title: Modulatory effect of neoadjuvant chemotherapy on biomarkers expression; assessment by digital image analysis and relationship to residual cancer burden in patients with invasive breast cancer.
abstract: The use of digital imaging techniques for biomarker assessment has gained recognition as a valid tool for clinical use. In this study, we used image analysis for evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2), Ki-67 index, and p53 in 172 patients with invasive breast cancer treated with neoadjuvant chemotherapy and compared it with an untreated group (100 cases). We also examined the relationship between biomarker expression and the extent of residual disease using the Web-based MD Anderson residual cancer burden (RCB) calculator. Residual disease was classified as RCB 0/I, II, and III corresponding to complete/near-complete response, moderate, and extensive residual disease, respectively. Overall change in ER, PR, and HER2 status in the treated group was seen in 9.02% (P = .0148), 18.4% (P = .011), and 12.0% (P = .0042), respectively. Change in HER2 status, positive to negative and negative to positive, occurred in 27.2% and 7.0%, respectively. The group with RCB 0/I was frequently younger (P = .0057) and showed higher ER(-) status (P = .0316), lower ER scores (P = .0103), higher Ki-67 index (P = .0008), and p53 (P = .0055) compared with those with RCB II and III. Pathologic tumor stage (P = .0072), lumpectomy versus mastectomy (P = .0048), and p53 expression (P = .0190) were independent predictors of recurrence-free survival. The RCB categories (P = .0003) and tumor grade (P = .0049) were independent predictors of overall survival. This is the first study to conduct a comprehensive analysis of biomarkers in neoadjuvant chemotherapy-treated patients versus an untreated group using the digital image analysis method. We have demonstrated for the first time the relationship between RCB, tumor biomarkers expression, and clinical outcome.
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, TX 77843, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Cockburn
authors.affiliation: Department of Clinical Science, UT Southwestern Medical Center, Dallas, TX 77843, USA.
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Clinical Science, UT Southwestern Medical Center, Dallas, TX 77843, USA.
authors.forename: Dewi
authors.initials: D
authors.lastname: Rahardja
authors.affiliation: Department of Surgery, UT Southwestern Medical Center, Dallas, TX 77843, USA.
authors.forename: David
authors.initials: D
authors.lastname: Euhus
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, TX 77843, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, TX 77843, USA.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, TX 77843, USA. Electronic address: venetia.sarode@utsouthwestern.edu.
authors.forename: Venetia
authors.initials: V
authors.lastname: Rumnong Sarode
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D012189:Retrospective Studies; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53
keywords: Breast biomarkers; Neoadjuvant chemotherapy; Residual cancer burden