Draft Recommendation Statement

USPSTF: Offer Medication to Reduce Breast Cancer Risk

January 25, 2019, 01:02 pm Chris Crawford – An estimated one in eight women will develop breast cancer at some point in their lifetime.

This draft recommendation does not apply to women who have a current or previous breast cancer diagnosis, the task force said.

The USPSTF found that medications such as tamoxifen, raloxifene or aromatase inhibitors can reduce a woman's chance of developing invasive breast cancer.

However, the task force said these medications can also lead to serious harms, some of which may be life-threatening. The likelihood of experiencing these harms depends on a woman's individual risk factors.

"When deciding whether or not to offer medications, clinicians should carefully consider their patients' risk factors for breast cancer and balance these against the potential harms from the medications," said USPSTF member Carol Mangione, M.D., M.S.P.H., in a news release. "These medications are not for everyone, and for women who are not at increased risk of breast cancer, the harms of these medications are likely to outweigh the benefits."

This draft recommendation statement is consistent with the task force's 2013 final recommendation on the same topic, which the AAFP supported at that time.

However, the draft recommendation now includes aromatase inhibitors as one of the medications clinicians can offer to women at increased risk for breast cancer.

Assessment of Breast Cancer Risk

The USPSTF said in its draft recommendation that family physicians can use various methods to identify women at increased risk for breast cancer, including clinical risk assessment tools or assessing breast cancer risk factors without using a formal tool.

Risk assessment tools such as the National Cancer Institute Breast Cancer Risk Assessment Tool estimate a woman's risk of developing breast cancer during the next five years. The Breast Cancer Surveillance Consortium Risk Calculator estimates both five-year and 10-year breast cancer risk.

However, the task force noted there isn't a single cutoff for defining risk for all women.

"Women at greater risk, such as those with at least a 3 percent risk for breast cancer in the next five years, are likely to derive more benefit than harm from risk-reducing medications and should be offered them if their risk of harms is low," the draft recommendation said.

Some women at lower risk for breast cancer were also included in trials documenting reduced risk for breast cancer when taking tamoxifen, raloxifene or aromatase inhibitors.

"However, when balancing the harms associated with these medications, the net benefit will be lower in women at lower risk," the USPSTF said.

The task force said as an alternative, clinicians may use combinations of risk factors (including some risk factors not included in risk assessment tools but that would have permitted enrollment in some of the risk reduction trials) to identify women at increased risk, such as

• atypical ductal or lobular hyperplasia or lobular carcinoma in situ on a prior biopsy,
  
• being age 65 or older with one first-degree relative with breast cancer,
  
• being age 45 or older with more than one first-degree relative with breast cancer or one first-degree relative who developed breast cancer before age 50, and
  
• being age 40 or older with a first-degree relative with bilateral breast cancer.

Risk-reducing Medications

According to the USPSTF, prescribing risk-reducing medications for breast cancer is an uncommon practice among primary care clinicians.

Based on limited survey data, 10 percent to 30 percent of primary care clinicians (depending on medication type) reported ever prescribing risk-reducing medications, and most have only done so a few times.

The reported use of risk-reducing medications among women also was relatively low; one meta-analysis of 26 studies found that overall, 16.3 percent of women at increased risk for breast cancer used risk-reducing medications.

A systematic review conducted for the USPSTF found that compared to placebo, tamoxifen reduced the incidence of invasive breast cancer by seven events per 1,000 women during a five-year period, and raloxifene reduced incidence by nine events per 1,000 women over five years.

The task force said the large Study of Tamoxifen and Raloxifene trial directly compared tamoxifen to raloxifene and found that tamoxifen reduced breast cancer risk more than raloxifene after long-term follow-up.

"For women with a predicted breast cancer risk of 3 percent or greater, the absolute benefits are likely even higher," the draft recommendation said. "Tamoxifen also reduces the incidence of invasive breast cancer in premenopausal women at increased risk for the disease; raloxifene should only be used in postmenopausal women. Tamoxifen and raloxifene have both been found to reduce risk for nonvertebral and vertebral fractures, respectively."

The third drug option of aromatase inhibitors was found to reduce the incidence of invasive breast cancer by 16 events per 1,000 women during a five-year period.

As with tamoxifen and raloxifene, the USPSTF said these absolute benefits are likely even higher for women with a predicted breast cancer risk of 3 percent or greater.

Alternatively, the task force found convincing evidence that the harms associated with tamoxifen and raloxifene were small to moderate.

"Tamoxifen and raloxifene increase risk for venous thromboembolic events; tamoxifen increases risk more than raloxifene and the potential for harms are greater in older women than in younger women," the draft recommendation said.

The USPSTF also found adequate evidence that tamoxifen, but not raloxifene, increased risk for endometrial cancer in women with a uterus, and of cataracts. Additionally, vasomotor symptoms are a common adverse effect of both medications.

For aromatase inhibitors, the task force also found adequate evidence that harms were small to moderate, including vasomotor symptoms, gastrointestinal symptoms, musculoskeletal pain and possible cardiovascular events, such as stroke.

The draft recommendation noted that aromatase inhibitors do not reduce, and may even increase, the risk of fractures.

Family Physician's Perspective

AAFP Commission on Health of the Public and Science member James Stevermer, M.D., of Fulton, Mo., told AAFP News that family physicians have an opportunity to reduce the number of women developing breast cancer.

"As it is the second leading cause of cancer death among women, there will certainly be women who would benefit from these medications," he said.

Unfortunately, Stevermer added, the medications are not perfectly effective, with a number needed to treat (NNT) of about 63 (over five years of therapy) for aromatase inhibitors, and an even worse NNT of more than 100 for five years of therapy for anti-estrogens (tamoxifen and raloxifene).

The USPSTF pointed out that the studies including these agents that it reviewed were done in populations of women that were different enough from each other that a head-to-head comparison of agents couldn't be completed, he said.

How the risks and benefits of these medications balance out will depend on each woman's personal preferences, Stevermer said.

"Some women will be very interested in reducing their risk of cancer and will weigh the risks of medication less than the potential benefit of avoiding a cancer, and thus, they'll be more likely to want to take a daily medication for that purpose," he said.

Based on their values, other patients will decide differently, Stevermer said. So, family physicians will need to help guide their patients through the shared decision-making process.

"I'd reassure patients that there is no right or wrong answer to this question for each individual woman, and their own personal values determine this decision," he said. "Women at higher risk should have the opportunity to get one of these medications, should they opt for it, and will benefit from having a trusted physician guide them through this decision."

Up Next

The USPSTF is accepting comments on its draft recommendation statement and draft evidence review on medications to reduce risk of breast cancer until 8 p.m. ET on Feb. 11. All comments received will be considered as the task force prepares its final recommendation.

The AAFP will review the USPSTF's draft recommendation statement and supporting evidence, and will provide comments to the task force. The Academy will release its own recommendation on the topic after the task force finalizes its guidance.

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