title: Possible clinical cure of metastatic breast cancer: lessons from our 30-year experience with oligometastatic breast cancer patients and literature review.
abstract: BACKGROUND
  Metastatic breast cancer (MBC) is generally incurable. However, 10-20-year relapse-free survival of MBC is approximately 2%, implying that at least a small subset of MBC patients achieve prolonged survival. We therefore analyzed long-term outcome in a particular subset, i.e., oligometastatic breast cancer (OMBC).
  
  
  METHODS
  Data of OMBC subjects (N = 75) treated in our institution from April 1980 to March 2010 were retrospectively analyzed. OMBC was identified as: one or 2 organs involved with metastatic lesions (excluding the primary lesion resectable by surgery), fewer than 5 lesions per metastasized organ, and lesion diameter less than 5 cm. Patients were generally treated with systemic chemotherapy first, and those who achieved complete response (CR) or partial response (PR) were further treated, if applicable, with local therapy (surgical or radiation therapy) to maintain CR or to induce no evidence of clinical disease (NED), with additional systemic therapy.
  
  
  RESULTS
  Median follow-up duration was 103 (6-329) months. Single or 2 organs were involved in, respectively, 44 (59%) and 31 (41%) cases with metastatic lesions, 48% of which were visceral. In cases where effects of systemic therapy, possibly in combination with other treatments, were evaluated (N = 68), CR or PR was achieved in 33 (48.5%) or 32 (47.1%), respectively, with overall response rate (ORR: CR + PR) of 95.6% (N = 65). In cases receiving multidisciplinary treatment (N = 75), CR or NED (CR/NED), or PR was induced in 48 (64.0%) or 23 (30.7%) cases, respectively, with ORR (CR/NED + PR) of 94.7% (N = 71). CR rates (60.5%) with systemic therapy and CR/NED rates (79.5%) with multidisciplinary treatment were significantly better in subjects with a single involved organ than in those with two involved organs (P = 0.047 and 0.002, systemic only or multidisciplinary treatments, respectively).                         Medians estimated by Kaplan-Meier method were: overall survival (OS) of 185.0 months and relapse-free interval (RFI) of 48.0 months. Estimated outcomes were: OS rates (OSR) of 59.2% at 10 years and 34.1% at 20 years, and relapse-free rates (RFR) of 27.4% at 10 years and 20 years. No disease progression was observed after 101.0 months as RFR. Cases with single organ involvement (N = 44) showed significantly better outcomes (OSR of 73% at 10 years and 52% at 20 years, RFR of 42% at 10 years and 20 years). Those who received local therapies (N = 35) also showed better prognosis: OSR of 82% at 10 years and 53% at 20 years, RFR of 38% at 10 years and 20 years. Three cases (4%) survived for their lifetime without relapse after achieving CR or NED, our definition of clinical cure.                         Multivariate analysis revealed factors favoring better prognosis as: none for OS, and single organ involvement with metastasis, administration of local treatment, and shorter disease-free interval (DFI) (P = 0.030, 0.039, and 0.042, respectively) for RFR. Outcomes in OMBC in literature were OSR of 35-73% at 10 years and 26-52% at 20 years, and RFR of 27-42% at 10 years and 26-42% at 20 years.
  
  
  CONCLUSIONS
  The present analyses clearly indicate that OMBC is a distinct subgroup with long-term prognosis superior to MBC, with reasonable provability for clinical cure. Further prospective studies to better characterize OMBC are warranted to improve prognosis in MBC.
authors.affiliation: Department of Clinical Oncology and Hematology, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan. tadkob-1@kk.iij4u.or.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ichiba
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Sakuyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Eijiroh
authors.initials: E
authors.lastname: Nagasaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aiba
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nogi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kawase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Toriumi
authors.forename: Ken
authors.initials: K
authors.lastname: Uchida
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kanehira
authors.forename: Masafumi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Naomi
authors.initials: N
authors.lastname: Ando
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Natori
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents