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ABSTRACT: Breast elastography (EG), which can objectively evaluate tumor stiffness, has been useful for differentiation of benign and malignant breast lesions. However, the value of EG for prediction of response to systemic therapy is poorly understood.
The baseline evaluations of EG in 55 patients who received neoadjuvant chemotherapy were reviewed. We investigated the correlation between tumor stiffness and response to neoadjuvant chemotherapy. Tumor stiffness was evaluated by the Tsukuba elasticity scoring system.
The mean EG scores were significant lower for the clinical and pathologic complete response (pCR) groups than for the others. When we categorized patients into two groups according to tumor stiffness, 26 patients were assigned to the low EG group (soft, scores from 1 to 3) and 29 patients were assigned to the high EG group (hard, score 4 and 5). The low EG group had significantly higher clinical complete response and pCR rates than the high EG group (clinical complete response, low EG group 38 % vs. high EG group 10 %, P = 0.024; pCR, low EG group 50 % vs. high EG group 14 %, P = 0.003, respectively). Furthermore, multivariate analysis indicated that estrogen receptor, human epidermal growth factor receptor 2, and low EG (odds ratio 13.04, 95 % confidence interval 1.19-458.28, P = 0.035) were independent predictive factors of pCR.
Tumor stiffness evaluated by EG bears predictive potential for response to neoadjuvant chemotherapy. Stiffness evaluated by EG may be recognized as a clinically significant tumor characteristic, comparable to other data obtained by functional imaging techniques.
Annals of Surgical Oncology 04/2012; 19(9):3042-9. · 4.17 Impact Factor
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ABSTRACT: Mucocele-like tumors (MLTs) of the breast are rare, with only 11 cases reported from Japan and 35 cases from other countries. MLTs of the breast were first described by Rosen in 1986. They are believed to be related to atypical ductal hyperplasia, ductal carcinoma, or mucinous carcinoma. It is difficult to diagnose this tumor preoperatively, and especially difficult to differentiate between benign and malignant forms. We report a case of MLT associated with ductal carcinoma in situ, which was initially diagnosed as fibroadenoma by mammography and ultrasonography, and as mucinous carcinoma by fine-needle aspiration cytology. We discuss the characteristic findings of imaging and the appropriate clinical treatment of this tumor. The characteristic image first signals the possibility of this tumor, following which the diagnosis can be confirmed by pathological examination of a fully excised tumor specimen. Breast-conserving surgery is recommended because of the low risk of high-grade malignancy, even when malignancy is confirmed, and lymph node dissection may be avoided.
Surgery Today 02/2012; 42(3):280-4. · 1.22 Impact Factor
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ABSTRACT: Insulin-like growth factor-1 receptor (IGF1R) plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. In a series of 325 primary invasive breast cancer patients, we performed a comprehensive analysis of IGF1R at the levels of gene copy number, mRNA expression and protein expression. The relationship between the IGF1R status and the clinicopathological characteristics and prognosis was evaluated. IGF1R mRNA levels not only correlated with protein expression, but also were significantly associated with several clinicopathological parameters and prognosis. Patients with low nuclear grade, negative axillary lymph nodes, positive hormone receptor, negative Her2, negative Ki67, and luminal subtype tumors showed higher expression levels of IGF1R mRNA, which was shown to be a significant univariate parameter for both relapse-free survival and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for BCSS. IGF1R protein expression showed an association with a prolonged BCSS in univariate analysis. In contrast, IGF1R gene copy number was not correlated with mRNA and protein expression, and harbored no prognostic value. When studied in the luminal tumor subtype groups, IGF1R mRNA level was still significantly associated with a better BCSS. Overall, our data indicated a correlation between IGF1R mRNA expression and protein expression in primary breast cancer. In particular, IGF1R mRNA expression appeared to be a good prognostic marker both in the entire cohort and in the luminal subtype group. These data may serve as background information for IGF1R-targeted therapy.
Breast Cancer Research and Treatment 07/2011; 130(1):307-17. · 4.43 Impact Factor
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ABSTRACT: Trastuzumab demonstrates significant clinical benefits in HER2-positive metastatic breast cancer (MBC), and recent clinical trials suggest that trastuzumab should be continued in combination with other chemotherapy beyond progression. There is an urgent need to assess if patients could substantially benefit from continuing trastuzumab-based therapy.
We reviewed 91 patients with HER2-positive MBC treated with trastuzumab and investigated correlations between survival and clinical response to first trastuzumab-based therapy and biological markers, time to first tumor progression (1st TTP), response rate (RR), estrogen receptor (ER), Ki-67, and p53 overexpression.
With a median follow-up of 33 months, 76 patients had received two or more lines of consecutive trastuzumab-based therapy. Median 1st TTP was 8.6 months; patients who received trastuzumab with chemotherapy had a longer 1st TTP and better RR than those without chemotherapy. In terms of survival after first progression, patients with a longer 1st TTP (≥ 8.6 months) had significantly better survival compared with those who had a shorter 1st TTP (24.3 months vs. 15.4 months, P = 0.024), and multivariate analysis revealed that 1st TTP was a significant prognostic factor (HR 0.44, 95% CI 0.23-0.82, P = 0.01). There were no correlations between survival and ER or Ki-67; however, there was a correlation with p53 overexpression (HR 1.92, 95% CI 1.01-3.64, P = 0.045).
1st TTP is a significant prognostic factor for patients who receive subsequent trastuzumab-based therapy. This factor should be considered when determining the efficacy of continuing trastuzumab or switching to another anti-HER2 therapy beyond progression.
International Journal of Clinical Oncology 05/2011; 16(6):694-700. · 1.41 Impact Factor
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ABSTRACT: To reveal heterogeneous properties of triple-negative (TN) breast cancers (estrogen receptor negative, progesterone receptor negative and HER2 negative) and to clarify whether the developmental pathways to TN breast cancer are single or multiple, we conducted clinicopathological and immunohistochemical studies on TN breast cancers, with special reference to comparison of the invasive component (iIC) and the ductal component (dcIC) of invasive TN breast cancer and pure TN ductal carcinoma in situ (TNDCIS). Tumor tissues were obtained from 97 patients with TN invasive carcinoma and 10 patients with TNDCIS. Two histological subclassifications, "atypical" medullary carcinoma (type A, n=16) and carcinoma with a central acellular zone (type B, n=11), were distinguished from conventional ductal carcinoma. Other invasive ductal carcinomas were classified as type C (n=64) and special types were classified as type D (n=5). The follow-up period for the 96 patients ranged from 5 to 147.8 months (mean, 47.6 months). Out of 97 cases, dcIC was present in 29 (30%) cases and type A and B had significantly few ductal components, 0% and 18%, respectively. There were only six (6%) cases with non-TN cells in dcIC and TN cells in iIC and five of them were type C. In 13 (13%) cases, epidermal growth factor receptor (EGFR) expression existed only in iIC. Therefore, most of the TN carcinoma develops originally and rapidly invades at the early stage, especially in types A and B. The relapse rate of type B was the highest (36.4%) and the overall survival of patients with type B was the shortest (P=0.02), which indicates that the prognosis of type B is significantly worse than the other types.
Cancer Science 03/2011; 102(3):656-62. · 3.33 Impact Factor
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ABSTRACT: Trastuzumab has shown significant clinical benefits in patients with operable and metastatic HER2-positive breast cancer. However, the biological mechanism of the additional effect of trastuzumab administered in combination with conventional chemotherapy is poorly understood. We performed a retrospective analysis of 55 patients with HER2-positive breast cancer treated with anthracycline and taxane (chemotherapy alone; CT), or trastuzumab in combination with taxane-based chemotherapy (CT+T) for neoadjuvant chemotherapy. We determined the therapeutic efficacies [clinical (CR) and pathological complete responses (pCR)] and changes in the proportion of positive cells for each biomarker pre- to post-neoadjuvant chemotherapy for each treatment regimen. Clinical-CR and quasi-pCR rates defined as the absence of invasive tumors or only a few remaining invasive tumor cells were 6.9 and 31.0% in the CT group and 46.2 and 65.4% in the CT+T group, respectively. In the CT group, the proportion of estrogen receptor (ER)-/progesterone receptor (PgR)-positive cells decreased significantly following treatment (ER, 73.5 vs. 50.9%; P=0.02). Changes in the proportion of ER-/PgR-positive cells were not noted in the CT+T group (ER, 81.9 vs. 80.3%; P=0.61), although a relatively greater decrease in the proportion of Ki-67-positive cells was found in the CT+T group than that in the CT group (-26.5 vs. -13.7%). These findings indicate that CT+T inhibits ER-negative and Ki-67-positive breast cancer cells. In conclusion, trastuzumab sensitized ER-negative proliferative cells to cytotoxic chemotherapy. This finding may indicate an additional clinical effect of trastuzumab when administered in combination with conventional chemotherapy as neoadjuvant chemotherapy for HER2-positive breast cancer.
Oncology letters 03/2011; 2(2):303-308. · 0.11 Impact Factor
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ABSTRACT: The choice of adjuvant systemic therapy is based on targeted therapy in line with the St. Gallen Consensus meeting. In addition to the traditional parameters, the panel recommended the use of proliferation markers and multigene assays. The purpose of the present study was to evaluate the clinical significance of proliferative activity using the Ki-67 index as a prognostic marker and as a predictor of recurrence time in breast cancer patients. The Ki-67 index was measured in 3,652 cases with primary breast cancer from 1987 to 2009. Out of these patients, 2,638 cases were evaluated simultaneously for estrogen receptor, progesterone receptor and HER2 from 1997, and these were analyzed as a prognostic factor according to their subtypes. The Ki-67 index exhibited a wide range of 1-99%, with a median of 20%, and cases were divided into 2 or 3 index groups; <20% and ≥20% (and ≥50%). The median Ki-67 index of tumors with luminal A was 17%, and that of luminal B type tumors was 29%. The Ki-67 index of HER2 tumors was 40% and that of triple negative tumors was 50%. A higher Ki-67 index significantly correlated with a higher grade of malignancy. Patients with a higher Ki-67 index had significantly lower disease-free survival (DFS) and overall survival rates. Moreover, there was a significant difference in the recurrence time. Multivariate analysis revealed that the Ki-67 index was a significant factor for DFS, irrespective of nodal status, and that Ki-67 was a significant marker only in luminal A type tumors. Furthermore, luminal A type cases with high Ki-67 had a similar DFS as the luminal B type cases. A higher Ki-67 index (≥20%) significantly correlated with other biological markers, poorer prognosis and early recurrence, particularly in luminal A type tumors. It is important to take the Ki-67 index into consideration in the treatment and follow-up of breast cancer patients.
Experimental and therapeutic medicine 01/2010; 1(5):747-754.
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ABSTRACT: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In recent years several biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were discovered to be predictive factors for the effectiveness of NAC to help individualize treatment. In this retrospective study, we focused on Ki-67 as a biological marker and examined the correlation between Ki-67 and chemosensitivity, and the prognosis after the start of treatment.
Between July 1996 and March 2008, 148 patients with tumors ≥ 3 cm in diameter or lymph node metastases received NAC and surgery. The items investigated were ER/PgR and Ki-67 from core needle biopsy. The treatment regimens were EC in 36 cases, ET in 51 cases, and FEC-DOC in 61 cases. The patients with FEC-DOC regimen had smaller tumors and higher Ki-67 values than the others.
Clinical response (cCR + cPR) was 79.7%, and the pathological complete response (pCR) was 14.2%. Multivariate analysis revealed that Ki-67 was significantly related to pCR. Moreover, there was no pathological responder in cases with Ki-67 < 25%. The Ki-67 values significantly decreased after NAC (median from 45.0 to 17.5%). Patients with cCR had significantly lower Ki-67 values after NAC than those with cPR, cSD, and cPD. There was a significant difference in the Ki-67 value in terms of the presence and the absence of recurrence (median 26.0% with recurrence vs. 12% without recurrence). The disease-free survival (DFS) rate after the start of treatment was significantly higher in the patients with Ki-67 < 12% after NAC than those with Ki-67 ≥ 12%.
The Ki-67 value before NAC was a significant predictive factor for the effectiveness of NAC. The Ki-67 values after NAC significantly decreased and correlated with clinical response and DFS. Therefore, higher Ki-67 values (≥ 25%) before NAC as well as lower values (<12%) after NAC might be clinically significant for treating patients.
Breast Cancer 09/2009; 17(4):269-75. · 1.36 Impact Factor
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ABSTRACT: A 57-year-old woman complained of a huge and rapid growing mass with bleeding in the left breast. Breast imaging (CT and MRI)showed a large, irregular and unevenly enhanced tumor with lymph node swelling in the left axilla. Mastectomy and axillary lymph node dissection were performed for control of bleeding from the tumor in the left breast. Pathological diagnosis was spindle cell carcinoma of the breast with transition from papillotubular carcinoma. Although the patient was treated with adjuvant chemotherapy and trastuzumab according to the treatment guideline for conventional breast cancer, she had an early relapse with mediastinal metastasis and died 9 months after operation. The tumor showed metaplastic change from epithelial tumor to spindle cell carcinoma. Because the epithelial part expressed weakly positive estrogen receptor(ER), progesterone receptor(PgR)-negative and HER2-positive, we used trastuzumab for adjuvant therapy. However, part of the spindle cell tumor mainly showed triple-negative, and ER, PgR and HER2 expression were negative, which might explain her poor prognosis for resistance to trastuzumab.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2009; 36(6):1017-9.
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Noritaka Yamaguchi,
Tetsunari Oyama,
Emi Ito,
Hitoshi Satoh,
Sakura Azuma, Mitsuhiro Hayashi,
Ken Shimizu,
Reiko Honma,
Yuka Yanagisawa,
Akira Nishikawa,
Mika Kawamura,
Jun-ichi Imai,
Susumu Ohwada,
Kuniaki Tatsuta,
Jun-Ichiro Inoue,
Kentaro Semba,
Shinya Watanabe
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ABSTRACT: ErbB2-negative breast tumors represent a significant therapeutic hurdle because of a lack of effective molecular targets. Although NOTCH proteins are known to be involved in mammary tumorigenesis, the functional significance of these proteins in ErbB2-negative breast tumors is not clear. In the present study, we examined the expression of activated NOTCH receptors in human breast cancer cell lines, including ErbB2-negative and ErbB2-positive cell lines. Activated NOTCH1 and NOTCH3 proteins generated by gamma-secretase were detected in most of the cell lines tested, and both proteins activated CSL-mediated transcription. Down-regulation of NOTCH1 by RNA interference had little or no suppressive effect on the proliferation of either ErbB2-positive or ErbB2-negative cell lines. In contrast, down-regulation of NOTCH3 significantly suppressed proliferation and promoted apoptosis of the ErbB2-negative tumor cell lines. Down-regulation of NOTCH3 did not have a significant effect on the ErbB2-positive tumor cell lines. Down-regulation of CSL also suppressed the proliferation of ErbB2-negative breast tumor cell lines, indicating that the NOTCH-CSL signaling axis is involved in cell proliferation. Finally, NOTCH3 gene amplification was detected in a breast tumor cell line and one breast cancer tissue specimen even though the frequency of NOTCH3 gene amplification was low (<1%). Taken together, these findings indicate that NOTCH3-mediated signaling rather than NOTCH1-mediated signaling plays an important role in the proliferation of ErbB2-negative breast tumor cells and that targeted suppression of this signaling pathway may be a promising strategy for the treatment of ErbB2-negative breast cancers.
Cancer Research 03/2008; 68(6):1881-8. · 7.86 Impact Factor
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ABSTRACT: The application of positron emission tomography with (18)F fluoro-2-deoxy-D-glucose (FDG-PET) has remarkably improved the management of cancer patients. However, some caution is necessary in the interpretation of FDG-PET images. Because of its low spatial resolution, it is difficult to identify the anatomical location of radiotracer uptake and to distinguish between normal physiological accumulation and pathological uptake. A novel combined PET/CT system has been developed that improves the capacity to correctly localize and interpret FDG uptake. Although only a few studies have been conducted on the potential role of PET/CT in the management of breast cancer patients, the advantage of this modality compared with PET alone should be relevant for application in the field of breast cancer. In this review, we describe the clinical impact of PET/CT on breast cancer diagnosis compared with PET alone with respect to disease restaging, treatment monitoring, preoperative staging and primary diagnosis. In addition, the possible role of PET/CT with iodine contrast is noted for evaluation of intra-ductal spreading.
Breast Cancer 02/2008; 15(3):224-30. · 1.36 Impact Factor
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ABSTRACT: Positron emission tomography (PET) is a non-invasive imaging modality used in the diagnosis and staging of breast cancer. However, several factors can affect fluoro-deoxyglucose (FDG) uptake by a tumor. To clarify the parameters that most affect FDG accumulation in tumors, the relationship between standardized uptake values (SUVs) and clinicopathological factors and immunohistopathological analysis was investigated in breast cancer.
PET studies were performed preoperatively on 37 patients with breast carcinoma. SUVs were counted at one hour (early phase) and at two hours (delayed phase) after FDG injection. The relationships between SUVs and 13 clinical, pathological and immunohistchemical factors were studied.
A significant association was found between FDG accumulation and early and delayed phase mitotic counts (p=0.0018 and 0.0010, respectively), Ki67 positive cell percentage (p=0.0098 and 0.0062, respectively), and nuclear grade (p=0.0232 and 0.0195, respectively). On the other hand, nodal status weakly correlated with the delayed phase (p=0.0907). However, other clinicopathological parameters and immunohistopathological status, which included tumor size, age, histology, estrogen receptor, progesterone receptor and Her2/neu overexpression, did not correlate significantly with FDG uptake.
Mitotic count and Ki67 reflect cellular aggressiveness. These parameters were strongly correlated with tracer uptake. Thus our data suggested that the biological behavior of breast cancer is reflected in the variation of FDG uptake by the tumor. However, whether FDG uptake is a true prognostic and predictive factor remains to be confirmed in larger studies over an extended period of time.
Breast Cancer 02/2007; 14(3):260-8. · 1.36 Impact Factor
