Aromatase Inhibitors May Increase Risk of Heart Disease

Aromatase inhibitors—hormonal therapy drugs commonly used in the treatment of postmenopausal breast cancer—may increase the risk of heart disease. These results were presented at the 2010 San Antonio Breast Cancer Symposium.

Tamoxifen and aromatase inhibitors are hormonal therapy drugs that are commonly used in the treatment of hormone receptor-positive breast cancer. Both types of drugs slow or stop breast cancer growth by reducing the effects of estrogen on the breast.

Aromatase inhibitors include ArimidexR (anastrozole), FemaraR (letrozole), and AromasinR (exemestane). In studies that compared aromatase inhibitors to tamoxifen in postmenopausal women, aromatase inhibitors tended to be more effective against breast cancer recurrence. As a result, treatment guidelines recommend that postmenopausal women with hormone receptor-positive breast cancer consider using an aromatase inhibitor at some point in their course of treatment.[1]

Adverse effects of tamoxifen and aromatase inhibitors differ. Blood clots and endometrial (uterine) cancer are more common with tamoxifen, and bone loss is more common with aromatase inhibitors. Previous studies have also raised questions about the effects of aromatase inhibitors on the heart.

To further evaluate the issue of heart problems, researchers collected information from seven large clinical trials that compared tamoxifen with an aromatase inhibitor among postmenopausal breast cancer patients.[2]

Compared with tamoxifen, use of an aromatase inhibitor was linked with a 26% increase in risk of heart disease. This is not a large increase in risk, but the researchers speculated that the risk may be greater for women who have other risk factors for heart disease. In a second study conducted using data from health insurance plans, there did not appear to be an increased risk of cardiac disease among women taking aromatase inhibitors. ?

Unfortunately, it is not possible to determine at this time if aromatase inhibitors truly increase the risk of heart problems. ?Women are encouraged to discuss potential risks and benefits of all treatments with their physicians.

References:

[1] Burstein HJ, Prestrud AA, Seidenfeld J et al. American Society of Clinical Oncology Clinical Practice Guidelines: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. Journal of Clinical Oncology. 2010; 28: 3784-3796.

[2] Amir E, Ocana A, Niraula S, Carlsson L, Seruga B. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients. Presented at the 33rd annual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract S2-7.

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BRCA1-2 Mutations Increase Risk of Cancer in Opposite Breast

Among women with breast cancer, those with a BRCA1 or BRCA2 gene mutation are much more likely than other women to develop a second breast cancer in the opposite breast. These results were published in the Journal of Clinical Oncology.

Some women who have been diagnosed with breast cancer will eventually develop a second breast cancer in the opposite breast. This is referred to as a contralateral breast cancer. The risk of a second breast cancer among women who have already had breast cancer is higher than the risk of a first breast cancer among women in the general population.

A factor that may influence the risk of contralateral breast cancer is the presence of BRCA1 or BRCA2 gene mutations. Inherited mutations in these genes—which can be passed down through either the mother’s or the father’s side of the family—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer.

To evaluate the relationship between BRCA1 or BRCA2 mutations and risk of a subsequent contralateral breast cancer, researchers conducted a study among more than 2,000 breast cancer patients, some of whom had been diagnosed with a contralateral breast cancer and some of whom had not. Women were only included in the contralateral breast cancer group if their contralateral cancer was diagnosed at least one year after their initial cancer. All of the women had been diagnosed with their first breast cancer before the age of 55.

All of the study participants were tested for BRCA1 and BRCA2 mutations.

Compared with women without a BRCA1 or BRCA2 mutation, risk of a subsequent contralateral breast cancer was 4.5 times higher among women with a BRCA1 mutation and 3.4 times higher among women with a BRCA2 mutation.

Among women with a BRCA1 mutation, a younger age at the time of initial breast cancer diagnosis increased the likelihood of a subsequent contralateral breast cancer.

Information about risk of a subsequent contralateral breast cancer may help guide breast cancer management among women with BRCA1 or BRCA2 mutations.

Reference: Malone KE, Begg CB, Haile RW et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. Journal of Clinical Oncology. [early online publication]. April 5, 2010.

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Weight Lifting May Not Increase Lymphedema Risk Among Breast Cancer Survivors

It may be safe for breast cancer survivors to lift weights, including upper-body exercises, without increasing risk for lymphedema. These results were reported in the Journal of the American Medical Association.

Lymphedema refers to swelling of the arm due to an accumulation of lymph fluid. It commonly affects women who have had axillary (underarm) lymph nodes removed for the staging of early breast cancer. The extensive removal of lymph nodes (known as axillary lymph node dissection) is more apt to cause lymphedema than the removal of only a small number of nodes (known as a sentinel lymph node biopsy), but lymphedema can occur following either procedure.

Because of concern that upper-body exercise may increase the risk of developing lymphedema or worsen existing lymphedema, breast cancer survivors are sometimes advised to avoid heavy lifting and other upper-body exercises. These recommendations, however, are based on little evidence.

Determining whether weight lifting is safe for breast cancer survivors is important because this type of exercise can provide important benefits, including an increase in bone density.

To determine whether breast cancer survivors may perform upper-body weight-lifting exercises without increasing risk for lymphedema, researchers compared lymphedema incidence between women who lifted weights and women who did not. Participants had completed treatment one to five years prior to the study and had at least two lymph nodes removed. None had clinical signs of lymphedema when the study began.

Those in the weight-lifting group were given gym memberships and 13 weeks of weight-training instruction. Instruction was provided twice a week and involved very gradual increases in the amount of weight used. After 13 weeks, women in the weight-lifting group continued their exercise programs for nine months without instruction. The remainder of study participants performed no exercise. When the study was completed, women in the no-exercise group were offered a one-year gym membership with 13 weeks of instruction.

At one year the following results were available for 134 participants:

11% of participants in the weight-lifting group experienced incident breast cancer-related lymphedema (determined by an increase in arm swelling of 5% or greater during 12 months) compared with 17% in the no-exercise group.In the weight-lifting group, among women who had five or more lymph nodes removed, 7% experienced incident breast cancer-related lymphedema versus 22% in the no-exercise group.

The researchers concluded that slowly progressive weight lifting does not increase the incidence of lymphedema among women who have been treated for breast cancer. Weight lifting is known to have many health benefits, and it may be safe for many breast cancer survivors to perform this type of exercise. It remains important, however, that all exercise programs are first discussed with a doctor.

Reference: Schmitz KH, Ahmed RL, Troxel AB, et al. Weight lifting for women at risk for breast cancer-related lymphedema. JAMA [early online publication]. December 8, 2010.

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Even Low Levels of Alcohol Slightly Increase Breast Cancer Risk

Women who have as few as three to six alcoholic beverages per week have a slightly increased risk of breast cancer. Heavier drinker further increases risk. These results were published in the Journal of the American Medical Association.?

Many previous studies have reported that higher levels of alcohol consumption increase the risk of breast cancer. The reasons for this are not well understood, but may involve alcohol’s effects on a woman’s estrogen levels.??

Whether low levels of alcohol also affect breast cancer risk has been less clear. To further explore the relationship between alcohol and breast cancer, researchers evaluated information from the Nurses’ Health Study. The study involved more than 105,000 women. Information about alcohol intake was collected at several different points between 1980 and 2006.?

Compared with nondrinkers, women who had three to six drinks per week had a 15% increase in risk of breast cancer. This means that if a woman has a 2% chance of getting breast cancer in the next 10 years, the chance is increased to 2.3%?Higher levels of alcohol intake further increased risk of breast cancer. Women who had at least two drinks per day had a 51% increase in risk of breast cancer.?When the researchers considered alcohol intake earlier in life (age 18 to 40) and later in life (after age 40), both time periods were important: alcohol intake during either time period increased breast cancer risk.?

These results suggest that even low levels of alcohol can increase breast cancer risk, although the effect is fairly small. The researchers note that “..an individual will need to weigh the modest risks of light to moderate alcohol use on breast cancer development against the beneficial effects on cardiovascular disease to make the best personal choice regarding alcohol consumption.”?

Reference: Chen WY, Rosner B, Hankinson SE, Colditz GA, Willett WC. Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. JAMA. 2011;306;1884-1890.?

Posted November 16, 2011

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Screening Radiation Exposure May Increase Breast Cancer Risk in Some BRCA Mutation Carriers

Radiation exposure from x-rays, mammograms, and other diagnostic tests prior to age 30 may increase the risk of breast cancer in women who carry BRCA1 or BRCA2 mutations, according to the results of a large, retrospective cohort study published in the British Medical Journal. ?

Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family.?

A mammogram is an X-ray of the breast. Screening mammography is performed in a woman without breast symptoms in order to detect breast cancer at an early stage when it is most easily treated. Currently, mammography is the most reliable tool for screening the general population for breast cancer and may even reduce the risk of death from breast cancer (due to early detection). Mammograms are most often used in women over the age of 40; however, women who carry BRCA mutations are considered high-risk and may benefit from earlier and more frequent screening. This earlier screening can come with the added risk of increased radiation exposure—and exposure to ionizing radiation, especially when it occurs at an early age, is an established risk factor for breast cancer.? ?

To examine the relationship between radiation exposure and breast cancer risk among BRCA1/2 mutation carriers, researchers from Europe followed nearly 2,000 women over age 18 with a BRCA1 or BRCA2 mutation. The women reported their history of procedures—such as x-rays or mammograms—that involved radiation to the chest or shoulders. The researchers then used this information to estimate the cumulative dose of radiation to the breast for each woman and compared this against confirmed breast cancer diagnoses among the women. ?

When compared with no exposure, any exposure to chest radiation prior to age 30 was associated with almost double the risk of breast cancer in BRCA1/2 mutation carriers. Exposure prior to age 20 was associated with a 62 percent increased risk. Women who received the highest doses or radiation prior to age 30 had almost four times the increased risk. In contrast, there was no evidence of an increased risk of breast cancer associated with exposure after age 30. ?

The researchers concluded that exposure to diagnostic radiation before age 30 among carriers of BRCA1/2 mutations was associated with an increased risk of breast cancer. What’s more—the increased risk of breast cancer was observed at radiation doses considerably lower than those associated with an increased risk among other populations. ?

Because women with BRCA1/2 mutations have an increased risk of developing breast cancer, some guidelines recommend earlier screening; however, the results of this study may indicate that BRCA1/2 carriers under age 30 might benefit from surveillance that uses non-ionizing radiation imaging, such as magnetic resonance imaging (MRI).?

Reference:?

Pijpe A, Andrieu N, Easton DF, et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK). British Medical Journal. 2012; 2012;345:e5660?

Posted October 2, 2012

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A BRCA Gene Mutation in the Family Does Not Increase Cancer Risk for Those Without the Mutation

For women who do not have a BRCA1 or BRCA2 gene mutation, having a close relative with one of these mutations does not increase breast cancer risk. These results were published in the Journal of Clinical Oncology.?

Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family.????

Women who test negative for a BRCA gene mutation—but who have family members with a mutation—are generally thought to have a risk of breast cancer that’s similar to that of women in the general population. A study published in 2007, however, raised concerns that relatives of BRCA mutation carriers may have a substantially increased risk of breast cancer even if they test negative for their family’s mutation.[1]?

To further explore cancer risk among close relatives of people with BRCA mutations, researchers conducted a study among more than 3,000 families with at least one case of breast cancer; 160 families had a BRCA1 mutation and 132 families had a BRCA2 mutation.[2]?

For women without a BRCA mutation, breast cancer risk was similar whether or not the woman’s family had a BRCA mutation. These results suggest that coming from a family with a BRCA1 or BRCA2 gene mutation does not increase cancer risk for those who test negative for the mutation.?????

Although this is reassuring news, women who test negative for their family’s gene mutation should continue to follow cancer screening guidelines. These women do not have the very elevated cancer risk that their affected relatives have, but they can still get cancer.???

References:?

Posted November 9, 2011

[1] Smith A, Moran A, Boyd MC et al. Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening. Journal of Medical Genetics. 2007;44:10-15.?

[2] Kurian AW, Gong GD, John EM et al. Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: findings from the Breast Cancer Family Study. Journal of Clinical Oncology. Early online publication October 31, 2011.?

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