In the JournalsPerspective

USPSTF issues breast cancer risk reduction recommendation

The US Preventive Services Task Force today recommended shared decision-making between clinicians and women at risk for breast cancer regarding the use of risk-reducing medications for breast malignancies.

The draft recommendation stipulates that clinicians should offer to prescribe medications such as tamoxifen or raloxifene — selective estrogen receptor modulators that block the effects of estrogen in breast tissue — to women at high risk for breast cancer and at low risk for adverse events associated with those medications.

Mark Ebell, MD, MS 

Mark Ebell

“Screening for breast cancer allows for early detection but does not prevent cancer from developing. We all want to find effective ways to prevent breast cancer,” task force member Mark Ebell, MD, MS, said in a press release. “While we need more and better solutions, some women at increased risk for breast cancer may choose to take available preventive medications to reduce their chances of developing breast cancer.”

The task force also recommended that medications such as tamoxifen or raloxifene should not be routinely used by women who do not have an increased breast cancer risk.

The recommendation coincided with the online publication of a review article today in Annals of Internal Medicine.

In the review, HeidiD. Nelson, MD, MPH, research professor in the departments of medical informatics and clinical epidemiology and medicine at Oregon Health & Science University, and colleagues examined databases and clinical trial registries for data involving the impact of tamoxifen and raloxifene on invasive breast cancer incidence.

Results from seven trials indicated that the drugs yielded a reduction of seven to nine cases per 1,000 women during a 5-year period when compared with placebo.

Findings from the STAR trial demonstrated that tamoxifen reduced breast cancer incidence by more than five cases per 1,000 compared with raloxifene.

The trials indicated broad benefit; however, subgroup analyses suggested that women at high risk for breast cancer may derive the most benefit with the least harms, Nelson and colleagues wrote.

Also, tamoxifen was associated with increases in thromboembolic events, endometrial cancer and cataracts. The USPSTF recommendation stipulates that neither drug should be used in women with a history of thromboembolic events.

“There are several serious harms associated with tamoxifen and raloxifene, which is why doctors must engage in a conversation with their patients and discuss the harms and benefits of these medications,” task force member Wanda Nicholson, MD, MPH, MBA, said in the press release.

Clinicians may discuss breast cancer risk-reducing medications if the patient exhibits risk factors that include:

  • Increasing age;
  • Family history of breast or ovarian cancer (especially among first-degree relatives and/or onset before age 50 years);
  • History of atypical hyperplasia or other nonmalignant high-risk breast lesions;
  • Previous breast biopsy; and
  • Extremely dense breast tissue.

The USPSTF statement notes that models can predict risk at the population level but not necessarily at the individual level.

The recommendation includes women aged 40 to 70 years who do not have a previous diagnosis of breast cancer, ductal carcinoma in situ or lobular carcinoma in situ.

The USPSTF will accept public comment on its draft recommendation until May 13.

The US Preventive Services Task Force today recommended shared decision-making between clinicians and women at risk for breast cancer regarding the use of risk-reducing medications for breast malignancies.

The draft recommendation stipulates that clinicians should offer to prescribe medications such as tamoxifen or raloxifene — selective estrogen receptor modulators that block the effects of estrogen in breast tissue — to women at high risk for breast cancer and at low risk for adverse events associated with those medications.

Mark Ebell, MD, MS 

Mark Ebell

“Screening for breast cancer allows for early detection but does not prevent cancer from developing. We all want to find effective ways to prevent breast cancer,” task force member Mark Ebell, MD, MS, said in a press release. “While we need more and better solutions, some women at increased risk for breast cancer may choose to take available preventive medications to reduce their chances of developing breast cancer.”

The task force also recommended that medications such as tamoxifen or raloxifene should not be routinely used by women who do not have an increased breast cancer risk.

The recommendation coincided with the online publication of a review article today in Annals of Internal Medicine.

In the review, HeidiD. Nelson, MD, MPH, research professor in the departments of medical informatics and clinical epidemiology and medicine at Oregon Health & Science University, and colleagues examined databases and clinical trial registries for data involving the impact of tamoxifen and raloxifene on invasive breast cancer incidence.

Results from seven trials indicated that the drugs yielded a reduction of seven to nine cases per 1,000 women during a 5-year period when compared with placebo.

Findings from the STAR trial demonstrated that tamoxifen reduced breast cancer incidence by more than five cases per 1,000 compared with raloxifene.

The trials indicated broad benefit; however, subgroup analyses suggested that women at high risk for breast cancer may derive the most benefit with the least harms, Nelson and colleagues wrote.

Also, tamoxifen was associated with increases in thromboembolic events, endometrial cancer and cataracts. The USPSTF recommendation stipulates that neither drug should be used in women with a history of thromboembolic events.

“There are several serious harms associated with tamoxifen and raloxifene, which is why doctors must engage in a conversation with their patients and discuss the harms and benefits of these medications,” task force member Wanda Nicholson, MD, MPH, MBA, said in the press release.

Clinicians may discuss breast cancer risk-reducing medications if the patient exhibits risk factors that include:

  • Increasing age;
  • Family history of breast or ovarian cancer (especially among first-degree relatives and/or onset before age 50 years);
  • History of atypical hyperplasia or other nonmalignant high-risk breast lesions;
  • Previous breast biopsy; and
  • Extremely dense breast tissue.

The USPSTF statement notes that models can predict risk at the population level but not necessarily at the individual level.

The recommendation includes women aged 40 to 70 years who do not have a previous diagnosis of breast cancer, ductal carcinoma in situ or lobular carcinoma in situ.

The USPSTF will accept public comment on its draft recommendation until May 13.

    Perspective

    The US Preventive Service Task Force (USPSTF) has summarized the basic findings of the tamoxifen and raloxifene breast cancer prevention trials, and their recommendations reflect the current attitudes and behavior of both physicians and patients. Available statistics show less than 1% of “eligible” patients actually take either of these selective estrogen modulators for primary prevention due to the benefit to risk–side effect ratio.

    Also, it is important to recognize that none of the prevention trials have shown an improvement in cancer or all-cause mortality. They were not powered nor designed to do so. Risk–benefit models have suggested that not all patients eligible based on the prevention trial eligibility and  FDA approved indications actually derive a greater predicted benefit than harm, in particular those at higher risk for thrombosis and — in the case of tamoxifen — those who have not had a hysterectomy and are at risk for uterine cancer. The USPSTF guidelines therefore individualize recommendations based on risk and benefit that is individualized based on available models. Although these guidelines seem vague and watered down, they do reflect the state of the evidence.

    • Debasish “Debu” Tripathy, MD
    • HemOnc Today Editorial Board member

    Disclosures: Tripathy reports no relevant financial disclosures.