Search

We aimed to examine palbociclib toxicity in patients aged 70 years and older with metastatic breast cancer(MBC). From December 2017 to August 2018, 32 patients with estrogen receptor(ER)-positive, human epidermal growth factor receptor 2(HER2)-negative MBC were included in this study. The most common adverse event(AE)observed was neutropenia, and comparative rates of grade 3 or 4 AE were identified in the groups of patients aged ≥70 years(n=11)and <70 years(n=21) (91% vs 81%). Febrile neutropenia occurred in one patient. Although dose interruption rate was higher in the older group (≥70 years of age)than in the younger group(<70 years of age)(100% vs 86%, respectively), reduction rates were similar between the two groups(64% vs 62%, respectively). Palbociclib was well-tolerated in Japanese older(≥70 years of age) MBC patients.

In a phase 3, double-blind, randomized, international study (the BOLERO-2), the addition of mTOR inhibitor everolimus to exemestane was evaluated in postmenopausal women with estrogen-receptor-positive (ER⁺) advanced/recurrent breast cancer that was refractory to any nonsteroidal aromatase inhibitor (NSAI). This report presents the safety and updated (18- month) efficacy results from the Japanese subset (n=106) of BOLERO-2. After a median follow-up of 18 months, the median progression-free survival time was 8.5 months with everolimus plus exemestane compared to 4.2 months with placebo plus exemestane. The most common adverse events (AEs) with everolimus plus exemestane were stomatitis, rash, dysgeusia, and non-infectious lung disease. The AEs reported with the combination therapy were mostly of grade 1 or 2 and manageable with appropriate intervention. In conclusion, this combination could be a useful addition to the armamentarium of treatments for Japanese postmenopausal women with ER⁺ advanced/recurrent breast cancer progressing on NSAIs.

A 62-year-old woman was diagnosed with primary left breast cancer during a follow-up for an ovarian tumor. She had at first undergone surgical resection of an ovarian tumor, and a pathological examination had revealed ovarian cancer. Gynecologists decided to treat her ovarian cancer with chemotherapy, and we were initially planning to provide treatment for breast cancer after that was completed. Sentinel lymph node biopsy performed before chemotherapy revealed no axillary metastases. The patient received six courses of intravenous PTX (175 mg/m2 on day 1, every 3 weeks) and intravenous CBDCA (AUC6 on day 1, every 3 weeks) as combination therapy. Abdominal lymph node dissection was performed between chemotherapy courses 3 and 4. The lump in the left breast showed partial clinical response, and partial resection of the left breast was performed after completion of chemotherapy. In Japan, few cases of primary breast cancer treated preoperatively using carboplatin-containing regimens have been described.

Background: We investigated predictors for axillary node metastasis at breast surgery after neoadjuvant chemotherapy (NAC) in patients with pre-chemotherapy-sentinel node positive breast cancer., Methods: Eighty-two patients were diagnosed as having positive sentinel lymph node (SLN), who had axillary lymph node dissection (ALND) performed after combination anthracycline/taxan based NAC, between 2002 and 2009., Results: Eighteen (22.0%) of the 82 patients had residual axillary metastases after NAC. Multivariate analysis revealed that SLNs status before NAC was an important factor in predicting residual axillary metastases. Predictors of residual nodal disease were the number of macrometastases and the percentage (>50%) of positive SLNs in all SLNs. Among a subgroup of hormone-receptor positive and HER2-negative tumors, the risk of residual nodal metastases were high sensitivity of hormone receptor, with more than 50% of tumor cells staining positive for ER and PgR., Conclusion: Patients with two or more positive SLNs before NAC had a high risk of residual nodal metastasis after NAC.

We carried out a survey of supportive care at institutions that participated in the JBCRG01 study (FEC followed by docetaxel) as neoadjuvant therapy for operable breast cancer. The purpose was to share the information of supportive care for the treatment effect of perioperative intensive chemotherapy among institutions. Appropriate supportive care for nausea, vomiting, edema and febrile neutropenia (FN) is important with respect to the safety of chemotherapy. According to the results of the questionnaire, support from the family and the relationships with doctors, nurses and pharmacists familiar with the chemotherapy were important. The equipment and service for outpatients' cancer chemotherapy center are also important. This multicenter study enhances the exchange of information among institutes. The results of this survey suggest that adequate supportive care makes anthracycline and taxane chemotherapy manageable in the outpatient setting.

As male breast cancer remains rare entity (less than 1% of cases of breast cancer), most of our current knowledge of it has been extrapolated from its female counterpart. The prevalence of male breast cancer increases with age, and the presentation occurs at an average age of approximately 60 years, 10 years older than in females with the disease. The majority of patients present with a painless, firm, subareolar mass, and the tumors are usually larger than 2 cm in diameter. There may be fixation to skin. Mammography and ultrasonography are useful to distinguish between breast cancer and gynecomastia. Pathologically, invasive ductal carcinoma is the predominant subtype, and lobular carcinoma is rare. Modified radical mastectomy is a principal surgical approach, and adjuvant therapy has been advocated in men based on the beneficial results of it in women. Hormonal manipulations constitute an essential part of adjuvant therapy, as male breast cancers have a high rate of hormone-receptor positivity. Although orchiectomy was practiced in the past, today, tamoxifen is the standard hormone therapy. With respect to systemic chemotherapy, the most common regimens are CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or other anthracyclin-based regimens. In cases of disease recurrence, hormonal manipulations, chemotherapy, or radiotherapy can be administered for palliative purposes. Several selective aromatase inhibitors are now available; however, there are limited data regarding their efficacy in men. The prognosis does not seem to be poor compared to that of females when age and stage are matched. Further studies are needed to characterize the biologic and molecular properties of male breast cancer and their prognostic significance, and to devise optimal treatment strategies. However, it is interesting to note that p53 and c-erbB-2, are expressed and angiogenesis occurs in male breast cancer. Moreover, male breast cancer patients can carry BRCA2 mutations.

We report two patients with lung metastasis of breast cancer who had durable complete responses (CR) with goserelin. The first patient was a 48-year-old woman diagnosed with left breast cancer (T1N0M0, Stage I) at the age of 40, for which she underwent mastectomy. The tumor was estrogen receptor (ER) and progesterone receptor (PgR) positive. She received tamoxifen for 2 years as adjuvant therapy. After 8 years and 7 months, a lung metastasis was found by chest X-p, and treatment with goserelin was started. After 11 months of this treatment a CR was achieved, and the response lasted 3 years and 5 months. The second patient was a 38-year-old woman with a diagnosis of lung metastasis. She underwent right mastectomy at the age of 29 for breast cancer (T2N1M0, Stage IIB), and the tumor was ER and PgR positive. She received tamoxifen and doxifluridine for 2 years as adjuvant therapy. Eight years and 6 months after the mastectomy, a lung metastasis was found by chest X-p, and goserelin treatment was started. After 8 months of this treatment, chest X-p and CT revealed a complete regression of the lung metastasis, and response lasted 1 years and 7 months. Serum estradiol levels were suppressed below 10 pg/ml during the treatment in both patients. These results indicate the usefulness of LH-RH agonist in the treatment of recurrent breast cancer.

To evaluate the feasibility and efficacy of a biweekly schedule of paclitaxel in advanced or recurrent breast cancer, 18 patients were enrolled in this pilot study. Paclitaxel of 120 mg/m2 was administered over 3 hours, and cycles were repeated every two weeks until disease progression or toxicity precluded further treatment. Patients received a median of 10 infusions with actual dose intensity of 55.9 mg/m2/wk, and median time to progression was 4.8 months. The overall response rate was 33.3%, and one patient achieved stable disease for at least 6 months. The responders included patients who received prior anthracycline and/or docetaxel treatment, and the response rate was consistent regardless of metastatic sites. Myelosuppression was the most common toxicity, and a few patients needed G-CSF support, treatment delay or dose reduction because of grade 3 or 4 neutropenia or leukopenia. Although one patient withdrew from this study because of grade 3 sensory disturbance, this regimen was generally well tolerated. A biweekly schedule of paclitaxel seems to be feasible and effective in patients with advanced or recurrent breast cancer.

To evaluate the safety and efficacy of weekly docetaxel (weekly TXT) in cases of advanced or recurrent breast cancer, 31 patients were enrolled in this pilot study of weekly TXT given at 25 mg/m2/w. Each cycle consisted of 3 weeks of therapy followed by a 1-week treatment break in an outpatient setting. Patients received a median of 15 infusions with a median cumulative dose of 680 mg. The median time to treatment failure was 8 months. The overall response rate was 32.3%, and 22.6% of patients had stable disease for at least 6 months. The response rate was consistent regardless of prior chemotherapy with anthracycline. There was no grade 3 or 4 toxicity, and the regimen was generally well tolerated. Although 37.5% of patients had grade 1 or 2 nail change, myelosuppression, fatigue, nausea, vomiting and fluid retention were mild. Weekly TXT seems to be an effective and feasible treatment for advanced or recurrent breast cancer patients.

Many new ideas to control tumor angiogenesis are now being tested in clinical trials. In considering strategies for clinical development of antiangiogenesis treatment, that of endocrine therapy might be particularly useful as a model. Endocrine therapy is a unique treatment used only for hormone-dependent tumors; however, its clinical fruits are exceptional in the entire history of cancer therapy. It is now clearly proven that long-term continuous treatment with antihormones brings a magnificent survival benefit for primary breast cancer patients. This benefit is tumor-phenotype oriented, where the hormone receptor is characterized as a potent predictive factor. Antiangiogenesis treatments seem to have several similarities with endocrine therapy, in that both treatments are cytostatic, stroma-targeting, time-dependent and less effective for large tumor burdens. A combination effect with chemotherapy is often observed with both treatments, at least in animal experiments. In a sense, anti-oncogene product therapy follows endocrine therapy in clinical development. Although antiangiogenesis treatments should be developed based on original concepts, the successful experience of endocrine therapy may provide many hints for the development of antiangiogenesis therapy.

Docetaxel 60 mg/m2 was administered via 1-hour intravenous infusion every 3-4 weeks to 20 patients with advanced/recurrent breast cancer who had previously received anthracycline therapy. The overall response rate was 30.0% (6/20), with 1 complete remission and 5 partial remissions. The median response duration was 120 days. Response rates classified by recurrence site were soft tissues 43.0%, liver 33.3%, lung 33.3%, and bone 23.1%, respectively. Stable disease (prolonged NC) which continued more than 6 months was observed in patients with bone metastasis. Grade 3-4 leukocytopenia and neutropenia were observed in 45.0% and 55.0%, respectively. Grade 3-4 leukocytopenia and neutropenia were frequently seen in patients who had received anthracycline of more than 500 mg/body as first-line chemotherapy. Docetaxel thus seems to be effective in patients with advanced/recurrent breast cancer who are refractory to anthracycline therapy.

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange and interleukin (IL-2) was investigated in 24 patients with advanced cancer. Partial response (PR) was found in 4 patients (20%), including 1 primary liver tumor, 1 metastatic lung tumor from renal cancer and 2 malignant pleural effusions from gastric and lung cancer. Based on these results new AIT in combination with plasma exchange, OK-432, IL-2 and cyclophosphamide was designed to target liver and lung tumors, in which LAK cells and other drugs were administered through the catheter located in the feeding artery of the tumor. Out of ten patients treated, 1 (10%) with metastatic liver tumor from gallbladder cancer was evaluated as PR. It is suggested that a strategy to enhance tumor accumulation and recognition of LAK cells should be attempted for development of gastrointestinal cancer therapy with AIT.

The c-erbB-2 oncogene, is a member of tyrosine kinase oncogene family and expected to play a role in the regulation of cell growth. In the present study, prognostic significance of the expression of c-erbB-2 oncoprotein was investigated by immunocytochemical assay with 130 primary breast cancer patients. The positive expression of c-erbB-2 oncoprotein was found in 53 out of 130 patients (40.8%). There was no significant correlation between expression of c-erbB-2 oncoprotein and conventional prognostic factors, estrogen receptor (ER), axillary lymph node metastasis and epidermal growth factor receptor (EGFR). Relapse free survival rate of the patients with positive c-erbB-2 expression was significantly worse than those with negative at 49 month after operation. Similar result was found in overall survival rate but the difference was not significant. Furthermore, when patients were stratified by regional nodal status, in the patients with lymph node metastasis, the prognosis of the patients with positive c-erbB-2 expression was significantly worse than those with negative, while no significant difference was found in the patients without lymph node metastasis. These results suggest that c-erbB-2 oncoprotein may act as a prognostic factor independently, predicting the prognosis of breast cancer patients.

Plasma exchange was undertaken to remove the immunosuppressive factors in 25 advanced cancer patients who did not respond to immunochemotherapy. In the present studies, a postcentrifugal filter was tried, and the filtrated autologous plasma was replaced in 10 patients replaced by about 1000 ml in eight and by about 1600 ml in two. The improvement of subjective symptoms and reduction of tumors were observed in 15 (60%) and seven (28%) patients, respectively. It was suggested that immunosuppressive factors of a large molecular size could be selectively removed by the postcentrifugal filter.

To elucidate the role of the spleen on the immunosuppression in gastric cancer patients, mechanism of the induction of suppressor cells in the spleen was investigated. Studies of tissue distribution of T cells using monoclonal antibodies revealed that spleen contained much higher proportion of OKT8 reactive T cells as compared with those in regional lymphnodes without metastasis. Lymphocytes released from the spleen during perfusion were taken to be representative of recirculating lymphocytes. Suppressor precursor cells were found to exist predominantly in perfusate from the spleen, while spontaneously activated suppressor cells were in the residual lymphocytes in the spleen after perfusion. Culture supernatants from splenic adherent cells induced suppressor cell activities as well as sera from splenic venous blood. These results suggest that suppressor precursor cells which could be mobilized slowly was more comparable to splenic lymphocytes and might be matured by factors released from splenic adherent cells, partly moving into peripheral blood. Furthermore, the effect of splenectomy on the prognosis of gastric cancer patients was investigated in randomized controlled trial. The patients who underwent total gastrectomy and had main location of the tumor on lesser curvature region were divided into two groups at random; splenectomy (+) and splenectomy (-) groups. A suggestive prolongation of survival time was observed in splenectomy (+) group. Thus, spleen seem to contribute to the immunosuppression in gastric cancer patients and splenectomy may lead to better prognosis.

Over the past 6 years, we have treated 25 cases of pancreatic cancer, 6 cases of cholangioma in pancreas-head and 3 cases of cancer in duodenal papilla (2 cases Stage I, 5 cases stage II, 2 cases stage III, 25 cases stage IV). Twelve cases (10 unresectable cases, 1 hepatic metastasis case, 1 recurrent case) were treated with intra-arterial infusion chemotherapy using implantable Drug Delivery System, combined with angiotensin-II to increase the concentration of anti-cancer agents in cancer tissue. Twenty-four cases (70%) died in less than one year, so operation is not effective except for curative resection of cholangioma and duodenal papilla cancer. But exploratory laparotomy or inoperable cases given intermittent transcatheter arterial infusion chemotherapy (5-FU + ADM + MMC + angiotensin-II), showed favorable results (decrease of tumor size and pain in 2 cases; recanalization of obstruction in choledochus of 1 case). Especially trans-femoral or left subclavian arterial catheterization proved to be effective therapy for possibly giant or recurrent inoperable pancreatic cancer and hepatic metastasis. Using the drug delivery system, the technical approach to arterial infusion therapy and angiography has been readily undertaken. Quality of life has been improved, and course observation of the patient has been possible by imaging diagnosis and multidisciplinary treatment for advanced pancreatic cancer.