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.

Long-term prognostic value of the GenesWell BCT score in Asian women with hormone receptor-positive/HER2-negative early breast cancer.

BACKGROUND: Accurate prediction of the risk of recurrence is crucial for optimal treatment decisions in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. The GenesWell BCT is a molecular assay to predict the 10-year risk of distant metastasis. In this study, we evaluated the long-term prognostic value of the GenesWell BCT assay. METHODS: The BCT score was assessed in patients with HR-positive/HER2-negative early breast cancer who did not receive chemotherapy. We compared the 15-year distant metastasis-free survival (DMFS) between risk groups classified based on the BCT score. The risk of early (0-5 years) and late (5-15 years) recurrence was evaluated based on the BCT score classification. RESULTS: According to the BCT score, 366 patients from Japan and Korea were categorized as BCT low risk (83.6%) and high risk (16.4%) for distant metastasis. Median follow-up time was 17.4 years. The 15-year DMFS rate was significantly lower in the BCT high-risk group (63.3%) than in the BCT low-risk group (93.6%) (P < 0.001). The BCT risk group was an independent prognostic factor for 15-year DMFS (hazard ratio, 4.59; 95% confidence interval 2.13-9.88; P < 0.001). Furthermore, the BCT score was a significant predictor of late recurrence (5-15 years) in patients aged ≤ 50 years and those aged > 50 years, and added prognostic information to traditional clinical prognostic factors. CONCLUSION: The BCT score can identify patients at low risk for recurrence who may not require adjuvant chemotherapy or extended endocrine therapy, regardless of age.

Satisfaction of Patients Who Received Breast-Conserving Surgery Using the Suture Scaffold Technique: A Single-Institution, Cross-Sectional Study.

BACKGROUND: Optimal cosmetic results after breast-conserving surgery (BCS) improve patient satisfaction. The suture scaffold technique (SST) is a breast reconstruction technique that all breast surgeons can perform without any extensive training in plastic surgery. OBJECTIVE: We aimed to investigate patient satisfaction after BCS and compare blood loss and operative duration between the SST, breast glandular flap technique (BGFT), and no oncoplastic technique (NOT). METHODS: This was a prospective, single-center, cross-sectional study. All patients who underwent BCS from August 2017 to September 2019 in our institution were included, with the exception of those with cT3 tumors or those who underwent nipple excision or bilateral breast surgery. The BREAST-Q™ was used to survey the patients, and the raw sum scale scores of the BREAST-Q™ were converted into BREAST-Q scores. RESULTS: Overall, we identified 421 eligible patients. The NOT was used in 47 (11.1%) patients, the BGFT was used in 231 (54.8%) patients, and the SST was used in 143 (33.9%) patients. In the univariable model, the BGFT and the SST had higher BREAST-Q scores than the NOT, while in the multivariable model, the SST had significantly higher BREAST-Q scores than the NOT (ß = +7.7, 95% confidence interval [CI] 0.9-13.7; p = 0.01). Blood loss was significantly less with the SST compared with the BGFT (ß = -4.4, 95% CI -7.3 to -1.4), and there was no difference in operative duration between the methods. CONCLUSIONS: Patient satisfaction with the SST was higher than with the NOT and was similar to the BGFT. The SST is an oncoplastic technique that all breast surgeons can perform and which requires comparable blood loss and operative duration in the NOT.

Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab.

OBJECTIVE: The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer. METHOD: Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays. PTEN (phosphatase and tensin homolog) and p95 expression was evaluated using immunohistochemistry and PIK3CA mutation using direct sequencing. RESULTS: The response rate to LC was 30%, clinical benefit rate was 51.3%, and the median progression-free survival (PFS) was 174.5 days. ER negativity significantly correlated with higher HER2 and p95HER2. The lower HER2 and PIK3CA mutations were often observed in the nonresponders. A high p95HER2 expression correlated with longer PFS especially in the high HER2- and ER-positive cases. Patients without the PIK3CA mutation showed longer PFS in the same subset. Overall survival after LC significantly correlated with the number of recurrence organs. CONCLUSION: LC therapy is effective in trastuzumab-refractory HER2-positive breast cancer. Moreover, the biomarker expression differed depending on ER status, and a high p95HER2 expression and wild-type PIK3CA gene correlated with longer PFS especially in the ER-positive cases.

A case of femoral diaphyseal fracture after long-term treatment with zoledronic acid.

We report here a case of femoral diaphyseal fracture thought to be caused by oversuppression of bone remodeling due to long-term bisphosphonate treatment. The patient was a 63-year-old postmenopausal woman. She had undergone left lumpectomy and sentinel node biopsy for left breast cancer at age 57. The case was diagnosed as pT2N0M0, stage IIA breast cancer. The biopsy sample was positive for hormone receptors and negative for HER2 protein. Postoperatively, exemestane was administered as adjuvant therapy. Right axillary lymph node metastasis was found at age 59, and right axillary lymph node dissection was performed. Postoperatively, epirubicin/cyclophosphamide and paclitaxel were administered. Subsequently, letrozole was administered. However, bone metastases to the first thoracic vertebra and right ilium were found at age 60, and zoledronic acid administration (4 mg/month) for bone metastasis was initiated. The patient developed a transverse fracture in the proximal left femoral diaphysis when she walked on a flat surface after zoledronic acid was administered for 2 years, 10 months. She was treated with an intramedullary nail for left femoral diaphyseal fracture. Cancellous bone of the medullary cavity was histopathologically examined, but there were no metastatic lesions from the breast cancer and no osteoblasts or osteoclasts were observed. Zoledronic acid was immediately discontinued in this patient. In recent years, cases of atypical femoral diaphyseal fractures caused by minor trauma in patients undergoing long-term bisphosphonate treatment have been reported. Thus, careful observation is required for patients who are anticipating bisphosphonate treatment.