ASCO Updates Breast Cancer Risk Reduction Guideline to Include Anastrozole

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ASCO has updated a guideline on pharmacologic interventions for breast cancer risk reduction in postmenopausal women at increased risk of developing breast cancer.1 The original clinical practice recommendations for breast cancer risk reduction were published in 1999 and updated in 2002, 2009, and 2013. This most recent update was prompted by a double-blind, randomized clinical trial (IBIS-2) that evaluated the use of anastrozole for reduction of estrogen receptor–positive breast cancers in postmenopausal women.2 The new recommendations add anastrozole to the list of endocrine options for breast cancer reduction in postmenopausal women based on IBIS-2 data.

Carol Fabian, MD, of the University of Kansas Medical Center and Guideline Co-Chair, said that the expert panel “wanted this update to have more of an impact than just adding an additional medication that can be used for primary breast cancer prevention.” As a result, the guideline update expanded its clinical considerations section to help with patient and agent selection.

Carol Fabian, MD

Carol Fabian, MD

Kala Visvanathan, MD, MHS

Kala Visvanathan, MD, MHS

“Our hope is that these recommendations will not only give women another option for breast cancer prevention, but also provide greater clarity about the women at increased risk of breast cancer who are most likely to benefit from endocrine therapy,” said Kala Visvanathan, MD, MHS, of Johns Hopkins Sidney Kimmel Cancer Center and Guideline Co-Chair.

Practice-Changing Results From IBIS-2

IBIS-2 was a United Kingdom–based study that assessed the safety and efficacy of the aromatase inhibitor anastrozole, at a dose of 1 mg per day orally for 5 years, in 3,864 postmenopausal women at increased risk of developing breast cancer.2 The median age of women enrolled on the trial was 59.5 years, and 18% were older than 65.

After a median follow-up of 5 years, 4% (85) of women in the placebo group and 2% (40) of women in the anastrozole group (2%) had developed invasive and noninvasive breast cancers (hazard ratio [HR] = 0.47, 95% confidence interval [CI] = 0.32–0.68; P < .0001). After 7 years, the predictive cumulative incidence of all breast cancers was more than two times higher in the placebo group (5.6% vs 2.0%). The 5-year adherence rate was only slightly less in the anastrozole group compared with the placebo group (68% vs 72%). As with other endocrine therapies, subgroup analyses revealed that the reduction in risk of invasive breast cancer was limited to estrogen receptor–positive and progesterone receptor–positive tumors (HR = 0.42, 95% CI = 0.25–0.7; P = .001).

Based on these findings, the expert panel drafted the following recommendations1:

  1. In postmenopausal women at increased risk of developing breast cancer, anastrozole (1 mg/d orally for 5 years) may be considered as an alternative to tamoxifen, raloxifene, or exemestane to reduce the risk of invasive breast cancer.
  2. Anastrozole, exemestane, or raloxifene is not suitable for breast cancer risk reduction in premenopausal women. Tamoxifen is still the only preventive agent for premenopausal women.
  3. The risks and benefits of anastrozole, and the other approved drugs for breast cancer risk reduction, should be part of a discussion between the patients and their health-care providers.
  4. Anastrozole should be used with caution in postmenopausal women with evidence of moderate bone mineral density loss. In these women, the addition of bone-protective agents, such as bisphosphonates and RANK ligand inhibitors, should be considered. Severe bone loss and/or osteoporosis are considered relative contraindications for anastrozole.
  5. Clinicians should discuss the possible side effects of anastrozole, such as hot flashes, vaginal dryness, joint stiffness, bone mineral loss, arthralgias, and hypertension, with women considering this treatment.

In addition to the previous recommendations, the updated guideline also defines the groups of women who are most likely to benefit from anastrozole. This includes women with hyperplasia or lobular carcinoma in situ or women between the ages of 35 and 59 with a 5-year absolute risk of ≥ 3%, or a 10-year absolute risk of 5%.

Clinical Considerations for Breast Cancer Prevention

The clinical considerations section of the guideline addresses some of the frequently asked questions that clinicians encounter in prescribing endocrine therapy to women at risk of breast cancer. The expert panel also defined the eligibility and benefit risk thresholds for endocrine therapy in women of different age groups.

“In general, we thought that the upper age limit [for endocrine therapy for primary prevention] should be 70, unless the risk of breast cancer was particularly high because of a cancer in situ diagnosis or a combination of atypical hyperplasia and family history,” Dr. Fabian said.

The expert panel also considered whether taking endocrine agents for less than 5 years would be beneficial based on evidence from a recently reported trial of low-dose tamoxifen as an alternative to standard-dose tamoxifen in women with intraepithelial neoplasia.3

That study, by DeCensi et al, “looked at low-dose tamoxifen (5 mg) vs placebo and found a 50% reduction in the incidence of breast cancer with this low dose when given for only 3 years,” Dr. Fabian said. “There probably is a benefit in giving these agents for a shorter period of time. The incidence of serious side effects, such as pulmonary embolism and uterine cancer, was no greater in the low-dose tamoxifen arm than in the placebo arm.”

Finally, the section on clinical considerations also includes new guidance for clinicians to assist them in deciding between using selective estrogen receptor  modulators, such as tamoxifen or raloxifene, vs aromatase inhibitors, like anastrozole or exemestane. 

DISCLOSURE: Dr. Fabian has received institutional research funding from DSM and Pfizer. Dr. Visvanathan holds an institutional license for a patent with Cepheid.


1. Visvanathan K, Fabian CJ, Bantug E, et al: Use of endocrine therapy for breast cancer risk reduction: ASCO Clinical Practice Guideline Update. J Clin Oncol. September 3, 2019 (early release online).

2. Cuzick J, Sestak I, Forbes JF, et al: Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): An international, double-blind, randomised placebo-controlled trial. Lancet 383:1041-1048, 2014.

3. DeCensi A, Puntoni M, Guerrieri-Gonzaga A, et al: Randomized placebo controlled trial of low-dose tamoxifen to prevent local and contralateral recurrence in breast intraepithelial neoplasia. J Clin Oncol 37:1629-1637, 2019.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, September 4, 2019. All rights reserved.