title: Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design (ECTO II).
abstract: Sequential doxorubicin/paclitaxel (AT) followed by CMF treatment was shown to be an active neoadjuvant chemotherapy regimen in the first European Cooperative Trial in Operable Breast Cancer (ECTO I trial). The aim of the current study (ECTO II) is to assess the complete pathological response (pCR) rate following three different anthracycline and taxane-containing neoadjuvant chemotherapy regimens, with or without capecitabine (X). Patients with operable, invasive breast cancer > 2.0 cm in diameter, were randomized to AT→CMF, AT→CMX or AC→TX regimens in two parallel, randomized, open-label, phase II trials (within a single study) in patients with estrogen receptor negative (ER-) and estrogen receptor positive (ER+) diseases, respectively. Exemestane was delivered concomitantly with neoadjuvant chemotherapy in ER+ tumors. Achievement of pCR was more common in ER- than ER+ women (45.3 vs. 10.4%). Capecitabine was only associated with a higher frequency of pCR in ER+ patients receiving AT→CMX. Overall response rates (ORR) ranged from 88 to 97%, and this translated into high rates of breast-conserving surgery (67% of ER- patients and 72% of ER+ patients). All three regimens were well tolerated. Febrile neutropenia and gastrointestinal effects were the most common grade ≥ 3 adverse events. As expected, the ECTO II study showed higher pCR rates in patients with ER- disease. Substituting capecitabine for fluorouracil (± methotrexate) in anthracycline/taxane-containing regimens appeared to be beneficial only in ER+ tumors. Translational studies investigating interactions between therapeutic agents and tumor biology are warranted to refine patient selection and improve the results of neoadjuvant chemotherapy.
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Milvia
authors.initials: M
authors.lastname: Zambetti
authors.forename: Mauro
authors.initials: M
authors.lastname: Mansutti
authors.forename: Patricia
authors.initials: P
authors.lastname: Gomez
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Christian
authors.initials: C
authors.lastname: Dittrich
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamagni
authors.forename: Eva
authors.initials: E
authors.lastname: Ciruelos
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pavesi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Elena
authors.initials: E
authors.lastname: De Benedictis
authors.forename: Fernando
authors.initials: F
authors.lastname: Gaion
authors.forename: Mario
authors.initials: M
authors.lastname: Bari
authors.forename: Paolo
authors.initials: P
authors.lastname: Morandi
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Gianni
authors.initials: G
authors.lastname: Luca
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D018365:Neoplasm, Residual; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D011960:Receptors, Estrogen / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D011960:Receptors, Estrogen; D003841:Deoxycytidine; D000069287:Capecitabine; D004317:Doxorubicin; D003520:Cyclophosphamide; C056516:exemestane; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate