title: Semiquantitative hormone receptor level influences response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer.
abstract: Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in hormone receptor-negative/HER2+ tumors is seen in 27-45% of cases. In contrast, estrogen receptor (ER)+/HER2+ tumors demonstrate pathologic complete response in ∼ 8% of cases and is generally limited to weak-to-moderate ER+/HER2+ tumors. It is speculated that addition of trastuzumab to neoadjuvant chemotherapy regimen will increase the pathologic complete response rates in all HER2+ tumors. A list of HER2+ patients who received neoadjuvant chemotherapy (with trastuzumab) in the years 2007-2010 was obtained from our hospital database. The 104 HER2+ tumors were classified into three groups based on semiquantitative hormone receptor and HER2 results as follows: ERBB2 (ER-/PR-[H-score ≤10]/HER2+), Luminal B-HER2 Hybrid (LBHH; weak to moderate ER+ [H-score 11-199]/HER2+), and Luminal A-HER2 Hybrid (LAHH; strong ER+[H-score ≥200]/HER2+). Pathologic complete response was defined as absence of invasive carcinoma in the resection specimen and in the lymph nodes. Percentage tumor volume reduction was also calculated based on pretherapy size and detailed evaluation of the resection specimen. In all, 52% (25 of 48 cases) of ERBB2 tumors showed pathologic complete response, which was significantly higher than the pathologic complete response rate in LBHH (33%; 10 of 30) and LAHH (8%; 2 of 26) tumors. Average percentage tumor volume reduction was also highest in ERBB2 tumors (86%), followed by LBHH (74%) and LAHH (64%) tumors. We conclude that addition of trastuzumab to neoadjuvant chemotherapy regimen significantly increases the pathologic complete response rates in all HER2+ tumors. However, the benefit of trastuzumab is highest in ER-negative tumors and progressively decreases with increase in tumor ER expression. This information can be utilized to counsel patients considered for neoadjuvant chemotherapy and the same principle could be applied in the adjuvant setting.
authors.affiliation: Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. rbhargava@mail.magee.edu
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhargava
authors.forename: David J
authors.initials: DJ
authors.lastname: Dabbs
authors.forename: Sushil
authors.initials: S
authors.lastname: Beriwal
authors.forename: Isil A
authors.initials: IA
authors.lastname: Yildiz
authors.forename: Preeti
authors.initials: P
authors.lastname: Badve
authors.forename: Atilla
authors.initials: A
authors.lastname: Soran
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Johnson
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.forename: Barry C
authors.initials: BC
authors.lastname: Lembersky
authors.forename: Kandace P
authors.initials: KP
authors.lastname: McGuire
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Ahrendt
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D000068878:Trastuzumab; C508053:ERBB2 protein, human