The Clinicopathological and Prognostic Significance of HER2-Low Breast Cancer: A Comparative Analysis Between HER2-Low and HER2-Zero Subtypes.

BACKGROUND: HER2-low breast cancer (BC) is a newly defined subset of HER2-negative BC. However, it is still uncertain whether HER2-low BC can be categorized as a distinct biological/clinical subgroup with any prognostic significance. METHODS: Invasive BC cases (n = 10,215) with Stage I-III were retrospectively analyzed to determine the HER2 status. The HER2 status was then divided into 3 groups: HER2-0, HER2-low, and HER2-positive. RESULTS: The HER2 status was classified as HER2-0 in 1,227 cases (12.0%), HER2-low in 7,209 cases (70.6%), and HER2-positive in 1779 cases (17.4%). HER2-low cases had more positive nodes and were significantly associated with positive ER/PgR, lower nuclear grade, and lower Ki-67 index. HER2-0 had the lowest OS rate in the primary cases and after recurrence. HER2-0 in the node positive group had the lowest OS and was significantly different from HER2-low in the same group. The pathological complete response (pCR) rate for NAC was lowest in the HER2-low group. The DFS after NAC was significantly better in all the pCR cases, regardless of the HER2 status. However, the DFS was significantly lower in the HER2-low non-pCR cases. CONCLUSION: HER2-low accounted for 70% of the cases and correlated with favorable biological markers. The HER2-low group had a significantly better OS than the HER2-0 group. However, the response to NAC was low in the HER2-low group, and this group had the poorest prognosis among all the non-pCR cases. These findings indicate that HER2-low may have a different biology and prognosis and therefore should be classified as a new entity.

Efficacy and safety of pegfilgrastim biosimilar MD-110 in patients with breast cancer receiving chemotherapy: Single-arm phase III.

INTRODUCTION: Pegfilgrastim is indicated to decrease the incidence of chemotherapy-induced febrile neutropenia. It is the first granulocyte-colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G-LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD-110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open-label, single-arm study investigated the efficacy and safety of MD-110 in early-stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy. METHODS: A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 (TC) for four cycles on day 1 of each cycle. MD-110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm3 ). The safety endpoints were adverse events and the presence of antidrug antibodies. RESULTS: The mean (SD) duration of severe neutropenia for MD-110 was 0.2 (0.4) days. The upper limit of the two-sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients. CONCLUSION: MD-110 was effective against chemotherapy-induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI-205230).

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.

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.

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.

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.

Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer.

Aim: To evaluate the efficacy and safety of neratinib as extended adjuvant therapy in patients from Asia based on exploratory analyses of the Phase III ExteNET trial. Patients & methods: A total of 2840 women with early stage HER2-positive breast cancer were randomly assigned to neratinib 240 mg/day or placebo for 1 year after trastuzumab-based adjuvant therapy. Results: A total of 341 patients were from Asia (neratinib, n = 165; placebo, n = 176). 2-year invasive disease-free survival rates were 92.8 and 90.8% with neratinib and placebo, respectively (HR: 0.70; 95% CI: 0.31-1.55), and 5-year rates were 91.9 and 87.2%, respectively (HR: 0.57; 95% CI: 0.27-1.13). Diarrhea was the most common adverse event with neratinib. Conclusion: Extended adjuvant therapy with neratinib reduces disease recurrences in Asian women with HER2-positive breast cancer. Trial registration: Clinicaltrials.gov NCT00878709.

Impact of sentinel lymph node biopsy by ultrasound-guided core needle biopsy for patients with suspicious node positive breast cancer.

PURPOSE: The purpose of this study was to investigate the accuracy of preoperative diagnostic tools for axillary lymph nodes (LNs) staging of breast cancer. MATERIALS AND METHODS: A total of 2464 consecutive patients with operable breast cancer were prospectively identified at our institution between April 2012 and March 2017. Patients with suspicious axillary LN of breast cancer were assessed using preoperative ultrasound(US) or computed tomography (CT), underwent fine-needle aspiration cytology (FNA) or core needle biopsy (CNB). The inclusion criteria for both FNA and CNB were a cortical thickness >3 mm or abnormal morphological characteristics. Patients with biopsy-proven metastasis underwent axillary lymph node dissection (ALND), and those with a negative FNA or CNB underwent sentinel lymph node biopsy (SNB). If the SNB was positive, ALND was performed. Diagnostic accuracy for SNB was calculated for both FNA and CNB. In addition, the patients in this study were divided into two groups as follows: the cN0-FNA group (suspicious LN but negative FNA) and cN0-CNB group (suspicious LN but negative CNB). RESULTS: A number of patients with negative US/CT findings of LNs were 1406, with 744 undergoing FNA and 272 undergoing CNB for suspicious LNs. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 65, 99, 99, 80, and 85% in FNA, and 87, 100, 100, 93 and 95% in CNB, respectively. SNB was performed in 172 (cN0-CNB group) of 272 CNB and 487 (cN0-FNA group) of 744 FNA patients. One hundred and seventy-two patients from the cN0-CNB group (Tis 6, T1 97, T2 66, T3 3 patients) treated with SNB were compared to 487 from the cN0-FNA group (Tis 21, T1 225, T2 233, T3 8 patients) in terms of number of LN metastasis. A number of patients with more than 3 positive SNB and positive LNs were 9 (5%) and 0 (0%) in cN0-CNB group, and 78 (16%) and 24 (5%) in cN0-FNA group, respectively. A number of patients who had complications such as haematoma and pain at the time of 7 to 14 days after CNB and FNA were 1 (0.5%) and 1 (0.5%) in cN0-CNB group, and were 0% and 0.2% in cN0-FNA group (p = 0.44), respectively. CONCLUSIONS: The preoperative diagnosis of axillary LNs was influenced by the diagnostic tool used. CNB is a reliable method for the preoperative diagnosis of LN metastasis.

Impact of host and histopathological factors on the discrepancies in estrogen receptor, and progesterone receptor, and HER2 status between core needle biopsy and surgically excised tumors.

PURPOSE: The high reliability and utility of core needle biopsy (CNB) have been previously described. Our aim in this study was to clarify the host and histopathological factors influencing the discrepancies in ER, PgR, and HER2 status between CNB and surgically excised tumors (SET). METHODS: All patients diagnosed with operable invasive breast cancer in our hospital between January 2005 and April 2015 were included in the study; patients who required neoadjuvant chemotherapy were excluded. ER, PgR, and HER2 expression were assessed between paired CNB and SET samples. ER and PgR status were determined using immunohistochemistry(IHC). HER2 status was determined using IHC and scored from 0 to 3+. Fluorescence in-situ hybridization analysis was carried out in HER2 2+ cases. The cut off point for ER and PgR positivity was set at 1%. RESULTS: A total of 1307 patients were assessed. The concordance rates of ER, PgR, and HER2 status in CNB and SET were 95%, 84% and 97%, respectively. Factors of discrepancy were nuclear grade, histological type, and menopausal status for ER and PgR, and none detected for HER2. The discrepancy factors were assessed with univariate and multivariate analysis. CONCLUSIONS: Using the largest known dataset to date of paired samples from a single institution, we evaluated the accuracy of CNB and the discrepancy factors between CNB and SET in breast cancer patients. We conclude that CNB for ER and PgR assessment in postmenopausal patients before treatment should be used with caution. Further research will contribute to increased CNB accuracy, improving patient treatment decisions.

[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).

Successful treatment of histiocytic sarcoma with induction chemotherapy consisting of dose-escalated CHOP plus etoposide and upfront consolidation auto-transplantation.

Histiocytic sarcoma (HS) is an extremely rare malignant neoplasm that often exhibits an aggressive clinical presentation. In this report, we describe the case of a 38-year-old female with advanced-stage HS who was found to have a subcutaneous tumor in the left calf and enlarged lymph nodes in the left inguinal and internal iliac regions. The subcutaneous tumor and inguinal nodes were resected operatively. Immunohistochemistry of the surgical specimens showed that the malignant cells stained positive for CD163, CD68, and related markers; a diagnosis of HS was established. Following the administration of induction chemotherapy consisting of dose-escalated CHOP plus etoposide, the remaining internal iliac tumors disappeared. At that point, high-dose chemotherapy with autologous stem cell transplantation was performed as consolidation treatment. The patient remains alive with no evidence of disease for 30 months post-treatment. This report provides valuable insight into the treatment of advanced HS.