PALB2 Mutation: A "New" Gene That Greatly Increases Breast Cancer Risk

Photo: Flickr/Micahb37

by Sarah Cortez

There’s been a recent surge in women asking for genetic testing for breast cancer, due in large part to Angelina Jolie’s public decision last year to get a prophylactic mastectomy after discovering she had a mutation in the BRCA1 gene. These days, another breast cancer gene has been making headlines, a gene called PALB2.

Mutations in BRCA1, and its related gene, BRCA2, are the two most important known genetic links to breast cancer risk. Well, new findings on PALB2 have some describing it as the “third gene” to be linked with breast cancer.

Previous studies have found that mutations in PALB2 combined with mutations in the BRCA genes increased the risk of breast cancer. PALB2 is even short for Partner and Localizer of BRCA2. What we didn’t know was how much the risk of breast cancer increased with a PALB2 mutation alone – that is without a related BRCA mutation.

In August, the New England Journal of Medicine published a study that characterized patients with only a PALB2 mutation. To do this, researchers identified patients who did not have a BRCA1/2 mutation but who had a history of breast cancer in at least one family member. These patients were then tested for the PALB2 mutation.

So, what did they find?

The results showed that a PALB2 mutation by itself increased the risk of breast cancer 9.5 times compared to the general population. They also showed that, for those with a mutation in PALB2, the risk of developing breast cancer by age 70 was about 33%, as compared to a 12% lifetime risk in the general population. Furthermore, for those with a PALB2 mutation who also had two first-degree relatives (like your mom and your sister) with breast cancer, the risk of developing breast cancer by age 70 increased to more than 50%. For comparison, a BRCA1 mutation increases your risk of developing breast cancer, by age 70, to 55-65%. So BRCA mutations are still considered more risky.

So what does all this new information mean to you?

Just like with the BRCA genes, it would only be recommended that you get screened for PALB2 mutation if you have a strong history of breast or ovarian cancer in your family, such as:

• Breast cancer in more than one family member

• Breast cancer diagnosed before the age of 50

• Breast cancer diagnosed in both breasts (bilateral breast cancer)

• Male breast cancer

• Breast cancer plus ovarian or pancreatic cancer

• Ashkenazi Jewish ethnicity

Many women at low risk for gene mutations are needlessly tested every year, which can cause a great deal of unnecessary anxiety.

If a woman tests positive for a BRCA mutation, we offer increased cancer screening, risk-reducing medications, prophylactic mastectomy, or some combination of these. While it’s likely such approaches will also help protect women with a PALB2 mutation, there is currently no evidence that they have benefit. More research is needed.

Genetic mutations like BRCA1/2 and PALB2 are frightening because they increase the risk of breast cancer by such a great degree. But it’s important to also keep in mind that they are rare. Around one in 400 women in the United States have a BRCA mutation, which translates to 0.25 percent of American women. And even women who have such mutations are not guaranteed to develop the disease.

For the large majority of women, the most important things they can do to improve their health and lower the risk of breast cancer is to focus on living an overall healthy lifestyle that includes: being physically active for at least 30 minutes a day, keeping weight in check, and drinking alcohol only moderately, if at all.

References

Antonis C. Antoniou, Ph.D., Silvia Casadei, Ph.D., Tuomas Heikkinen, Ph.D., Daniel Barrowdale, B.Sc., Katri Pylkäs, Ph.D., et al. Breast-Cancer Risk in Families with Mutations in PALB2. N Engl J Med 2014; 371:497-506.

Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of Clinical Oncology 2007; 25(11):1329–1333.

Hormonal IUDs and Breast Cancer: Is There a Link?

by Sarah Cortez

It certainly goes without saying that birth control has been a major news story the past couple of months. Much of this coverage, of course, has revolved around the recent Supreme Court ruling and reactions to it. Outside of that media storm, there have been some other health-related birth control stories as well, a number of which have focused on the potential of a specific type of IUD - the levonorgestrel IUD - to increase breast cancer risk. 

Photo: Flickr/Theilr

So what do the data actually say about this link? Let’s take a look.

In case you are unfamiliar with the levonorgestrel IUD (brand name Mirena or Skyla), it is a small, plastic, T-shaped device that is inserted into your uterus by a healthcare provider, usually your gynecologist. It prevents pregnancy by releasing a hormone called levonorgestrel and can be left in your uterus for up to five years.

Much of this recent interest in levonorgestrel-releasing IUDs was sparked by a study published in Obstetrics & Gynecology that looked at the records of all 30-49 year old women in Finland who used a levonorgestrel IUD to treat menorrhagia (heavy periods).

The study reports finding that the Finnish women who used the levonorgestrel IUD for 5 years had a 19% increased rate of breast cancer compared to the general Finnish population. That’s bad, right? Well, hold on.

The study also reports that, for these women, ovarian cancer was decreased by 40% and endometrial (uterine) cancer was decreased by 54%. Seeing if the IUD could decrease the risk for, or prevent, endometrial (uterine) cancer was the actual goal of the study.

Remember, these women were receiving a levonogrestrel IUD to treat very heavy periods. Periods, which if caused by endometrial hyperplasia (overgrowth of the uterine lining), put them at increased risk for endometrial cancer. So the study showed that it helped prevent endometrial (uterine) cancer in women who used it to treat very heavy periods.

But, what about the increase in breast cancer?

The authors of the study advised not being too quick to assume that this increase in breast cancer is real. Prior studies have never found an association between levonogrestrel IUD use and breast cancer. So, the finding could just be an outlier or something else could be going on. We don’t know, for example, whether a group of women with very heavy periods has the same breast cancer risk as the general population.

Exactly how this finding translates from Finnish women to American women is also unclear, since the IUDs available in Finland are not exactly the same as those available in the United States

So before you decide to get rid of your IUD because of concerns about breast cancer risk, have an in-depth talk to your doctor. Discuss your family-planning goals, your family history, and your personal risk for breast, endometrial, and ovarian cancer. If your overall risk for breast cancer is low, the levonogrestrel IUD isn’t likely to put you in the high-risk category.

The three most important things women of child-bearing age can do to prevent breast cancer are: be physically active, stay at a healthy weight, and drink only moderate amounts of alcohol – if at all.


Reference

Soini T, Hurskainen R, Grenman S, Maenpaa J, Paavonen J, Pukkala E. Cancer Risk in Women Using the Levonorgestrel-Releasing Intrauterine System in Finland. Obstet Gynecol 2014;124:292-299.