Cell Block-Based Two-Dimensional and Immunocytochemical Analyses Could Reduce Atypical/Indeterminate Case Frequency in Breast Fine-Needle Aspiration Cytology: A Retrospective Analysis.

INTRODUCTION: In fine-needle aspiration of the breast (FNAB), the "atypical" category encompasses both benign and malignant lesions, particularly papillary proliferative lesions, as per the latest WHO classification. We aimed to reduce atypical cases and improve diagnostic accuracy by investigating the utility of cell block (CB) analysis. METHODS: FNAB CB samples (2018-2022) were reviewed using smear only or CBs. CB-based diagnosis was performed with 2D morphological analysis and immunocytochemistry using ER, CK5/6, p63, SMA, and CD56. Samples were reclassified as "benign," "atypical," "suspicious of malignancy," "malignant," or "insufficient/inadequate." Atypical cases were reexamined. Diagnoses were validated histologically. RESULTS: On examining the FNAB samples (n = 149; 32 atypical), 2D CB sectioning achieved a clearer definition of myoepithelial cells and fibrovascular cores than Papanicolaou staining. Immunocytochemistry was evaluated for 36 cases: estrogen receptor (ER)- and CK5/6+ tumors were reclassified as benign; ER+ and CK5/6- tumors as malignant; p63- tumors as invasive; papillary malignant tumors with a smooth muscle actin (SMA)+ fibrovascular core and p63- myoepithelial cells as encapsulated papillary carcinoma; and CD56+ carcinomas as neuroendocrine carcinoma. Diagnostic rates were as follows: benign (44% FNAB, 51% CB), atypical (21% FNAB, 3% CB), suspicious of malignancy and malignant (28% FNAB, 40% CB), and insufficient/inadequate (7% FNAB, 6% CB). CB achieved >85% sensitivity, specificity, and positive and negative predictive values. CONCLUSION: CBs represent 3D FNA cell morphology using 2D sections, enabling adaption of pathology criteria to the cytological material. Immunocytochemical staining of CBs can predict low nuclear grade papillary tumors and reduce atypical case frequency, improving diagnostic accuracy.

Preferences Regarding Breast Surgery Omission Among Patients With Breast Cancer Who Receive Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. PATIENTS AND METHODS: We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. RESULTS: Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). CONCLUSION: The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.

A prospective analysis of two studies that used the 5-mm interval slices and 5-mm margin-free method for ipsilateral breast tumor recurrence after breast-conserving surgery without radiotherapy.

BACKGROUND: Breast-conserving surgery with radiotherapy is one of standard treatments for early breast cancer. However, it is regarded as an option to treat elderly patients with small hormone receptor-positive breast cancer with breast-conserving surgery and hormone therapy without radiotherapy. We conducted two sequential prospective studies to examine the feasibility of breast-conserving surgery without radiotherapy since 2002 and present the results. PATIENTS AND METHODS: Primary female breast cancer patients who fulfilled the strict eligibility criteria were prospectively enrolled in two sequential studies named WORTH 1 and 2. The surgical materials were sliced in 5-mm intervals and all slices were examined microscopically. Postoperative radiotherapy was not allowed, but tamoxifen or anastrozole was administered for 5 years. Ipsilateral breast tumor recurrence (IBTR)-free survival was the primary outcome. RESULTS: The data of the two studies were combined (N = 321). The median follow-up period for IBTR was 94 months (4-192 months). Only three patients were treated with adjuvant chemotherapy. The 5- and 10-year IBTR-free rates were 97.0% and 90.5%, respectively. The age at operation and PR status affected IBTR rates independently. When we calculated IBTR-free rates of patients who were 65 years of age or older at the time of surgery and had PR-positive tumors, the 5- and 10-year IBTR rates were both 98.4%. CONCLUSIONS:  Our "5-mm-thick slice and 5-mm free-margin" method may be effective to select patients who can be treated by breast-conserving surgery and hormone therapy without radiotherapy.

Validation of a nuclear grading system for resected stage I-IIIA, high-risk, node-negative invasive breast carcinoma in the N·SAS-BC 01 trial.

BACKGROUND: This retrospective observational study validated nuclear grading criteria developed to identify a high-risk group with recurrence rate ≥20-30% and local pathology diagnosis used in a previous multi-institutional randomized N·SAS-BC 01 trial, where the efficacy of adjuvant chemotherapy regimens was evaluated in 733 high-risk node-negative invasive breast cancer patients. METHODS: Of 545 patients with long-term follow-up data (median 12.1 years), pathology slides, and local pathology diagnosis, 530 eligible patients were subjected to central pathology review (CPR) for histological type and nuclear grade (NG). Concordance in NGs was compared with local diagnosis. The 10/15-year recurrence-free survival (RFS) and overall survival (OS) rates stratified by NG and histological type were calculated. RESULTS: Local diagnoses were invasive ductal carcinoma (IDC)-NG2, IDC-NG3, invasive lobular carcinoma (ILC), and metaplastic carcinoma (MC) in 158/327/38/7 patients, respectively. The 10/15-year RFS rates were 87.2/82.6% for IDC-NG2 and 81.8/75.0% for IDC-NG3 (p = 0.061), and OS rates were 95.0/92.8% for IDC-NG2 and 90.8/85.7% for IDC-NG3 (p = 0.042). CPR graded 485 locally diagnosed IDCs as IDC-NG1/NG2/NG3/unknown in 98/116/267/4 patients, respectively. No significant difference was found among survival curves for the three NG groups. Although the agreement level between local and CPR diagnoses was low (κ = 0.311), both diagnoses identified a patient group with a 15-year recurrence rate ≥ 20%. The 10/15-year RFS rates were 79.4/63.5% for ILC and 68.6%/unknown for MC. CONCLUSIONS: The N·SAS grading system identified a patient group with high-risk node-negative invasive breast cancer, suggesting that local diagnosis was performed efficiently in the N·SAS-BC 01 trial. TRIAL REGISTRATION NUMBER: UMIN000022571. Date of registration: June 1, 2016.

Relationships between pathological factors and long-term outcomes in patients enrolled in two prospective randomized controlled trials comparing the efficacy of oral tegafur-uracil with CMF (N·SAS-BC 01 trial and CUBC trial).

PURPOSE: To evaluate the efficacies of cyclophosphamide, methotrexate, and fluorouracil (CMF) and tegafur-uracil (UFT) as adjuvant therapy in patients with resected stage I-IIIA breast cancer by immunohistochemistry (IHC)-based subtype and to determine the relationships between clinicopathological factors and long-term outcomes. METHODS: A pooled analysis of the randomized controlled N·SAS-BC 01 and CUBC studies was conducted. Expression of hormone receptors (HRs; estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and Ki67were assessed by IHC. Tumor-infiltrating lymphocytes (TILs) and nuclear/histological grades were determined by hematoxylin and eosin staining. Relapse-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier analysis and hazard ratios were determined by Cox model adjusted for baseline tumor size and nodal status. RESULTS: A total of 689 patients (342 CMF and 347 UFT) were included in the analyses with a median follow-up of 11.1 years. There was no significant difference in RFS or OS between the two cohorts (RFS: 0.96 [95% confidence interval: 0.71-1.30], log-rank test p = 0.80; OS: 0.93 [0.64-1.35], p = 0.70). There was no difference in RFS or OS between the two cohorts for HR+/HER2- and HR+/HER2+ subtypes. RFS was significantly longer in patients treated with UFT compared with CMF in patients with HR-/HER2+ subtype (0.30 [0.10-0.88], p = 0.03). A high TILs level was associated with a better OS compared with low TILs level (p = 0.02). CONCLUSIONS: This long-term follow-up study showed that RFS and OS were similar in patients with luminal-type breast cancer treated with CMF and UFT.

Comparative evaluation of nuclear and histological grades as prognostic factors for invasive breast cancer.

BACKGROUND: Although tumor grade, defined by either the nuclear grade (NG) or the histological grade (HG), is widely accepted as one of the prognostic factors for breast cancer, there is a limited direct comparison between these two grading systems. The object of the current study was to compare their prognostic capabilities on the same specimen in a single institutional cohort. METHODS: We collected data from 1125 patients with breast cancer who underwent surgery at Kaizuka City Hospital between 2002 and 2016 and analyzed the prognostic capability of NG and HG in comparison with other clinicopathological factors. Pathological diagnoses were performed by a single pathologist throughout the study period. RESULTS: The median follow-up was 52.9 months. During the follow-up period, 103 distant recurrences were observed. The concordance rate of grades between NG and HG was 72.1%. The 5-year recurrence-free survival (RFS) rates for patients with NG1, NG2, and NG3 were 90.6%, 91.8%, and 82.2%, respectively, and the rates for patients with HG1, HG2, and HG3 were 92.7%, 88.6%, and 82.5%, respectively. Significant differences in RFS were noted among each grade for HG. However, this was not true for NG; a significant difference was not noted between NG1 and NG2. In terms of subtypes, both NG3 and HG3 were significantly associated with worse outcomes in patients with ER-positive/HER2-negative tumors. CONCLUSIONS: Although not a few patients exhibited discordant results between NG and HG, both NG and HG predict outcomes for breast cancer patients, but the latter might appear to be superior as a three-grade classification scale.

Fine-needle aspiration cytology for the diagnosis of solid basaloid adenoid cystic carcinoma of the breast: Its role, limitation, and perspective.

Solid basaloid adenoid cystic carcinoma (SB-AdCC) is a subtype of breast AdCC which shows more aggressive clinical behavior than other subtypes. Fine-needle aspiration (FNA) cytology is a useful diagnostic tool for breast malignancies. However, most of the diagnostic cytological characteristics of AdCC are not present in SB-AdCC and cytomorphological studies of this subtype are limited. Here, we evaluated the utility of FNA in the diagnosis of SB-AdCC of the breast. A search of the pathology archives of our institutions for FNA specimens of histologically confirmed SB-AdCC between 2012 and 2019 identified four patients with SB-AdCC of the breast. All patients were female and the average age was 60 years. Cytologically, one case was classified as malignant, two as indeterminate, and one as unsatisfactory. Smears had low to moderate cellularity. All smears showed ribbon-like material surrounding the clusters and a vertical nuclear arrangement toward the peripheral rim. Hyaline globules appeared only in one case. Cells in all cases showed an oval, angular, and spindle shape hyperchromatic nuclei with mild to severe atypia, and also dispersed naked nuclei similar to the cells of the clusters were detected in one case. In histological sections, these cytological findings were compatible with the histological findings and divergent histological differentiation was detected. Diagnosing of few cellular smears of SB-AdCC is difficult whereas the features of peripheral rim of the clusters, naked nuclei, and the divergent differentiation may be important for diagnosing SB-AdCC of the breast.

Atypical pseudoangiomatous stromal hyperplasia showing rapid growth of the breast: Report of a case.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign lesion manifesting as myofibroblastic proliferation and anastomosing slit-like spaces. Atypical PASH is an extremely rare lesion characterized by cytological alteration of myofibroblast, presenting as myofibroblastic sarcoma arising from PASH. To our knowledge, only one other case has been reported since the first report of Rosen. We present a case of atypical PASH. A 39-year-old female presented with a round, elastic hard, painless mass in the left breast. Mammography and ultrasonography revealed no definitive sign of malignancy. Core needle biopsy report was suggestive of atypical PASH. Five months later, the mass had grown rapidly with pain. Considering the clinicopathological features, excision was performed. Pathological examination revealed the spindle cells proliferation in collagenous stroma. The spindle cell involved the adipose tissue and lobules and lined peudoangiomatous spaces. These cells exhibited marked cytological atypia and mitotic activity. Immunohistochemically, these spindle cells were positive for SMA, CD10, and bcl-2, and negative for podoplanin, p63, CD31, ERG and cytokeratins. The final diagnosis was atypical PASH. She is tumor-free on 12 months follow-up. The nature of atypical PASH remains unknown. Further studies are required for a clear definition, a new histological entity and diagnostic criteria.

Evaluation of ALDH1 expression in ipsilateral breast cancer recurrence.

Aldehyde dehydrogenase 1 (ALDH1) is a cancer stem cell (CSC) marker that is easily evaluable. The expression and clinical significance of ALDH1 in ipsilateral breast tumor recurrence (IBTR) has yet to be investigated. In the present study, the expression profile of ALDH1 and its correlation with prognosis in IBTR tissues was examined. Patients with IBTR from eight institutions were retrospectively enrolled in the study. Immunohistochemistry was used to examine ALDH1 expression patterns in the tissue specimens of primary cancers and IBTRs. ALDH1 expression levels were investigated in 182 IBTR tumors, which included cases of invasive carcinoma selected from 271 consecutive patients with IBTR. ALDH1 was expressed in 23% of the IBTR tissue samples. The rate of concordant expression between primary cancer and IBTR tissues was 68%. There was no significant association between disease-free survival (DFS) and ALDH1 expression levels in IBTR. IBTRs that expressed ALDH1 and Ki-67 had a poorer prognosis and this expression pattern was significantly associated with DFS (P=0.0073). The percentages of ALDH1 positive expression in each tissue subtype were as follows: Luminal A, 20%; luminal B, 24%; human epidermal growth factor 2 (HER2), 35%; triple-negative, 21%. There was a significant correlation between DFS and ALDH1 expression levels in HER2-type IBTR tissue specimens (P=0.034). In conclusion, it is possible that ALDH1 and Ki-67 expression levels may be useful for predicting prognosis in patients with HER2-type tumors.

Accuracy assessment methods of tissue marker clip placement after 11-gauge vacuum-assisted stereotactic breast biopsy: comparison of measurements using direct and conventional methods.

BACKGROUND: The objective of the study was to compare direct measurement with a conventional method for evaluation of clip placement in stereotactic vacuum-assisted breast biopsy (ST-VAB) and to evaluate the accuracy of clip placement using the direct method. METHODS: Accuracy of clip placement was assessed by measuring the distance from a residual calcification of a targeted calcification clustered to a clip on a mammogram after ST-VAB. Distances in the craniocaudal (CC) and mediolateral oblique (MLO) views were measured in 28 subjects with mammograms recorded twice or more after ST-VAB. The difference in the distance between the first and second measurements was defined as the reproducibility and was compared with that from a conventional method using a mask system with overlap of transparent film on the mammogram. The 3D clip-to-calcification distance was measured using the direct method in 71 subjects. RESULTS: The reproducibility of the direct method was higher than that of the conventional method in CC and MLO views (P = 0.002, P < 0.001). The median 3D clip-to-calcification distance was 2.8 mm, with an interquartile range of 2.0-4.8 mm and a range of 1.1-36.3 mm. CONCLUSION: The direct method used in this study was more accurate than the conventional method, and gave a median 3D distance of 2.8 mm between the calcification and clip.

Identification of potential breast cancer markers in nipple discharge by protein profile analysis using two-dimensional nano-liquid chromatography/nanoelectrospray ionization-mass spectrometry.

PURPOSE: This research aimed to establish a diagnostic technique for breast cancer using nipple discharge (ND), with the objective of preventive diagnosis. ND has been proposed as a source of secreted proteomes that reflect early pathological changes in the ductal-lobular epithelial microenvironment, and could thus provide breast-specific cancer biomarkers that could be accessed noninvasively as a new clinical diagnostic technique. EXPERIMENTAL DESIGN: Minute amounts of ND from patients with and without breast cancer (n = 19 and 12, respectively) were collected at the hospital and kept frozen until just before use. They were analyzed using high-pH RP peptide fractionations/low-pH RP 2D nano-LC/ESI-MS/MS. Biomarker candidates were also investigated using Western blot analysis and sandwich ELISA on ND and/or sera. RESULTS: We found distinct tendencies in protein expression and three candidate breast cancer biomarkers (carbonic anhydrase 2, catalase, and peroxiredoxin-2) whose levels differed significantly between ND specimens from patients with and without breast cancer. CONCLUSIONS AND CLINICAL RELEVANCE: These tendencies in protein expression and markers provide new ways to identify breast cancer patients. Therefore, RP/RP 2D LC/MS/MS analyses of ND and the above three markers are supported as a new breast cancer diagnostic technique.

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer.

BACKGROUND: There is limited information on indocyanine green (ICG) fluorescence and blue dye for detecting sentinel lymph node (SLN) in early breast cancer. A retrospective study was conducted to assess the feasibility of an SLN biopsy using the combination of ICG fluorescence and the blue dye method. METHODS: Seven hundred and fourteen patients with clinically node-negative breast cancer were included in this study. They underwent SLN biopsy using a combination of ICG fluorescence and the blue dye method from March 2007 to February 2014. The ICG (a fluorescence-emitting source) and patent blue (the blue dye) were injected into the patients' subareolar region. The removed lymph nodes that had ICG fluorescence and/or blue dye uptake were defined as SLNs. The results of the SLN biopsies and follow-up results of patients who underwent SLN biopsy alone were investigated. RESULTS: In 711 out of 714 patients, SLNs were identified by a combination of ICG fluorescence and the blue dye method (detection rate, 99.6 %). The average number of SLNs was 2.4 (range 1-7), and the average number of resected swollen para-SLNs was 0.4 (range 0-5). Ninety-nine patients with an SLN and/or para-SLN involvement during the intraoperative pathological diagnosis underwent axillary lymph node resection (ALND). In addition, two of three patients whose SLN was not identified also underwent ALND. In 46 of 101 patients with an ALND, non-SLN involvement was not found. Follow-up results were analyzed in 464 patients with invasive carcinoma excluding those with ductal carcinoma in situ (n = 148) and those who underwent ALND (n = 101). During the follow-up period (range 4.4-87.7 months; median, 38 months), two patients (0.4 %) developed axillary lymph node recurrence. They were successfully salvaged, and to date, no further locoregional recurrence has been observed. CONCLUSIONS: A high rate of SLN detection and low rate of axillary lymph node recurrence were confirmed by an SLN biopsy using a combination of ICG fluorescence and the blue dye method. Therefore, it is suggested that this method may replace the combination of dye and radioisotope methods.

[Evaluation of Pre-Therapeutic Ki-67 as a Predictive Marker for Histological Response to Neoadjuvant Therapy in Breast Cancer].

There is controversy as to whether the proliferative marker Ki-67 is useful as a predictive marker for response to neoadjuvant therapy in breast cancer. We evaluated Ki-67 levels in pre-therapeutic breast cancer core biopsies from 52 breast cancer patients. These patients underwent anthracycline and taxane-based chemotherapy (n=48) or endocrine therapy (n=4) followed by surgery between March 2010 and February 2015. Expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki-67 were examined by immunohistochemistry in the core-needle biopsy specimens. Ki-67 levels were categorized into 3 groups: low (<20%), intermediate (20-50%), and high (≥50%). Pathological response rates were 29%, 15%, and 48% in the low, intermediate, and high-risk groups, respectively. In univariate analysis, pre-therapeutic high levels of Ki-67, as well as negative ER status were significantly associated with the responder group (p<0.05). However, neither Ki- 67 nor ER status were significantly associated with a response in multivariate analysis. Ki-67 appears to be a promising parameter for histological response to neoadjuvant therapy in breast cancer.

The cell cycle profiling-risk score based on CDK1 and 2 predicts early recurrence in node-negative, hormone receptor-positive breast cancer treated with endocrine therapy.

The Cell Cycle Profiling - Risk Score (C2P-RS) based on CDK1 and CDK2 specific activities was significantly associated with relapse in breast cancers. We evaluated the prognostic value of the C2P-RS classification using a Japanese cohort including node-negative, hormone receptor-positive breast cancers treated with adjuvant endocrine therapy alone as systemic therapy. Of 266 patients, 22 (8.3%) relapsed within 5 years after surgery. The distribution of each C2P-RS group was 71.8% in the low group, 12.0% in the intermediate group, and 16.2% in the high group. The 5-year relapse-free survival rate in the low C2P-RS group (97.3%) was significantly higher than that in the intermediate C2P-RS group (84.3%) or the high C2P-RS group (74.4%) (P < 0.001). The univariate analysis demonstrated that age, tumor size, histologic grade, and HER2 had no significant correlations with relapse but the C2P-RS classification (P < 0.001) and Ki-67 (P = 0.009) were significantly associated with relapse. Multivariate analysis showed only that the C2P-RS classification was a significant independent prognostic indicator. The C2P-RS classification might be a significant predictor of earlier recurrence in node-negative, hormone receptor-positive breast cancers treated with endocrine therapy.

Steroid treatment increases the recurrence of radiation-induced organizing pneumonia after breast-conserving therapy.

Radiation-induced organizing pneumonia (RIOP) is an important complication of postoperative radiotherapy for breast cancer. Unfortunately, conventional corticosteroid therapy is frequently associated with relapses. The aim of this retrospective study was to evaluate the outcomes of steroid treatment in patients with RIOP. In total, 26 patients diagnosed with RIOP from among 2404 women who received radiotherapy after breast-conserving surgery for breast cancer were included and classified into steroid (n = 7) and nonsteroid (n = 19) groups. Serum, sputum, and bronchoalveolar lavage composition; subjective symptoms (cough, fever, and dyspnea); migratory progression; and RIOP relapse were compared between the groups. Treatment type did not affect the duration of the subjective symptoms, which was 1.6 and 1.7 months for the steroid and nonsteroid groups, respectively. In contrast, RIOP relapse and new pulmonary lesions developed in five patients in the steroid group and only three patients in the nonsteroid group (P = 0.014). By assessing RIOP duration as the time to resolution of symptoms and discontinuation of therapy, the median duration of RIOP was significantly longer in the steroid (17.1 months) than that in the nonsteroid group (2.3 months, P = 0.005), primarily because of frequent relapses. After remission, persistent pulmonary dysfunction did not occur in the nonsteroid group. This single-center retrospective study demonstrates that steroid therapy results in frequent relapses and significantly prolongs RIOP duration. Corticosteroid treatment is considered a critical factor in RIOP recurrence.

Phase II study of neoadjuvant anastrozole and concurrent radiotherapy for postmenopausal breast cancer patients.

BACKGROUNDS: The aim of this study was to assess the efficacy and safety of neoadjuvant anastrozole and radiation in postmenopausal breast cancer patients with hormone-receptor-positive tumors. In addition, we assessed the predictive factors for clinical and pathological response for concurrent anastrozole and radiotherapy. METHODS: Patients with tumors 3 cm or larger were treated with neoadjuvant anastrozole for 24 weeks, and concurrent radiation was administered from 12 weeks after the start of anastrozole. Core biopsies were obtained at baseline and 12 weeks after the start of anastrozole. After completing neoadjuvant treatment, patients underwent definitive surgery. The primary endpoint was the overall objective response. In addition, we assessed the predictive factors for clinical and pathological response for concurrent anastrozole and radiotherapy. This trial is registered with the UMIN Clinical Trials Registry, no. UMIN000002266. RESULTS: The overall objective response rate was 92 %. Toxicity during neoadjuvant therapy was acceptable, with no grade 3 toxicities. After surgery, grade 3 toxicities occurred in 2 of 25 patients (8 %). CONCLUSIONS: Our preliminary data suggest that neoadjuvant anastrozole and radiation therapy in postmenopausal breast cancer patients with hormone-receptor-positive tumors has a high potential for clinical response.

Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2.

BACKGROUND: The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported. METHODS: Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety. RESULTS: Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients. CONCLUSION: Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

Repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: the impact of radiotherapy on second IBTR.

OBJECTIVES: There are limited data on the outcomes of patients treated with repeat lumpectomy at the time of ipsilateral breast tumor recurrence (IBTR). Especially, the impact of radiotherapy (RT) on a second IBTR is unknown. METHODS: We retrospectively analyzed 143 patients from 8 institutions in Japan who underwent repeat lumpectomy after IBTR. The risk factors of a second IBTR were assessed. RESULTS: The median follow-up period was 4.8 years. The 5-year second IBTR-free survival rate was 80.7 %. There was a significant difference in the second IBTR-free survival rate according to RT (p = 0.0003, log-rank test). The 5-year second IBTR-free survival rates for patients who received RT after initial surgery, RT after salvage surgery, and no RT were 78.0, 93.5, and 52.7 %, respectively. Multivariate analysis revealed that RT was a significantly independent predictive factor of second IBTR-free survival. CONCLUSION: Repeat lumpectomy plus RT is a reasonable option in patients who did not undergo RT at the initial surgery. In contrast, caution is needed when RT is omitted in patients who have undergone repeat lumpectomy.