. These are responsible for about 5% to 10% of all breast cancers.

There are even more uncommon mutations that occur in families that can be passed on from generation to generation that are also associated with an increased risk of breast cancer. These include a mutation in the p53 gene (otherwise known as Li Fraumeni syndrome), where people are not only at risk for breast cancer but numerous other cancers, and there are many other uncommon family syndromes such as Cowden syndrome (which is a change in a gene called p10), as well as ataxia telangiectasia. There are a number more but these are some of the most well-known.

Cancer Network: What are some of the environmental factors that are known to increase the risk of breast cancer?

Dr. Partridge: Environmental factors have been studied extensively. And as you can imagine, it can be very difficult to study the environment of any given individual, because people move around, and they are exposed at different times in their lives to different things.

There was just a report published by the Institute of Medicine that focused on this and recommended, as we study this in the future, a life-course approach, in terms of viewing exposures in the environment. And so far, the major exposures that are clear in our external environment are things like exposure to ionizing radiation, which in general we try to avoid unless the benefits outweigh the risks. These include therapeutic radiation, but of course one needs therapeutic radiation for certain diseases to improve their outcomes. There are also exposures in the environment. The most egregious examples is the atomic bomb explosions in the 1940s. And then there are other environmental exposures that our governments and our society have to try to help us limit.

There are also certain chemicals that have been shown pretty clearly [to increase risk], at least with biologic plausibility, as well as with animal data-its harder to show cause and effect within individual human beings. These include things that we can be exposed to in the environment, chemicals through pollution or through workplace exposure. So we try to limit those so they don’t affect the risk of breast cancer.

The greatest “environmental exposure” that most people face are the exposure of lifetime reproductive factors, and these are sometimes modifiable and sometimes not. These include things like when you had your first child, whether or not a person took hormonal replacement therapy for menopausal symptoms, as well as factors related to when you had your first period. Again, some of these things are modifiable and some certainly are not. But that is our evolution of thinking with regard to environmental exposures, both external exposures like radiation and certain toxic chemicals, as well as more internal or personal choice or life experience exposures with regard to the reproductive and menstrual factors for women.

Cancer Network: Aside from a mastectomy for those women who carry a genetic risk of breast cancer, what are some of the clinical interventions that have been shown to mitigate the risk of breast cancer?

Dr. Partridge: There are a number of things that have been clearly shown to reduce breast cancer risk. As you alluded to, there are prophylactic surgeries that can be done such as a bilateral mastectomy for women who are at high risk. And removal of the ovaries can cut the risk nearly in half for women who keep their breasts and who have a clear predisposition and are therefore at high risk.

Short of the surgical interventions, there are medications that can be used for all patients and are likely to be effective in women of high risk, although they are not as well tested in these women-the women who have a genetic mutation. These medications are tested in women who are at high risk with regard to more standard risk factors like age and prior benign breast biopsies, etc. So these medicines that can be used include tamoxifen, which clearly reduces the risk of getting a new primary breast cancer, and a drug called raloxifene, which is related to tamoxifen but doesn’t have some of the more risky side effects such as risk of cancer of the uterus. Raloxifene may not be quite as effective as tamoxifen, but it does reduce the risk of breast cancer. Aromatase inhibitors have also been shown to reduce the primary risk of breast cancer. Those are the drugs that unlike tamoxifen-which blocks estrogen where it works-lower estrogen in postmenopausal women, and they have been shown to reduce the risk of developing breast cancer in women at risk. These are the primary medicinal options that are available.

Then of course, one can modify the environment, including internal and external, to reduce breast cancer risk, and this is where a number of us focus these days for those at risk. This includes the environment in terms of avoiding exposures that we just discussed, but also entails avoiding weight gain after the age of 18 and avoiding more than just moderate alcohol intake, because both of these things have been associated with increased risk of breast cancer. Avoiding exogenous hormones or extra hormones or hormonal replacement therapy, because that is associated with increased risk of breast cancer.

And the other big thing beyond weight gain is exercise. Exercise has been associated with a decreased risk of breast cancer over and over again. So a prudent lifestyle-exercise, eating in moderation, alcohol in moderation, having what we refer to as energy balance where input equals output (if you are of healthy weight) have all been associated with doing better from a breast cancer risk standpoint, and these are things that are at an individual’s control and therefore we should be able to make some headway in terms of breast cancer prevention in our society. So that is where we focus a lot these days.

Cancer Network: The clinical interventions that you mentioned, are those specific for hormone receptor–positive disease or have these also been shown to mitigate the risk for the other breast cancer subtypes?

Dr. Partridge: That’s a good point. So in terms of the clinical interventions with medicines, they typically only reduce the risk of hormone receptor–positive breast cancer. Interestingly, in gene carriers who have a BRCA1 or BRCA2 mutation, removal of the ovaries, even though this is a hormone manipulation, reduces the risk dramatically in women who have a BRCA1 or BRCA2 mutation, and women with a BRCA1 mutation are much more likely to get hormone receptor–negative breast cancer, and so it’s interesting that removal of the ovaries reduces this risk as well. So the hormone story is not as clear cut as one might think it is in terms of how changing the hormonal milieu effects risk of either estrogen receptor–positive or estrogen receptor–negative breast cancer. In general, reducing the risk of hormone receptor–positive breast cancer may also reduce the risk of hormone receptor–negative breast cancer. Although this is not clear cut, this is one example where this is the case, even though the intervention is hormonal manipulation.

Cancer Network: Lastly, do you see clinicians embracing the non-medical recommendations that you mentioned that are risk modifying, are clinicians trying to persuade patients to exercise more, for example. Are these becoming more prominent compared with the clinical interventions?

Dr. Partridge I think more and more people are realizing this, and especially in the United States, where people are increasingly becoming overweight and obesity is more prevalent. I think we are increasingly recognizing that that is associated with a lot of different comorbidities, including increasing the risk of certain tumors, such as breast cancer and colon cancer and prostate cancer. I think more and more healthcare providers who are on the frontlines, especially primary care doctors, are becoming more aware, and counseling our patients is becoming more of our systems-based approach to reduce risk across the board and for specific individuals. But it’s a challenge because these things are modifiable, but changing habits and starting an exercise plan or getting people to lose weight, as we all know, can be quite challenging. There are lots of potential opportunities for risk reduction for breast cancer in particular, but it’s not an easy thing to do. It’s not as easy as taking a pill, let’s say.

Cancer Network: Thank you so much for joining us today Dr. Partridge and enjoy the symposium!

Dr. Partridge: Thank you!