The U.S. Preventive Services Task Force has issued updated recommendations on the use of chemoprevention for breast cancer that emphasize the need for informed, shared decision-making.
"It’s a complicated decision, and there are a lot of moving parts, if you will," USPSTF member Dr. Mark Ebell said in an interview.
New research since the original 2002 guidance, including updates from the pivotal STAR trial (Cancer Prev. Res. 2010;3:696-706) and a recent meta-analysis of risk-reducing medications (Ann. Intern. Med. 2013;158:604-14), have helped clarify the balance of benefits and harms by a woman’s age, breast cancer risk, race, and whether she’s had a hysterectomy.
The 2013 guidelines, published in Annals of Internal Medicine, plug those data into a series of tables that present the net benefit as stratified by those risk factors. For example, Table 1 is for white, non-Hispanic women who have a uterus.
"So, you’d go there, look up [the patient’s] 5-year projected risk, look up [the patient’s] age, and it provides a general color-coded assessment of whether there are more risks or harms," Dr. Ebell said. "It’s a tough decision, and two women with similar risk factors may make different decisions, and that’s perfectly okay. Everyone’s different; everyone assesses risk differently and has different values. We just wanted to make sure they have the best possible information when they make their decision."
Both the original and updated versions carry the same overall recommendation: Women who are at an average or low risk should not use chemoprevention, while women at high risk should consider therapy if they don’t have any contraindications.
The 2013 recommendations are trying, however, to be a bit more explicit about which medications have been approved by the Food and Drug Administration (FDA) for breast cancer chemoprevention, said Dr. Ebell, a family physician with the College of Public Health, University of Georgia, Athens.
The USPSTF recommends the use of the selective estrogen receptor modulators tamoxifen and raloxifene (Evista) to reduce the incidence of invasive breast cancer in asymptomatic women aged 35 years and older who are without a prior diagnosis of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ and who are at increased risk of breast cancer. The daily doses are 20 mg and 60 mg, respectively, for 5 years.
Tamoxifen is FDA approved for this use in women aged 35 years and older, while raloxifene is approved for this indication in postmenopausal women.
In a draft version of the guidance released this April, the target audience for the recommendation was asymptomatic women aged 40 years and older, but the age limit was lowered to 35 years in the final version because the Breast Cancer Prevention Trial enrolled women over age 35, Dr. Ebell said.
Notably absent in the new guidelines is an endorsement of the aromatase inhibitor exemestane (Aromasin). Updated chemoprevention guidelines issued earlier this year by the American Society of Clinical Oncology recommend that exemestane be discussed as an alternative to reduce the risk of invasive, estrogen receptor–positive breast cancer in postmenopausal women (J. Clin. Onc. 2013;31:2942-62).
The task force only considers FDA-approved medications for the indication of breast cancer chemoprevention, and exemestane is only approved for breast cancer treatment, Dr. Ebell explained.
The aromatase inhibitor anastrozole (Arimidex) is not recommended by either ASCO or the USPSTF, with data awaited from the ongoing phase III, placebo-controlled British IBIS II (Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer) study.
Dr. Joanna Cain, professor of obstetrics/gynecology at the University of Massachusetts, Worcester, said the task force made the decision regarding exemestane on the basis of the present evidence.
"UPSTF has a level of standards that exemestane does not yet meet, while ASCO is willing to move with less evidence," she said in an interview. "They are not ruling it out but saying by their criteria, it does not yet meet this. Having said all that, if a patient is intolerant of tamoxifen and raloxifene and needs chemopreventive therapy, we would consider using exemestane as an alternative."
Dr. Cain noted that she welcomes the 2013 guidance, particularly the appropriate caution about individual patient risks for these medications such as age, venous thrombosis, and endometrial cancer, which also includes the risk conferred by obesity and genetics such as Lynch syndrome.
"In particular, the clarity around benefit, and therefore, use only for those at increased risk, is helpful," she said.
The use of risk-reducing medications is quite low, but that’s because only about 5% of women are really appropriate candidates and only a minority of these actually take the medication, Dr. Ebell said.