title: Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II-III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance).
abstract: It had been previously shown that patients who receive neoadjuvant systemic therapy (NST) are more likely to undergo breast-conserving therapy (BCT) than those who have primary surgery. However, the frequency with which patients who are not BCT-eligible prior to NST convert to BCT-eligible with treatment is unknown. To document this conversion rate in a subset of patients expected to have a high clinical response rate to NST, we studied surgical assessment and management of patients enrolled on a randomized neoadjuvant trial for stage II-III HER2-positive breast cancer (HER2 + BC)(CALGB 40601).
  
  
  
  The treating surgeon assessed BCT candidacy based on clinico-radiographic criteria both before and after NST. Definitive breast surgical management was at surgeon and patient discretion. We sought to determine (1) the conversion rate from BCT-ineligible to BCT-eligible (2) the percentage of BCT-eligible patients who chose breast conservation, and (3) the rate of successful BCT. We also evaluated surgeon-determined factors for BCT-ineligibility and the correlation between BCT eligibility and pathologic complete response (pCR).
  
  
  
  Of 292 patients with pre- and post-NST surgical assessments, 59 % were non-BCT candidates at baseline. Of the 43 % of these patients who converted with NST, 67 % opted for BCT, with an 80 % success rate. NST increased the BCT-eligible rate from 41 to 64 %. Common factors cited for BCT-ineligibility prior to NST including tumor size (56 %) and probable poor cosmetic outcome (26 %) were reduced by 67 and 75 %, respectively, with treatment, while multicentricity, the second most common factor (33 %), fell by only 16 %. Since 23 % of the BCT-eligible patients chose mastectomy, BCT was the final surgical procedure in just 40 % of the patients. Patients considered BCT-eligible both at baseline and after NST had a pCR rate of 55 %, while patients who were BCT-ineligible prior to NST had the same pCR rate (44 %) whether they converted to BCT-eligible or not.
  
  
  
  Many patients with HER2 + BC deemed ineligible for BCT at baseline can be converted to BCT-eligible with NST; excluding patients with multicentric disease substantially increases that percentage. In converted patients who opt for BCT, the success rate is similar to that of patients considered BCT-eligible at baseline. Whether a BCT-ineligible patient converts to BCT eligibility or not does not appear to affect the likelihood of achieving a pCR. Despite the efficacy of NST in this patient cohort, only 40 % of patients had successful BCT; further research into why BCT-eligible patients often opt for mastectomy is needed.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. mgolshan@partners.org.
authors.forename: Mehra
authors.initials: M
authors.lastname: Golshan
authors.affiliation: Alliance Statistics and Data Center, Duke University Medical Center, Durham, NC, USA.
authors.forename: Constance T
authors.initials: CT
authors.lastname: Cirrincione
authors.affiliation: Program in Women's Oncology, Women and Infants Hospital of Rhode Island and Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Sikov
authors.affiliation: Department of Medical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.affiliation: Alliance Statistics and Data Center, M D Anderson Cancer Center, Houston, TX, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Overmoyer
authors.affiliation: Department of Medical Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Nora L
authors.initials: NL
authors.lastname: Henry
authors.affiliation: Department of Medical Oncology, City of Hope Medical Center, Los Angeles, CA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.affiliation: Department of Surgery, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Port
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.affiliation: Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Winer
authors.affiliation: Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Ollila
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008408:Mastectomy; D015412:Mastectomy, Segmental / Q000379:methods; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast conserving therapy; HER2-positive breast cancer; Neoadjuvant therapy