Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer

AI: aromatase inhibitor; FSH: follicle-stimulating hormone; GnRHa: gonadotropin-releasing hormone agonist.
* For women with breast cancer who were premenopausal at diagnosis, particularly those treated with adjuvant chemotherapy, amenorrhea is not a reliable indicator of menstrual status. We agree with the following definitions of menopause used by the National Comprehensive Cancer Network:^[1]

• Women 60 years and older are postmenopausal.
• Women less than 60 years are postmenopausal if one of the following conditions is met:
  • They previously underwent a bilateral oophorectomy.
  • They have not had any menstrual periods for 12 months or more in the absence of tamoxifen, chemotherapy, or ovarian suppression, and the serum estradiol is in the postmenopausal range.
  • They are amenorrheic on tamoxifen, and FSH and serum estradiol are in the postmenopausal range.

¶ For postmenopausal women with non-metastatic, hormone receptor-positive breast cancer, we suggest an AI rather than tamoxifen as adjuvant endocrine treatment. While AIs are associated with improved outcomes compared with tamoxifen, both agents reduce recurrences and new primary breast cancers, and some women may tolerate the risks and toxicities of tamoxifen better than an AI. For women who wish to discontinue an AI, it would be reasonable to switch to tamoxifen. Refer to UpToDate topic on adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer.
Δ Although AIs with ovarian suppression (or ablation) are the preferred option for premenopausal women with breast cancer that has high-risk features, decisions regarding treatment are individualized based on patients' preferences, other health issues, and tolerance of therapy. Alternative options for select patients may include ovarian suppression with tamoxifen or tamoxifen alone. For those initiating ovarian suppression, we typically start with a GnRHa and continue it for the duration of endocrine therapy, or offer oophorectomy, if ovarian suppression has been well tolerated.
◊ In counseling patients regarding a possible transition to an AI, we discuss the modest improvements in efficacy with AIs over tamoxifen, as well as the respective side effect profiles. Decisions regarding treatment are individualized based on patients' preferences, anticipated remaining duration of therapy (both if continuing on tamoxifen or if transitioning to an AI), tolerance of therapy, and other health issues. Refer to UpToDate discussions on adjuvant endocrine therapy for hormone receptor-positive breast cancer.
§ Depending on duration of remaining treatment, one could reassess FSH and estradiol in 12 months, and consider a transition to an AI at that time, if values are in the postmenopausal range.