The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients.

BACKGROUND: There is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients. METHODS: Postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed. RESULTS: Among 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p < 0.05). CONCLUSIONS: PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.

Differences in Transient Fluid Retention and Lymphedema With Breast Cancer Treatment for Lymphatic Microsurgery.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a common complication. Repeated taxane-based chemotherapy has been shown to induce endothelial inflammation, leading to fluid retention. Patients with transient fluid retention only have upper limb edema without lymphatic dysfunction. Therefore, indocyanine green lymphography revealed linear findings, and lymphatic microsurgery is not required. This study aimed to investigate the difference between BCRL and fluid retention and present the indication for lymphatic microsurgery for these patients. METHODS: The study population was divided into BCRL and fluid retention groups. Age, body mass index, laterality, surgery type (lymph node, breast, or no surgery), disease stage, regional lymph node irradiation, hormone therapy, chemotherapy type (taxane- or non-taxane-based group), and treatment with trastuzumab were compared. RESULTS: The BCRL and fluid retention groups consisted of 168 and 73 patients, respectively. The BCRL group had significantly higher rates of axillary lymph node dissection (96.4%) and lymph node irradiation (51.8%) than the fluid retention group (53.4% and 24.7%, respectively; P < 0.001 for both). The fluid retention group had a significantly higher rate of taxane-based chemotherapy (100%) than the BCRL group (92.9%; P = 0.02). No significant differences in other characteristics, including treatments with hormone and trastuzumab, were observed. CONCLUSIONS: Lymphatic microsurgery should be performed after confirming the diagnosis by indocyanine green lymphography, particularly for patients with fluid retention induced by taxane-based chemotherapy. Because the generalized swelling induced by taxane-based chemotherapy is resolved 6 months after chemotherapy, we should wait at least 6 months to perform lymphatic microsurgery.

Clinical impact of the biology of synchronous axillary lymph node metastases in primary breast cancer on preoperative treatment strategy.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the utility of determining the biological features of synchronous axillary lymph node (syLN) metastasis of breast cancer in evaluating the efficacy of preoperative systemic chemotherapy (PST). MATERIALS AND METHODS: The retrospective subjects initially comprised 59 patients (T1c-4 N1-3 M0) diagnosed with syLN metastasis via core needle biopsy who received PST. The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status in each patient was assessed in primary breast tumor (pBT) and syLNs using immunohistochemistry, and the patients were classified into HR(+), HER2(+), and triple negative breast cancer (TN) subtypes. RESULTS: Subtype shift (SS) of pBT in syLNs was observed in 28% cases for HR(+), in 6% cases for the HER2(+), and in 16% cases for the TN. The pCR rate of the pBT and syLNs types were 45% and 36% in the HR(+), 45% and 39% in the TN, and 94% and 100% in the HER2(+), respectively. In SS cases, the pCR rate was significantly higher in 75% cases compared with 33% of the no-SS cases. CONCLUSION: A SS in syLNs was more frequent in HR(+) than in other types.

[Ruptured Spinal Arteriovenous Malformation Mimicking Bacterial Meningitis:A Case Report].

A 23-year-old woman was referred to our hospital with progressive headache and back pain. Cerebrospinal fluid(CSF)analysis revealed hypoglycorrhachia and pleocytosis. However, imaging studies did not reveal evidence of subarachnoid hemorrhage(SAH), and she was diagnosed with bacterial meningitis. CSF analysis repeated after antibiotic treatment continued to show evidence of blood. Spinal SAH was suspected, and MRI revealed a spinal arteriovenous malformation(AVM). Spinal digital subtraction angiography revealed the nidus and a feeder aneurysm, which was implicated as the source of bleeding;therefore, she was diagnosed with spinal SAH secondary to spinal intramedullary AVM(SAVM). She underwent endovascular treatment for the spinal aneurysm and was discharged without worsening neurological symptoms. SAVMs presenting without neurological findings and/or evidence of bleeding on plain CT images are diagnostically challenging;notably, findings on CSF analysis could mimic those observed in cases of infectious disease. We should cite vascular diseases such as SAVM.

[A Case of Pediatric C1 Dysplasia with Ruptured Aneurysm in Collateral Plexiform Arterial Network].

A 3-year-old girl was admitted to our hospital with symptoms including headache, nausea, and vomiting. Head CT scan showed subarachnoid hemorrhage in the right carotid cistern. Digital subtraction angiography revealed right internal caortid artery(ICA)malformation at the C1 segment with collateral plexiform arterial network. The right ICA branched into posterior communicating artery and anterior choroidal artery(AChoA)and the ICA was decreased in caliber. The distal portion of the C1 segment of the ICA continued to the collateral plexiform arterial network, forming a saccular aneurysm. The plexiform arterial network connected to the right AChoA and the anterior communicating artery and continued to the distal portion of the right M1 segment. Right cervical carotid artery was normal. There was no transdural collateral flow from the right external carotid artery. Genetic analysis of a variant of RING finger protein 213 was negative. We diagnosed this patient with C1 dysplasia. We performed coil embolization for the aneurysm. The patient was discharged without any neurological deficit. Four months after the surgery, recurrence of the aneurysm was observed. We suspected that the aneurysm was formed due to hemodynamic mechanism and vulnerability of the collateral plexiform arterial network.

Randomized phase II study of nab-paclitaxel as first-line chemotherapy in patients with HER2-negative metastatic breast cancer.

Weekly administration of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has been shown to be a safe and effective treatment for metastatic breast cancer (MBC) in clinical studies. We conducted a multicenter, randomized, open-label phase II study to compare the efficacy and safety of weekly nab-paclitaxel and docetaxel in Japanese patients with human epidermal growth factor receptor 2-negative MBC. The primary endpoint was progression-free survival (PFS). Patients were randomized to receive nab-paclitaxel (150 mg/m2 nab-paclitaxel once per week for 3 of 4 weeks; n = 100) or docetaxel (75 mg/m2 docetaxel every 3 weeks; n = 100). The median PFS by independent radiologist assessment was 9.8 months (90% confidence interval [CI]: 8.5-11.2) for nab-paclitaxel and 11.2 months (90% CI: 8.4-13.8) for docetaxel (hazard ratio: 1.25, P = 0.363), and the median overall survival was 42.4 months and 34.0 months, respectively. The overall response rate was 56.1% for nab-paclitaxel and 52.5% for docetaxel. Adverse events in both treatment arms were similar to previous reports. Neutropenia was the most common adverse event in both arms, with 35.0% of patients in the nab-paclitaxel arm and 89.0% in the docetaxel arm experiencing grade 4 neutropenia. Grade 3 peripheral sensory neuropathy occurred in 22.0% of patients in the nab-paclitaxel and 5.0% in the docetaxel arm. In this study, although weekly nab-paclitaxel 150 mg/m2 did not show superiority in PFS compared with docetaxel, efficacy outcomes were similar in patients treated with weekly nab-paclitaxel and docetaxel.

[Usefulness and Problems of Intraoperative Monitoring for Unruptured Aneurysm Surgery with the Motor Evoked Potential].

It has been pointed out that the motor evoked potential(MEP)with a subdural electrode is useful in the intraoperative monitoring for unruptured aneurysm surgery. However, in some cases, we experienced postoperative ischemic complications despite evaluating the motor function via MEP monitoring. Herein, we have reported the usefulness and problems of intraoperative monitoring with MEP to evaluate brain dysfunction caused by insufficiency of cerebral blood flow. Out of 279 aneurysm surgery procedures, we performed MEP monitoring in 142 cases and successfully recorded in 126 cases. We compared the ischemic complication rate of the group for which MEP was monitored with that of the group for which MEP was not monitored. The whole ischemic complication rate was decreased in the group that underwent MEP monitoring. Thus, it was suggested that MEP monitoring was useful for avoiding ischemic complications. In internal carotid artery aneurysms, the amplitude of MEP changed and recovered in 2 cases and disappeared in one case. In anterior cerebral artery aneurysms, the amplitude of MEP changed and recovered in 2 cases. In middle cerebral artery aneurysms, the amplitude of MEP changed and recovered in 5 cases. We could avoid ischemic complications by intraoperative MEP monitoring in many cases. However, in some cases, we found ischemic complications that were not detected by MEP monitoring with a subdural electrode. In these cases, transcranial stimulation in combination with subdural electrode might be effective in avoiding ischemic complications that might occur after dural closure.

Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients.

BACKGROUND: Previous large trials with trastuzumab (TZM) showed improved outcome in patients with HER2-positive early-stage breast cancer. However, the efficacy and safety of TZM in Japanese patients have not been fully evaluated. We have therefore conducted an observational study in Japan. METHODS: This was a retrospective and a prospective observational study in which data on women with histologically confirmed HER2-positive invasive breast cancer who received TZM for stage I-IIIC disease were collected from 56 institutions that participated in the Japan Breast Cancer Research Group and the efficacy of each treatment regimen analyzed. RESULTS: A total of 2,024 patients treated between July 2009 and June 2011 were initially enrolled in this study; in August 2013, the patient cohort comprised 2,009 patients. Of these, 142 (7.5 %) were aged ≥70 years, 1,097 (58.1 %) had clinically node-negative (cN0) breast cancer, and 883 (47.4 %) were estrogen receptor-positive. Treatment options were neoadjuvant therapy (662 patients) and adjuvant therapy with TZM (1,228 patients). Three-year overall survival (OS) rates in the entire cohort and in the neoadjuvant and adjuvant cohorts, respectively, were 98.9 [95 % confidence interval (CI) 98.2-99.3], 98.3 (95 % CI 96.8-99.1 %), and 99.2 % (95 % CI 98.4-99.6), respectively. Three-year disease-free survival (DFS) rates in the entire cohort and in the neoadjuvant and adjuvant cohorts, respectively were 94.2 (95 % CI 93.0-95.2), 94.8 (95 % CI 93.0-95.9), and 93.1 (95 % CI 90.7-94.9 %), respectively. Multivariate analysis showed that age and nodal status negatively correlated with DFS. Age was the only factor which correlated with OS rate. Adverse events (AEs) associated with TZM and grade 3/4 AEs were reported in 356 (18.8 %) and 14 (0.6 %) patients, respectively. Grade 3/4 cardiac toxicities were reported in 11 patients. CONCLUSION: Based on data from our patient cohort of Japanese women with HER2-positive early-stage breast cancer, the efficacy and safety of systemic therapy with TZM are comparable to data from previously conducted large trials. Progress in anti-HER2 therapy for patients aged ≥70 years who have a poorer prognosis is needed.

[Administration Order of FEC-DOC in Breast Cancer Adjuvant Chemotherapy Has an Effect on Toxicity].

Sequential administration of anthracycline - and taxane-based regimens has been established as standard adjuvant chemotherapy for breast cancer. In our hospital, FEC(5-FU/EPI/CPA) followed by docetaxel therapy has been used for this indication. Recently, we changed the sequence of FEC and docetaxel to reduce skin toxicities during the docetaxel phase. Since the effect of the administration order on efficacy and toxicity is not clear, we retrospectively compared the toxicities and relative dose intensity (RDI) of the administration orders. From January to December of 2012, 46 patients received FEC followed by docetaxel (AT group), while 42 patients underwent docetaxel followed by FEC during the same period in 2013(TA group). The incidence of severe hematological and major non-hematological toxicities was similar in the two groups. There was no significant difference in RDI between groups. However, grade 2 or higher hand-foot syndrome(HFS)during the docetaxel phase, which can be a reason for dose reduction or treatment termination, was more frequently observed in the AT group than in the TA group(54% vs 33%, p<0.05). Our data shows that the risk of HFS was reduced when the taxane was administered first. Interestingly, HFS significantly increased in the winter, regardless of the administration order(p<0.01).

Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression.

Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response (pCR) rates. We evaluated the efficacy and safety of carboplatin and weekly paclitaxel (wPTX) followed by cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as neoadjuvant chemotherapy for HER2-negative breast cancer. Patients with stage II/IIIA HER2-negative breast cancer were randomly assigned to preoperatively receive CP-CEF (four 3-week cycles of carboplatin [area under the curve 5 mg/mL/min, day 1] and wPTX [80 mg/m(2), day 1, 8, 15] followed by four 3-week cycles of CEF [500/100/500 mg/m(2)] or P-CEF (four cycles of wPTX followed by four cycles of CEF). The primary objective was pCR rate. Of 181 eligible patients, 89 were randomly assigned to the CP-CEF and 92 to the P-CEF. Two patients in each arm refused to receive neoadjuvant chemotherapy. Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety. The pCR rate in the CP-CEF was significantly higher than that in the P-CEF (31.8 vs. 17.6 %, one-sided P = 0.01). Among patients with triple-negative breast cancer, the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [61.2 (23/37) vs. 26.3 % (10/38), P = 0.003]. Grade 3-4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF (65.9 vs. 38.5 %). Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity.

Final results of a safety and efficacy trial of preoperative sequential chemoradiation therapy for the nonsurgical treatment of early breast cancer: Japan Clinical Oncology Group Study JCOG0306.

OBJECTIVE: To explore the possibility of nonsurgical treatment of primary breast cancers by a sequential treatment of chemotherapy and radiotherapy. METHODS: We conducted a safety and efficacy trial of chemotherapy and radiation therapy sequentially as primary therapy in patients with stage I-IIIA breast cancer. All patients underwent mastectomy or lumpectomy 12-16 weeks after the completion of radiation therapy to maximize the effect of radiation therapy. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Between June 2004 and April 2005, one hundred eight patients were enrolled. Thirty six percent of the entire population achieved a pCR, which could not reject the null hypothesis. The pCR rate was 57% in patients with hormone receptor (HR)-negative/HER-2-positive tumors and 52% in patients with triple-negative tumors. While 7% of the HR-negative/HER2-positive patients recurred, a higher incidence of recurrence (24%) was observed in triple-negative tumors in a follow-up of 4.5 years. The rate of breast-conserving surgery was 88.9% (96/108). CONCLUSION: The pCR rate was not high enough, even though preoperative sequential chemoradiation therapy did not increase the risk of operative complications and could achieve a high rate of breast-conserving surgery.

Clinical Impact of Fine Needle Aspiration Cytology on Sentinel Node Biopsy after Preoperative Chemotherapy for Core Needle Biopsy-Proven Metastatic Lymph Nodes.

INTRODUCTION: Sentinel node biopsy (SNB) has been increasingly performed for patients with lymph node (LN)-positive (cN1) breast cancer that converted to LN-negative (ycN0) status after neoadjuvant chemotherapy (NAC). This study aimed to clarify the SNB avoidance rates using fine needle aspiration cytology (FNAC) for metastatic LNs after NAC. METHODS: This study included 68 patients with cN1 breast cancer undergoing NAC from April 2019 to August 2021. Patients with biopsy-proven metastatic clip-marked LNs (clipped LNs) underwent eight cycles of NAC. Ultrasonography (US) was performed to evaluate the effect of the treatment on the clipped LNs, and FNAC was performed after NAC. Patients with ycN0 status determined using FNAC underwent SNB. Those with positive results for FNAC or SNB underwent axillary LN dissection. Histopathology results and FNA were compared for clipped LNs after NAC. RESULTS: Of the 68 cases, 53 were ycN0 and 15 were clinically positive LNs after NAC (ycN1) on US. Further, 13% (7/53) of all ycN0 and 60% (9/15) of all ycN1 cases showed residual metastasis in the LNs on FNAC. CONCLUSION: FNAC was diagnostically useful for patients with ycN0 status on US imaging. Using FNAC for LNs after NAC helped avoid unnecessary SNB in 13% of the cases.

Utility of the intraflap perfusion procedure for abdominal free flap in unilateral breast reconstruction.

BACKGROUND: Heparin prophylaxis for venous thromboembolism can be used in microsurgery. If vein anastomosis is performed before the artery, heparin irrigation into the artery can be performed locally without systematic effect. This study aimed to introduce this "intraflap perfusion procedure" in autologous breast reconstruction. METHODS: Among the 220 patients with unilateral breast cancer who had received the free abdominal flap, we retrospectively compared those that had undergone the intraflap perfusion procedure (n = 108) and those who did not (n = 112). A 10 mL injection of heparinized physiological saline solution (100 units/mL) was administered into the deep inferior epigastric artery. Intraflap perfusion was performed before, during, and after vein anastomosis, without the vessel clip of the vein. Artery anastomosis was performed without the use of a vein clamp. Further, vein anastomosis was performed tightly to prevent leakage from the vein anastomosis site during artery anastomosis. RESULTS: The rates of superficial inferior epigastric vein (SIEV) superdrainage (18.5% vs. 42.0%, P < 0.001), and intraoperative flap congestion (0.9% vs. 8.0%, P = 0.01) were significantly lower in patients undergoing this procedure. There were no significant differences regarding other factors (age, BMI, laterality, comorbidities, and other operative details). CONCLUSIONS: Intraflap perfusion prevented long-term stasis at the venous anastomosis site and capillary level. It could reduce flap congestion. SIEV superdrainage was performed to manage flap congestion, particularly in patients who did not undergo this procedure. Consequently, it can be inferred that this procedure reduces the rate of superdrainage.

Fascia turnover procedure at breast reconstruction using free TRAM flap for decreasing umbilical migration.

BACKGROUND: The ideal umbilical position is midway between the two iliac crests. Some patients complained that the umbilicus position shifted from the midline after the breast reconstruction with a free muscle-sparing transverse rectus abdominis musculocutaneous (MS-TRAM) flap. We considered that the fascia of the external oblique muscle could be applied to the rectus abdominis fascia defect. This study aimed to introduce this "fascia turnover procedure" and compare the umbilical position in this procedure with that in primary fascial closure for the MS-TRAM flap of breast reconstruction. METHODS: A total of 152 patients were enrolled (80 patients with fascia turnover (+) vs. 72 patients (-)). The patients' demographics were compared. Horizontal distances (right side: a; left side: b) were measured bilaterally from the lateral abdominal wall to the center of the umbilicus. Frontal abdominal photographs were taken preoperatively (a1, b1) and postoperatively (a2, b2). The rate of umbilical migration (= | (a1 - b1) / (a1 + b1) - (a2 - b2) / (a2 + b2) | × 100%) was calculated. Because the aponeurosis of the external oblique muscle is confirmed in front of the lateral side of the anterior rectus sheath, this procedure could be performed in cases with a medial defect. RESULTS: No significant differences in the patients' demographics, including abdominal bulging rates and abdominal wall defect widths were observed between the two groups. The rate of umbilical migration showed a significant difference (median 1.78% vs. 3.70%, P < 0.001). CONCLUSIONS: This procedure could decrease the rate of umbilical migration.

Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) Study under the Patient-proposed Health Services.

Introduction: Due to the increase in the number of early-stage breast cancer patients, there is growing interest in minimally invasive local therapies for breast cancer. Radiofrequency ablation (RFA) therapy is one of the most promising minimally invasive treatments. The Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (RAFAELO) study, a multicenter collaborative study that aims to validate the efficacy and safety of RFA and to standardize its use for early-stage breast cancer, was conducted under the Advanced Medical Care B system in 2013. This study enrolled the expected number of patients in November 2017; moreover, it is currently in the follow-up period. Some patients with early-stage breast cancer who are eligible for RFA could not receive the RFA treatment, as it is still not covered by insurance. Therefore, the Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) study under the Patient-proposed Health Services (PPHS) was proposed and approved in March 2019. Methods: The PPHS is a system that allows patients to receive prompt access to advanced medical care at a medical facility close to them, starting with their request. This system is considered a part of the specific and special medical coverage. The PO-RAFAELO study is the only study in the surgical field utilizing the PPHS, aiming to help in achieving regulatory approval and insurance coverage of RFA for breast cancer. Results: As of January 2023, 120 patients have undergone RFA using the PPHS and no grade 3 or higher early adverse events have occurred. Conclusions: A certain number of patients with early-stage breast cancer prefer nonsurgical treatment, and it is important to provide information regarding the availability of RFA for early-stage breast cancer under the PPHS.Trial registration: registered with Japan Registry of Clinical Trial on March 06, 2019 (Trial ID: jRCTs032180187).

Randomized phase II study of three doses of oral TAS-108 in postmenopausal patients with metastatic breast cancer.

This randomized phase II study was intended to identify the optimal dose of TAS-108, a novel steroidal antiestrogen, for the treatment of breast cancer in postmenopausal Japanese women. The potential clinical effects of TAS-108 on the uterus, bone, serum lipids, and hormones were also investigated. Postmenopausal women with hormone receptor-positive metastatic breast cancer who had previously received one or two endocrine therapies were randomly assigned to one of the three possible dose levels of TAS-108 (40, 80 or 120 mg/day). Oral TAS-108 was given daily, and the efficacy and safety of the three doses were evaluated. A total of 97 patients (33, 32, and 32 in the 40-, 80-, and 120-mg groups, respectively) were treated with TAS-108. The clinical benefit rate was 30.3% for the 40-mg, 25.0% for the 80-mg, and 25.0% for the 120-mg group. The 40-mg group achieved the prespecified target threshold. TAS-108 at all dose levels was well tolerated and appeared to have no harmful effects in terms of the variables examined in this study. We conclude that the optimal dose of TAS-108 among the three doses is 40 mg, once daily, for further studies. JAPIC Clinical Trials Information number: Japic CTI - 121754.

Treatment Strategy for Patients with HR-Positive HER2-Negative Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitors.

Background/Aims: The study aim was to evaluate if mTOR inhibitors can be considered as a treatment option for HR+ HER2- metastatic breast cancer (MBC) after progression on CDK4/6 inhibitors in clinical practice. Methods: We retrospectively collected the clinicopathological data of patients with HR+ HER2- MBC treated with CDK4/6 inhibitors and subsequent therapies at our institution between 2014 and 2020. The patients were divided into 3 groups according to the type of subsequent treatment: (A) exemestane plus everolimus, (B) endocrine monotherapy, and (C) chemotherapy. Overall survival (OS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. The efficacy and adverse events (AEs) of each subsequent treatment were assessed by using Fisher's exact tests. Results: Eighty-six patients (34 in group A, 20 in group B, 32 in group C) were included. The most common endocrine therapy in group B was fulvestrant (40%). The major chemotherapy regimen in group C was eribulin (25%). The median OS times after stopping CDK4/6 inhibitors were 34.5 months (95% confidence interval, 17.2 to NA), 13.6 months (3.9 to NA), and 19.5 months (18.8 to NA) in group A, group B, and group C, respectively. The only significant difference in OS was observed between group A and group B (20.9 months; p = 0.003). There was no difference in the incidence of grade 3 AEs between groups A and C or in the frequency of treatment discontinuation because of AEs among the 3 groups. Conclusion: Our study shows that mTOR inhibitors might be an effective treatment option for patients with HR+ HER2- MBC previously treated with CDK4/6 inhibitors.

Investigation of the Association Between Breast Cancer-Related Lymphedema and the Side Effects of Taxane-Based Chemotherapy Using Indocyanine Green Lymphography.

Background: Breast cancer-related lymphedema (BCRL) is a common complication. Docetaxel (DOC) and paclitaxel (PTX) have been used in taxane-based chemotherapy for breast cancer and to induce fluid retention. The purpose of this study was to investigate the association between lymphatic functionality and the side effects of taxane-based chemotherapy using indocyanine green (ICG) lymphography. Methods and Results: One hundred and eighty breast cancer cases who underwent full-dose taxane-based chemotherapy (DOC or PTX) and complained of upper extremity edema were enrolled in this study. BCRL was diagnosed exclusively on the basis of ICG lymphography results. The characteristics (age, body mass index, laterality, surgery type, regional lymph node irradiation, hormone therapy, and chemotherapy type) of patients diagnosed with BCRL (+) and BCRL (-; fluid retention only) were compared. The side effects were compared in eight categories (neutropenia, skin toxicity, nail changes, myalgia/arthralgia, peripheral neuropathy, stomatitis, dysgeusia, and digestive disease). BCRL (+) consisted of 116 patients and BCRL (-) consisted of 64 patients. BCRL (+) had significantly higher rates of axillary lymph node dissection (98.3%), lymph node irradiation (68.1%), neoadjuvant chemotherapy (14.7%), and DOC (62.9%) than BCRL (-) patients (56.3%, 20.3%, 3.1%, and 34.4%, respectively; p = 0.002 for neoadjuvant rate, p < 0.001 for the other rates). BCRL (+) patients had significantly higher rates of peripheral neuropathy (60.3%) than BCRL (-) patients (40.6%; p = 0.01). Conclusions: The occurrence rate of BCRL increased for the patients with peripheral neuropathy induced by taxane-based chemotherapy. This implies that peripheral neuropathy can induce BCRL.

Synchronous early-stage breast cancer and axillary follicular lymphoma diagnosed by core needle biopsy: A case report.

Synchronous double cancers are an infrequent finding. The focus of this study was a case of diagnosed synchronous double breast cancer (BC) and axillary (Ax) follicular lymphoma (FL). The patient was a 73-year-old woman who had been visiting her local doctor for follow-up of a fibroadenoma of the left breast, and was referred to our hospital after being diagnosed with invasive ductal carcinoma (IDC) of the left breast. Ultrasonography (US) revealed enlarged Ax lymph nodes (LNs) and US-guided core needle biopsy (CNB) was performed. CNB revealed no metastasis of IDC; however, a diagnosis of FL was made. Therefore, the patient was diagnosed with synchronous double BC and Ax FL and underwent partial surgical resection of the BC and close monitoring of the FL. To the best of our knowledge, this is the first case of malignant lymphoma diagnosed by CNB of Ax LNs during preoperative BC screening. CNB allows for a shorter waiting time for the examination, and it is considered to be minimally invasive, cost-effective and non-inferior to surgical resection in terms of specimen volume. Therefore, active preoperative evaluation of Ax LNs using US-guided CNB may contribute to BC staging, and may also help diagnose synchronous cancers.

Does Routine Follow-Up after Patients Have Completed Adjuvant Therapy for Early-Stage Breast Cancer at a Cancer Center Improve Prognosis?

Introduction: This study aimed to assess whether follow-up of patients with operative breast cancer at cancer centres (CCs) improved prognosis compared with follow-up by family physicians (FPs). Methods: The study included 254 patients who relapsed within 7 years from the first postoperative period. The patients were divided into two groups according to the follow-up facility: the CC and FP groups (the follow-up of patients was structured in the same way between FPs and CCs). There are 146 and 108 cases of recurrence in the CC and FP groups, respectively. The analysis targets of the two groups were determined using the propensity matching method based on the following 7 factors: oestrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, St. Gallen category, menopausal status, surgical procedure, and receipt of postoperative chemotherapy at the time of surgery. Overall survival (OS) in both groups was analysed using the Kaplan-Meier method and compared using the log-rank test. Results: Overall, 97 patients each in the CC and FP groups who relapsed were analysed using the propensity matching method. The median recurrence-free survival periods were 1,676 and 994 days in the FP and CC groups, respectively, and were significantly longer in the FP group. However, the median OS starting from the day of surgery was 3,424 and 2,794 days in the FP and CC groups, respectively, with no significant difference. Conclusion: This study revealed that regular follow-up at CCs did not improve survival compared with regular follow-up by FPs.