Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer Endocrine Therapy of Metastatic Breast Cancer
Endocrine Therapy of Metastatic Breast Cancer Version 2002: Gerber / Friedrichs Version 2003 2009: Fersis / Friedrich / Gerber / Huober / Janni / Jonat / Kaufmann / Lück / Nitz / Schneeweiß Version 2010: Müller / Stickeler
Endocrine Therapy in Metastatic Breast Cancer Indication Oxford LoE: 1a GR: A AGO: ++ Endocrine therapy represents the first choice for metastatic breast cancer with positive (unknown) hormone receptor status. Exception: acute life threatening disease Cave: HR might change during the course of the disease. Histology of recurrent site should be obtained, when possible
Comparison ER/PR and HER2 Metastasis vs. Primary Tumor 137 pts. with evaluable histopathological results in primary tumors and metastases 10% discordance rate for ER status 25% discordance rate for PR status 3% discordance rate for HER2 status Biopsy of metastases lead to changes of treatment strategy in 18% of all pts. (24/137) Thompson AM, SABCS 2009 # 4053
Endocrine Therapy in Premenopausal Patients with HER2 Negative Metastatic Breast Cancer GnRHa + tamoxifen (vs. OFS or Tam) 1a A ++ Ovarian function suppression (OFS) 2b B + Tamoxifen 2b B + GnRHa + AI after GnRHa + Tam 2b B + Aromatase inhibitors without OFS 3 D - -
Endocrine Therapy in HER2 Negative Metastatic Breast Cancer Treatment options for postmenopausal patients pretreated by adjuvant tamoxifen or nothing Aromatase inhibitors (3rd gen) (> non-ai*) 1a A ++ Tamoxifen (vs no therapy) 1a A ++ Fulvestrant (= AI)** 2b B + Toremifen (= tamoxifen) 1a A +/- MPA/MA (< AI) 1a A +/- Fulvestrant + Anastrozole 2b a B - *There is no evidence for superiority of a single aromatase inhibitor.
Cochrane Meta-Analysis 2009 AI vs. Non-AI in MBC Totally, 31 trials were analyzed Subject: AI (any) vs. non-ai-treatment in MBC pts. 11,403 patients Subgroup analysis: AIs in current clinical use vs. Non-AI treatment: Significant overall survival benefit (HR 0.88, (95% CI 0.80 to 0.96) equivalent to a 12% benefit over all subgroups HR similar for all three Ais Data for PFS not significant (HR 0.93, 95% CI 0.78-1.17); significant heterogeneity Significantly higher rate of CB (HR 0.80, 95% CI 0.66 to 0.97); significant heterogeneity Significantly higher objective response rate (HR 0.79, 95% CI 0.65 to 0.97); significant heterogeneity
Endocrine Therapy in Postmenopausal HER2 Negative Metastatic Breast Cancer Patients after Adjuvant Tamoxifen or no Prior Endocrine Treatment Treatment sequence 1 st line: aromatase inhibitors (3rd gen)* 1a A ++ AI und Celecoxcib 2b B - 2 nd line: fulvestrant 2b B + tamoxifen 3b C + aromatase inhibitor** 2b B + Further lines: MPA/MA 4 D + repeating of previous treatments 5 D + To date, there is no evidence for superiority of a single aromatase inhibitor. ** steroidal or non-steroidal depending on previous AI
Endocrine Therapy in Postmenopausal HER2 Negative Metastatic Breast Cancer Patients after Adjuvant AI Treatment sequence 1 st line: tamoxifen 2b B ++ steroidal after non-steroidal AI non-steroidal after steroidal AI 2b B + 2 nd line: fulvestrant 2b B + tamoxifen (if previously not given) 5 D + Further lines: MPA/MA 4 C + repeating of previous treatments 5 D +/-
Endocrine Therapy in Postmenopausal HER2 Neg. Metastatic Breast Cancer Pts. after Switch Adjuvant Tamoxifen AI If short treatment free intervall: fulvestrant 4 D + aromatase inhibitor* 4 D + tamoxifen 4 D +/- If treatment free intervall > 1 year: tamoxifen 4 D + aromatase inhibitor* 4 D + fulvestrant 4 D +/- * Steroidal or non-steroidal depending on previous AI
Endocrine Therapy in Postmenopausal HER2 Positive Metastatic Breast Cancer Patients Anastrozole and trastuzumab 2b B +/- Letrozole and trastuzumab 2b a B +/- Letrozole and lapatinib 2b B +/- Poor efficacy of endocrine therapy alone. Consider chemotherapy + anti-her2-therapy!
Combination of AI with Anti-HER2-Treatment Treatment PFS (mo) Response OS (mo) (no. of pats) (CBR) Trastuzumab + anastrozole vs. anastrozole (n=207) 4.8 vs. 2.4 (5.6 vs. 3.8 with central comfirmed receptor status) 42.7% vs. 27.9%; 28.5 vs. 23.9 mo; n.s. Trastuzumab + letrozole vs. letrozole (n=57) Lapatinib + letrozole vs. letrozole (n=219) 14 vs. 3.3 27% vs. 13% n.r. 8.2 vs. 3.0 48% v 29% 33.3 vs. 32.3 mo
Concomitant or Sequential Endocrine-Cytostatic Treatment Concomitant endocrine-cytotoxic treatment 1b A - - Increases response rates without prolongation of progression free interval or overall survival Increases toxicity Maintenance endocrine therapy after chemotherapy induced response 3 C ++ Increases progression free interval and overall survival