title: Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype.
abstract: Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)-targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor-negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor-negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Caimiao
authors.initials: C
authors.lastname: Wei
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Gould
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Andrew
authors.initials: A
authors.lastname: Walls
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Alex
authors.initials: A
authors.lastname: Bousamra
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Maheshwari
authors.initials: M
authors.lastname: Ramineni
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sinn
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hunt
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Abenaa M
authors.initials: AM
authors.lastname: Brewster
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Stacy
authors.initials: S
authors.lastname: Moulder
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Christos
authors.initials: C
authors.lastname: Hatzis
authors.affiliation: W. Fraser Symmans, Caimiao Wei, Rebekah Gould, Xian Yu, Ya Zhang, Maheshwari Ramineni, Kelly Hunt, Thomas A. Buchholz, Vicente Valero, Aman U. Buzdar, Wei Yang, Abenaa M. Brewster, Stacy Moulder, and Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston; Andrew Walls, Uniformed Services University of the Health Sciences, San Antonio, TX; Mei Liu, The General Hospital of People's Liberation Army, Beijing, China; Alex Bousamra, Allegheny General Hospital, Pittsburgh, PA; Bruno Sinn, Charite-Universitatsmedizin, Berlin, Germany; and Lajos Pusztai and Christos Hatzis, Yale University School of Medicine, New Haven, CT.
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual; D017239:Paclitaxel / Q000008:administration & dosage; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D018570:Risk Assessment; D015996:Survival Rate; D013997:Time Factors; D000068878:Trastuzumab / Q000008:administration & dosage; D047368:Tumor Burden
chemical_list: D003520:Cyclophosphamide; D004317:Doxorubicin; D015251:Epirubicin; D005472:Fluorouracil; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human