November 2017 VOL 8, NO 11
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Treatment Options for Premenopausal Women with Hormone Receptor–Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced Breast Cancer (ABC)
Jill Schwartz Gomez, RN; Mary Lynn Breslin, RN, BSN, OCN
MD Anderson Cancer Center, Houston, TX
Background: Breast cancer occurs predominantly in older, postmenopausal women (>50 years), although the incidence of ABC in younger, premenopausal women is increasing.1 Younger patients often experience aggressive disease and are more likely to die of their cancer compared with older women.2,3 Current treatment guidelines recommend endocrine therapy (ET) as the standard treatment for HR+, HER2-negative ABC; however, acquired resistance to therapy usually occurs. In the postmenopausal setting, addition of targeted agents to first-line ET has substantially extended median progression-free survival (PFS) from ~15 to ~25 months with no adverse effect on quality of life.4,5 There remains an unmet need for improved treatment outcomes in the premenopausal population.
Objectives: Summarize available data on the treatment of premenopausal women with HR+, HER2-negative ABC and highlight ongoing studies.
Methods: A literature search of PubMed was performed (search terms: “premenopausal,” “breast cancer,” “HR+,” “hormone receptor positive,” “estrogen receptor positive,” “HER2,” “HER2-negative,” “metastatic,” “advanced”). Results were filtered for relevance, HER2 status, and clinical trials. Clinicaltrials.gov was searched to evaluate ongoing studies.
Results: PubMed yielded 160 publications, with 13 studies considered relevant. Use of tamoxifen ±gonadotropin-releasing hormone agonists (GnRHa) is an established therapy for premenopausal ABC, with median PFS ~8 to 11 months and objective response rate (ORR) 30% to 39% (meta-analysis of patients with any HER2 status).6 Of the 695 patients enrolled in prospective, interventional studies of premenopausal HR+, HER2-negative ABC, 552 (79%) were from Asian countries. One study (N = 35; USA) tested a first-line intervention, anastrozole plus goserelin, with median PFS 8.3 months and ORR 37.5%.7 Of the second-line studies, the longest reported median PFS was 13 months for exemestane plus goserelin, with ORR 38.6% (N = 44; China).8 Common adverse events from ET ±GnRHa include hot flashes, joint pain, and fatigue. Only 1 study tested a combination targeted therapy plus GnRHa: PALOMA-3 investigated palbociclib plus fulvestrant plus goserelin versus placebo plus fulvestrant plus goserelin in a subset of pre/perimenopausal patients (median PFS 9.5 months vs 5.6 months; ORR 25% vs 11%; N = 108; international); common adverse events were neutropenia, leukopenia, fatigue, and infections.9 Seventeen ongoing clinical trials allowing enrollment of premenopausal patients were identified, including 3 phase 3 studies (all requiring GnRHa): MONARCH-2 is a placebo-controlled study of abemaciclib plus fulvestrant in women progressing on ET with a premenopausal subset; COMPLEEMENT-1 is a single-arm study of ribociclib plus letrozole as first-line treatment (any menopausal status); and MONALEESA-7 is a placebo-controlled study of ribociclib plus tamoxifen/nonsteroidal aromatase inhibitor as first-line treatment for premenopausal women. MONALEESA-7 is the only phase 3 study that is dedicated entirely to premenopausal women. Additional interventions being tested in phase 1/2 studies include novel double and triple combinations of ET plus other targeted therapies and/or chemotherapy.
Conclusions: There is an unmet need for improved treatment options for premenopausal ABC, with the current longest reported median PFS being 13 months. Data are eagerly anticipated from MONALEESA-7, the largest trial of first-line combined targeted therapy for premenopausal patients (N ≈ 672). Finally, nurse awareness of trials and enrollment opportunities could facilitate greater participation among premenopausal women.
Disclosure: This study was supported by Novartis Pharmaceuticals Corporation.
- Johnson RH, Chien FL, Bleyer A. Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. JAMA. 2013;309:800-805.
- Anders CK, Hsu DS, Broadwater G, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008;26:3324-3330.
- Partridge AH, Hughes ME, Ottesen RA, et al. The effect of age on delay in diagnosis and stage of breast cancer. Oncologist. 2012;17:775-782.
- Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC). J Clin Oncol. 2017;35(suppl). Abstract 1038.
- Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375:1925-1936.
- Klijn JG, Blamey RW, Boccardo F, et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol. 2001;19:343-353.
- Carlson RW, Theriault R, Schurman CM, et al. Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor-positive, metastatic carcinoma of the breast in premenopausal women. J Clin Oncol. 2010;28:3917-3921.
- Wang J, Xu B, Yuan P, et al. Phase II trial of goserelin and exemestane combination therapy in premenopausal women with locally advanced or metastatic breast cancer. Medicine (Baltimore). 2015;94(26):e1006.
- Loibl S, Turner NC, Ro J, et al. Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 results. Oncologist. 2017;22:1028-1038.
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