A nomogram to predict the pathological complete response in patients with breast cancer based on the TILs-US score.

BACKGROUND: The tumor-infiltrating lymphocytes-ultrasonography score is a calculation system for predicting lymphocyte-predominant breast cancers in surgical specimens. A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score was developed to predict the pathological complete response in breast cancer treated with neoadjuvant chemotherapy. METHODS: A retrospective evaluation was conducted on 118 patients with breast cancer treated with neoadjuvant chemotherapy at Hiroshima University Hospital. Tumor-infiltrating lymphocytes-ultrasonography scores ≥4 were classified as high. A nomogram was developed using a stepwise logistic regression model for pathological complete response (ypT0 ypN0), based on the smallest Akaike information criterion. The predictive ability and clinical usefulness of the nomogram were also evaluated. RESULTS: Among 118 patients, 34 (28.8%) achieved a pathological complete response, and 52 (44.1%) exhibited high tumor-infiltrating lymphocytes-ultrasonography. In multivariate logistic regression analysis, high tumor-infiltrating lymphocytes-ultrasonography (odds ratio, 6.01; P < 0.001), clinical complete response (odds ratio, 4.83; P = 0.004) and hormone receptor (odds ratio, 3.48; P = 0.038) were independent predictors of pathological complete response. A nomogram based on tumor-infiltrating lymphocytes-ultrasonography score, clinical complete response, hormone receptor and clinical N status was developed. The nomogram showed an area under the curve of 0.831 and a bias-corrected area under the curve of 0.809. The calibration plot showed a good fit between the expected and actual pathological complete response values. Decision curve analysis also showed the clinical utility of the nomogram for predicting pathological complete responses. CONCLUSIONS: A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score exhibited a favorable predictive ability for pathological complete response in patients with breast cancer, which can be useful in predicting the residual disease status after neoadjuvant chemotherapy.

[A Case of Breast Metastasis from Renal Cell Carcinoma].

The patient was a woman in her 90s. Right radical nephrectomy for right renal cell carcinoma had been performed 2 years and 6 months ago. Since then, there had been no recurrence. However, computed tomography during postoperative follow- up period showed a 3 cm mass in the right breast, and the patient was referred to our department. Breast ultrasonography indicated a well-circumscribed, oval, and almost smooth-surfaced tumor, 27 mm in size, located in the D region of the right breast. Results of a core needle biopsy showed metastatic renal cell carcinoma and clear cell carcinoma. Preoperative examination confirmed intramammary metastases of renal cell carcinoma. Given that the patient did not experience systemic metastases, partial mastectomy of the right breast was performed. Metastatic renal cell carcinoma is associated with poor prognosis. Generally, standard treatment in this disease is chemotherapy. However, surgical resection is selected with the aim of improving the prognosis and achieving radical cure of patients with this complication if these patients are in an oligometastatic state and complete resection of metastatic lesions is feasible, as in the present case. To achieve radical cure, the patient underwent partial mastectomy under local anesthesia, which is a relatively minimally invasive surgery.

Performance of dedicated breast positron emission tomography in the detection of small and low-grade breast cancer.

PURPOSE: This study compares the sensitivity of dedicated breast positron emission tomography (DbPET) and whole body positron emission tomography (WBPET) in detecting invasive breast cancer based on tumor size and biology. Further, we explored the relationship between maximum standardized uptake value (SUVmax) of DbPET and biological features of the tumor. METHODS: A total of 639 invasive breast cancer lesions subjected to both DbPET and WBPET before surgery, between January 2016 and May 2019, were included in the study. The sensitivity of DbPET and WBPET in detection and the biology of the tumor according to the clinicopathological features were retrospectively evaluated. RESULTS: The overall sensitivity of DbPET was higher than that of WBPET (91.4% vs. 80.3%, p < 0.001). Subcentimetric tumors were significant (80.9% vs. 54.3%, p < 0.001). Regardless of the nuclear grade, DbPET could detect more lesions than WBPET. The SUVmax was positively correlated with tumor size (R = 0.395, p < 0.001) and the nuclear grade (p < 0.001). Luminal A-like breast cancer had significantly lower SUVmax values than the other subtypes (p < 0.001). CONCLUSIONS: DbPET is superior to WBPET in the detection of subcentimetric, low-grade breast cancers. Further, by using SUVmax, DbPET can distinguish luminal A-like breast cancer from the other subtypes.

Febrile neutropenia and role of prophylactic granulocyte colony-stimulating factor in docetaxel and cyclophosphamide chemotherapy for breast cancer.

PURPOSE: Febrile neutropenia (FN) incidence during docetaxel and cyclophosphamide (TC) chemotherapy, known as a high-risk regimen, differs among countries. The role of prophylactic granulocyte colony-stimulating factor (G-CSF) in FN is unclear. This study aimed to investigate FN frequency and relative dose intensity (RDI) of TC chemotherapy in patients with breast cancer and identify the correct population requiring prophylactic G-CSF. METHODS: In total, 205 patients with breast cancer were scheduled for TC chemotherapy (docetaxel/cyclophosphamide 75/600 mg/m2, every 3 weeks, 4 cycles) as adjuvant chemotherapy. Trastuzumab (8 mg/kg; continued with 6 mg/kg) was administrated intravenously for human epidermal growth factor receptor 2 (HER2)-positive cancer. Fifty-five patients received primary prophylactic measures (G-CSF: 20 and antibiotics: 35). We investigated the frequency of FN and hospitalization, RDI, and the factors related to FN, adverse events, hospitalization, and RDI. RESULTS: FN occurred in 70 patients (35.7%). FN incidence was noted in 41.1% without any prophylactic measures and in 5.0% with prophylactic G-CSF. In multivariate analysis, the independent risk factors of FN were older age (≥ 60 years, P = 0.017) and without primary prophylactic G-CSF (P = 0.011). Eleven patients (5.6%) were hospitalized of which 8 (72.7%) were elderly. The median RDIs of docetaxel and cyclophosphamide were 96.7% and 99.7%, respectively. CONCLUSION: FN frequency during TC chemotherapy was high, and primary prophylactic G-CSF reduced FN incidence. Primary prophylactic G-CSF is an effective therapy for preventing FN during TC chemotherapy. However, prophylactic G-CSF should be considered for elderly patients based on the low hospitalization rate and the high RDI.

The relationship between ring-type dedicated breast PET and immune microenvironment in early breast cancer.

PURPOSE: 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) is related to the biological parameters and prognosis of breast cancer. However, whether whole-body PET (WBPET) and dedicated breast PET (DbPET) can reflect the tumor microenvironment is unclear. This study investigated the relationship between stromal tumor-infiltrating lymphocytes (TILs) and maximum standardized uptake value (SUVmax) in WBPET and DbPET. METHODS: A total of 125 invasive breast cancers underwent WBPET and ring-type DbPET and resected specimens were pathologically assessed. The impact of SUVmax on the tumor biological parameters and TILs was retrospectively evaluated. SUVmax was classified as high and low relative to the median values (WBPET-SUVmax: 2.2 and DbPET-SUVmax: 6.0). RESULTS: SUVmax correlated with tumor size, nuclear grade, Ki-67 labeling index, and TILs in both WBPET and DbPET (all p < 0.001). In multiple linear regression analysis, tumor size, Ki-67 labeling index, and TILs predicted SUVmax in WBPET and DbPET. The cutoff values of tumor size, Ki-67 labeling index, and TILs predicting high SUVmax were 20 mm, 20%, and 20%, respectively. In multivariate analysis, the predictive factors for high SUVmax were tumor size and Ki-67 labeling index for WBPET and tumor size and TILs for DbPET. High SUVmax in DbPET was related to high numbers of TILs after propensity score matching analysis; however, WBPET was not (p = 0.007 and p = 0.624, respectively). CONCLUSIONS: Both SUVmax values in WBPET and DbPET predicted TIL concentration of the primary breast cancer. In DbPET, SUVmax represented the immune microenvironment after adjusting for tumor biological factors.

Prediction of biological characteristics of breast cancer using dual-phase FDG PET/CT.

PURPOSE: The aim of this study was to assess whether the retention index (RI) determined using dual-phase 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) reflects the malignant features of breast cancer. METHODS: A total of 1,523 patients with breast cancer were retrospectively evaluated. PET/CT scans were performed at 1 h and 2 h after FDG administration before treatment. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumour and RI were calculated. Primary tumour tissues were evaluated in terms of biological features, such as histology, nuclear grade, lymphovascular invasion and molecular subtype. RESULTS: Of the 1,523 patients, 463 (30.4%) had luminal A-like, 661 (43.4%) had luminal B-like, 229 (15.0%) had human epidermal growth factor receptor 2-positive (HER2-positive), and 157 (10.3%) triple-negative breast cancer. The median SUVmax1, SUVmax2 and RI values were 2.2, 2.3 and 2.6%, respectively. These metabolic parameters were correlated with tumour size, nodal metastasis, histology, nuclear grade, lymphovascular invasion, and molecular subtype (all P < 0.001). The median RI values were 0% in luminal A-like, 5.3% in luminal B-like, 6.9% in HER2-positive, and 11.4% in triple-negative breast cancer. RI was associated with malignant features when the tumour accumulated a significant amount of FDG. In a subanalysis of patients with tumours of stages T2 to T4, RI was correlated with nodal metastasis, histology, nuclear grade, and molecular subtype (luminal A-like 4.8%, luminal B-like 12.3%, HER2-positive 15.8%, and triple-negative 16.3%). CONCLUSION: RI determined using delayed-phase FDG PET/CT is associated with malignant features in breast cancers with significant FDG uptake. Dual-phase imaging was helpful in distinguishing luminal A-like breast cancer from luminal B-like, HER2-positive, and triple-negative breast cancers.

Identification of Axillary Lymph Node Metastasis in Patients With Breast Cancer Using Dual-Phase FDG PET/CT.

OBJECTIVE. The aim of this study was to assess the diagnostic performance of dual-phase 18F-FDG PET/CT in detecting axillary lymph node metastasis in patients with breast cancer. MATERIALS AND METHODS. A total of 826 patients with breast cancer were retrospectively evaluated. PET/CT scans were performed 1 hour and 2 hours after FDG administration before treatment. The maximum standardized uptake value (SUVmax) in the axillary lymph node at both time points (hereafter referred to as SUVmax1 and SUVmax2, respectively) and the retention index (RI) were calculated. RESULTS. Axillary lymph node metastasis was detected in 285 of 826 patients (34.5%). The median axillary SUVmax1, SUVmax2, and RI in patients with nodal metastasis were higher than those in patients without metastasis (1.5 vs 0.6, 1.6 vs 0.5, and 7.7 vs -3.7, respectively; all p < 0.001). The diagnostic accuracy of axillary SUVmax1 and SUVmax2 was equivalent, and the sensitivity and specificity of SUVmax1 were 74.7% and 83.4%, respectively. Although the performance of the axillary RI was inferior to that of SUVmax1 and SUVmax2, both the SUVmax and the RI were independent predictors of nodal metastasis, and a positive RI suggested axillary lymph node involvement when the SUVmax1 was significantly high. Of 533 patients with category T1-2 breast cancer without lymph node swelling, 101 (19.0%) had pathologic lymph node involvement; the negative predictive value of axillary SUVmax1 was 86.8%. CONCLUSION. Delayed phase imaging identified axillary lymph node metastasis as accurately as standard PET/CT. A high negative predictive value of PET/CT for the detection of nodal metastasis is helpful to avoid surgical axillary assessment in patients with category T1-2 breast cancer without lymph node swelling.

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

PURPOSE: Dedicated 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: The 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.

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.

18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Predicts Tumor Immune Microenvironment Function in Early Triple-negative Breast Cancer.

BACKGROUND/AIM: The maximum standardized uptake value (SUVmax) obtained using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is presumed to indicate tumor and active immune cells in the tumor immune microenvironment (TIME) based on their glycolysis activity. Therefore, this study investigated whether the metabolic parameter SUVmax could provide information regarding TIME in triple-negative breast cancer (TNBC) patients. PATIENTS AND METHODS: Fifty-four patients with TNBC underwent FDG PET/CT before neoadjuvant chemotherapy. Pretreatment biopsy specimens were pathologically evaluated. Expression statuses of CD8, forkhead box P3 (FOXP3), programmed cell death-1 (PD-1), and programmed cell death-ligand 1 (PD-L1) were assessed by immunohistochemistry. The relationships between immunological factors, including the tumor-infiltrating lymphocyte (TIL) grade and SUVmax or pathological complete response (pCR), were investigated. RESULTS: CD8, FOXP3, PD-1, and PD-L1 were high in 15 (27.8%), 39 (72.2%), 18 (33.3%), and 26 (48.2%) patients, respectively. SUVmax was significantly correlated with tumor size, Ki-67 labeling index, and CD8/FOXP3 ratio. Multiple linear regression analysis indicated that tumor size and the CD8/FOXP3 ratio predicted SUVmax. Seventeen patients (31.5%) achieved a pCR; TILs, the CD8/FOXP3 ratio, PD-1, and PD-L1 were significantly correlated with pCR rate. Multivariate analysis indicated that the CD8/FOXP3 ratio was the only independent predictive factor for pCR. CONCLUSION: SUVmax could provide metabolic information regarding TIME for TNBC patients and might be beneficial for formulating a treatment strategy and predicting pCR after neoadjuvant chemotherapy.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

PURPOSE: Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. METHODS: A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. RESULTS: The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106 CFU/mL, cycle 3: 4.61 × 106 CFU/mL, cycle 4: 5.85 × 106 CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. CONCLUSION: FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

[A resected case of complete response after treatment with S-1 for recurrent squamous cell carcinoma component of the breast].

A resected case of complete response after treatment with S-1 for recurrent squamous cell carcinoma component of the breast is presented.A 65-year-old woman was admitted to another hospital because of a left breast tumor. A tumor approximately 6 cm in diameter was palpable in the subareolar-lower (DBE) region of the left breast; the diagnosis was breast cancer. We performed mastectomy and axillary lymph node dissection. The pathological diagnosis revealed squamous cell carcinoma of the left breast(pT3N1M0, Stage III A). FEC chemotherapy, a standard chemotherapy regimen for general breast cancer, was performed as first-line adjuvant therapy, but was withdrawn after 1 course due to sepsis shock. Weekly PTX chemotherapy as second-line treatment was also withdrawn after six courses due to interstitial pneumonia. Few skin rashes were observed along the incision scar of the left breast, but biopsy revealed skin invasion by local recurrence of squamous cell carcinoma of the breast. Treatment with S-1 was performed for 8 months, and she underwent resection of left skin, fat tissue, and underlying muscle, including the recurrent region. No residual primary carcinoma foci was found in the resected specimen; therefore, the pathological diagnosis revealed complete response for the squamous cell carcinoma component.

Malignant prediction of incidental findings using ring-type dedicated breast positron emission tomography.

The classification according to uptake patterns and metabolic parameters on ring-type dedicated breast positron emission tomography (dbPET) is useful for detecting breast cancer. This study investigated the performance of dbPET for incidental findings that were not detected by mammography and ultrasonography. In 1,076 patients with breast cancer who underwent dbPET, 276 findings were incidentally diagnosed before treatment. Each finding was categorized as focus (uptake size ≤ 5 mm), mass (> 5 mm), or non-mass (multiple uptake) according to uptake patterns. Non-mass uptakes were additionally classified based on their distributions as-linear, focal, segmental, regional, or diffuse. Thirty-two findings (11.6%) were malignant and 244 (88.4%) were benign. Visually, 227 (82.3%) findings were foci, 7 (2.5%) were masses, and 42 (15.2%) were non-masses. Malignant rates of focus, mass, and non-mass were 9.7%, 28.6%, and 19.0%, respectively. In the non-mass findings, 23 were regional and diffuse distributions, and presented as benign lesions. Focus uptake with low lesion-to-background ratio (LBR) and no hereditary risk were relatively low (2.7%) in breast cancer. In multivariate analysis, LBR and hereditary risk were significantly associated with breast cancer (p = 0.006 and p = 0.013, respectively). Uptake patterns, LBR, and hereditary risk are useful for predicting breast cancer risk in incidental dbPET findings.

Monitoring of Programmed Cell Death Ligand-1 Blockade Using FDG PET/CT for Microsatellite Instability-High Metastatic Breast Cancer.

ABSTRACT: Microsatellite instability-high/mismatch repair deficiency is one of biomarkers predicting the response to pembrolizumab, an immune checkpoint inhibitor for metastatic solid tumors. A 44-year-old woman with stage IIIC right breast cancer was treated with mastectomy and axillary node dissection after primary systemic chemotherapy followed by radiation, chemotherapy, and hormonal therapy. Eighteen months after surgery, recurrent diseases were revealed and refractory to multiple treatments. The recurrent site biopsy showed microsatellite instability-high, and programmed cell death ligand-1 inhibitor pembrolizumab was administrated. FDG PET/CT showed complete metabolic response over 12 months and is useful to monitor the response of active immunotherapy.

Dual-phase FDG PET/CT for predicting prognosis in operable breast cancer.

PURPOSE: We aimed to investigate the role of dual-phase FDG PET/CT in predicting the prognosis of patients with operable breast cancer. METHODS: We retrospectively reviewed the data of 998 patients who underwent radical treatment for breast cancer. Before treatment, PET/CT scans were performed 1 and 2 h after FDG administration. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumor and the retention index (RI) were calculated. PET recurrence risk (PET-RR) was determined based on the SUVmax1 and RI, and disease-free survival (DFS) and overall survival (OS) were evaluated according to the metabolic parameters. Propensity score matching was performed to adjust for biological characteristics. RESULTS: The cut-off values for SUVmax1 and RI were 3 and 5%, respectively. The 5-year DFS was 94.9% and 86.1% (P < 0.001), and the 5-year OS was 97.6% and 92.7% (P < 0.001) in the low and high PET-RR groups, respectively. In multivariate analysis, high T status, nodal metastasis, the triple-negative subtype, and high PET-RR were independent factors of poor DFS. Propensity score matching revealed similar findings (5-year DFS 91.8% vs. 88.6%, P = 0.041 and 5-year OS 97.1% vs. 94.2%, P = 0.240, respectively). CONCLUSION: The combined parameters of SUVmax1 and RI on dual-phase FDG PET/CT were useful for predicting prognosis of patients with breast cancer. Patients with a high SUVmax1 and a negative time course of FDG uptake had a favorable prognosis.

Effect of Secondary Prophylactic G-CSF on the Occurrence of Febrile Neutropenia in Breast Cancer.

BACKGROUND/AIM: Docetaxel and cyclophosphamide (TC) combination therapy is widely used as adjuvant chemotherapy for early-stage breast cancer and is associated with a high incidence of febrile neutropenia (FN). Granulocyte colony-stimulating factor (G-CSF) is recommended in the primary prevention of febrile neutropenia (FN). This study aimed to evaluate the FN-suppressing effect of G-CSF in patients with breast cancer receiving TC. PATIENTS AND METHODS: We performed 272 treatment cycles after FN onset in 106 patients with breast cancer receiving TC. We retrospectively evaluated the effect of G-CSF as secondary prophylaxis. The frequency of FN was calculated based on the treatment cycles to adjust for differences in the number of cycles per case and FN occurrence. RESULTS: FN occurred in 58 cycles (21.3%). The incidence of FN with and without secondary prophylactic G-CSF was 10.1% and 25.9%, respectively (p=0.003). Multivariate analysis showed secondary prophylactic G-CSF administration to be an independent predictor of FN incidence [odds ratio (OR)=0.33, 95% confidence interval (CI)=0.14-0.74, p=0.007]. CONCLUSION: Secondary prophylaxis with G-CSF is recommended for patients with breast cancer undergoing TC chemotherapy to reduce the incidence of FN.

The TILs-US score on ultrasonography can predict the pathological response to neoadjuvant chemotherapy for human epidermal growth factor receptor 2-positive and triple-negative breast cancer.

BACKGROUND: The tumor-infiltrating lymphocyte (TIL)-ultrasonography (US) score determined through characteristic US findings has predictive performance of lymphocyte-predominant breast cancer (LPBC). This study aimed to investigate whether the TIL-US score before neoadjuvant chemotherapy (NAC) can predict the pathological complete response (pCR). METHODS: We evaluated patients with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (n = 55) and triple-negative breast cancer (TNBC) (n = 24) who underwent surgery after NAC from November 2012 to April 2019. Pre-NAC biopsy examination was performed to examine stromal TILs; the cutoff value for predicting pCR was defined as ≥50% stromal TILs. The TILs-US score was calculated from the pre-NAC US findings. Based on previous data, the cutoff value for predicting pCR was set at ≥4 points. RESULTS: Forty-six patients achieved pCR. The TIL-US score was significantly associated with the pCR rate (p = 0.003) but not the pre-NAC biopsy findings (p = 0.055). Multivariate logistic regression analysis revealed that a TILs-US score ≥4 and HER2 positivity were significant pCR predictors (odds ratio [OR] 3.69; p = 0.031; OR 8.74; p = 0.025). CONCLUSIONS: TILs-US scores can be used to evaluate the therapeutic effect of NAC, and may be used as a non-invasive, convenient, and an alternative method to assess stromal TILs in pre-treatment biopsies.

The tumor-infiltrating lymphocyte ultrasonography score can provide a diagnostic prediction of lymphocyte-predominant breast cancer preoperatively.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) are known to predict the therapeutic effect in breast cancer. Although a preoperative tissue biopsy can be used to evaluate TILs, TILs that are heterogeneously distributed might require examination of all preoperative tissue biopsy samples. We have recently reported that the TIL ultrasonography (US) score, as determined by characteristic US findings, provides excellent predictive performance for lymphocyte predominant breast cancer (LPBC). We herein aimed to determine whether the preoperative TIL-US score can more accurately predict LPBC than preoperative tissue biopsy. METHODS: We assessed 161 patients with invasive breast cancer that were treated with curative surgery between January 2014 and December 2017. Stromal lymphocytes were examined on preoperative tissue biopsy tissues and surgical pathological specimens. Breast cancer samples with ≥ 50% stromal TILs were defined as pre-LPBC (preoperative tissue biopsy) and LPBC (surgical pathological specimens). Useful factors for predicting LPBC were searched among clinicopathological factors. RESULTS: The TIL-US score cutoff value for predicting LPBC was 4 points based on the receiver operating characteristic curves (area under the curve: 0.88). Several significant predictors for LPBC were revealed by the undertaken multivariate logistic regression analysis (odds ratios: TIL-US score, 26.8; pre-LPBC, 18.6; HER2, 9.2; all, p < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.74, 0.89, 0.85, 0.67, and 0.92 for the TIL-US score, respectively, and 0.51, 0.98, 0.87, 0.91, and 0.86 for the pre-LPBC, respectively. CONCLUSION: TIL-US scores can predict LPBC preoperatively and are characterized by a significantly high sensitivity and negative predictive value.

A case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy after primary treatment of triple-negative breast cancer.

We report a case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy 6 years after primary treatment of triple-negative breast cancer. The primary tumor was negative for HER-2 as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) (1+, and ratio, 1.1), but examination of the recurrent lymph node metastasis showed positivity for HER-2 by FISH (ratio, 5.2). No lesions were detected in either her left breast or in other organs, and the patient was diagnosed as having HER-2-positive recurrent disease. Combination chemotherapy using weekly paclitaxel and trastuzumab was initiated, and a clinically complete response was achieved. This report suggests the benefit of routine evaluation of HER-2 status in recurrent breast cancer with the introduction of HER-2-targeting agents.

Breast cancer detection by dedicated breast positron emission tomography according to the World Health Organization classification of breast tumors.

OBJECTIVE: Considering the difficulty in detecting primary breast cancers using whole-body positron emission tomography (WBPET) owing to its limited spatial resolution, we aimed to evaluate the detectability of breast cancer by ring-type dedicated breast PET (DbPET) on the World Health Organization (WHO) histological classification in comparison with WBPET. METHODS: A total of 938 patients with breast cancer underwent WBPET and ring-type DbPET, and 1021 lesions were histologically assessed based on the WHO classification of tumors of the breast. The findings of WBPET and DbPET were retrospectively evaluated and compared. RESULTS: The size-related sensitivity of DbPET was superior to that of WBPET for subcentimetric tumors (81.9% vs. 52.4%, P < 0.001). The histological distribution was as follows: 11 lobular carcinoma in situ, 158 ductal carcinoma in situ, 738 infiltrating duct carcinoma not otherwise specified (NOS), 12 lobular carcinoma NOS, 40 mucinous adenocarcinoma, 13 tubular carcinoma, 36 invasive breast carcinoma others, and 13 papillary neoplasms. WBPET had low sensitivity for lobular carcinoma in situ, ductal carcinoma in situ, lobular carcinoma NOS, mucinous adenocarcinoma, and tubular carcinoma. DbPET showed improved sensitivity for all the above except lobular and tubular carcinoma. The maximum standardized uptake values (SUVmax) of DbPET were significantly higher than those of WBPET for histological types, excluding lobular carcinoma in situ. The SUVmax of papillary neoplasms was high regardless of low-grade histology and Ki-67 labeling index. CONCLUSIONS: DBPET was found to have high sensitivity and SUVmax values for all histologic types that showed low sensitivity of detection on WBPET, except lobular carcinoma in situ.