Nobuaki Sato

Routine clinical use of the one-step nucleic acid amplification assay for detection of sentinel lymph node metastases in breast cancer patients: results of a multicenter study in Japan.

The objective of this study was to confirm, by means of a multicenter study conducted in Japan, the reliability and usefulness of the one‐step nucleic acid amplification (OSNA) assay in routine clinical use for sentinel lymph node biopsy (SLNB) of breast cancer patients.

Docetaxel Followed by Fluorouracil/Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy for Patients with Primary Breast Cancer

OBJECTIVE This multicenter, open-label, single-arm, Phase II study assessed the efficacy of a neoadjuvant chemotherapy with docetaxel (75 mg/m(2) q3w) followed by 5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) q3w in patients with early-stage breast cancer. METHODS Women with resectable breast cancer (T1c-3 N0 M0 or T1-3 N1 M0) were enrolled. Before surgery, patients received four cycles of docetaxel followed by four cycles of 5-fluorouracil, epirubicin, and cyclophosphamide. The primary endpoint was the pathological complete response (pCR) rate defined for the breast alone, assessed by a central review committee. Secondary endpoints included clinical response and safety. RESULTS One hundred and thirty-seven patients were enrolled. Of the 132 patients assessable for pathologic response, 23% (95% confidence interval, 16-31%) experienced a pathological complete response and 6% (95% confidence interval, 3-12%) had a near pathological complete response (few remaining cancer cells), resulting in a quasi-pathological complete response of 29% (95% confidence interval, 21-37%). Clinical response rate following the initial docetaxel regimen was 64%. The overall clinical response rate after completion of 5-fluorouracil, epirubicin, and cyclophosphamide was 79%; breast-conserving surgery was performed in 79% of patients. More patients with triple-negative disease (estrogen/progesterone receptors negative; human epidermal growth factor 2 negative) experienced a pathological complete response [14/29, (48%); 95% confidence interval, 29-68%] versus those with other molecular subtypes. The safety profile was acceptable. CONCLUSIONS Eight cycles of neoadjuvant chemotherapy-docetaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide-are tolerable and conferred high rates of pathological complete response and breast-conserving surgery. Patients with triple-negative disease were more likely to achieve pathological complete response versus other subtypes, suggesting that selecting appropriate neoadjuvant chemotherapy based on molecular subtype could be possible.

Ki67 index changes, pathological response and clinical benefits in primary breast cancer patients treated with 24 weeks of aromatase inhibition

Aromatase inhibitor shows efficacy for hormone receptor positive postmenopausal breast cancer. We evaluated the activity of 24 weeks of aromatase inhibition with exemestane for primary breast cancer in a neoadjuvant setting. Patients with stage II/IIIA invasive breast cancer with estrogen receptor (ER) and/or progesterone receptor (PgR)‐positive status were eligible. Primary endpoints were objective response rate (ORR) and safety. A steroidal aromatase inhibitor exemestane of 25 mg/day was administered for 16 weeks with an 8‐week extension. Secondary endpoints were rates of breast‐conserving surgery (BCS), and change of Ki67 index and ER/PgR expression in central laboratory analyses. Between March 2006 and December 2007, 116 patients were enrolled. Among those, 102 patients completed 24 weeks of administration. The ORR was 47% (55/116) at Week 16 and 51% (59/116) at Week 24, respectively. No serious toxicity was seen. ORR was associated with ER Allred scores but not with PgR scores. The significant reduction in Ki67 index was confirmed. No progression was experienced in tumors with less than 15% Ki67 index. Pathological response was observed in 28 (30%) of 94 evaluated cases. No statistical correlation between pre‐treatment Ki67 index and pathological response was detected; however, a trend of correlation was found between the post‐treatment preoperative endocrine prognostic index (PEPI), a prognostic score and the pathological response. At diagnosis, 59 patients (51%) would have required mastectomy but 40 patients were converted to BCS, showing an increase in the rate of BCS (77%). The 24‐week aromatase inhibition provided preferable clinical benefits with significant reduction in Ki67 index. More precise mechanisms of the response need to be investigated. (Cancer Sci 2011; 102: 858–865)

Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study.

The purpose of this study is to evaluate how beverages containing Lactobacillus casei Shirota (BLS) and soy isoflavone consumption since adolescence affected the incidence of breast cancer. In a population-based case-control study, three hundred and six cases with breast cancer and 662 controls aged 40 to 55 were matched for age and residential area and included in the analyses. Diet, lifestyle and other breast cancer risk factors were investigated using the self-administered questionnaire and interview. Odds ratios (ORs) of BLS and soy isoflavone consumption for breast cancer incidence were independently and jointly estimated using a conditional logistic regression. The ORs of BLS consumption (≥ four times a week against < four times a week) was 0.65 and statistically significant (p = 0.048). The analysis of association between soy consumption and breast cancer incidence showed the more the isoflavone consumption is, the lower the odds of breast cancer becomes. Adjusted ORs for breast cancer in the second, the third and the fourth quartiles of soy consumption against the first quartile were 0.76, 0.53 and 0.48, respectively (trend test, p = 0.0002). The BLS-isoflavone interaction was not statistically significant; however, a biological interaction was suggested. Regular consumption of BLS and isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women.

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in a Patient with Operable Breast Cancer

PurposeThis study was undertaken to assess the feasibility of performing a sentinel lymph node biopsy (SLNB) for a patient with operable breast cancer after undergoing neoadjuvant chemotherapy (NAC).MethodBetween January 2002 and December 2003, women with primary breast cancer who had a breast tumor measuring larger than 3 cm in unilateral diameter were eligible for NAC. All patients who had completed NAC underwent lymphatic mapping with labeled 99mTc phytate on the day before surgery. Sentinel lymph node biopsy followed by a full axillary lymph node (AXLN) dissection (ALND) was performed in all patients. Sentinel lymph nodes (SLN) were sent for a frozen-section examination.ResultsThe rate of SLN identification was 71%. Both the sensitivity and negative predictive value of SLNB were 100%. The false negative rate was 0%. When candidates for SLNB were restricted to patients with a breast tumor measuring less than 3 cm and clinically negative nodes after NAC, the rate of SLN identification increased to 93% from 71% while still maintaining the 0% false negative rate.ConclusionSentinel lymph node biopsy after NAC is therefore considered to be a feasible and accurate method to predict the AXLN status in patients who have a breast tumor measuring less than 3 cm in unilateral diameter and a clinically negative AXLN status at the time of surgery after NAC.

No increase of breast cancer incidence in Japanese women who received hormone replacement therapy: overview of a case-control study of breast cancer risk in Japan

Hormone replacement therapy (HRT) has been considered one of the main risk factors for breast cancer. Studies demonstrating the relationship between HRT and breast cancer incidence were conducted in Western countries and the target populations were mainly Caucasians. Since the Women’s Health Initiatives demonstrated that HRT increased the risk of breast cancer with statistical significance, the number of HRT users in the United States has dramatically decreased. A recent case-control study has investigated the relationship between HRT and breast cancer in Japan, and here we review the results of this study to compare any discrepancy in breast cancer risk between Japanese and Western populations. For this case-control study, at seven institutions, women between the ages of 45 through 69 years, with histologically confirmed breast cancer, were selected as the case group. An age-adjusted control group was selected, using hospital-based data, including records of those screened for lung, gastrointestinal, and gynecological cancer. Questionnaires were administered, and items questioned included various factors related to the incidence of breast cancer: age at diagnosis, body mass index (BMI), smoking habit, age at menopause, birth history, number of births, number of children, history of breast feeding, familial background, and menopausal status. In total, 6183 samples (98.4% of the estimated samples) were put into the database. Data from 276 samples were excluded due to ineligibility. Finally, 5861 samples (3434 cases and 2427 controls) were analyzed. In 3316 cases, 164 (5.0%) patients received hormone-replacement therapy (HRT); on the other hand, 253 (10.7%) of 2355 controls received HRT. The odds ratio was 0.432 (95% confidence intervals [CI], 0.352–0.53), and there was a significantly negative correlation between HRT use and breast cancer. The risk factors in Japanese women showed similar profiles to those in women in Western countries. However, we did find some different profiles of breast cancer risk in the Japanese women. Changing of lifestyle may increase breast cancer risk in Japan.

Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast-conserving treatment after receiving neoadjuvant chemotherapy: risk factors of IBTR and validation of the MD Anderson Prognostic Index.

There is limited information about the risk factors for ipsilateral breast tumor recurrence (IBTR) after patients undergo breast‐conserving surgery plus radiotherapy (breast‐conserving treatment [BCT]) subsequent to neoadjuvant chemotherapy (NAC). The objective of the current study was to analyze these risk factors.

Value of Three-Dimensional Helical CT Image-Guided Planning for Made-to-Order Lumpectomy in Breast Cancer Patients.

Abstract:  The authors reviewed Niigata Cancer Center Hospitals experience treating patients with lumpectomy to evaluate the utility of three‐dimensional helical computed tomography (3D‐CT) image‐guided made‐to‐order lumpectomy and determine a positive margin rate. From April 1993 to September 2000, 251 breasts in 248 patients were treated with lumpectomy with a 1 cm macroscopic free margin. In 213 breasts (85%), 3D‐CT image‐guided made‐to‐order lumpectomy was performed. Thirty‐eight breasts (15%) underwent a lumpectomy without 3D‐CT. The lumpectomy specimen was sectioned at 5 mm intervals. Margin status was classified as negative (no invasive or ductal carcinoma in situ (DCIS) within 2 mm from the cut surface) or positive. Positive margins were classified as focally positive (invasive or DCIS transected at the margin within 5 mm or one slide) or massively positive. With 3D‐CT image‐guided Iumpectomy, 21% (45/213) of lesions had a positive margin and 42% (16/38) of lesions without 3D‐CT image‐guided lumpectomy had a positive margin (p = 0.0055). For lesions with massively positive margins, the rates were 9% (4/45) for 3D‐CT image‐guided lumpectomy and 38% (6/16) for lumpectomy without 3D‐CT (p = 0.0152). 3D‐CT image‐guided made‐to‐order lumpectomy decreased the positive surgical margin rate. Among patients with positive margins, those with 3D‐CT image‐guided lumpectomy have less residual cancer than those without 3D‐CT.

Evaluation of the usefulness of breast CT imaging in delineating tumor extent and guiding surgical management: a prospective multi-institutional study.

Objective: The aim of the present study was to evaluate the usefulness of computed tomographic (CT) imaging in delineating tumor extent and guiding surgical management. Background: The routine use of preoperative magnetic resonance imaging (MRI) is a controversial issue in breast cancer management. Negative studies with regard to the utility of MRI might be due to differences in positioning during imaging and subsequent surgery. Methods: Candidates for breast-conserving surgery were eligible for the study. The surgeons marked the line of planned excision on the skin, which was also recorded on the CT image. Contrast-enhanced breast CT was performed in the supine surgical position. The CT results were used to help determine the extent of resection. The pathological findings were then compared with the CT-guided surgical plans. Results: A total of 297 patients were involved. The surgeons widened the extent of resection in 42 (14.1%, 95% confidence interval 10.1%–18.1%) patients on the basis of the CT findings. Among the 6 patients whose procedures were changed to mastectomy, 4 had pathologically multicentric tumors and 2 had widely spread intraductal components. The remaining 36 patients underwent quadrantectomy instead of wide excision on the basis of the CT images. There were 3 patients in whom conversion from wide excision to quadrantectomy resulted in overexcision. Preoperative breast CT may have reduced the positive margin rate and also correctly changed the extent of surgery in 13.1% of patients. Conclusions: This prospective study suggests that breast CT, carried out in the supine position, is useful in the preoperative determination of the optimal surgical procedure.

Relationship between body mass index and preoperative treatment response to aromatase inhibitor exemestane in postmenopausal patients with primary breast cancer

BACKGROUND Some studies have shown that high body mass index (BMI) is associated with inferior outcome after adjuvant therapy with anastrozole in breast cancer patients. We aimed to investigate predictive effect of BMI on clinical response to neoadjuvant therapy with exemestane in postmenopausal patients with primary breast cancer. PATIENTS AND METHODS The study group consisted of 109 patients from the JFMC 34-0601 neoadjuvant endocrine therapy trial. Patients were categorized into three groups according to BMI: low (BMI < 22 kg/m(2)), intermediate (22 ≤ BMI < 25 kg/m(2)) and high (BMI ≥ 25 kg/m(2)). Statistical analyses were performed to explore the predictive effect of BMI on clinical response. RESULTS Higher BMI correlated with positive progesterone receptor status (p < 0.01) and low Ki-67 index (p = 0.03). Objective response rates (ORR) were 21.7% in low BMI, 56.0% in intermediate BMI and 60.6% in high BMI, respectively (p = 0.01). In a multivariate analysis, low BMI was an independent negative predictor of clinical response. CONCLUSION Low BMI was associated with a decreased ORR to neoadjuvant endocrine therapy with exemestane. Our results may suggest that the predictive effect of BMI varies according to the type of aromatase inhibitor and objective outcome.