Predicting Nonsentinel Lymph Node Metastasis in Breast Cancer: A Multicenter Retrospective Study.

BACKGROUND: Sentinel lymph node (SLN) biopsy has been the standard modality for breast cancer patients with clinically node negative disease. In patients who undergo axillary lymph node dissection (ALND) due to SLN metastasis, the harvested nodes (non-SLNs) often contain no metastasis. Here, we evaluated the predictive factors associated with non-SLN metastasis in breast cancer patients. MATERIALS AND METHODS: This was a retrospective study of patients with operable cT1-3, cN0 invasive breast cancer who underwent SLN biopsy followed by ALND due to SLN metastasis. The clinicopathologic factors and predictive factors of non-SLN metastasis were analyzed. The optimal cutoff for the Ki67 index and the number of positive and negative SLNs that were predictive of non-SLN metastasis were evaluated using receiver operating characteristic curves. RESULTS: The median number of SLN and non-SLN was 3 and 11, respectively. Of the 150 patients, 52 (35.0%) had metastases in non-SLNs. The optimal cutoffs for the Ki67 index and the number of positive and negative SLNs were of 12%, 2, and 1, respectively. In the univariate analysis, the Ki67 index and the number of positive SLNs≥2 and negative SLNs≤1 were higher in the non-SLN + group than that in the non-SLN - group. The number of negative SLNs was as a predictive factor for non-SLNs metastasis in the multivariate analysis. CONCLUSIONS: The number of negative SLNs predicts the risk of non-SLN metastasis in breast cancer. When deciding on whether to omit ALND, the number of positive and negative SLNs should be considered.

Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

Background: There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. Methods: We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. Results: The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Conclusions: Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

Stratification of Prognosis by Biological Features Following Neoadjuvant Chemotherapy in Luminal Breast Cancer.

BACKGROUND/AIM: There are few models predicting breast cancer prognosis among patients receiving neoadjuvant chemotherapy (NAC) for estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (luminal) breast cancer. We examined whether biological features (BFs) of residual tumors are prognostic factors following NAC. PATIENTS AND METHODS: We enrolled patients with remnant tumors following NAC for luminal breast cancer and evaluated clinical stage, pathological stage, BFs prior to NAC, and BFs following NAC as prognostic factors. BFs were divided into high and low risk using the previously reported YR-IHC4 model calculated according to ER, progesterone receptor (PgR), HER2, and the proliferation marker Ki-67. RESULTS: A total of 57 patients were enrolled in the current study. We observed a statistically significant difference in relapse-free survival (RFS) between the BF risk categories via YR-IHC4 predictions following NAC (p=0.044). The 5-year RFS rates of the BF low- and high-risk groups following NAC were 84.2% and 52.5%, respectively. CONCLUSION: BFs of residual tumors following NAC may be important prognostic factors in luminal breast cancer.

A case of matrix-producing carcinoma of the breast treated with preoperative chemotherapy.

Background: Matrix-producing carcinoma (MPC) is a rare tumor accounting for 0.1% of all breast cancers. Although MPC is usually triple-negative breast cancer, there have been few reports of preoperative chemotherapy for MPC that is considered chemotherapy-resistant. Herein, we report a case of MPC that was successfully treated with preoperative chemotherapy. Case Description: The patient was a 47-year-old woman diagnosed with right multiple breast cancer, clinical stage IIA. One of the tumors was identified as MPC and the other was invasive ductal carcinoma. The maximum tumor diameter of MPC was 3.8-cm. On immunohistochemistry, the tumor cells of MPC tested negative for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). The Ki67 index was 90%. Preoperative chemotherapy was performed. EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) was administered every 3 weeks for a total of 4 courses, followed by 12 courses of weekly paclitaxel (80 mg/m2). Then, she underwent right skin-sparing mastectomy, sentinel lymph node biopsy, and deep inferior epigastric perforator flap reconstruction. There was no metastasis to the sentinel lymph nodes. Postoperative pathological results showed that the residual tumor of the MPC measured only 0.1 cm. On the other hand, the residual tumor of the invasive ductal carcinoma was 0.7 cm. Endocrine therapy with oral tamoxifen was initiated for the invasive ductal carcinoma. Three years after surgery, no recurrence was observed. It has been reported that prognosis was correlated with residual cancer after preoperative chemotherapy. In addition, preoperative chemotherapy is of high clinical significance for the selection of postoperative treatment. Conclusions: Although our case of MPC was successfully treated with preoperative chemotherapy, the standard of care for MPC remains uncertain. Development of a new targeted therapy for MPC is warranted.

Clinical Impact of a Novel Model Predictive of Oncotype DX Recurrence Score in Breast Cancer.

BACKGROUND/AIM: Oncotype DX recurrence score (RS) for breast cancer is a useful tool for determining chemotherapy indication but it is expensive and time-consuming. We determined whether four immuno-histochemical markers, namely human epidermal growth factor 2 (HER2), estrogen receptor (ER), progesterone receptor (PgR), and Ki-67, are predictive of an RS ≥26 in Japanese patients. PATIENTS AND METHODS: The study included 95 Japanese patients evaluated for RS. A predictive model was created using logistic regression analysis. RESULTS: The discriminant function was calculated as follows: p=1/{1+exp [-(4.611+1.2342×HER2-0.0813×ER- 0.0489 ×PgR+0.0857×Ki67)]}. Using a probability of 0.5 as the cutoff, the accuracy, sensitivity, specificity, positive predictive and negative predictive values were 90.5%, 72.2%, 94.8%, 76.4% and 93.5%, respectively. CONCLUSION: The model had a high negative predictive value in predicting RS ≥26 in Japanese patients, indicating that Oncotype DX testing may be omitted in patients with a negative result according to the predictive model.

Outcomes of surgery for 2010 WHO classification-based intraductal papillary neoplasm of the bile duct: Case-control study of a single Japanese institution's experience with special attention to mucin expression patterns.

INTRODUCTION: The World Health Organization (WHO) proposed an integrated classification for intraductal papillary neoplasm of the bile duct (IPNB) in 2010. However, IPNB reportedly shows considerable geographic variation. This Japanese single-institution study examined outcomes of surgery for IPNB and the prognostic impact of immunohistochemical mucin expression patterns. MATERIALS AND METHODS: Patients with IPNB were identified from 413 patients who underwent curative-intent surgery for biliary tract (excluding gallbladder) neoplasms from 1992 to 2016 by retrospective macro- and microscopic reevaluation of resected specimens. Their clinicopathological variables were analyzed. RESULTS: Twenty-two (5%) 2010 WHO classification-based patients with IPNB were identified. The other 391 patients had common-type cholangiocarcinoma. The histopathological grade was low/intermediate in 2 patients (9%), high in 8 (36%), and invasive carcinoma (ICa) in 12 (55%). The 10-year overall survival rate was 100% in 10 patients with low-high grade IPNB and 69% in 12 patients with ICa. These rates were significantly (p = 0.018) or marginally (p = 0.089) better than that (38%) of 391 other-cholangiocarcinoma patients. In the 12 patients with ICa, R0 or R1 resection, MUC5AC, and MUC6 expression significantly affected survival. Notably, all seven patients with ICa exhibiting MUC5AC expression survived throughout the study period, while four of five patients with ICa who did not exhibit MUC5AC expression died of recurrence (with vs. without MUC5AC: 10-year overall survival, 100% vs. 60%, respectively; p = 0.018). CONCLUSION: Our 24-year, single institution's experience suggests that Japanese patients with IPNB favorably respond to surgery, even with ICa. MUC5AC and MUC6 expression may be predictive of favorable outcomes.

A case of synchronous multiple bilateral breast cancer after breast augmentation.

Breast cancer after breast augmentation is not rare, but cases of bilateral breast cancer after augmentation are not often reported. A 43-year-old woman attended our hospital because of a mass in her left breast. She had undergone breast augmentation by implants 4 years before at a cosmetic surgery clinic. There were operative scars in her bilateral axilla. A detailed examination revealed bilateral breast cancer, and we performed nipple-sparing mastectomy in both breasts. Sentinel lymph node biopsy using dye was performed and it identified stained lymph nodes on both sides. The sentinel lymph node biopsy was negative for metastasis on both sides, so axillary lymph node dissection was not performed.

Variability in measuring the Ki-67 labeling index in patients with breast cancer.

BACKGROUND: Luminal-type breast cancer is divided into types A and B, depending on the Ki-67 labeling index (LI). However, the area at which Ki-67 is measured and the choice of specimen greatly affects the results. The aim of the present study was to evaluate the Ki-67 LI variability using different measurement methods and specimens. We also evaluated how the chemotherapy indication changed for luminal-type breast cancer using the different measurements. MATERIALS AND METHODS: The Ki-67 levels in 87 patients with breast cancer were assessed, and the Ki-67 LI was calculated. Five measurement sites were randomly selected, including the most densely labeled areas (hot spots) in both core needle biopsy (CNB) and surgical specimens. RESULTS: The intraclass correlation coefficient of the CNB and surgical specimens was 0.91 and 0.95, respectively. If the hot spot was used, the correlation coefficient (CC) between the CNB and surgical specimens was 0.635. If the average score was used, the CC was 0.730. If the average score was used, the CNB specimens indicated that 49 patients had a high Ki-67 LI, and 48 patients had a high Ki-67 LI using surgical specimens. If the hot spot was used, 60 patients using the CNB specimens and 58 patients using the surgical specimens had a high Ki-67 LI. If the average score was used, 17 patients were identified as being in different groups, and if the hot spot was used, 16 patients were identified as being in different groups, depending on the specimens that were used. CONCLUSION: The results differed according to the method and specimen type that was used.

Serum p53 antibody in breast cancer.

BACKGROUND: The significance of the measurement of anti-p53 antibodies in serum remains undisclosed. The aim of this study was to assess anti-p53 antibodies in the serum of patients with breast cancer, and correlate these results with various clinicopathologic parameters. METHODS: We analyzed serum anti-p53 antibody levels in 124 patients with breast cancers and 7 patients with benign disease between April 2012 and March 2013, as well as levels of serum carcinoembryonic antigen (CEA) and cancer antigen (CA) 15-3. RESULTS: Twenty-two of 124 patients with breast cancer had an increased concentration of anti-p53 antibodies. By distribution of clinical stage, in stage 0-II the positive ratio of anti-p53 antibodies was significantly higher than that of CEA (p=0.03) and CA15-3 (p=0.01). There was a significant correlation between anti-p53 antibodies and family history (p=0.03). Triple-negative cancer also showed a significant correlation with anti-p53 antibodies (p=0.007). In patients with multiple and/or bilateral breast cancer, the level of anti-p53 was significantly higher than in unilateral breast cancer (62.5% vs 14.7%, p=0.004). CONCLUSION: Measurement of anti-p53 antibodies is useful for the prevention of oversight in the evaluation of multiple and/or bilateral breast cancer.