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The aim of the study was to determine the feasibility and validity of a newly developed patient-based instrument--the Patient Neurotoxicity Questionnaire (PNQ)--for grading chemotherapy-induced peripheral neuropathy (CIPN).We prospectively collected data from 300 female patients who were treated with taxane chemotherapy for primary breast cancer as part of a national multicenter phase III randomized trial (N-SAS BC 02). We evaluated patient compliance with the PNQ and several validation parameters, including concordance between CIPN grades noted by physicians (National Cancer Institute Common Toxicity Criteria) and patients (PNQ), and the concurrent validity and responsiveness of the PNQ versus the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) utilizing data at pre-treatment and before three, five, and seven treatment cycles.The questionnaire completion rate was90% at all assessments. Evaluation by physicians always resulted in lower neuropathy assessment scores compared with those reported directly by patients (weighted kappa coefficients, 0.02-0.06). Both PNQ sensory and motor scores were significantly correlated with the FACT/GOG-Ntx (r = 0.66 and 0.51, respectively). In the repeated measures analysis of variance model, PNQ grades increased considerably as treatment continued, indicating progressively worsening CIPN over time.The PNQ has an applicable degree of feasibility and validity, useful for the diagnosis of CIPN as well as for clinical treatment decision-making, where the development of CIPN is a potential treatment-limiting consideration. Physicians underreport and underestimate the severity of CIPN symptoms compared with patients, thereby supporting the importance of assessing patient-reported outcomes using the PNQ.

症例は62歳，女性．35歳時当科にて左乳癌に対し，定型的乳房切除術を施行した．皮膚および胸筋に浸潤し，また腋窩リンパ節転移を認めたため，cyclophosphamideならびに5FUによる術後補助化学療法を2年間行った．今回は半年前頃よりの湿性咳を主訴に来院された．胸部CTにて，前縦隔に5cm大の腫瘤を認めた．FDG-PETでは同部位ならびに胸骨柄左側にFDGの集積がみられた．前縦隔腫瘍と胸骨柄より各々CTガイド下生検を施行，ともに乳癌の再発との結果であった．ER(1+)，PR(－)，HER2(1+)．まずは両病変に対し，放射線照射60Gyを行った．照射野に関しては12カ月後においても良好に制御されていたが，新たに左肩甲骨と右肋骨に骨転移の出現を認めたため，化学療法を開始した．再発時期および部位ともに，極めて稀な症例と思われたので，若干の文献的考察を加え報告する．

Newborn Sprague-Dawley rats were inoculated intracranially with JC virus (Tokyo-1), a human polyomavirus, which had been isolated by Nagashima et al. from the autopsied brain of a patient with progressive multifocal leukoencephalopathy in Japan. Twenty-one to 70 weeks later, 21 of 27 rats developed brain tumors in the cerebrum, but not in the cerebellum. Most of the tumor cells were of an undifferentiated neuroectodermal nature and showed nuclear palisades and pseudorosettes. In some tumor cells glial fibrillary acidic protein was positive immunohistochemically, and many glial filaments were demonstrated ultrastructurally. Neuronal differentiation was not proved. Two continuous lines of cultured tumor cells were established, and T antigen of JCV (Tokyo-1) was present in both cell lines. Glial differentiation was confirmed also in the tumors produced by subcutaneous transplantation of cultured tumor cells.

Objective: Since there is now growing interest in the incorporation of patient-reported outcome measures in cancer clinical trials, a patient-based questionnaire, the Patient Neurotoxicity Questionnaire (PNQ) was developed to quantify the symptoms and severity of chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to evaluate the physicians’ perspectives regarding the utility and diagnostic value of PNQ. Methods: A questionnaire was sent to 61 physicians who participated in a Phase III randomized trial of adjuvant chemotherapy in breast cancer (AC followed by taxane versus taxane alone) that used the PNQ to assess CIPN. Results: Forty-seven out of 61 physicians (77%) responded. The majority considered neurosensory symptoms the diagnostic hallmark for CIPN and most regarded interference with activities of daily living (ADLs) as definite justification for treatment modifications. For neurosensory disturbance, the majority of physicians indicated that Grade D severity (moderate to severe symptoms interfering with ADLs) should result in treatment postponement and Grade E severity (severe symptoms preventing most ADLs) should result in treatment discontinuation. Similarly, for neuromotor disturbance, over half of the physicians replied that Grade C (moderate symptoms not interfering with ADLs), D and E severity should result in dose reduction, treatment postponement and treatment discontinuation, respectively. Eighty-four percentage of the physicians reported that the use of the PNQ was helpful in the diagnosis and assessment of patients at risk of CIPN. Conclusions: The PNQ appears to be a useful instrument for the diagnosis and grading of CIPN, as well as for clinical decision-making regarding treatment modifications secondary to CIPN.

Background: Magnetic resonance imaging mammography is performed to determine the extent of lesions and to detect occult lesions, but preoperative diagnosis by breast computed tomography (CT) is less common. Methods: We performed a retrospective study of detection of mammographically occult multiple lesions using breast CT. The subjects were 407 female patients (median age: 56 years old; median tumor size: 1.9 cm) with breast cancer who underwent preoperative, contrastenhanced breast CT. Results: CT detected 73 incidental-enhanced breast nodules (median size: 0.8 cm) in 73 patients that were undetectable by conventional methods. Age, size of the main lesion or laterality of lesions did not differ between patients with and without incidental nodules, but the frequency of mastectomy was significantly higher in those with incidental nodules. Of the 73 incidental nodules, 22 (30%) were in the same quadrant as the main lesion, 26 (36%) were in other quadrants and 25 (34%) were in the opposite breast. On qualitative diagnosis by CT, 48 were suspected to be malignant (66%), 17 benign (23%) and eight non-specific (11%). In histological evaluation of 44 of the 48 nodules suspected to be malignant, 24 were malignant (invasive carcinoma: 22, non-invasive carcinoma: 2); of seven of the 17 nodules suspected to be benign, all were benign; and of three of the eight non-specific nodules, one was non-invasive carcinoma. The discovery rate of clinically and mammographically occult multiple lesions by preoperative breast CT was 6%. Conclusion: We conclude that breast CT is useful for the detection of occult lesions and choice of surgical procedure.

We report two cases of occult breast cancer in which masses were completely nonpalpable and positron emission tomography-computed tomography (PET-CT) was extremely helpful in identifying the primary tumor. Case 1 involved a 56-year-old woman with enlarged lymph nodes 3 cm in size in the axilla. Based on excisional biopsy, axillary lymph node metastasis of breast cancer was suspected but an obvious primary tumor in the breast was not identifiable on mammography, contrast-enhanced CT, or ultrasonography. Faint accumulation of fluorodeoxyglucose (FDG) was noted only on PET-CT, so the site was considered to be the primary site, and operation was performed. As a result of postoperative pathological examination, ductal carcinoma in-situ (DCIS) was diagnosed. Case 2 involved a 55-year-old woman with enlarged lymph nodes 3 cm in size in the axilla. Based on the excisional biopsy, axillary lymph node metastasis of breast cancer was suspected. In this case as well, an obvious primary tumor was not identifiable with palpation or mammography. On PET-CT, faint accumulation of FDG was noted in the vicinity of the CD regions, or upper and lower outer quadrants. When contrast-enhanced CT and ultrasonography were performed, a faint nodular opacity less than 1 cm in size corresponding to this site was found and diagnosed as the primary site, operation was subsequently performed. Pathologic diagnosis indicated invasive cancer. PET-CT is a helpful option for the diagnosis of occult breast cancer with primary sites that conventional imaging studies have difficulty identifying.

Background: The local recurrence rate of phyllodes tumors is high and ensuring a sufficient surgical margin is considered important for local control. However, the preoperative diagnosis rate of phyllodes tumors is low and we often encounter cases in which a sufficient surgical margin is not achieved, since in routine medical practice the lesion may not be diagnosed as phyllodes tumor until postoperative biopsy of a mammary mass. Furthermore, there are no established therapeutic guidelines for surgical stump-positive phyllodes tumors. We reviewed the outcomes of excision of phyllodes tumors to investigate factors involved in local recurrence and to determine the indication for re-excision in stump-positive cases. Methods: The subjects were 45 patients treated for phyllodes tumors at our institution from January 1980 to July 2005. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical stump status were analyzed. Results: Median age was 45 years old (range 28‐75) and tumor size was 1‐17 cm (median 3.5 cm). Pathologic diagnoses were benign, borderline and malignant in 31, five and nine cases, respectively, and the surgical stump was negative in 27 lesions and positive in 15. Median follow-up was 101 months (range 1‐273), with local recurrence in six cases and distant metastasis in one. The local recurrence-free rate was 88, 88 and 84% and the disease-free rate was 85, 85 and 81% after 5, 10 and 15 years, respectively. Overall 10-year survival was 97%. In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery (P ¼ 0.0034, 0.0003, 0.026). A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (RR 0.086; 95% CI 0.01‐0.743, P ¼ 0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P ¼ 0.0139). Conclusion: Wide excision is the preferred therapy for phyllodes tumor and preoperative diagnosis is important for good local control. Re-excision is recommended in cases with a positive surgical margin and stromal overgrowth and malignancy.

More effective methods of preventing and treating breast cancer are being sought by clinicians every day, and new drugs and interventions for overcoming this cancer are being energetically evaluated. At present, there are wide treatment options and many different objectives for breast cancer. These circumstances led us to seek information about the relative costs of the different medical options for the prevention and treatment of breast cancer and to try to ascertain whether one course of action is more efficient than other courses. Economic evaluation of healthcare is indispensable for selection of the best alternatives among medical interventions which are becoming more diverse day after day. The total medical expenditure continues to rise each year and some sort of evaluation from an objective and external viewpoint is required to provide the information with which to suppress this rise. This paper surveys the three major reports published on this topic to date, for the purpose of demonstrating the importance and necessity of performing an economic analysis of the treatment and prevention of breast cancer. The three reports to be surveyed pertain to: (1) cost-effectiveness analysis of adjuvant chemotherapy for patients with lymph node negative breast cancer, (2) cost utility analysis of first-line hormonal therapy in advanced breast cancer, namely comparison of two aromatase inhibitors to tamoxifen, and (3) cost-effectiveness analysis of tamoxifen in the prevention of breast cancer. In addition, this paper discusses the advantages, limitations and perspective for the future of the economic evaluation of healthcare for breast cancer. (1) The authors concluded that if the average risk of all women of undergoing recurrence after this therapy is assumed to be 4% per year, adjuvant chemotherapy is definitely of benefit for node-negative, estrogen receptor-negative breast cancer patients. They additionally stated that this benefit decreases markedly if the changes in long-term survival are less than those in disease-free survival. In this connection, they pointed out that the benefit is considerably smaller among postmenopausal 60-year-old women. (2) The incremental cost per quality-adjusted progression-free life year (QAPFY) for letrozole and anastrozole, relative to tamoxifen, was Can $12, 500-19, 600, which was lower than the criterion level (US $50, 000). On the basis of this result, the authors concluded that these two drugs are economically acceptable. Furthermore, when efficacy and cost effectiveness were analyzed together, it was concluded that letrozole is in fact preferable to anastrozole. (3) The model analysis of tamoxifen’s cost effectiveness among women at increased risk for breast cancer yielded the following results. In the base-case analysis, involving the calculation of the costs and benefits of 5-year tamoxifen administration, the incremental cost effectiveness of tamoxifen was $41, 372 per life-year gained for women age 35 to 49 years, whereas for women age 50 to 59 years and 60 to 69 years, these values were $68, 349 and $74, 981, respectively. For women who had undergone hysterectomy and thus had no risk of the onset of endometrial cancer, the incremental cost effectiveness of tamoxifen was $46, 060 per life-year gained. Medico-economic evaluation of breast cancer is very significant and valuable and is expected to stimulate efficient utilization of healthcare resources. It can provide important information to physicians, patients, insurers, pharmaceutical and other industries, healthcare policy planners, and others.

Most of the discordant cases between biochemical and immunohistochemical (IHC) assays for hormone receptor (HR) status in breast cancers are due to negative findings from the biochemical assay but positive IHC findings. However determining HR status based on IHC only in biochemically HR negative breast cancers has never been studied. The aim of this study is to examine the histological characteristics in immunohistochemically HR positive but biochemically HR negative breast cancers.IHC staining for HRs in 345 biochemically HR-negative breast cancers was done. The relationship between HR status by IHC and the histological characteristics was assessed.In 345 cancers, 105 (30.4%) were estrogen receptor- (ER) or progesterone receptor- (PR) positive by IHC. The enzyme-immunoassay (EIA) HR titer was higher in immunohistochemically HR-positive tumors (ER: 2.7 fmol/mg protein; PR: 0.8 fmol/mg protein) than in negative tumors (0.6 fmol/mg protein in both HRs). IHC-assessed ER positivity on histological sections was high in some tumor types, such as mucinous carcinoma (77.8%), invasive micropapillary carcinoma (66.7%), and infiltrating ductal carcinoma of no special type with abundant stroma (60.2%). Among infiltrating ductal carcinomas of no special type, low nuclear grade tumors were all ER positive and high nuclear grade tumors showed low ER positivity by IHC, even in biochemically HR negative cancers.The IHC-assessed HR status may reflect tumor cell behavior, such as overall and disease-free survival and endocrine response, better than HR status as assessed by the enzyme-immunoassay method. Immunohistochemically HR-positive but biochemically HR-negative breast cancers include infiltrating ductal carcinomas of no special type with low nuclear grade and some tumor types with high stromal content. We can assess the true HR status by IHC especially these tumors.

The next step for breast cancer specialists, who have created and published the Breast Cancer Treatment Guidelines to evaluate of health care quality and who are ahead of many other clinicians in this respect, is to articulate the ideal form of evaluation that adequately combines evaluations from various perspectives.

Since standard radical mastectomy was established by Halsted for breast cancer, surgical procedures for breast cancer have been changed according to the results of randomized controlled trials. Breast-conserving treatment is now regarded as a standard local treatment for early breast cancer. More recently, sentinel node biopsy is becoming popular as an alternative procedure to axillary node dissection for nodal staging. These new procedures have been believed to be better in terms of patients' quality of life in comparison with previous surgical procedures without impairing prognosis. Many studies regarding the quality of life (QOL) of patients after such procedures have been reported. Here we review those data, especially of studies comparing quality of life of patients after mastectomy and breast-conserving treatment, and of those after axillary node dissection and sentinel node biopsy. Viewpoints and issues on surgical treatment-related QOL are discussed.

The primary purpose of this large cohort study is to investigate the effects on breast cancer outcomes of modifiable lifestyle factors after breast cancer diagnosis. These factors include physical activity, smoking, alcohol consumption, obesity and weight gain after diagnosis, alternative medicine and dietary factors. Women diagnosed with Stage 0 to III breast cancer are eligible for participation to this study. Lifestyle, use of alternative medicine, psychosocial factors, reproductive factors and health-related quality of life will be assessed using a questionnaire at the time of breast cancer diagnosis (baseline), and 1, 2, 3 and 5 years after diagnosis. Clinical information and breast cancer outcomes will be obtained from a breast cancer database. The primary endpoint will be disease-free survival. Secondary endpoints are overall survival, health-related quality of life, breast cancer-related symptoms and adverse events. Patient recruitment commenced in February 2013. Enrollment of 2000 breast cancer patients is planned during the 5-year recruitment period. The concept of the study is described in this article.

An 80-year-old woman visited our hospital with a massive ulcerated tumor in the upper lateral quadrant of the right breast. Her performance status was 2. Histopathologically, a mass consisting of a huge primary tumor and metastatic axillary lymph nodes was seen and invasive ductal carcinoma was diagnosed. Both estrogen and progesterone receptors were negative. Herceptest (DakoCytomation, Glostrup, Denmark) showed 2 + staining and HER2 amplification was detected by fluorescent in situ hybridization. CT revealed multiple lung metastases. Her old age and performance status of 2 made aggressive chemotherapy difficult. After receiving 5'-DFUR 600 mg/day as the first line treatment for two months, the tumors progressed. As second-line treatment, single agent therapy with a loading dose, a trastuzumab 4 mg/kg followed by 2 mg/kg weekly was recommended. The patient also received 60 Gy radiotherapy. Six months after the second line treatment, the breast tumor disappeared and only a scar remained on the chest wall and axilla. CT showed no lung tumors. During the trastuzumab treatment, no adverse effect was observed. Her performance status improved to zero, and she is alive and free from the disease 24 months after the disappearance of the tumor.

Seroma, a collection of serous fluid, is the most common problem after breast surgery. The aim of this study was to review the effect of mechanical closure of dead space on seroma formation after breast surgery. There are two mechanical methods for closure of the dead space beneath skin flaps: compression by external pressure, and fixation of the flaps with sutures. There is no evidence to suggest that the routine use of a pressure garment or compression dressing is beneficial. However, it appears that suture flap fixation does reduce seroma formation, simplify postoperative care and dressing, and thus allow early removal of drains and discharge. Drains are helpful for mechanical closure of dead space, but in breast-conserving surgery this technique may preclude the use of a drain. However, previous studies have often been small in scale and poor in quality. Further studies should examine the effect of this technique on quality of life, cosmesis, and medical economics.

We present a patient with pulmonary metastasis from breast cancer who received S-1 (TS-1) and maintained complete response for approximately 10 years after recurrence. A 51-year-old woman underwent modified radical mastectomy for left breast cancer in November 1991. Her cancer was postoperatively classified as pT2 pN0 M0 Stage IIA. As postoperative adjunctive treatment, tamoxifen and hexylcarbamoyl 1-5-FU (HCFU) were given. During the administration period (30 months after surgery), a solitary pulmonary metastasis occurred. Three months after the start of S-1 (100 mg/body/day), the tumor disappeared on images. Thereafter she took S-1 orally for approximately 10 years, and the pulmonary metastatic focus maintained complete response. In addition, no recurrent focus was observed. The adverse events observed during S-1 treatment were nausea, low-grade neutropenia and pigmentation of fingers. All were mild, and S-1 could be continued. Our case illustrates two important characteristics of S-1. First, S-1 was effective even though this patient had a lung metastasis during adjuvant treatment with HCFU. S-1 is a combined formulation containing 5-chloro-2, 4-dihydroxypyrimidine (CDHP; gimestat), which inhibits an enzyme that metabolites 5-FU, dihydropyrimidine dehydrogenase (DPD). Therefore, high 5-FU concentrations are maintained with S-1, and S-1 may be effective in the patients who do not respond to other fluoropyrimidine agents. Second, since S-1 toxicity was mild, long-term treatment for approximately 10 years was possible. Since S-1 contains potassium oxonate (OXO; otastat), gastrointestinal toxicities, the main adverse events of 5-FU agents, could be reduced. The purpose of treatments for metastatic breast cancer is to maintain favorable quality of life (QOL), as well as to improve survival. S-1 could be a valuable agent for breast cancer treatments, since it showed clinical efficacy and mild toxicity, and can be given orally.

Background: Seroma is a common problem in breast surgery. The aim of this systematic review was to identify risk factors for seroma formation. Methods: Articles published in English were obtained from searches of Medline and additional references were found in the bibliographies of these articles. Risk factors were graded according to the quality and strength of evidence and to the direction of association. Results: One meta-analysis, 51 randomized controlled trials, 7 prospective studies and 7 retrospective studies were identified. There was no risk factor supported by strong evidence, but there was moderate evidence to support a risk for seroma formation in individuals with heavier body weight, extended radical mastectomy as compared with simple mastectomy, and greater drainage volume in the initial 3 days. On the other hand, the following factors did not have a significant influence on seroma formation: duration of drainage; hormone receptor status; immobilization of the shoulder; intensity of negative suction pressure; lymph node status or lymph node positivity; number of drains; number of removed lymph nodes; previous biopsy; removal of drains on the fifth postoperative day versus when daily drainage volume fell to minimal; stage; type of drainage (closed suction versus static drainage); and use of fibrinolysis inhibitor. In contrast, sentinel lymph node biopsy reduced seroma formation. Evidence was weak, or unproven, for other factors that were commonly cited in the literature. Conclusions: Although a number of factors have been correlated with seroma formation, strong evidence is still scarce. However, there is evidence showing that sentinel lymph node biopsy reduces seroma formation.

BACKGROUND The clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long-term follow-up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group. METHODS Patients (N = 1901)with unilateral breast cancer ≤ 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan–Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR. RESULTS At a median follow-up time of 107 months, the 10-year overall and disease-free survival rates were 83.9% and 77.8%, respectively. The 10-year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10-year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676–5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis. CONCLUSIONS Young age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases. Cancer 2006. © 2005 American Cancer Society.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign breast disease that presents as a localized breast mass. Breast tissue affected by PASH is characterized by a dense, collagenous proliferation of mammary stroma, forming interanastomosing capillary-like spaces. The importance of this benign lesion lies in distinguishing it from low grade angiosarcoma. We report a case of a 38-year-old woman who presented with a rapidly growing breast tumor. She visited our hospital with a complaint of a painless right breast mass. Physical examination revealed a 3.6 x 2.2 cm, oval, elastic-firm, well-defined and easily movable mass. Mammograms revealed no discrete mass or calcifications. Sonographic examination revealed a 3.5 x 2.5 x 2.2 cm, oval, well-defined and homogenous hypoechoic mass without a cyst. A fine-needle aspiration sample of the breast mass showed some clusters of epithelial cells with small papillary structures and many scattered stromal cells with naked nuclei. Based on these findings, a provisional diagnosis of fibroadenoma was made and the patient was followed up. One year after the first visit, the mass enlarged rapidly and a follow-up mammogram revealed an 8.2 x 5.5 cm circumscribed mass without calcifications. Given the history of rapid growth of the mass, tumor excision was performed. The excised tumor was well demarcated and had a smooth external surface. Histologic examination revealed normal breast ducts and lobules, and specific proliferative epithelial changes were not seen. The lobular and duct structure of the breast parenchyma were separated by an increased amount of stroma. The fibrous stroma contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared intermittently at the margins of the spaces resembled endothelial cells. Immunohistochemical staining showed that endothelial cells lining true blood vessels were positive for Factor VIII-related antigen, but the spindle cells were negative for Factor VIII. Pseudoangiomatous stromal hyperplasia was diagnosed.

A rare case of intracystic papillary carcinoma (IPC) with invasion had synchronous metastases to the liver at presentation. A 57-year-old postmenopausal woman noticed a right breast tumor 7 months prior to admission. Mammography showed an oval mass measuring 3.1 cm in diameter with no calcification, and ultrasonography showed an intracystic tumor with a papillary growth pattern. Fine-needle aspiration cytology revealed adenocarcinoma. Excisional biopsy revealed intracystic solid papillary carcinoma with invasion. The tumor was a clear-cell type with extracellular mucin. Two months after the initial biopsy, a screening ultrasonographic examination of the liver showed multiple hyperechoic masses. Abdominal contrast-enhanced CT scan and magnetic resonance imaging (MRI) showed multiple hypervascular masses compatible with metastatic tumors. No suspicious lesions were detected on examinations for malignancy in other organs. Distant metastases in cases of IPC with invasion are very rare. The potential of distant metastasis in IPC with invasion and the difficulty of evaluating invasive foci should be recognized. Careful evaluation of distant metastases is recommended.

Two rare cases, each with a solitary brain metastasis from breast cancer with extensive nodal metastases as the first site of distant metastasis, were locally treated with surgery and irradiation. The outcome of the two treated cases indicated an excellent and non-recurrent post-therapeutic survival period of more than 3 and 8 years, respectively. In a 50-year-old woman (Case 1), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with doxorubicin and tegafur-uracil (UFT) and hormonal therapy with tamoxifen for left breast cancer. The brain metastasis was treated twice surgically followed by radiotherapy. One year and 6 months later, local recurrence of the brain metastasis appeared and was treated surgically again. No other treatment was done thereafter. Since then, no other distant or lymph node metastasis occurred, and to date her outcome has been non-eventful for 8 years and 5 months. In a 63-year-old woman (Case 2), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with cyclophosphamide, epirubicin and fluorouracil (CEF) for right breast cancer. The brain metastasis was treated locally with surgery and irradiation of 50 Gy. She thereafter received no further treatments. Since then neither distant metastases nor local recurrence have developed, and to date the post-treatment outcome has been uneventful for 37 months. Our findings suggest that patients who developed a solitary brain metastasis as the first site of distant metastasis from breast cancer have a chance of achieving long-term disease-free survival when treated with aggressive local therapy, even in the presence of extensive lymph node metastases at the primary surgery site for breast cancer.

Ipsilateral breast tumor recurrences (IBTR) after breast-conserving treatment include two different entities: true recurrence (TR) thought to occur when residual cancer cells grow gradually to detectable size and new primary (NP) thought to be de novo cancer independently arising in the preserved breast. The patients with ipsilateral breast tumor recurrence (IBTR) are potentially at high risk for subsequent distant metastasis, but many studies do not distinguish between these types of recurrence. The aim of this study is to clarify the biological difference between TR and NP, and to show the clinical significance of classifying IBTR into these two types of recurrence.A total of 172 patients with IBTR after breast-conserving therapy from the cohort of a long-term large scale study (Research of cancer treatment from the Ministry of Health, Labor and Welfare of Japan (no.13-9)) were analyzed. We classified IBTRs as TR or NP based on tumor location and pathological findings. The characteristics of the primary tumors of TR and NP were compared. Survival rates and risk factors of each type of IBTR were examined by the Kaplan-Meier method. The results of salvage surgery were also analyzed.Of the 172 patients, 135 patients were classified as TR and 26 as NP. Eleven cases could not be categorized. The primary tumor of TR was characterized by a high rate of lymph node metastasis (37.8%) and short disease-free interval (mean DFI; 46.6 months) while that of NP showed a rather low lymph node positivity (8.7%) and longer DFI (62.1 months). The risk factors for TR were young age, positive surgical margin, omission of irradiation and positive lymph node metastasis. Those for NP were young age, omission of irradiation and contralateral breast cancer after the primary operation. The 5-year survival rates after IBTR were 71.0% in TR and 94.7% in NP (p=0.022). Salvage operation was performed in 136 IBTRs. Eighty-one patients underwent salvage mastectomy and 55 patients underwent repeat lumpectomy. Five-year survival rates after salvage operation were 75.7% for mastectomy and 84.2% for lumpectomy (N.S.). Twenty percent of patients who underwent repeat lumpectomy developed secondary local relapse within 5 years after salvage treatment. The risk factors for secondary local relapse were analyzed. Limited to cases of IBTR which received radiation therapy after the primary operation, NP was the only factor influencing secondary local relapse by univariate analysis.TR and NP show clinically quite different features; time to occurrence, characteristics of the original tumor, prognosis and risk factor profile for IBTR were all different. Classifying IBTR as TR or NP can provide clinically significant data for the management of IBTR.

The effects of psychosocial group interventions on improving quality of life (QOL) for patients with recurrent breast cancer are not well known. The objective of this study was to assess the feasibility of a psychosocial group intervention in Japanese women with first recurrence of breast cancer. The subjects were consecutively selected from among patients who were diagnosed with a first recurrence of breast cancer. We conducted a 6-week psychosocial group intervention. QOL was assessed using the Profile of Mood States (POMS), the Impact of Event Scale—Revised, the Mental Adjustment to Cancer (MAC) scale, and the European Organization for Research and the Treatment of Cancer (EORTC) Quality of Life Questionnaire—Cancer 30/Breast module 23 (QLQ-C30/Br23) at baseline then immediately and 3 and 6 months after completion of the intervention. Among 58 eligible patients, written consent was obtained from 28 (48%), and the final evaluation was conducted on 19 subjects. The repeated measured analysis of variance (ANOVA) revealed a significant change in tension–anxiety, depression–dejection, anger–hostility and total mood disturbance on the POMS, helplessness/hopelessness on the MAC scale, and body image and future perspective on the QLQ-C30/Br23. Dunnett’s test revealed a significant difference in these scores between baseline and 3 months after the intervention but no difference between baseline and 6 months after the intervention. These results suggested the possibility of a short-term effectiveness of the intervention; however the results were inconclusive because of selected small samples.

Background: Although many clinical data regarding breast-conserving treatment have already been reported from European and North American countries, few clinical data with long-term follow-up have been reported from Japan. Method: We collected information on therapeutic and possible or developed prognostic factors and follow-up data for Japanese women who had received breast-conserving treatment consisting of wide excision of the primary tumor, axillary dissection and radiotherapy for unilateral breast cancer considered suitable for breast-conserving treatment from 18 Japanese major breast cancer treating hospitals; 1561 patients were registered. Results: The median follow-up period was 77 months. Five-year disease-free and overall survival rates were 89.4 and 95.9%, respectively. The 5-year local recurrence-free rate was 96.3%. The patients with histologically positive margins (P < 0.0001) or estrogen receptor negative tumor (P = 0.0340) or younger than 40 years old (P < 0.0001) developed statistically significantly more local recurrences. Adjuvant endocrine therapy was essential for the estrogen receptor positive patients to have a lower local recurrence rate. Endocrine therapy did not change the local recurrence rate among estrogen receptor negative patients at all. Multivariate analysis showed histological margin status and the combination of estrogen receptor status and endocrine therapy were independent prognostic factors for local recurrence. Conclusion: The 5-year local recurrence rate of Japanese breast cancer patients who were treated with breast-conserving treatment using radiotherapy was 3.7%. Independent prognostic factors for local recurrence were histological margin status and the combination of estrogen receptor status and adjuvant endocrine therapy.

The incidence of pulmonary embolism(PE)has been increasing although it considered lower in Japan than in the West. We report 5 cases of PE after gastrointestinal surgery from January 1994 to March 2001 representing 0.2% of surgically treated patients during that period. In 4 cases except a light PE patient it oc‑ curred when they first walked after surgery. 1 case of PE occurred despite using intermittent pneumatic compression(IPC)during surgery to prevent it. We diagnosed PE by pulmonary perfusion scintigraphy or thoracic computed tomography(CT) . We conducted anticoagulant therapy using heparin and thrombolytic therapy using urokinase or tissue plasminogen activator(t‑PA)immediately after the diagnosis. We could save 3 patients including 1 with light PE and 2 treated by t‑PA. Serious complications in thrombolytic therapy occurred in 3(2 massive bleedings and 1 extensive cerebral hemorrhage). PE is the most critical complication after gastrointestinal surgery so more prevention as low‑dose unfractionated heparin or elastic stockings may be necessary in high risk group of PE.

Four hundred and forty-eight breasts of 443 female patients were treated with breast-conserving therapy (BCT) consisting of wide excision, axillary dissection, and radiotherapy for early-stage breast cancer at the National Shikoku Cancer Center between July 1989 and December 1999. The average age at operation was 48.7 years, and the mean tumor size by palpation was 1.9 cm. Three hundred and twenty cases (71.4%) were pathologically node-negative. During a median follow-up period of 53 months, 13 patients developed local recurrence. The 5-year overall survival and local recurrence rate registered 94.5% and 3.0%, respectively. Age at operation (35 years or younger vs. 36 years or older; P = 0.0184), pathological lymph node status (P = 0.0261), adjuvant chemotherapy (P = 0.0198), and the combination of estrogen receptor (ER) status and adjuvant tamoxifen (TAM) (ER+ and TAM+ vs. ER- or TAM-; P = 0.0136) were statistically significantly associated with local recurrence. Histological margin status associated with local recurrence was marginally significantly (P = 0.0751). The results of multivariate analysis revealed that age at operation, pathological lymph node status, the combination of ER status and adjuvant TAM, and histological margin status were statistically independent predictors for local recurrence. In conclusion, BCT consisting of wide excision, axillary dissection and radiotherapy is useful and effective for patients with early-stage breast cancer.

Thermography is a technique to measure the body surface temperature and is used in medical applications. We evaluated its prognostic value in 340 female patients with unilateral invasive breast cancer without distant metastases. The difference of mean temperatures of the tumor area and corresponding area of the contralateral breast was defined as AT. The patients with hot tumors (delta Tor = 0.9 degrees C) had significantly worse disease free and specific survival than those with cold tumors (delta T0.9 degrees C) (p = 0.0003 and p0.0001, respectively). AT was significantly correlated with tumor size, histological nodal status and nuclear grade, positively. But AT did not have any relation with estrogen receptor status. Multivariate analyses including those conventional prognostic factors showed that AT was a marginally significant prognostic factor for disease-free survival (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 0.99-2.66, p = 0.0557) and an independent significant prognostic one for disease specific survival (HR = 1.95; 95% CI = 1.09-3.49, p = 0.0251). However, AT did not have prognostic impact on the node negative patients. AT might be a useful prognostic factor in node positive breast cancer, especially in patients who plan to be treated with preoperative systemic therapy.

e12107 Background: Curebest™ 95GC Breast (95GC) is one of the multi-gene assays to predict prognosis of node negative and estrogen receptor (ER) - positive breast cancer patients, developed using 95 gene-set without overlap with that used in Oncotype DXⓇ(ref 1). It has been shown to have the capability to classify the “intermediate” patients determined using Recurrence Online (microarray-based simulation model for Oncotype DXⓇ) but was validated only using the data from single institute and public database. Here we report the result of the first multi-center validation study for this multi-gene assay. Methods: ER-positive and T1-2/N0/M0 breast cancer patients who received adjuvant hormonal therapy were enrolled retrospectively. Fresh frozen tissues were applied to the assay, resulting classification into “L” and “H”, which was used for the validation on 5 year recurrence free survival (5Y-RFS) data of each patient. Results: 73 cases out of 150 enrolled cases were eligible and analyzed. 46 patients were classified as “L” whose 5Y-RFS was 96.5% (95%CI:89.5-98.9) while 27 patients were classified as “H” whose 5Y-RFS was 79.0% (95%CI:63.6-88.5). There was a statistically significant difference between RFS of “L” and “H” group by Log-Rank test (p = 0.0016). Significant association with 95GC were seen in histological grade (p = 0.0012), Recurrence Online (p < 0.001) and PAM50 (p < 0.001). The assay could classify the patients of histological grade 2, intermediate group by Recurrence Online (RS > 17, RS < 31) and Luminal B patients into “L” and “H”. Conclusions: Curebest™ 95GC Breast was well validated by this first multi-centered retrospective study on 5Y-RFS of the ER positive, node-negative patients who received only hormonal therapy in adjuvant setting. This result indicates the usefulness of 95GC as a novel multi-gene assay, as it can classify target patients into 2 groups, “H” and “L” according to predicted prognosis of 5Y-RFS. Reference: 1. Naoi et al. Breast Cancer Res Treat (2011) 128:632-641

From 1972 to 1989, 6 randomized controlled trials (RCT) of breast-conserving surgery followed by radiotherapy and radical mastectomy were performed. The two groups did not significantly differ in long-term survival rate after 20 years [1, 2]. Breast-conserving therapy is now a standard of care for Stage I and II breast cancer. As for ductal carcinoma in situ (DCIS), no RCTs compared breast-conserving therapy with mastectomy, but many published case series, reviews and meta-analyses showed good local control rates and high overall survival (OS) results [3]. Most Stage 0–II breast cancers are candidates for breastconserving therapy, but as the EBCTCG’s meta-analysis showed that local recurrence adversely affected survival rates [4], caution is warranted regarding indication or contraindication for breast-conservation therapy and extent of resection.

Radiotherapy should be recommended (Grade A). Although breast-conserving surgery without radiotherapy is performed for some of patients with early-stage breast cancer in Japan, it was found that the rate of local recurrence in the conserved breast was significantly decreased in seven randomized controlled trials (RCTs) from different parts of the world [1–7], a meta-analysis of these clinical trials analyzed by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) [8] with the conclusion that postoperative radiotherapy is essential. The recent meta-analysis of these RCTs confirmed that postoperative radiotherapy significantly improved patient survival rates [8, 9].

FNAC and CNB are recommended as diagnostic procedures for breast lesions (Grade B). For palpable breast lesions, FNAC has been in use as one of the most reliable diagnostic modalities for many decades. This technique is valuable because of its simplicity, cost-effectiveness, minimal invasiveness and low rate of complications. However, due to limitations of the diagnosis of breast lesions by FNAC, for instance, the difficulty of classifying a breast cancer into noninvasive or invasive carcinoma, its high rates of inadequacy and questionable accuracy, the role of FNAC has been debated recently [1]. In a previous review, the sensitivity of FNAC was reported to range from 65 to 98 % and its specificity from 34 to 100 % [2]. In Japan, a large-scale survey regarding the accuracy of FNAC by the Working Group of the Japanese Society of Clinical Cytology was conducted [3]. The survey showed that the cytological diagnosis had an inadequacy rate of 17.7 %, an indeterminate rate of This article is an English digested edition of the Nyugan Shinryo guideline 2013 nen ban, published by Kanehara & Co., LTD.

Purpose: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients. Methods and Materials: Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause. Results: BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome. Conclusions: BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.

In the National Surgical Adjuvant Study for Breast Cancer (NSAS-BC), node-negative breast cancers were divided into higher- and lower-risk groups according to the histopathological nuclear grade given at individual collaborating hospitals, and the higher-risk group was entered into a randomized protocol of adjuvant therapy. Because the nuclear grade was the composite of nuclear atypia and mitotic counts, maintenance of interobserver agreement in mitotic counts was indispensable for the success of the protocol study. Fourteen pathologists participating in the protocol judged whether or not 20 photomicrographs suspected of showing mitotic cancer-cell figures truly showed mitoses. After standardizing the counting method, these pathologists counted the number of mitotic figures per 10 high-power fields of hematoxylin-eosin-stained main-tissue sections of 20 tumors. Areas where mitotic counts were considered to be the most frequent by each pathologist were compared for these tumors. For the judgment of whether the photomicrograph indicated mitosis, the level of interobserver agreement was moderate (kappa = 0.569). In the observations of 20 tumors, interobserver agreement level of mitotic counts was moderate (kappa = 0.506), that of nuclear atypia scoring was fair (kappa = 0.265), and that of nuclear grading was substantial (kappa = 0.633). The counted area was almost the same among the observers in 9 tumors, split into two areas in 6, and dispersed in 5. Concordance in judgment was achieved in 7 of the first 9 and in all of the third 5, but only in one of the second 6. The cause of discordance was mostly derived from tumor heterogeneity and the difference in the site where mitoses were counted. Interobserver agreement level was considered to be satisfactory, and it was expected that the case entry would be performed appropriately in the protocol study. The selection of the counting area was confirmed to be important for the acquisition of high-level agreement level in mitotic counts.

It is difficult to cure recurrent or metastatic breast cancer (MBC). Therefore, it is important to continue treatment for MBC with maintenance of quality of life (QOL). Gemcitabine has been approved for MBC since February 2010. We administered gemcitabine to 39 patients with MBC between February 1, 2010 and March 31, 2012. Depending on the case, taxane or trastuzumab was added. Almost all patients had received prior chemotherapy or hormonal therapy. The median age of patients was 61 years (range, 33-82 years), and the median number of previous treatment regimens was 3 (range, 0-6). The response rate was 15.4%, the disease control rate was 56.4%, and the clinical benefit rate was 33.3%. The main hematological adverse event was neutropenia, and the main non-hematological adverse event was fatigue. Neutropenia could be managed by reducing the gemcitabine dose or withdrawing treatment. Adverse events requiring hospitalization were not observed. These findings suggest that gemcitabine-based regimens are feasible in terms of efficacy and maintenance of QOL for patients with MBC.

Although the progress in understanding human genetics regarding cancer has been applied to the medical practice of treating hereditary cancers in developed western countries, it is not widely implemented in Japan. We started treating hereditary cancers at NHO Shikoku Cancer Center in November 2000. Our institution has a multidisciplinary team that provides medical care and genetic counseling for patients with hereditary cancers, and their relatives. The team consists of doctors from several related departments, and paramedics including a genetic counselor who participated as of 2009. Medical care of patients with hereditary cancers should not be separated from general oncological practice, but incorporate all medical professionals, including doctors of related departments and paramedic. We have attempted to identify patients with hereditary cancer and their family members and relatives at high risk; we followed them up and provided risk-reducing therapies for them at our cancer center. Here we present the framework of our practice in treating hereditary cancers. We discuss appropriate goals and future perspectives in the field of hereditary cancer in Japan.

e23274Background: S-1 is oral fluoropyrimidine which is a biochemically modulated drug to increase 5-FU concentration and to avoid gastrointestinal toxicities. SELECT-BC, a randomized phase III tri...

The aim of this study was to assess the efficacy and safety of neoadjuvant anastrozole and radiation in postmenopausal breast cancer patients with hormone-receptor-positive tumors. In addition, we assessed the predictive factors for clinical and pathological response for concurrent anastrozole and radiotherapy. Patients with tumors 3 cm or larger were treated with neoadjuvant anastrozole for 24 weeks, and concurrent radiation was administered from 12 weeks after the start of anastrozole. Core biopsies were obtained at baseline and 12 weeks after the start of anastrozole. After completing neoadjuvant treatment, patients underwent definitive surgery. The primary endpoint was the overall objective response. In addition, we assessed the predictive factors for clinical and pathological response for concurrent anastrozole and radiotherapy. This trial is registered with the UMIN Clinical Trials Registry, no. UMIN000002266. The overall objective response rate was 92 %. Toxicity during neoadjuvant therapy was acceptable, with no grade 3 toxicities. After surgery, grade 3 toxicities occurred in 2 of 25 patients (8 %). Our preliminary data suggest that neoadjuvant anastrozole and radiation therapy in postmenopausal breast cancer patients with hormone-receptor-positive tumors has a high potential for clinical response.

The aim of healthcare providers is to help patients regain their health and/or maintain or increase their happiness. The quality of healthcare can be assessed objectively by using indices such as survival rates, but subjective assessment is sometimes more important than objective evaluation, because whether patients feel healthy or happy or not is their major concern. Quality of life (QOL) research is a typical approach to subjective assessment of health. Self-administered health-related QOL (HRQOL) questionnaires are used to obtain patient-reported outcome (PRO) data. PRO is defined by the US Food and Drug Administration (FDA) as any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else. PRO data are regarded as more accurate than clinician-rated ones in terms of assessing patients' symptoms and HRQOL. The Comprehensive Support Project for Health Outcome Research of the Public Health Research Foundation has conducted much PRO research in collaboration with the Comprehensive Support Project for Oncology Research, especially in randomized controlled trials (RCTs). Here, we review the results of PRO research in RCTs conducted in Japan and examine future perspectives in this field.

To elucidate whether adjuvant taxane monotherapy is a feasible and tolerable for postoperative breast cancer patients, we evaluated the severity of chemotherapy-induced peripheral neuropathy (CIPN) and the relative tolerability of regimens by health-related quality of life (HRQOL) assessment in node-positive breast cancer patients treated with taxane-containing regimens.We evaluated CIPN and HRQOL in the first 300 patients enrolled in a larger (1,060 total) multicenter phase III trial randomized to one of four adjuvant regimens: (1) anthracycline-cyclophosphamide followed by paclitaxel (ACP), (2) AC followed by docetaxel (ACD), (3) paclitaxel alone (PTX), or (4) docetaxel alone (DTX). CIPN was assessed by the Patient Neurotoxicity Questionnaire (PNQ) and the National Cancer Institute Common Toxicity Criteria, and HRQOL by Functional Assessment of Cancer Therapy-General (FACT-G). CIPN and HRQOL scores were compared between ACP and ACD vs. PTX and DTX, and ACP and PTX vs. ACD and DTX.PNQ sensory scores were significantly higher in patients treated with taxane monotherapy compared to treatment with AC followed by taxane (P = .003). No significant differences in PNQ sensory scores were observed between the ACP and PTX vs. ACD and DTX regimens (P = .669). Regardless of taxane regimen, PNQ severity scores for CIPN appear to be largely reversible within 1 year of adjuvant treatment. No significant difference in FACT-G scores was observed between any regimens during the study treatments.Patient-reported CIPN was significantly more severe with single-agent adjuvant taxane compared to AC followed by taxane treatment; however, the HRQOL findings support that single-agent taxane treatment is tolerable.

Imaging diagnostic methods except for mammograms are not recommended for follow-up of postoperative breast cancer patients in order to detect small recurrences because of the poor survival improvement in earlier randomized trials. However, the use of new imaging modalities may improve survival by detection of small isolated regional lymph node recurrences which are potentially curable. Between April 2006 and December 2008, we used PET–CT to find small recurrences in follow-up of 1,907 postoperative breast cancer patients. A total of 3,280 PET–CT imagings were performed. The median age at PET–CT imaging was 58 years, with a median 48-month interval from definitive surgery to the PET–CT imaging. Twenty-two patients were found to have isolated ipsilateral regional recurrences only by PET–CT (axillary node recurrences in 6, infraclavicular node recurrences in 5, supraclavicular node recurrences in 6, and parasternal node recurrences in 5). All of those recurrences were missed by palpation or were nonpalpable. The pathological lymph node status at the definitive surgery for the primary breast cancer of 22 patients with the isolated ipsilateral regional lymph node recurrences was positive in 17 patients. If patients are limited to those who had pathologically positive node(s) at definitive surgery, the incidence of patients with isolated regional lymph node recurrences found only by PET–CT would be 2.6% (17/663 patients). Seventeen other asymptomatic cancers including contralateral breast cancers were found only by PET–CT. Early detection of isolated loco-regional recurrences of breast cancer is suggested to result in improved survival. Therefore, the use of PET–CT in follow-up of postoperative node-positive breast cancer patients may improve their survival because of early detection of isolated regional lymph node recurrences which are still potentially curable, and screening of other asymptomatic cancers.

BACKGROUND In this Tamoxifen Exemestane Adjuvant Multinational Japan sub-study, we evaluated the time course of changes in serum lipids in postmenopausal women with hormone-sensitive early breast cancer treated with exemestane, anastrozole, or tamoxifen for postoperative adjuvant therapy. PATIENTS AND METHODS A total of 154 breast cancer patients were assigned to receive exemestane, anastrozole, or tamoxifen in this randomized open-label study. Serum lipid parameters including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during 1 year of treatment. RESULTS TC and LDL-C rapidly decreased in patients treated with tamoxifen at 3 months. Compared with anastrozole and exemestane patients, TC and LDL-C were significantly lower at all assessment time points in tamoxifen patients (P

We earlier reported a significant association between the cytochrome P450 2D6 (CYP2D6) genotype and the clinical outcome in 282 Japanese breast cancer patients receiving tamoxifen monotherapy. Although many research groups have provided evidence indicating the CYP2D6 genotype as one of the strongest predictors of tamoxifen response, the results still remain controversial. We hypothesized that concomitant treatment was one of the causes of these controversial results. We then studied 167 breast cancer patients who received tamoxifen-combined therapy to evaluate the effects of concomitant treatment on the association analysis and observed no significant association between CYP2D6 genotype and recurrence-free survival (P=0.44, hazard ratio: 0.64, 95% confidential interval: 0.20-1.99 in patients with two variant alleles vs. patients without a variant allele). When we carried out two subgroup analyses for nodal status and tumor size, we observed a positive association between the CYP2D6 genotype and the clinical outcome only in patients who received tamoxifen monotherapy. This study explained a part of the discrepancies among the reported results.

Endocrine therapy is the preferred systemic treatment for metastatic breast cancer to prolong disease control. Aromatase inhibitors (AIs) are becoming the first choice for postmenopausal patients with metastatic breast cancer. AIs are divided into non-steroidal and steroidal agents. We retrospectively analyzed 81 patients with metastatic breast cancer who were administered Exemestane (EXE). The response rate (RR) and clinical benefit rate (CBR) were evaluated. No significant differences were observed between the first-line treatment group and the second- and third-line treatment groups with respect to the CBR. With respect to the CBR, patients with metastases only of the bone and soft tissue had superior results than those with visceral metastasis. There were no significant differences in the RR and CBR of EXE because of differences in prior treatments. On the other hand, no clinical response was achieved in any patients for whom Anastrozole (ANA) was used following EXE. With regard to the switch from EXE to tamoxifen and to medroxyprogesterone acetate, a CB response was not achieved in those receiving EXE, but it was achieved in the others. EXE following ANA had moderate efficacy, with a CBR of 39%. Moreover, a clinical response was achieved in 3 out of 10 patients in whom no response had been achieved with ANA. EXE seems to be a useful alternative treatment when the first-line treatment has not been effective. If the use of both agents, ANA and EXE, is planned, it might be desirable to initiate treatment with ANA and then switch to EXE.

To investigate whether the health-related quality of life (HRQOL) of patients switching from tamoxifen to anastrozole in a randomized trial is identical to that of those who continued tamoxifen after 1–4 years of adjuvant tamoxifen in Japanese postmenopausal breast cancer patients. Eligible patients for the randomized trial, the National Surgical Adjuvant Study of Breast Cancer 03, were recurrence-free postmenopausal women who had received definitive surgery for primary breast cancer with positive hormone receptor(s), and had been taking tamoxifen for 1–4 years postoperatively. They were randomly assigned to continue tamoxifen or to switch to anastrozole for a total duration of five years. Subjects were asked to reply to a self-administered QOL questionnaire survey to assess HRQOL (FACT-B [breast cancer scale], FACT-ES [endocrine symptom scale]) and psychological distress (CES-D: Center for Epidemiologic Studies Depression scale) at randomization (baseline), 3 months, 1, and 2 years after randomization, respectively. At baseline 694 patients (346 in the tamoxifen group and 348 in the anastrozole group) responded to the survey. The total scores of FACT-G, FACT-ES, and those of the FACT-G physical well-being subscale were statistically significantly better in the tamoxifen group than in the anastrozole group (P = 0.042, 0.038, and 0.005, respectively). However, there was no statistically significant difference between the treatment groups in the CES-D scores. Continuation of tamoxifen treatment after adjuvant tamoxifen for 1–4 years may provide Japanese breast cancer patients with better HRQOL than by switching to anastrozole.

Objective: The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [docetaxel (DTX)/cyclophosphamide (CPA)] to doxorubicin/CPA therapy. To introduce TC therapy in Japan, the verification of the safety and tolerability is essential. We performed a collaborative prospective safety study with Okayama University to introduce TC therapy. Methods: The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008. As post-operative adjuvant chemotherapy, four cycles of TC (DTX 75 mg/m 2 þ CPA 600 mg/m 2 ) were administered at 3-week intervals. Adverse events were evaluated based on National Cancer Institute—Common Terminology Criteria for Adverse Events ver. 3.0. The safety and completion rate were evaluated as the primary and secondary endpoints, respectively. Results: Regarding hematological toxicity, Grade (G) 4 neutropenia occurred in 71.7% and G3 in 26.4%. G3‐4 leukopenia developed in 32.1% and 56.6%, respectively, G4 anemia in 1.9% and G1‐2 anemia in 26.4%. Regarding non-hematological toxicity, systemic malaise, skin eruption, edema, myalgia, arthralgia and nausea were noted in most patients. The completion rate was 94.3%, dose reduction was necessary in 7.5% and granulocyte colonystimulating factor (G-CSF) support was required in 17.0%. On comparison between patients aged 65 years or older and younger than 65 years, the completion rate, dose reduction and incidence of febrile neutropenia (FN) were higher in the elderly patients. G-CSF support was more often needed in this subgroup. Conclusions: TC therapy is tolerable for Japanese patients, but attention should be paid to the development of FN and neutropenia. The completion rate was lower in the elderly patients, showing that tolerability was not necessarily favorable.

Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 10-35% of the patients don't benefit from this treatment. This study was designed to evaluate predictive values of biological markers in response of breast cancers treated with docetaxel alone as neoadjuvant chemotherapy.36 patients received the planned four courses of preoperative docetaxel(60-75 mg/m(2)) every 3 weeks. We evaluated the relationship between the response rate to neoadjuvant chemotherapy and hormonal receptor, HER2 status or nuclear grades.Clinical response rate was 57.2%. Pathological complete response rate was 5.6%. Clinical response rate by each factors were as follows; 9(50%)in ER-positive tumors, 10(66.7%)in ERnegative( p=0.27), 7(50%)in PgR-positive, 12(63.3%)in PgR-negative(p=0.34), 5(55.6%)in HER2-positive, 14 (58.3%)in HER2-negative(p=0.71), 4(50%)in tumors of low nuclear grade and 13(65%)in ones of high nuclear grade(p=0.38).The possibility that tumors with negative hormonal receptors or of high nuclear grade tend to respond to neoadjuvant chemotherapy with docetaxel alone more likely was suggested. It is thought breast cancers respond to neoadjuvant chemotherapy of docetaxel alone regardless of HER2 status.

Objective: Sentinel node biopsy (SNB) is indicated for axillary lymph node metastasisnegative cases (N0), but clarification of the indication may increase treatment efficiency. Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may have a high positive predictive value in diagnosis of axillary lymph node metastasis. Methods: Ninety-two breasts/axillae were analyzed retrospectively in 90 patients (median age 54.6-year old, median primary tumor 1.7 cm). FDG-PET/computed tomography was used to indicate SNB in N0 cases. Axillary lymph node dissection (ALND) was performed in cases that were axillary lymph node metastasis-positive (PET Nþ) on FDG-PET/CT. Results: Seventy-four (80.4%) and 18 (19.6%) of the 92 axillae were diagnosed as metastasis-negative (PET N0) and PET Nþ, respectively, by FDG-PET/CT. SNB was performed in 51 of the 74 PET N0 axillae. ALND was performed in 23 PET N0 axillae (at the patients’ request) and in all 18 PET Nþ axillae. Of the 74 PET N0 axillae, 14 were metastasis-positive (pNþ) and 60 were pN0 pathologically, and of the 18 PET Nþ axillae, 13 were pNþ and five were pN0. The sensitivity and specificity of FDG-PET/CT for diagnosis of axillary metastasis were 48.1 and 92.3%, respectively, and the positive and negative predictive values were 72.2 and 81.1%, respectively. Conclusion: The positive detection rate on FDG-PET/CT was insufficient for determining an indication of SNB. However, use of an appropriate cut-off for SUVmax (the positive rate was 90.9% with a cut-off of 2.0) and exclusion of surgically biopsied cases may achieve a clinically applicable positive detection rate.

Vinorelbine is a newanti-cancer drug that is available for advanced or metastatic breast cancer, approved by the Japanese Ministry of Health, Labour and Welfare in May 2005. At present, we evaluated the efficacy and safety of vinorelbine in our hospital. 51 patients were treated with vinorelbine since April 1, 2006 to August 20, 2007. Average age was 55.9 years old and period of treatment was 161.9 days. Average number of previous treatments was 2.2, and 37 patients(72.6%)were treated with anthracyclines and taxanes. The response rate was 19.6%, there was one complete responder, and nine partial responders. Especially, the response rate was 16.2% in patients pretreated with anthracyclines and taxanes. The major toxicity was grade 3 or 4 neutropenia(15.7%), and superficial phlebitis(7.8%). Vinorelbine will be a standard treatment agent for patients pretreated with anthracyclines and taxanes.