Adjuvant therapy decisions for premenopausal ER+ve breast cancer are challenging. An analysis from TEXT found that therapy varied by geography.1 Approximately half the women with node negative tumors enrolled from North America received optional adjuvant chemotherapy, in addition to protocol ovarian suppression plus oral endocrine therapy, while only one quarter of women with node negative tumors enrolled from Italy received chemotherapy. For women with node positive tumors, the use of chemotherapy was almost universal (93%) in North America, while 27% enrolled from Italy did not receive chemotherapy.

Use of multigene assays may reduce future use of chemotherapy in ER+ve breast cancer, however limited information exists for outcomes of young women with low risk assay results, treated with tamoxifen alone. Among 6,693 women enrolled in MINDACT, only 44 women were under age 35 with low genomic risk.2 Only 58 women aged 40 or under were included in the Tailor-X Recurrence Score 0-10 cohort and not all received tamoxifen alone.3

Chemotherapy may provide an indirect endocrine effect in premenopausal ER+ve breast cancer, due to suppression of ovarian estrogen production. The EBCTCG meta-analysis published in 1998 reported that 5 years of adjuvant tamoxifen was effective, regardless of age, menopausal status or chemotherapy.4 Adjuvant ovarian ablation is effective for women under 50 as a sole adjuvant therapy,5 but the value of ovarian suppression/ablation in premenopausal women with ER+ve tumors who also receive tamoxifen, with or without adjuvant chemotherapy, has been uncertain.6

SOFT randomized premenopausal women with hormone receptor-positive breast cancer to receive 5 years of tamoxifen or tamoxifen plus ovarian suppression or exemestane plus ovarian suppression.7 The initial results, after median 5.6 years follow-up, did not show a significant benefit from addition of ovarian suppression to tamoxifen in the overall premenopausal population. SOFT was stratified by use of prior chemotherapy and in the cohort who did not receive chemotherapy, women allocated tamoxifen alone had few recurrences and virtually no distant recurrences during the first 5 years. However, for patients in SOFT deemed at sufficient risk to receive chemotherapy and who remained premenopausal, the addition of ovarian suppression to tamoxifen did reduce risk of invasive recurrence during the first 5 years, and the use of exemestane with ovarian suppression further reduced recurrence. The joint analysis of TEXT and SOFT found that exemestane plus ovarian suppression significantly improved DFS compared with tamoxifen plus ovarian suppression.8 The absolute benefit of endocrine therapies that included ovarian suppression in SOFT and TEXT, as compared with tamoxifen alone, was most striking in women under age 35, although women with a high risk of recurrence from a combination of clinical-pathologic factors (composite risk) could also derive benefit.9

References:

1. Regan et al. Ann Oncol 2008; 19: 1231-1241

2. Cardoso et al. NEJM 2016; 375:718-29

3. Sparano et al. NEJM 2015; 373:2005-14

4. EBCTCG. Lancet 1998; 351:1451-67

5. EBCTCG. Lancet 1992; 339:1-15

6. EBCTCG. Lancet 2007; 369:1711-23

7. Francis et al. NEJM 2015; 372: 436-446

8. Pagani et al, NEJM 2014; 371:107-18

9. Regan et al. J Clin Oncol 2016; 34: 2221-31

Citation Format: Francis PA. Adjuvant endocrine therapy for premenopausal ER+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr CS1-1.