Women diagnosed with hormone receptor-positive breast cancer who are postmenopausal should be offered adjuvant endocrine therapy with one of the following options: (A) Tamoxifen for a duration of 10 years; or (B) An aromatase inhibitor for a duration of 5 years. There are insufficient data currently to recommend an aromatase inhibitor for a duration of greater than 5 years; or (C) Tamoxifen for an initial duration of 5 years, then a switch to an aromatase inhibitor for up to 5 years, for a total duration of up to 10 years of adjuvant endocrine therapy; (D) Tamoxifen for a duration of 2-3 years and a switch to an aromatase inhibitor for up to 5 years, for a total duration of up to 7-8 years of adjuvant therapy.

Many women with node-negative breast cancer are potential candidates for and may be offered extended aromatase inhibitor therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors. However, as the recurrence risk is lower, the benefits are likely narrower for such patients. Women with low-risk node-negative tumors should not routinely be offered extended therapy.

Women with node-positive breast cancer should be offered extended aromatase therapy for up to a total of 10 years of adjuvant endocrine treatment.

Women who receive extended adjuvant endocrine therapy should receive no more than 10 years of total treatment.

As a prevention of secondary or contralateral breast cancers is a major benefit extended aromatase inhibitor therapy and overall survival is not, the risk of second breast cancers (or not) based on prior therapy should inform the decision to pursue extended treatment.

Extended therapy carries ongoing risks and side effects, which should be weighed against the potential absolute benefits of longer treatment, in a shared decision-making process between the clinical team and the patient.

To date, none of the studies have shown improvement in overall survival with longer-duration aromatase therapy. As such, the recommendations on extended adjuvant aromatase inhibitor therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers [Qualifying statement].

A specific marker or clinical subset that predicts which adjuvant treatment strategy (tamoxifen alone, aromatase inhibitor alone, or aromatase inhibitor and tamoxifen based) is best has not been identified.

Among men with breast cancer, tamoxifen remains the standard adjuvant endocrine treatment.

The CYP2D6 genotype is not recommended to select adjuvant endocrine therapy. Caution with concurrent use of CYP2D6 inhibitors (such as bupropion, paroxetine, or fluoxetine) and tamoxifen is recommended because of drug-drug interactions.

Clinicians should consider adverse effect profiles, patient preferences, and pre-existing conditions when they discuss adjuvant endocrine strategies. Adverse effect profiles should be discussed with patients when available treatment options are presented. Clinicians may recommend that patients change treatments if adverse effects are intolerable or patients are persistently noncompliant with therapy.

Women diagnosed with hormone receptor-positive breast cancer who are pre/perimenopausal should be offered adjuvant endocrine therapy as follows: (A) Tamoxifen for an initial duration for 5 years; (B) After 5 years, women should receive additional therapy based on menopausal status.

If women are pre/perimenopausal or if menopausal status is unknown or cannot be determined, they should be offered continued tamoxifen for a total duration of 10 years.

If women have become definitively postmenopausal, they should be offered continued tamoxifen for a total duration of 10 years or should switch to up to 5 years of aromatase inhibitor for a total duration of up to 10 years of adjuvant endocrine therapy.

Meaningful clinical differences between the commercially available third-generation aromatase inhibitors have not been demonstrated to date. The Update Committee believes that postmenopausal patients intolerant of one aromatase inhibitor may be advised to consider tamoxifen or a different aromatase inhibitor.

Women who are postmenopausal and are intolerant of either tamoxifen or an aromatase inhibitor should be offered the alternative type of adjuvant endocrine therapy.

If women have received an aromatase inhibitor but discontinued treatment at <5 years, they may be offered tamoxifen for a total of 5 years.

If women have received tamoxifen for 2-3 years, they should be offered a switch to an aromatase inhibitor for up to 5 years, for a total duration of up to 7-8 years of adjuvant endocrine therapy.

Women who have received 5 years of tamoxifen as adjvuant endocrine therapy should be offered additional adjuvant endocrine treatment.

If women are postmenopausal, they should be offered continued tamoxifen for a total duration of 10 years of should switch to up to 5 years of aromatase inhibitor for a total duration of up to 10 years of adjuvant endocrine therapy.

If women are pre/perimenopausal or menopausal status cannot be ascertained, they should be offered 5 additional years of tamoxifen for a total of 10 years of adjuvant endocrine therapy.

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

The Panel notes that two prospective studies did not show 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 [Qualifying statement].

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

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

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

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 [Qualifying statement].

To date, there is no adequate evidence to assess the beenfit of adjuvant ovarian suppression in women at sufficient risk to warrant chemotherapy with 10 years of tamoxifen [Qualifying statement].

There is no current role for ovarian suppression as adjuvant therapy in estrogen receptor-negative breast cancers [Qualifying statement].

The long-term effects of ovarian suppression on breast cancer risk and survival are not yet established [Qualifying statement].

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

Tamoxifen and aromatase therapy differ in their adverse effect profiles, which may affect patient preferences [Qualifying statement].

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