title: First do no harm: population-based study shows non-evidence-based trastuzumab prescription may harm elderly women with breast cancer.
abstract: Trastuzumab, although cardiotoxic, is associated with improved survival in HER2-positive breast cancer. Non-compliance with HER2 testing guidelines before prescribing trastuzumab occurs in practice; however, the clinical consequences are unclear. Using SEER-Medicare database (2000-2009), we assessed differences in baseline characteristics between women ≥ 65 with breast cancer who received and did not receive HER2 testing prior to trastuzumab prescription. We used propensity score matched-pair analysis to balance the confounders between these two groups. We assessed the differences in overall survival and 3-year rates of avoiding congestive heart failure (CHF) between women who received trastuzumab without HER2 testing (trastuzumab group) and women who had chemotherapy but did not receive trastuzumab (irrespective of testing) (chemo-only group). Based on the matched data, we used Cox regression in these assessments with double robust estimation or with stratification. Among women who received trastuzumab, 140 (4.7 %) had no documentation of HER2 testing. Breast surgery, south residential region, and an earlier year of diagnosis were predictive of no HER2 testing in multivariate logistic regression. Women in the chemo-only group had similar overall survival (HR = 1.28; P = 0.108) over an 8-year follow-up post-diagnosis and significantly higher likelihood of avoiding CHF over 3 years after the first administration of chemotherapy or trastuzumab (HR = 1.66, P = 0.036) compared to women in the trastuzumab group, using the propensity score-matched data. Non-evidence-based prescription of trastuzumab is associated with increased rates of CHF with no additional survival benefit among older women with breast cancer. Inappropriate prescriptions of targeted therapies agent can lead to detrimental health and financial consequences.
authors.affiliation: Section of Hospital Medicine, Department of Medicine, Program in the Economics of Cancer, The University of Chicago, 5841 S Maryland Avenue, MC 5000, 60637, Chicago, IL, USA, tshih@bsd.uchicago.edu.
authors.forename: Ya-Chen Tina
authors.initials: YC
authors.lastname: Shih
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Wenli
authors.initials: W
authors.lastname: Dong
authors.forename: Fabrice
authors.initials: F
authors.lastname: Smieliauskas
authors.forename: Sharon
authors.initials: S
authors.lastname: Giordano
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000367:Age Factors; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab