ASCO has released a focused update of its clinical practice guideline on adjuvant endocrine therapy in women with hormone receptor–positive breast cancer.¹ The focused update, formulated by Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues in the ASCO Update Committee and published in Journal of Clinical Oncology, was warranted by emergence of data on optimal duration of treatment, particularly with adjuvant tamoxifen. The update includes review of evidence on duration of tamoxifen treatment of > 5 years. Recommendations regarding duration of adjuvant endocrine therapy < 5 years, sequencing of therapy, and aromatase inhibitor treatment appear in the 2010 ASCO guideline update on adjuvant endocrine therapy.²

The focused update was developed by a multidisciplinary group of experts (the update committee), who conducted a systematic review of randomized clinical trials from January 2009 to June 2013 and analyzed three historical trials. The recommendations are based on the clinical trial evidence and clinical experience.

What’s New

In brief, five studies of tamoxifen treatment of > 5 years were identified, with the two largest studies with longest follow-up showing a breast cancer survival advantage with a 10-year duration of tamoxifen treatment. In addition, extended therapy with tamoxifen for 10 years compared with 5 years was associated with lower risks of breast cancer recurrence and contralateral breast cancer. 

Previous ASCO guidelines recommended treatment with 5 years of tamoxifen in premenopausal women with hormone receptor–positive breast cancer and a minimum of 5 years of adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor (in sequence) in postmenopausal women. The guideline update recommends that pre- or perimenopausal women who have received 5 years of adjuvant tamoxifen should be offered 10 years total duration of tamoxifen. Postmenopausal women who have received 5 years of adjuvant tamoxifen should be offered the choice of continuing tamoxifen or switching to an aromatase inhibitor for 10 years total adjuvant endocrine therapy.

Recommendations

The central question for the focused update was: What is the recommended duration of adjuvant endocrine monotherapy? The recommendations are summarized below, along with notations for type of evidence, evidence quality, and strength of recommendation.

Pre- or Perimenopausal Women

Women with hormone receptor–positive breast cancer who are pre- or perimenopausal should be offered adjuvant endocrine therapy with tamoxifen for an initial duration of 5 years. After 5 years, women should receive additional therapy based on menopausal status.

Pre- or perimenopausal women and those in whom menopausal status is unknown or cannot be determined should be offered continued tamoxifen for a total duration of 10 years (type = evidence-based, evidence quality = high, strength of recommendation = strong). Women who have become definitively postmenopausal should be offered continued tamoxifen for a total duration of 10 years or a switch to up to 5 years of aromatase inhibitor therapy, for a total duration of treatment of up to 10 years (type = evidence-based, evidence quality for tamoxifen = high, evidence quality for aromatase inhibitor = high, strength of recommendation = strong.)

Postmenopausal Women

Postmenopausal women with hormone receptor–positive breast cancer should be offered adjuvant endocrine therapy with one of the following: (1) tamoxifen for a duration of 10 years (type = evidence-based, evidence quality = high, strength of recommendation = strong); (2) an aromatase inhibitor for 5 years; there are insufficient data to recommend an aromatase inhibitor for a duration > 5 years (type =evidence-based, evidence quality = high, strength of recommendation = strong); (3) tamoxifen for an initial duration of 5 years with a switch to an aromatase inhibitor for up to 5 years, for a total duration of therapy of up to 10 years (type = evidence-based, evidence quality = high, strength of recommendation = strong); or (4) Tamoxifen for a duration of 2 to 3 years with a switch to an aromatase inhibitor for up to 5 years, for a total duration of up to 7 to 8 years (type = evidence-based, evidence quality = high, strength of recommendation = strong).

Appropriate Sequence

Women who are postmenopausal and are intolerant of either tamoxifen or an aromatase inhibitor should be offered the alternative type of endocrine therapy. Women who have discontinued aromatase inhibitor treatment at < 5 years may be offered tamoxifen for a total of 5 years (type = informal consensus, evidence quality = low, strength of recommendation = weak). Women who have received tamoxifen for 2 to 3 years should be offered a switch to an aromatase inhibitor for up to 5 years, for a total duration of up to 7 to 8 years of therapy (type = evidence-based, evidence quality = high, strength of recommendation = strong).

Women who have received 5 years of tamoxifen as adjuvant therapy should be offered additional adjuvant endocrine treatment.  Postmenopausal women should be offered continued tamoxifen for a total duration of 10 years or a switch to aromatase inhibitor treatment for up to 5 years, for a total duration of up to 10 years of therapy (type = evidence-based, evidence quality =high, strength of recommendation = strong). Pre- or perimenopausal women and women in whom menopausal status cannot be ascertained should be offered 5 additional years of tamoxifen, for a total duration of 10 years (type = evidence-based, evidence quality = high, strength of recommendation = strong).

Benefits and Risks

Prospective benefits of implementation of the new recommendations include increased overall survival and distant disease-free survival and reduced breast cancer–specific mortality, risk of recurrence, and risk of contralateral breast cancer.

Potential harms include risk of endometrial cancer (in women continuing tamoxifen), hot flashes and other menopausal symptoms (with either tamoxifen or aromatase inhibitors), deep-vein thrombosis or pulmonary embolism (with tamoxifen), ischemic heart disease (with aromatase inhibitor), osteopenia/osteoporosis (with aromatase inhibitor), and uterine cancer (with tamoxifen).

Qualification

There are no specific patient populations or subgroups, except for menopausal status subgroups that appear to derive differing degrees of benefit from an aromatase inhibitor vs tamoxifen or for the adjuvant treatment durations recommended. Clinicians and patients should discuss a patient’s individual risk-benefit profile.

Patient information on this topic can be found at www.cancer.net. ■

Disclosure: Dr. Burstein reported no potential conflicts of interest. For full disclosures of all the guideline authors, visit jco.ascopubs.org.

References

1. Burstein HJ, Temin S, Anderson H, et al: Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol 32:2255-2269, 2014.

2. Burstein HJ, Prestrud AA, Seidenfeld J, et al: American Society of Clinical Oncology clinical practice guideline: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 28:3784-3796, 2010.