Clinicians should be alert to the possibility of incomplete ovarian suppression with gonadotropin-releasing hormone agonist therapy and evaluate patients for whom there is concern about residual ovarian function.

— Harold J. Burstein, MD, PhD and colleagues

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As reported in the Journal of Clinical Oncology by Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues, ASCO has released a clinical practice guideline update on ovarian suppression as part of the extant guideline on adjuvant endocrine therapy in hormone receptor–positive breast cancer.¹ The update is based on an update panel review of recent randomized clinical trial data on ovarian suppression. The panel recommendations are reproduced here.

Guideline Questions

The guideline update addressed the following questions with regard to premenopausal women with stage I to III hormone receptor–positive breast cancer:

(1) Should premenopausal women with estrogen receptor–positive tumors receive adjuvant ovarian suppression in addition to standard adjuvant therapy, and, if so, in which subsets of patients?

(2) If ovarian suppression is recommended, should ovarian suppression be administered in combination with tamoxifen or an aromatase inhibitor?

Recommendation 1

1.1—The panel recommends that higher-risk patients should receive ovarian suppression in addition to adjuvant endocrine therapy, whereas lower-risk patients should not.

Qualifying Statement: The panel notes that two prospective studies did not show an overall clinical benefit for the addition of ovarian suppression to tamoxifen in premenopausal, estrogen receptor–positive breast cancer. However, in a large subset of women with higher-risk cancers, nearly all of whom received chemotherapy but remained premenopausal, ovarian suppression added to tamoxifen reduced the risk of breast cancer recurrence. Because of the design of the clinical trials, there are few definitive criteria by which to define risk.

1.2—Women with stage II or III breast cancers who would ordinarily be advised to receive adjuvant chemotherapy should receive ovarian suppression in addition to endocrine therapy.

1.3—Women with stage I or II breast cancers at higher risk of recurrence, who might consider chemotherapy, may also be offered ovarian suppression in addition to endocrine therapy.

1.4—Women with stage I breast cancers not warranting chemotherapy should receive endocrine therapy but not ovarian suppression.

1.5—Women with node-negative cancers 1 cm or less (T1a, T1b) should receive endocrine therapy but not ovarian suppression.

[Benefits: increasing disease-free survival, freedom from breast cancer, and freedom from distant recurrence. Harms: worse menopausal symptoms and sexual functioning, including hot flashes, sweating, weight gain, vaginal dryness, and decreased libido.] [Evidence quality = intermediate. Recommendation type = evidence-based and consensus. Recommendation strength = moderate.]

Qualifying Statements

• The standard duration of ovarian suppression in the included trials was 5 years. With no comparative data available on alternative durations, the panel supports ovarian suppression for 5 years.
• To date, there is no adequate evidence for assessing the benefit of adjuvant ovarian suppression in women at sufficient risk to warrant chemotherapy compared with 10 years of tamoxifen.
• There is no current role for ovarian suppression as adjuvant therapy in estrogen receptor–negative breast cancers.
• There are substantial adverse effects to ovarian suppression. Clinicians and patients should consider the trade-offs of adverse effects when choosing ovarian suppression.
• The long-term effects of ovarian suppression on breast cancer risk and survival are not yet established.

Recommendation 2

2—Ovarian suppression may be administered with either tamoxifen or an aromatase inhibitor.

[Benefits: increasing disease-free survival, freedom from breast cancer, and freedom from distant recurrence. Harms: worse menopausal symptoms and sexual functioning, including hot flashes, sweating, weight gain, vaginal dryness, and decreased libido; osteopenia/osteoporosis.] [Evidence quality = high. Recommendation type = evidence based. Recommendation strength = strong.]

Qualifying Statements

• Tamoxifen and aromatase inhibitor therapy differ in their adverse-effect profiles, which may affect patient preferences.
• Clinicians should be alert to the possibility of incomplete ovarian suppression with gonadotropin-releasing hormone agonist therapy and evaluate patients for whom there is concern about residual ovarian function. ■

Disclosure: For full disclosures of the study authors, visit www.jco.ascopubs.org.

Reference

1. Burstein HJ, Lacchetti C, Anderson H, et al: Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression. J Clin Oncol 34:1689-1701, 2016.

Editor’s note: As we went to press, further recommendations about endocrine therapy for hormone receptor–positive metastatic breast cancer were published online in the Journal of Clinical Oncology by Hope S. Rugo, MD, of University of California, San Francisco, Comprehensive Cancer Center, and colleagues. Watch future issues of The ASCO Post for highlights of this clinical practice guideline.