Usefulness of Breast MRI for Safe Omission of Axillary Lymph Nodes Dissection in Sentinel Node-Positive Breast Cancer Patients

Background: Preoperative identification of patients with extensive lymph node metastasis (LNM) is important for safe omission of axillary lymph node dissection (ALND) in sentinel node (SN)-positive (SN+) breast cancer patients. Methods: We evaluated retrospectively the collected data of 758 breast cancer patients who underwent axillary surgery between 2008 and 2017, excluding those who received neoadjuvant chemotherapy. Results: Of the 758 patients, 607 were not suspicious to have LNM by axillary ultrasound (AUS-), but 38 suspicious cases were found by breast magnetic resonance imaging (MRI). Of 15 patients undergoing axillary fine needle biopsy (AFNA) due to second-look axillary ultrasound (AUS), 9 underwent ALND because of a positive AFNA (AFNA+). Among 81 (10.9%) patients undergoing ALND due to SN+ findings, 6 (7.4%) had extensive LNM (LNM ≥ 4). If MRI was not performed, among the 90 of 673 patients undergoing ALND who had SN+ findings, 12 (13.3%) had LNM ≥ 4. Conclusions: The proportion of cases with LNM ≥ 4 was reduced from 13.3% to 7.4% among patients undergoing SN biopsies combined with breast MRI. ALND might be omitted safely in SN+ cases according to detailed preoperative evaluations using additional breast MRI to ultrasound.

The Reliability of Assessment of Ki-67 Expression on Core Needle Biopsy and the Surgical Specimens of Invasive Breast Cancer: Comparison of Local Pathologists’ Assessment and Central Review

Purpose: The aim of this study was to assess the reliability of Ki-67 expression on core needle biopsy (CNB) and the surgical specimens of invasive breast cancer. We examined the concordance rate of Ki-67 expressions, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status from a CNB with from a surgery in invasive breast cancer. Methods: A retrospective study was conducted on a clinical database of patients who underwent surgery for early breast cancer. Of these, 193 patients who underwent CNB before the surgery were enrolled. A cut-off value of 20% was used for Ki-67-positive criteria. Expression of estrogen receptor (ER), progesterone receptor (PgR), and HER2 were examined and compared with that of Ki-67. To evaluate discordance between the pathologists’ earlier assessments, we re-examined Ki-67 expression among the Ki-67 discordant group in a central laboratory. Results: The concordance rate for Ki-67 expression between the two specimen types was 77.7%, which was significantly lower than that for ER, PgR, and HER2 expression (95.9%, 88.1%, and 91.6%, respectively). The concordance rate for re-examined Ki-67 expression among the Ki-67 discordant group improved to 93.8% and was not significantly different from that for the other receptors. Conclusion: The concordance rate for Ki-67 expression between biopsy and surgical specimens was significantly lower than that for ER, PgR, and HER2 expressions, but re-examination of Ki-67 expression in a central laboratory revealed no significant difference among the receptors, suggesting the need for standard pathological assessment of Ki-67 expression for clinical use as a predictive marker of breast cancer.

Standardized Assessment of Ki-67 in Breast Cancer Patients Using Virtual Slides and an Automated Analyzer in Comparison to Central/Local Pathological Assessments

Purpose: To standardize the methods to measure Ki-67, there is an interest in automating the assessment of Ki-67. Therefore, we reviewed the possibility of introducing an automated analyzer to standardize the Ki-67 evaluation method. Methods: We retrospectively reviewed a clinical database of patients who underwent surgery for early breast cancer at Tokyo-West Tokushukai Hospital. Among them, those who underwent preoperative core needle biopsy (CNB) were enrolled. The concordance rates of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 by local pathologists were reviewed (valuations made by local pathologists), and nonmatching cases (from August 2008 to October 2011) were reassessed both by central review and using an automated analyzer with virtual slides. The results were compared with the evaluations made by local pathologists, and we reexamined the concordance rate by using central review and the automated analyzer. Results: The concordance rate of Ki-67 evaluations made by local pathologists in the preoperative CNB and surgical specimens was 78.7% in 287 cases pathologically assessed from October 2008 to March 2013. This rate was significantly lower (p < 0.01) than that of ER (95.6%), PgR (88.5%), and HER2 (91.6%). Reassessment of the 37 cases of nonmatching Ki-67 values from 2008 to October 2011 using central review and an automated analyzer resulted in clear improvement in matching of 22 (92.1%) and 24 (93.1%) of 37 cases, respectively. Conclusion: The concordance rate of Ki-67 in preoperative CNB and surgical specimens was lower than that of other biological markers;however, they were nearly equal by reassessment using central review and an automated analyzer.

Intraoperative Open-Cavity Implant for Accelerated Partial Breast Irradiation Using High-Dose Rate Multicatheter Brachytherapy in Japanese Breast Cancer Patients: A Single-Institution Registry Study

Background: Previous research has compared the efficacies of accelerated partial breast irradiation (APBI) and wholebreast irradiation (WBI). APBI immediately after surgery may provide more benefit after intraoperative insertion of catheters. Although balloon catheter-based APBI is available in the US, it is difficult in Japanese women, who have relatively small breasts. With the applicators being implanted during tumor removal, APBI can be started immediately after surgery. The aim of this study was to assess the safety and efficacy of APBI using the intraoperative open-cavity implant technique. Method: Patients (age≥40 years) with invasive breast cancer (diameter≤3 cm) were enrolled. Before lumpectomy, the insertion of applicators and delivery doses were simulated by computed tomography (CT). After confirmation of free margins and negative sentinel nodes (SNs) using frozen section analysis, applicators were inserted. Postoperative CT-based dose distribution analysis was performed using dose-volume histograms. APBI was started on the day of surgery, delivering 32 Gy in 8 fractions over the following 5-6 days, and it covered a distance of 2 cm from tumor margins. This observational study was approved by the institutional review board of our hospital. Results: From October 2008 to July 2012, 157 women (160 lesions) were enrolled (age 55.0 years, <40:9, SN+: 25, for patients’ request). The mean number of applicators used was 6.4 (2-15) and mean planning target volume was 35.8 cm3 (6.5-137.1 cm3). All radiotherapy-related toxicities were mild. However, 12 patients (7.5%) experienced wound breakdown because of surgical site infection. Two patients developed ipsilateral breast tumor recurrence (1 marginal, 1 at a distant site). Conclusions: Despite the small number of participants and a short follow-up period, our results suggest that this technique could be helpful in establishing clinical safety and efficacy.

Sentinel-Node-Driven Personalized Radiation Techniques Ranging from Partial Breast Irradiation to Regional Nodal Radiation after Breast-Conserving Surgery

Background: Breast-conserving surgery (BCS) followed by whole breast irradiation (WBI) has become the standard of care for treating patients with early-stage breast cancer. Recently, various radiation techniques followed by BCS have been reported. We have been investigating “personalized radiotherapy after BCS” ranging from accelerated partial breast irradiation (APBI) to WBI with regional nodal irradiation (RNI) based on the axillary node status. In this study, we compared different cohorts that received personalized radiotherapy. Method: Of 317 consecutive patients who underwent BCS followed by radiotherapy since November 2007, 187 who received APBI and 122 who received WBI were analyzed. Results: The local-only recurrence rate was 1.1% in the APBI group and 3.3% in the WBI group, and the regional-only recurrence rate was 1.1% for APBI and 0.8% for WBI. Conclusions: The clinical efficacy of APBI for local control after BCS was comparable to that of WBI ± RNI. Although this study was based on a small number of patients with a short follow-up period, the feasibility of breast-conserving therapy using multicatheter brachytherapy to achieve acceptable clinical outcomes was demonstrated.

Comparing Oncotype DX Recurrence Score Categories with Immunohistochemically Defined Luminal Subtypes

Background: At the 13th St Gallen International Breast Cancer Conference in 2013, a new definition of luminal A-like and luminal B-like breast cancer was proposed, involving the expression of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67. We examined the rate of concordance between the risk groups using the Oncotype DX recurrence score (RS) and the previous and newly proposed luminal subtypes with the standardized Ki-67 assessment. Method: The relationship between a previously and newly proposed, immunohistochemically defined luminal A and B subtype with the Oncotype DX RS of 41 cases of T1-2 N0-1 M0 (ER positive, HER2 negative) breast cancer was assessed. We first classified the patients into the previously defined luminal A and B subtypes, according to the level of Ki-67 as either “low” (<14%) or “high” (≥14%), as assessed by local pathologists. Next, to consider the necessity for standardizing Ki-67 measurement methods, we re-examined Ki-67 with a central review. By introducing PgR positivity (≥20%), we classified these patients to newly proposed luminal subtypes and compared them with the risk groups stratified by Oncotype DX RS. Results: In the previously proposed luminal subtypes, the concordance rate between luminal A and the low RS category was 76.5% according to local pathologists and 90.1% by central review, whereas the rate between luminal B and the intermediate to high RS category was 46.7% and 45.8%, respectively. In newly proposed luminal subtypes, the concordance rate between luminal A and low RS category was 100% and between the luminal B and intermediate to high RS category was 53.6%. Conclusions: Although this study was based on a retrospective chart review of a small sample size, the newly proposed luminal subtypes including addition of PgR positivity with the standardized Ki-67 assessment appeared to improve the concordance rate especially between luminal A and low RS category.