Treatment outcome for locally advanced non-small-cell lung cancer using TomoDirect plan and its characteristics compared to the TomoHelical plan.

INTRODUCTION: TomoDirect (TD) is an intensity-modulated radiotherapy system that uses a fixed gantry angle instead of the rotational beam delivery used in the TomoHelical (TH) system. This study was performed (1) to evaluate the treatment outcome of the TD plan for locally advanced non-small-cell lung cancer (NSCLC) and (2) to compare the characteristics of TD plans with those of TH plans. METHODS: Twenty-one patients with NSCLC were treated using the TD system. The prescribed dose was 40 Gy/20 Fx for the initial planning target volume (PTV), which included the gross tumour volume (GTV) and lymph node regions. A boost plan of 20 Gy/10 Fx was then applied, focusing on the GTV. For the planning study, matched TH plans of 40 Gy for the initial PTV were created for each patient, to meet the same dosimetric constraints specified in the TD plans. RESULTS: The 2-year overall survival, progression-free survival and local control rates were 47%, 45% and 74% respectively. Grade 2 treatment-related pneumonitis occurred in three (14%) patients. The planning study comparing TD and TH showed that dose distribution to GTV and PTV were not significantly different. The lung V5 Gy was lower in the TD plans than TH plans (46.4 ± 5.4 vs. 52.3 ± 8.5), while the V20 Gy was higher (26.2 ± 4 vs. 24 ± 4.3). The TD plans had a significantly shorter treatment time than TH plans (4.5 ± 1.3 min vs. 9.8 ± 1.5 min). CONCLUSIONS: TD is a clinically acceptable treatment option for NSCSL. The quality of the TD and TH plans are comparable.

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions.

In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

Second-look US Using Real-time Virtual Sonography, a Coordinated Breast US and MRI System with Electromagnetic Tracking Technology: A Pilot Study.

Our aim was to retrospectively evaluate the utility of second-look ultrasound (US) using real-time virtual sonography (RVS) for detection of conventional B-mode (cB-mode) occult magnetic resonance imaging (MRI)-detected breast lesions. Between July 2011 and May 2015, 53 consecutive patients who underwent second-look US to identify lesions detected by prone MRI were enrolled in this study. Second-look US using RVS was performed for cB-mode occult MRI-detected breast lesions after an additional supine MRI. In the 53 patients, 59 lesions were initially detected by prone MRI, followed by second-look US. Of the 59 lesions, 20 (34%) were identified by second-look US using cB-mode. Of the 39 (66%) cB-mode occult lesions, 38 (97%) were detected in supine MRI and 33 (85%) were detected by second-look US using RVS. MRI morphology types of the 33 lesions were as follows: mass, 16; non-mass enhancement, 5; and focus, 12. US-guided biopsy under RVS or excisional biopsy demonstrated that of the 33 lesions, 8 (24%) were malignant and the remaining 25 (76%) were benign. A total of 53 (90%) MRI-detected lesions were sonographically identified using both cB-mode and RVS (p < 0.001). All five remaining US-occult lesions could be followed up under RVS after the enhancing area was marked on the breast surface using RVS. Although further prospective studies are required, the findings of our pilot study suggest that second-look US using RVS with additional supine MRI may improve the sonographic and histopathologic detection rate of cB-mode occult MRI-detected breast lesions.

Investigation of Glycochenodeoxycholate Sulfate and Chenodeoxycholate Glucuronide as Surrogate Endogenous Probes for Drug Interaction Studies of OATP1B1 and OATP1B3 in Healthy Japanese Volunteers.

PURPOSE: To assess the use of glycochenodeoxycholate-3-sulfate (GCDCA-S) and chenodeoxycholate 3- or 24-glucuronide (CDCA-3G or -24G) as surrogate endogenous substrates in the investigation of drug interactions involving OATP1B1 and OATP1B3. METHODS: Uptake of GCDCA-S and CDCA-24G was examined in HEK293 cells transfected with cDNA for OATP1B1, OATP1B3, and NTCP and in cryopreserved human hepatocytes. Plasma concentrations of bile acids and their metabolites (GCDCA-S, CDCA-3G, and CDCA-24G) were determined by LC-MS/MS in eight healthy volunteers with or without administration of rifampicin (600 mg, po). RESULTS: GCDCA-S and CDCA-24G were substrates for OATP1B1, OATP1B3, and NTCP. The uptake of [3H]atorvastatin, GCDCA-S, and CDCA-24G by human hepatocytes was significantly inhibited by both rifampicin and pioglitazone, whereas that of taurocholate was inhibited only by pioglitazone. Rifampicin elevated plasma concentrations of GCDCA-S more than those of other bile acids. The area under the plasma concentration-time curve for GCDCA-S was 20.3 times higher in rifampicin-treated samples. CDCA-24G could be detected only in plasma from the rifampicin-treatment phase, and CDCA-3G was undetectable in both phases. CONCLUSIONS: We identified GCDCA-S and CDCA-24G as substrates of NTCP, OATP1B1, and OATP1B3. GCDCA-S is a surrogate endogenous probe for the assessment of drug interactions involving hepatic OATP1B1 and OATP1B3.

Digital volumetric measurement of mammographic density and the risk of overlooking cancer in Japanese women.

BACKGROUND: Breast density often affects cancer detection via mammography (MMG). Because of this, additional tests are recommended for women with dense breasts. This study aimed to reveal trends in breast density among Japanese women and determine whether differences in breast density differentially affected the detection of abnormalities via MMG. METHODS: We retrospectively analyzed 397 control women who underwent MMG screening as well as 269 patients who underwent surgery for breast cancer for whom preoperative MMG data were available. VolparaDensity™ (Volpara), a three-dimensional image analysis software with high reproducibility, was used to calculate breast density. Breasts were categorized according to the volumetric density grade (VDG), a measure of the percentage of dense tissue. The associations between age, VDG, and MMG density categories were analyzed. RESULTS: In the control group, 78% of women had dense breasts, while in the breast cancer group, 87% of patients had dense breasts. One of 36 patients with non-dense breasts (2.7%) was classified as category 1 or 2 (C-1 or C-2), indicating that abnormal findings could not be detected by MMG. The proportion of patients with breast cancer who had dense breasts and were classified as C-1 or C-2 was as high as 22.3%. CONCLUSIONS: The proportions of Japanese women with dense breasts were high. In addition, the false-negative rate for women with dense breasts was also high. Owing to this, Japanese women with dense breasts may need to commonly undergo additional tests to ensure detection of breast cancer in the screening MMG.

Targeted sonography using an image fusion technique for evaluation of incidentally detected breast lesions on chest CT: a pilot study.

BACKGROUND: With increasing use of computed tomography (CT), incidentally detected breast lesions are being encountered more frequently. The aim of our study was to verify the utility of targeted sonography using an image fusion technique, real-time virtual sonography (RVS) that coordinates real-time sonography images with previously obtained CT images using a magnetic position tracking system, for evaluation of incidentally detected breast lesions on chest CT. METHODS: Eleven lesions in 11 women with no history of breast cancer who were referred to our unit for assessment of breast lesions incidentally detected on CT were enrolled in this study. To assess the efficacy of targeted sonography using RVS, we analyzed the frequency of sonographic detection of incidentally detected breast lesions and the difference between sonography- and CT-determined diameters. RESULTS: Using RVS guidance, all 11 lesions were sonographically detected. Ten (91 %) of 11 lesions underwent sonography-guided biopsy, yielding a success rate of 90 % (9/10). The remaining sonography-guided biopsy failure lesion required surgical biopsy for definitive diagnosis; this was performed after RVS was used to mark CT imaging information onto the breast surface. Four (36 %) lesions subsequently proved to be malignant. The mean diameters provided by RVS were 14.9 ± 6.7 mm for sonography and 16.8 ± 7.5 mm for CT (p = 0.538). CONCLUSION: Using RVS, a sonographic probe was precisely guided to the lesions. Our results suggest that targeted sonography using RVS is a useful technique for identifying incidentally detected breast lesions on chest CT.

Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

BACKGROUND: Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. METHODS: We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. RESULTS: With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p < 0.0001). Seventy-one patients (72.4 %) had TM data at the time of CTC testing. To study the relationship between CTCs and TMs, we divided patients into normal TM and high TM groups. In the normal TM group, the CTC-negative patients had statistically significant survival than the CTC-positive patients (p = 0.005). The data suggested that CTC count could provide additional prognostic information beyond TMs for advanced/metastatic breast cancer. In multivariate analysis, the only significant predictor of overall survival was CTC ≥ 1 (hazard ratio, 3.026; 95 % confidence interval 1.350-6.784). CONCLUSION: We found that a CTC cut-off value of 1 is appropriate in patients with advanced/metastatic breast cancer. CTCs could yield additional information beyond CEA and CA15-3.

Tangent field technique of TomoDirect improves dose distribution for whole-breast irradiation.

TomoDirect (TD) is an intensity-modulated radiotherapy system that uses a fixed gantry angle instead of rotational beam delivery. Here, we investigated the effect of the multiple beam technique of TomoDirect on dose distribution compared with commonly-used tangential beams. We included 45 consecutive patients with right breast cancer who underwent postoperative radiotherapy in our institute in the present study. Clinical target volume (CTV) was the whole right breast. The planning target volume (PTV) was created by expanding the CTV by a 0.5 cm margin. Paired TD plans were generated for each patient; a two-beam plan using paired tangential beams and a six-beam plan with four additional beams with modified gantry angles of ± 5° from the original tangential beam set. A prescribed dose of 50 Gy was defined for 50% isodoses of the PTV. The six-beam plan delivered significantly more homogeneous doses to the PTV than the two-beam plan; and the mean dose to the PTV in the six-beam plan more closely reflected the prescribed dose. V20Gy and mean dose to the right lung and mean dose to the whole body were also significantly decreased in the six-beam plan. However, duration of radiation exposure was 1 min longer in the six-beam plan than in the two-beam plan. The dose distribution to the target and organs at risk were improved with the six-beam plan relative to the two-beam plan without increasing the whole-body radiation dose. The six-beam plan using TD is a simple technique that can be routinely applied to whole-breast irradiation in clinical practice.

Reproducible surveillance breast ultrasound using an image fusion technique in a short-interval follow-up for BI-RADS 3 lesions: a pilot study.

The aim of our study was to verify the utility of surveillance ultrasound (US) using real-time virtual sonography (RVS)--to coordinate present US images with past US images reconstructed from previously acquired US volume data using an image fusion technique--for short-interval follow-up of Breast Imaging-Reporting and Data System (BI-RADS) category 3 mass lesions. We enrolled 20 women (23 lesions) with more than 24 mo of follow-up after classification as BI-RADS category 3 during initial US. US surveillance was scheduled at 6, 12 and 24 mo. Measurement of the target lesion diameter was performed after the probe was adjusted to include the maximum diameter of a past US image at each visit. RVS was technically successful in 100% of patients. All target lesions were detected, including two iso-echoic lesions. The mean target lesion diameters at baseline and at 6, 12 and 24 mo were 8.2 ± 4.2, 8.4 ± 4.5, 8.1 ± 4.5 and 8.3 ± 5.0 mm, respectively (p = 0.785). Our results suggest that RVS is a reproducible, operator-independent technique for comparison of US images of BI-RADS category 3 mass lesions obtained at different time points.

A case of quadruple primary malignancies including breast, tongue, and thyroid cancers and osteosarcoma in a young female without karyotype abnormality.

The patient was a 41-year-old, premenopausal woman with a chief complaint of well-circumscribed palpable, right breast mass without nipple discharge. Although she noticed the lump 3 months previously, the size of the tumor (1.1 × 0.9 cm(2)) had been stable. The patient's mother suffered from gastric cancer. Her previous history of the triple different malignancies was as follows: (1) left osteosarcoma [amputation of left lower leg at 15 years old (y/o)]. After the operation, she was treated with various kinds of anticancer drugs including a total of 45 g ifosphamide and 342 g methotrexate; (2) tongue cancer (right radical neck resection; 23 y/o); and (3) thyroid cancer (right lobectomy; 40 y/o). There was no evidence of recurrence of these malignancies at the present consultation. At the time of tongue cancer operation, chromosome abnormality was investigated, but the results were normal. Physical examination showed a well-delimited, elastic-firm, mobile tumor in the central outer right breast. Regional lymph nodes were not palpable. Mammography showed a focal asymmetry in the right upper breast on the mediolateral oblique view. Ultrasonography revealed a hypoechoic mass with irregular margins. Distant metastases could not be detected by whole-body computed tomography scan. The histology of the Mammotome(®) (vacuum-assisted core needle biopsy) specimen revealed that this tumor was low-grade ductal carcinoma in situ (DCIS). She underwent breast-conserving surgery with sentinel lymph node biopsy. On permanent histopathological examination, the diagnosis of the tumor was intracystic papilloma with low-grade DCIS. Surgical margin was negative, and sentinel lymph node metastases could not be observed. Estrogen and progesterone receptor (ER/PR) were strongly positive, but human epidermal growth factor receptor-2 (HER-2) overexpression was not tested because the lesion was DCIS. She has received no adjuvant therapy and is currently disease free 3 months after surgery.

p53 expression in pretreatment specimen predicts response to neoadjuvant chemotherapy including anthracycline and taxane in patients with primary breast cancer.

While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p＝0.045) and histological grade 3 (p＝0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC.

Impact of real-time virtual sonography, a coordinated sonography and MRI system that uses an image fusion technique, on the sonographic evaluation of MRI-detected lesions of the breast in second-look sonography.

The aim of this study was to verify the utility of second-look sonography using real-time virtual sonography (RVS)-a coordinated sonography with an MRI system that uses an image fusion technique with magnetic navigation-on the sonographic evaluation of MRI-detected lesions of the breast. Of the 196 consecutive patients who were examined with breast MRI in our hospital from 2006 to 2009, those patients who underwent second-look sonography to identify MRI-detected lesions were enrolled in this study. MRI was performed using a 1.5-T imager with the patient in a supine position. To assess the efficacy benefits of RVS, the correlations between lesion detection rates, MRI features, distribution, and histopathological classification on second-look sonography using conventional B-mode or RVS were analyzed. Of the 196 patients, 55 (28 %) demonstrated 67 lesions initially detected by MRI, followed by second-look sonography. Of the 67 MRI-detected lesions, 18 (30 %) were identified with second-look sonography using conventional B-mode alone, whereas 60 (90 %) lesions were detected with second-look sonography using RVS (p < 0.001). The detection rates of 16 focal lesions, 46 mass lesions, 16 lesions sized <5 mm, 45 lesions sized 5-10 mm, 26 lesions situated within the mammary gland, 41 lesions situated around mammary fascia, 24 malignant lesions, and 43 benign lesions were, respectively, 25, 26, 25, 24, 42, 17, 33, and 23 % by conventional B-mode, and were significantly higher, respectively, at 94, 89, 94, 89, 88, 90, 92, and 88 % by RVS. Of the seven lesions with no sonographic correlates, five could be biopsied by marking MRI information onto the body surface using RVS. Overall, 65 of 67 (97 %) MRI-detected lesions were confirmed by histopathological results. Our results suggest that the additional use of RVS on second-look sonography significantly increases the sonographic detection rate of MRI-detected lesions without operator dependence.

Loss of heterozygosity on chromosome 16q suggests malignancy in core needle biopsy specimens of intraductal papillary breast lesions.

It is often difficult to make a definitive diagnosis of papillary breast lesions using core needle biopsy (CNB) specimens. We studied loss of heterozygosity (LOH) on chromosome 16q in order to assess its diagnostic use for papillary breast lesions in CNB specimens. Of 25 patients with intraductal papillary breast tumors, we extracted DNA from paired samples of tumor cells from CNB specimens and non-tumor cells from subsequent excision specimens and analyzed LOH at the D16S419 and D16S514 loci on chromosome 16q. LOH analysis results were compared with final diagnoses based on pathological features of the resected specimens. On the CNB specimens, 21 tumors were histologically diagnosed as indeterminate or suspicious for malignancy, while four tumors were unambiguously malignant. Of the 21 indeterminate or suspicious tumors, 11 were finally diagnosed as benign and ten as malignant, and on these, LOH analyses were informative for 8 of the 11 benign tumors and 7 of the 10 malignant tumors. LOH was also informative on two of the four tumors unambiguously malignant on CNB. None of the eight informative benign tumors showed LOH on 16q. Six of the eleven informative malignant tumors showed LOH on 16q. LOH on 16q was significantly different between CNB specimens of benign and malignant intraductal papillary tumors (P = 0.007). Analysis of LOH on 16q may be helpful in making a definitive diagnosis in cases of papillary breast lesions, in both excised and CNB specimens.

A case of estrogen receptor positive secretory carcinoma in a 9-Year-old girl with ETV6-NTRK3 fusion gene.

The patient was a 9-year-old premenarcheal pediatric female, whose chief complaint was a well-circumscribed palpable right breast mass without nipple discharge. Although the patient had noticed the lump 2 years prior to hospital admission, its size (1.5 × 1.3 cm) had been stable. There was no family history or previous history of malignancies. Physical examination showed a well-delimited, elastic-firm and movable tumor just beneath the nipple and areolar complex. Regional lymph nodes were not palpable. Ultrasonography and breast computed tomography revealed a subareolar oval-shaped tumor exhibiting homogeneous echogenicity with clear margins. Distant metastases could not be detected using whole-body computed tomographic scans. A fine-needle aspiration cytology specimen showed atypical cells with prominent nucleoli and abundant intracellular secretory material, suggesting the possibility of secretory carcinoma. Histopathological analysis of the core needle biopsy specimen revealed that the tumor was a secretory carcinoma. The patient underwent total mastectomy with sentinel lymph node biopsy. Metastases were not observed in the removed lymph nodes. Estrogen receptor was weakly positive and progesterone receptor was negative. Human epidermal growth factor receptor 2 expression was also negative. In addition, the ETV6 (exon 5) and NTRK3 (exon 13) fusion gene was detected using the reverse transcription-polymerase chain reaction method. This gene is considered specific for secretory carcinoma. Immunohistochemistry revealed weak basal differentiation [cytokeratin 5/6(CK5/6)(+), vimentin(+) and epidermal growth factor receptor(+)]. The patient has received no adjuvant therapy and is currently disease free at 12 months after surgery.

Real-time virtual sonography, a coordinated sonography and MRI system that uses magnetic navigation, improves the sonographic identification of enhancing lesions on breast MRI.

This study verified that recently developed real-time virtual sonography (RVS) to coordinate a sonography image and the magnetic resonance imaging (MRI) multiplanar reconstruction (MPR) with magnetic navigation was useful. The purpose of this study was to evaluate the accuracy of RVS to sonographically identify enhancing lesions by breast MRI. Between December 2008 and May 2009, RVS was performed in 51 consecutive patients with 63 enhancing lesions. MRI was performed with the patients in the supine position using a 1.5-T imager with a body surface coil to achieve the same position as with sonography. To assess the accuracy of the RVS, the following three issues were analyzed: (i) The sonographic detection rate of enhancing lesions, (ii) the comparison of the tumor size measured by sonography and the MRI-MPR and (iii) the positioning errors as the distance from the actual sonographic position to the expected MRI position in 3-D. Among the 63 enhancing lesions, 42 (67%) lesions were identified by conventional B-mode, whereas the remaining 21 (33%) initial conventional B-mode occult lesions were identified by RVS alone. The sonographic size of the lesions detected by RVS alone was significantly smaller than that of lesions detected by conventional B-mode (p < 0.001). The mean tumor size provided by RVS was 12.3 mm for real-time sonography and 14.1 mm for MRI-MPR (r = 0.848, p < 0.001). The mean positioning errors for the transverse and sagittal planes and the depth from the skin were 7.7, 6.9 and 2.8 mm, respectively. The overall mean 3D positioning error was 12.0 mm. Our results suggest that RVS has good targeting accuracy to directly compare a sonographic image with MRI results without operator dependence.

[Chemotherapy of a 2-week S-1 administration followed by 1-week rest for advanced and metastatic breast cancer].

When treating advanced and metastatic breast cancer patients with chemotherapy, it is mandatory to maintain the patients quality of life while keeping an acceptable level of antitumor activity. For these purposes, oral administration of S-1, fluorinated pyrimidine, is a good choice of treatment. Conventionally, a 4-week administration followed by a 2-week rest has been the treatment of choice with S-1. However, we applied a new regimen for 16 patients with advanced and metastatic breast cancer, in which one course consisted of a 2 week-administration followed by a week of rest, repeated twice. The median age of the patients who received this treatment was 59 years old(range 46. 8-80. 6). The response rate was 31. 2%, and the median values of time to progression and overall survival were 5. 1 and 17. 9 months, respectively. One case of thrombocytopenia as an adverse event was recognized. Our new S-1 regimen is likely to show an acceptable anti-tumor effect with minimal adverse events. The fidings suggest that this new regimen is clinically applicable for advanced and metastatic breast cancer patients.

Prognostic factors in young Japanese women with breast cancer: prognostic value of age at diagnosis.

OBJECTIVE: The primary objective of this study was to verify whether breast cancer patients aged <35 at diagnosis have poorer prognoses than those aged 35-39, in other words, to identify the prognostic value of age in younger premenopausal patients under 40 years old. The secondary objective was to assess prognostic factors specific for younger premenopausal patients. METHODS: We identified 242 consecutive patients who were diagnosed with stage I-III breast cancer before the age of 40 and underwent surgery between 1990 and 2004. We compared disease-free survival and overall survival in patients aged <35 years and those aged 35-39 years, and evaluated clinicopathological factors associated with disease-free survival or overall survival in each age group and in all patients under the age of 40. RESULTS: Ninety-nine (41%) patients were younger than 35 years and 143 (59%) were between 35 and 39 years. No significant difference in disease-free survival or overall survival was found between the two groups. In our cohort of patients under the age of 40, the independent factors associated with poor disease-free survival and overall survival included positive axillary lymph nodes and triple-negative status, but not age at diagnosis. Adverse prognostic factors also did not differ considerably between the two age groups. CONCLUSIONS: Age at diagnosis was not an independent prognostic factor in our study. Our findings suggest that other clinicopathological features rather than age should be used to determine individualized treatment courses for breast cancer patients younger than 40 years.

Evaluation of Oncotype DX Recurrence Score as a prognostic factor in Japanese women with estrogen receptor-positive, node-negative primary Stage I or IIA breast cancer.

PURPOSE: We sought to evaluate the use of the Onco type DX Breast Cancer Assay for identifying candidates for adjuvant therapy in patients with estrogen receptor (ER)-positive, node-negative primary Stage I or IIA breast cancer. METHODS: A retrospective case-control study was conducted on 40 patients who underwent surgery between 2000 and 2008. Cases (n = 10) were patients who had metastases after surgery. Controls (n = 30) were patients who did not develop metastases and were individually matched to their case with respect to age. All patients were analyzed with regard to age, tumor size, histological grade, HER2 status, and the values of Recurrence Score (RS), ER score and PgR score generated by Onco type DX. We also divided the patients into low, intermediate or high-risk groups according to individual RS values. RESULTS: RS, risk category and histological grade were associated with metastases in patients with ER-positive, node-negative Stage I or IIA breast cancer. However, ER status, tumor size and PgR status were not associated with metastases. Histological grade was associated with RS value and the distribution pattern of risk category (P < 0.001 for each). CONCLUSIONS: Both histological grade and risk-category classification were effective in identifying women at risk of developing distant metastases after initial therapy for ER-positive, node-negative Stage I or IIA breast cancer. These patients may benefit from the addition of adjuvant therapy at diagnosis.

Intracystic invasive papillary carcinoma of the male breast with analyses of loss of heterozygosity on chromosome 16q.

A 64-year-old man noticed a right subareolar mass in May 2005. On physical examination, an oval-shaped, well-circumscribedthe tumor (6.0 x 5.5 cm in size) was located just beneath the right nipple. The tumor was elastic, firm and freely movable. Neither axillary nor supraclavicular lymph nodes were palpable. Mammography demonstrated a 5 x 5-cm, relatively distinct and dense mass without microcalcifications or spiculations. There were no findings of concurrent gynecomastia. Ultrasonography revealed a large multilocular cyst with a mural hypoechoic protruding lesion exhibiting wide-based morphology with an irregular margin. On contrast-enhanced computed tomography, the inner lesion enhanced, but direct invasion of the tumor to the major pectoral muscle was not found. An intracystic papillary lesion, possibly papillary carcinoma, was suspected. In December 2007, wide excision of the tumor was performed. On histopathological examination, the tumor had a papillary pattern with a small cribriform component in the cystic wall with microinvasion of the stroma. Marginal status was negative. The final diagnosis of the disease was a microinvasive intracystic papillary carcinoma of low grade without axillary lymph node metastases. Immunohistochemically, estrogen receptor and progesterone receptor were both positive, but negative for HER-2 protein. No LOH on 16q could be detected. The prognosis of the disease was unclear; however, the malignant potential of this condition may be more clearly determined by studying the LOH on chromosome 16q.