Possible clinical cure of metastatic breast cancer: lessons from our 30-year experience with oligometastatic breast cancer patients and literature review.

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.

Miliary tuberculosis associated with chronic neutrophilic leukemia.

We report a case of miliary tuberculosis associated with chronic neutrophilic leukemia (CNL). A 70-year-old woman was referred to our hospital complaining of a 1-month history of persistent fever and anorexia. Chest and abdominal computed tomography images revealed diffuse small nodular lesions in the bilateral lung fields and extreme splenomegaly. Sputum cultures isolated Mycobacterium tuberculosis. After anti-tuberculous therapy for 1 year, the patient underwent splenectomy for massive splenomegaly and progressive leukocytosis. The presence of the homozygous JAK2 V617F tyrosine kinase mutation was also demonstrated in the peripheral blood. She was finally diagnosed as having miliary tuberculosis associated with CNL based on the histopathological examination of spleen. The patient was treated with a daily dose of 500 mg of hydroxyurea. As a result, 18 months after the splenectomy, her leukocyte count was decreased and her clinical condition was markedly improved; there was no relapse of the CNL.

[Four cases of therapy-related leukemia in multiple myeloma].

We have experienced 4 cases of therapy-related leukemia (TRL) in 119 patients with multiple myeloma (MM) who had received combination chemotherapy including alkylating agents between 1988 and 1998. All 4 cases were acute myelogenous leukemia, 3 were males and 1 was female. Median age at diagnosis of MM was 60 years, and median time to TRL from diagnosis of MM was 5.5 years. The chromosome abnormalities were found in 3 of those cases. All 4 cases were resistant to antileukemic chemotherapy, and median survival time from TRL was only 5.5 months. The TRL in MM is thought to be a more important problem, because recently the treatment for this disease has become more intensive, including high-dose chemotherapy supported by autologous stem cell transplantation.

Prognostic significance of the serum phosphorus level and its relationship with other prognostic factors in multiple myeloma.

We studied the serum phosphorus (P) level of 110 patients with multiple myeloma (MM) (age range 42-83 years, median 62 years) and evaluated the relationship between that and other prognostic factors. Serum P level significantly correlated with the prognostic factors that are relevant to renal dysfunction: serum creatinine (P<0.00000001), serum beta2-microglobulin (P=0.00000088), serum uric acid (P=0.0000014), and corrected serum calcium (cCa P=0.000067). Although it also correlated with the percentage of plasma cells in bone marrow nucleated cells (BMPC%) and the hemoglobin (Hb) and leukocyte counts, the significance was less than for the other four prognostic factors. Serum creatinine, BMPC%, leukocyte count, serum uric acid, bone lesions, beta2-microglobulin, and serum cCa were all significantly higher and Hb significantly was lower in the MM patients with hyperphosphatemia (serum P>3.8 mg/dl). The survival time was significantly shorter in these patients (P=0.000087). Multivariate analysis (Cox's proportional hazards regression model) showed that the serum P level is a significant negative prognostic factor in MM patients.