4.1. Combination of ovarian suppression either exemestane or tamoxifen in premenopausal women

In patients with ER+ tumors, pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective

Tamoxifen is the best established SERM, has favorable effects on breast cancer control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For

Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity

The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced breast cancer compared with SERMs. In postmenopausal patients with ER+ breast cancer adjuvant treatment with AIs should be performed, either as

According to NCCN guidelines [49], subdivide the adjuvant endocrine therapy recommendations in HR+ breast cancer patients based on the menopausal status of women. Three main subgroups are (i) postmenopausal at initial diagnosis, (ii) premenopausal at initial diagnosis and remain premenopausal after 5 years of adjuvant ET, (iii) premenopausal at initial diagno-

• initially tamoxifen for 2–3 years followed by an AI to complete 5 years of adjuvant

• tamoxifen for 4.5–6 years followed by 5 years of an AI (category 1) or consideration

• Five years up to 10 years of tamoxifen without AI should only be given to patients

ii. premenopausal at initial diagnosis and remain premenopausal after 5 years of adjuvant ET

• tamoxifen with or without ovarian suppression for 5 years (category 1)

iii. premenopausal at initial diagnosis, but become postmenopausal during adjuvant ET.

Decision of menopausal status is the most important point because amenorrhea does not mean menopause, because ovaries may continue to product estrogens in amenorrheic women. Thus, before starting AI without ovarian suppression, serum LH, FSH and estra-

• an AI with ovarian suppression for 5 years (category 1)

• initially tamoxifen for 2–3 years followed by 5 years of AI (category 2B),

than adjuvant chemotherapy alone.

in the uterus.

136 Breast Cancer and Surgery

these reasons, other SERMs have been developed.

sequential treatment after tamoxifen or as upfront therapy.

sis, but become postmenopausal during adjuvant ET.

of tamoxifen for up to 10 years.

who have a contraindication to AI.

• tamoxifen continuing up to 10 years

• an AI as initial adjuvant therapy for 5 years (category 1),

i. postmenopausal at initial diagnosis:

ET (category 1),

diol must be evaluated.

The initial results from the Suppression of Ovarian Function Trial (SOFT) indicate that tamoxifen is a suitable therapy for premenopausal women with low risk clinical-pathologic features. For women at sufficient risk to receive chemotherapy who have premenopausal E2 levels within 8 months of completion, the addition of ovarian suppression to tamoxifen for 5 years resulted in some reduction of recurrence. The use of ovarian suppression combined with an AI exemestane for 5 years resulted in further reduction of recurrence [50, 51].

The joint analysis of SOFT and Tamoxifen and Exemestane Trial (TEXT) found the combination of ovarian suppression and exemestane significantly reduced recurrence, compared with ovarian suppression plus tamoxifen. Premenopausal women with ER+ve HER2-negative breast cancer with high-risk features can derive a meaningful improvement in 5-year invasive breast cancer-free interval with exemestane plus ovarian suppression, as an alternative to tamoxifen. Very young women under age 35 with ER+ve breast cancer have higher risks of recurrence, and the use of ovarian suppression with oral endocrine therapy should be considered.
