Board Review

A 43-year-old woman undergoes follow-up evaluation following a recent diagnosis of estrogen receptor–positive, progesterone receptor–positive, HER2-negative, grade 2 invasive ductal carcinoma of the left breast. The patient was treated with surgery, adjuvant chemotherapy, and radiation therapy. This is her first postradiation visit. She currently takes no medications. She is premenopausal.

On physical examination, vital signs are normal. Well-healed incisions of the left breast and left axilla are present. There is no lymphadenopathy and no right breast masses. The remainder of the examination is unremarkable.

Results of a complete blood count and serum chemistry panel are normal.

Which of the following is the most appropriate therapy?

A) Exemestane alone

B) Tamoxifen alone

C) Maintenance chemotherapy with oral capecitabine

D) No additional adjuvant therapy

Answer: B - Tamoxifen alone

Objective: Treat a premenopausal patient who has completed breast cancer therapy with antiestrogen therapy.

Key Point

The recommended adjuvant endocrine therapy following breast cancer treatment for a premenopausal patient is tamoxifen for at least 5—preferably 10—years.

This patient, who has completed breast surgery, adjuvant chemotherapy, and primary breast radiation, should now be started on antiestrogen therapy. Tamoxifen has been the standard treatment in premenopausal women. As her breast cancer is estrogen receptor positive, adjuvant antiestrogen therapy will reduce her risk of distant recurrence by 40% to 50%. For premenopausal women with hormone receptor–positive early-stage breast cancer, tamoxifen should be used for at least 5 years—preferably 10 years based on the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and Adjuvant Tamoxifen Treatment Offers More (aTTom) trials.

Exemestane is an aromatase inhibitor that blocks peripheral conversion of androgens to estrogens. Aromatase inhibitors are therefore used only in postmenopausal women in whom the primary source of estrogen is peripheral conversion of adrenal androgens; therapy with exemestane alone would therefore not be appropriate in the woman with residual ovarian function. However, exemestane has recently been compared with tamoxifen in conjunction with ovarian suppression in premenopausal women. The Tamoxifen and Exemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT) trials have shown improved disease-free survival at 5 years for exemestane with ovarian suppression compared to tamoxifen with ovarian suppression, and this is now an option that can be discussed with premenopausal patients, particularly those at high risk of recurrence. There is at present no difference in breast cancer mortality between these two treatments and the toxicity analysis of these treatments with ovarian suppression compared to tamoxifen alone has not yet been done. A recent study has demonstrated that extending aromatase therapy for 10 years resulted in higher disease free survival and reduced cancer in the contralateral breast.

There is no evidence that maintenance chemotherapy is effective in early stage breast cancer and it has not been used outside of a clinical trial.

Without antiestrogen adjuvant therapy, the patient's risk of distant recurrence will increase. As above, antiestrogen therapy reduces the risk of breast cancer distant recurrence by 40 to 50% and also decreases the risk of contralateral breast cancers by 50%. Its use should be recommended in this patient with hormone receptor–positive early-stage breast cancer.

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. 2014 Jul 20;32(21):2255-69. Link Out