ABSTRACT
PURPOSE: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. PATIENTS AND METHODS: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). RESULTS: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. CONCLUSIONS: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.
Subject(s)
Aromatase Inhibitors , Breast Neoplasms , Polymorphism, Single Nucleotide , Humans , Female , Aromatase Inhibitors/therapeutic use , Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Middle Aged , Aged , Prospective Studies , Anastrozole/therapeutic use , Anastrozole/adverse effects , Anastrozole/administration & dosage , Cohort Studies , Postmenopause , Aged, 80 and over , Patient Reported Outcome Measures , Aromatase/geneticsABSTRACT
Background and Presentation: In this study, we present the case of a 64-year-old female with a chief complaint of abdominal pain and bloating, which had been persistent over a period of 4 months. Imaging revealed a 6.1-cm left-sided pancreatic mass as well as a 19.1-cm multiloculated cystic lesion in the pelvis, later revealed to be replacing the left ovary. The pancreatic mass was biopsied through endoscopic ultrasound-guided fine needle aspiration, and diagnosed as adenocarcinoma by cytology. The patient was treated with neoadjuvant chemotherapy and radiation before laparotomy for resection of the pancreas and left adnexal mass. Her response to treatment was followed radiologically and biochemically with cancer antigen (CA) 19-9 (114-35 U/mL), carcinoembryonic antigen (12-4.8 ng/mL), and CA-125 (119-15.3 U/mL) levels. She subsequently underwent an Appleby procedure, and resection of left pelvic mass and bilateral oophorectomy. Permanent sections revealed residual pancreatic ductal carcinoma with treatment effect, and a multicystic epithelial neoplasia of the left ovary for which the differential was primary ovarian carcinoma versus metastatic disease. Conclusions: Molecular mutational analysis was performed on sections of both the ovarian tumor and the pancreatic tumor to aid in diagnosis. The ovarian tumor in this case showed exactly the same mutations, KRAS G12R and TP53 G245S, as in the treated pancreatic cancer. This raised the high probability that these tumors originated from the same clonal event. The findings suggested that the ovarian tumor was an isolated metastasis of the pancreatic primary, despite the morphologic ambiguity between the two sites of neoplasia.
