Akiko Emi

Role of FDG-PET/CT in evaluating surgical outcomes of operable breast cancer – Usefulness for malignant grade of triple-negative breast cancer

BACKGROUND The aim of this study was to evaluate the significance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers. METHODS Of 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined. RESULTS Receiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUVmax) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUVmax ≤ 3.8 and 91.6% for patients with a tumor of SUVmax > 3.8 (p < 0.001). High value of SUVmax was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUVmax (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUVmax ≤ 8.6 and 42.9% for patients with a tumor of SUVmax > 8.6 (p = 0.002), and high SUVmax was the only significant independent prognostic factor (p = 0.047). CONCLUSION FDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype.

The Efficacy and Safety of Preoperative Chemotherapy With Triweekly Abraxane and Cyclophosphamide Followed by 5-Fluorouracil, Epirubicin, and Cyclophosphamide Therapy for Resectable Breast Cancer: A Multicenter Clinical Trial

BACKGROUND It has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy, and that cyclophosphamide combined with taxane shows an enhanced antitumor effect. We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC. PATIENTS AND METHODS From September 2011 to September 2013, 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer. In patients with HER2-positive breast cancer, tri-weekly Trastuzumab was administered with TRI-ABC. The primary end point was the pathological complete response (pCR) rate in the breasts and lymph nodes. RESULTS The treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy. All patients underwent radical surgery, and the overall pCR rate of 37% (20 of 54) was achieved. The pCR rates according to each subtype were 8% (2 of 24) in hormone receptor (HR)-positive HER2-negative breast cancer, 56% (5 of 9) in HR-positive HER2-positive breast cancer, 63% (5 of 8) in HR-negative HER2-positive breast cancer, and 62% (8 of 13) in triple-negative breast cancer. Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR. Clinical response was observed in 49 patients (91%). The safety profile was acceptable. CONCLUSION Preoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety. Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane-anthracycline regimens.

Ability of contrast-enhanced ultrasonography to determine clinical responses of breast cancer to neoadjuvant chemotherapy

OBJECTIVE We aimed to determine whether contrast-enhanced ultrasonography can predict the effects of neoadjuvant chemotherapy on breast cancer. METHODS The clinical responses of 63 consecutive patients with breast cancer (T1-4, N0-1, M0) to neoadjuvant chemotherapy between October 2012 and May 2015 were assessed using contrast-enhanced magnetic resonance imaging, positron emission tomography/computed tomography and contrast-enhanced ultrasonography. Perfusion parameters for contrast-enhanced ultrasonography were created from time-intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography, magnetic resonance imaging and positron emission tomography/computed tomography to predict a pathological complete response were compared after confirming the pathological findings of surgical specimens. RESULTS Twenty-three (36.5%) of the 63 patients achieved pathological complete response. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography for predicting pathological complete response were 95.7% (82.5-99.2%), 77.5% (69.9-79.5%) and 84.1% (74.5-86.7%). The sensitivity of contrast-enhanced ultrasonography was significantly greater than that of magnetic resonance imaging (95.7 vs. 69.6%, P = 0.047). The specificity and accuracy were significantly greater and tended to be greater, respectively, for contrast-enhanced ultrasonography than positron emission tomography/computed tomography (specificity, 77.5 vs. 52.5%, P = 0.02; accuracy, 84.1 vs. 69.8%, P = 0.057). CONCLUSIONS Contrast-enhanced ultrasonography might serve as a new diagnostic modality when planning therapeutic strategies for patients with breast cancer after neoadjuvant chemotherapy.

Role of FDG-PET/CT in Prediction of Underestimation of Invasive Breast Cancer in Cases of Ductal Carcinoma In Situ Diagnosed at Needle Biopsy

BACKGROUND The aim of this study was to evaluate the significance of FDG-PET/CT for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy. PATIENTS AND METHODS Of 83 consecutive cases with diagnoses of DCIS at primary needle biopsy who underwent curative surgery between 2010 and 2013, the association between the SUVmax on FDG-PET/CT before excision and the underestimation of invasive breast cancer was examined. RESULTS There were 29 (34.9%) cases diagnosed to have invasive breast cancer at excision. Receiver operating characteristics curve analysis showed the cutoff value of the SUVmax to predict underestimation of invasive breast cancer was 1.6. The rates of underestimation were 61.5% for patients with a tumor of SUVmax > 1.6 and 11.4% for patients with a tumor of SUVmax ≤ 1.6 (P < .001). A high value of SUVmax was significantly associated with symptomatic presentation (P < .001), palpability (P < .001), mass formation (P = .013), high Breast Imaging Reporting and Data System category (P = .011), and core needle biopsy (P = .007). In multivariate analysis, high SUVmax was only a significant predictive factor of underestimation of invasive breast cancer (hazard ratio, 11.7; 95% confidence interval, 3.70-37.0; P < .001). CONCLUSION SUVmax on FDG-PET/CT is useful for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy.

Technical Feasibility and Cosmetic Advantage of Hybrid Endoscopy-Assisted Breast-Conserving Surgery for Breast Cancer Patients

BACKGROUND We developed a new procedure called hybrid endoscopy-assisted breast-conserving surgery (EBCS), which consists of a combination of plastic surgery and endoscopic surgery techniques. The purpose of this study was retrospectively to analyze the clinical outcome of hybrid EBCS and compare the cosmetic outcomes between hybrid EBCS and conventional breast-conserving surgery (CBCS). PATIENTS AND METHODS We reviewed medical records of patients who had undergone hybrid EBCS (n=73) or CBCS (n=90) between May 2005 and April 2011 and had been followed up in our department until March 2012. The clinical outcomes and cosmetic outcomes of these two groups were compared. The safety of hybrid EBCS was also analyzed by confirming its complications and pathological surgical margin. RESULTS In the hybrid EBCS group, operation time was longer by 30-50 minutes. Blood loss was not significantly different between the two groups. The surgical margin of hybrid EBCS was as follows: 1 patient (1.4%) had a positive margin, 4 patients (5.5%) had a margin of <2 mm, in 9 patients (12.3%) the margin was ≥2 mm and <5 mm, and in 59 patients (80.8%) it was ≥5 mm. Seven cases (9.6%) of postoperative complications occurred in 6 hybrid EBCS patients. To date, no local recurrence has been observed in hybrid EBCS patients (postoperative observation period, 18.1±5.6 months). Compared with the CBCS group, the hybrid EBCS group had better cosmetic results, especially with a less noticeable operative scar (P<.01). CONCLUSIONS Hybrid EBCS can provide sufficient free margin, and its surgical curability is acceptable. Additionally, this method is superior to CBCS in terms of cosmetic outcome.

Evaluation of Malignancy Grade of Breast Cancer Using Perflubutane-Enhanced Ultrasonography

Whether the contrast effects of perflubutane on contrast-enhanced ultrasonography can predict the malignancy grade of breast cancer is unknown. We analyzed associations between perfusion parameters created from time-intensity curves based on enhancement intensity and temporal changes in contrast-enhanced ultrasonography and clinicopathologic factors in 100 consecutive patients with invasive breast cancer. Values of perfusion parameters were significantly greater in estrogen receptor-negative than -positive tumors (peak intensity, p = 0.0002; ascending slope, p = 0.006; area under the curve, p = 0.0006). Variations in the peak intensity of Ki-67 were significantly correlated in all tumors (r = 0.54, p < 0.0001) and in luminal (r = 0.43, p = 0.0002), human epidermal growth factor receptor type 2-positive (r = 0.47, p = 0.047) and triple-negative (r = 0.55, p = 0.043) tumors. Perfusion parameters on contrast-enhanced ultrasonography can provide excellent predictive value for high-grade malignancy and might help to determine appropriate therapeutic strategies.

Abstract P6-07-26: Prognostic significance of the maximal value of the baseline standardized uptake value on fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for predicting pathologic malignancy of operable breast cancer with neoadjuvant chemotherapy

PURPOSE: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is potentially useful in predicting pathological complete response (pCR), disease free survival (DFS) and overall survival (OS) of breast cancer patients with neoadjuvant chemotherapy. MATERIALS AND METHODS: 77 breast cancer patients (mean age ± SD: 52.6 ± 11.2 years) with clinical Stage I∼III between January 2006 and December 2011, were prospectively evaluated (median follow up period:26.5 months). Neoadjuvant chemotherapy of an anthracycline-based regimen and taxane was performed, and patients underwent a whole-body FDG PET/CT before and after chemotherapy. The maximal value of the baseline standardized uptake values (SUVmax) were assessed for predicting pCR, DFS and OS. For the evaluation of relationship between SUVmax values and prognosticators such as hormone receptors, human epidermal growth factor receptor 2 (HER2), nuclear grade, lymph node metastasis and tumor size, statistical analyses were performed using Student t test and log-rank test, and p values of less than 0.05 were considered to indicate statistically significant differences. RESULTS: Clinical Stage included were I (n = 2, 2.6%), II (n = 62, 80.5%) and III (n = 12, 15.6%). Tumors with estrogen receptor positive were 52 (67.5%) and negative were 24 (31.2%). Therapeutic response by neoadjuvant chemotherapy was obtained in 15 patients (19.5%) with pCR and 60 (77.9%) without pCR. Patients were divided into two groups according to cut-off SUVmax established on the basis of receiver operating characteristic (ROC) analysis ( There was a significant difference in OS between two groups (p = 0.05), but, pCR (OR:1.07, 95%Cl:0.34–3.40, p = 0.86) and DFS (p = 0.07) did not show strong relationship with SUVmax values. CONCLUSION: SUVmax on FDG PET/CT before neoadjuvant chemotherapy have a predictive value for high-grade malignancy and prognosis in clinical Stage I∼III breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-26.

Which type of breast cancers is undetectable on ring-type dedicated breast PET?

OBJECTIVES To assess the factors causing tumor undetectability on ring-type dedicated breast positron emission tomography (DbPET). METHODS A total of 265 patients (288 tumors) underwent DbPET and contrast-enhanced magnetic resonance imaging (MRI) in a prone position. The distance between the shallowest part of the breast tumor and the front end of the pectoralis major muscle on MRI was considered as the tumor-to-chest wall distance. RESULTS Twenty-four tumors (8.3%) were not visualized via DbPET. The tumor-to-chest wall distance for undetectable tumors was shorter than that of the detectable tumors (23.0 mm vs 38.5 mm, P < 0.001). Multivariate analysis indicated that proximity to the chest wall and low-grade tumors were independent predicting factors for undetectable cancers. Among the 24 undetectable cancers, 15 tumors were proximal to the chest wall, suggesting that they were outside or at the edge of field of view (FOV), and 7 were low-grade tumors, suggesting insignificant 18F-fluorodeoxyglucose (FDG) uptake. CONCLUSIONS The factors of undetectable breast cancers on DbPET are classified into two types; outside or at the edge of FOV and insignificant FDG uptake.

Intratumoral heterogeneity on dedicated breast positron emission tomography predicts malignancy grade of breast cancer

PurposeDedicated breast positron emission tomography (DbPET) provides detailed high-resolution images and can detect intratumoral heterogeneity using 18F-fluorodeoxyglucose (FDG). We aimed to evaluate the correlation between FDG uptake on DbPET and the clinicopathological features of breast cancer, particularly those with an intratumoral heterogeneous distribution of FDG on DbPET.MethodsWe evaluated 195 consecutive patients with invasive breast cancer who underwent preoperative whole-body PET (WBPET) and DbPET concurrently between January 2016 and March 2017. The relationships between clinicopathological factors and the maximum standard uptake values (SUVmax) of DbPET and WBPET, including clinical stage, nuclear grade, Ki67 proliferation index, estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2) statuses, and the intratumoral heterogeneous distribution of FDG on DbPET, were evaluated.ResultsThe SUVmax of DbPET was significantly correlated with clinical T stage, N stage, nuclear grade, and Ki67 proliferation index (all p < 0.001) as well as the ER (p = 0.006) and HER2 (p = 0.040) statuses. Intratumoral heterogeneous distribution of FDG on DbPET was significantly related with high nuclear grade (p = 0.016) and high Ki67 proliferation index (p = 0.015) but not with clinical T stage, N stage, and ER and HER2 statuses.ConclusionsThe SUVmax of DbPET correlates with clinicopathological factors and also WBPET does. In addition, intratumoral heterogeneity on DbPET provides predictive value for malignancy grade and could inform therapeutic decisions.

Role of 18F-PET/CT in Predicting Prognosis of Patients With Breast Cancer After Neoadjuvant Chemotherapy

Micro‐Abstract In 130 consecutive patients with primary breast cancer assessed using positron emission tomography/computed tomography before and after neoadjuvant chemotherapy (NAC), the maximum standardized uptake value (SUVmax) after NAC correlated significantly with the pathologic complete response (pCR) and recurrence‐free survival in those with human epidermal growth factor receptor 2‐positive (HER2+) and triple‐negative (TN) breast cancer. However, the SUVmax before NAC and the change in the SUVmax did not. These results suggest that the SUVmax after NAC can predict the pCR and the prognosis of patients with operable HER2+ and TN breast cancer in clinical practice. Background: Breast cancer can be assessed preoperatively and postoperatively using 18F‐fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We prospectively analyzed the maximum baseline standardized uptake value (SUVmax) derived from FDG PET/CT to predict the outcomes after neoadjuvant chemotherapy (NAC) for breast cancer. Patients and Methods: We assessed 130 consecutive female patients with primary breast cancer (mean age, 53.9 years) using PET/CT before and after NAC. The SUVmax before (pre‐SUVmax) and after (post‐SUVmax) NAC and the SUVmax reduction rates (&Dgr;SUVmax) after NAC with sequential anthracyclines and a taxane were assessed to predict the pathologic complete response (pCR) and prognosis. Results: Of the 130 patients, 30 (23.1%) achieved a pCR. The pCR rate of the patients with human epidermal growth factor receptor 2‐positive (HER2+) and triple‐negative (TN) breast cancer was 52.8% and 40.0%, respectively. In contrast, only 1.4% of those with estrogen receptor‐positive and HER2− cancer achieved a pCR. The post‐SUVmax correlated closely with the pCR (area under the curve, 0.700) but not with the pre‐SUVmax and &Dgr;SUVmax (area under the curve, 0.414 and 0.589, respectively) in patients with HER2+ and TN breast cancer. The post‐SUVmax was associated with the pCR (P = .019), and multivariate analysis selected post‐SUVmax as a significant prognostic factor (P = .014). The post‐SUVmax correlated significantly with recurrence‐free survival and recurrence (P = .026, log‐rank test). Conclusion: The SUVmax determined after NAC using FDG PET/CT can predict for the pCR and the prognosis of patients with operable HER2+ and TN breast cancer. In the future, additional chemotherapy will be applied according to the post‐SUVmax after standard NAC to achieve a pCR or omit surgery.