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.

Therapeutic predictors of neoadjuvant endocrine therapy response in estrogen receptor-positive breast cancer with reference to optimal gene expression profiling.

PURPOSE: Neoadjuvant endocrine therapy (NAET) for estrogen receptor-positive primary breast cancer causes adequate tumor shrinkage, and is expected to be helpful for breast-conserving surgery, but the adaptation criteria, especially in regard to treatment duration, have never been elucidated. Re-visiting past gene expression profiles, we explored the data for specialized pre-therapeutic predictors and validated the results using our in-house clinical cohorts. METHODS: We sorted the genes related to a > 30% tumor volume reduction through NAET from a cDNA microarray data-set of GSE20181, then selected the top 40 genes. We validated these gene expression levels using pre-therapeutic biopsy samples obtained from patients treated with long-term NAET (over 4 months; N = 40). A short-term (2-8 weeks; N = 37) NAET cohort was also validated to clarify whether expression of these genes is also related to a rapid response of Ki67 and PEPI score. RESULTS: In the long-term group, higher expression of KRAS, CUL2, FAM13A, ADCK2, and LILRA2 was significantly associated with tumor shrinkage, and KRAS, MMS19, and IVD were related to lower PEPI score (≤ 3). Meanwhile in the short-term group, none of these genes except CUL2 showed a direct correlation with Ki67 reduction or PEPI score. This suggested that tumor shrinkage by NAET might be induced by response to the hypoxic environment (CUL2, FAM13A, KRAS) and activation of tumor immune system (LILRA2), without involving inhibition of proliferation. CONCLUSION: Expression of specific genes may allow selection of the most responsive patients for maximum tumor shrinkage with NAET.

Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2-negative primary breast cancer.

Recently, research into the development of new targeted therapies has focused on specific genetic alterations to create advanced, more personalized treatment. One of the target genes, fibroblast growth factor receptor-1 (FGFR1), has been reported to be amplified in estrogen receptor (ER)-positive subtype breast cancer, and is considered one possible mechanism of endocrine resistance through cross-talk between ER and growth factor receptor signaling. We performed a comprehensive analysis of FGFR1 at the levels of gene copy number, transcript and protein expression, and examined the relationships between FGFR1 status and clinicopathological parameters, including prognosis in 307 ER-positive/HER2-negative primary breast cancer patients treated with standard care at our institute. Most notably, a high level of FGFR1 protein expression was observed in 85 patients (27.7%), and was positively associated with invasive tumor size (P = 0.039). Furthermore, univariate analysis revealed that high FGFR1 protein expression was significantly correlated with poor relapse-free survival rate (P = 0.0019, HR: 2.63, 95% confidence interval: 1.17-5.98), and showed a tendency towards an increase in recurrent events if the observation period extended beyond the 5 years of the standard endocrine treatment term. FGFR1 gain/amplification was found in 43 (14.0%) patients, which was only associated with higher nuclear grade (P = 0.010). No correlation was found between FGFR1 mRNA expression levels and any clinicopathological factors. Overall, the level of FGFR1 protein expression may be a biomarker of ER-positive/HER2-negative primary breast cancer with possible resistance to standard treatment, and may be a useful tool to identify more specific patients who would benefit from FGFR-1 targeted therapy.

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.

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.

Predictive and prognostic significance of BRCAness in HER2-negative breast cancer.

BACKGROUND: BRCAness is characterized as the phenotypes shared between some sporadic tumors and BRCA1/2 mutation cancers resulting in defective homologous recombination. The predictive or prognostic value of BRCAness in HER2-negative breast cancer patients who have received neoadjuvant chemotherapy (NAC) is not fully elucidated. METHODS: We retrospectively selected 101 high-risk HER2-negative patients diagnosed with stage I-III breast cancer who underwent NAC treatment and evaluated BRCA1-like phenotype using multiplex ligation-dependent probe amplification assay. In an analysis of BRCAness, 95 out of 101 patients were analyzed. RESULTS: In total, 70 (74%) patients had sporadic-type tumors and 25 (26%) had BRCA1-like tumors according to pre-treatment samples. The BRCA1-like phenotype was not associated with pathological complete response (pCR) rate in the entire cohort. In survival analysis, pre-treatment BRCA1-like phenotype was not associated with survival. On the other hand, post-treatment BRCA1-like patients apparently showed shorter relapse-free survival (log-rank P = 0.016) and breast cancer-specific survival (P < 0.001) compared with sporadic features. In multivariate analysis, only the post-treatment BRCA1-phenotype was significant prognostic factors (HR 5.67, 95% CI 1.19-29.3). Furthermore, we found phenotype change between BRCA1-like and sporadic type through NAC in 19% of non-pCR patients. Post-treatment Ki67 significantly decreased in the persistent sporadic tumors during treatment or sporadic tumors changed after NAC (P < 0.0001, P = 0.0078, respectively). CONCLUSIONS: BRCAness may be useful biomarkers to predict prognosis for HER2-negative breast cancer refractory to standard chemotherapy. Our results pave the way for identifying patients who require alternative therapies.

Exosomal miRNA profiles of triple-negative breast cancer in neoadjuvant treatment.

Triple-negative breast cancer (TNBC) is characterized by aggressive clinicopathological features and is associated with a poor prognosis. Identifying patients that are non-responsive to chemotherapy remains a critical goal for effective personalized therapies. In the present study, the predictive value of exosomal microRNAs (miRNAs) was investigated in patients with TNBC. Exosomes were isolated from patients with TNBC undergoing neoadjuvant chemotherapy. Microarray-based miRNA profiles were compared between patients with pathological complete response (pCR; n=12) and non-pCR (n=12). Furthermore, the miRNA profiles of non-pCR patients with breast cancer recurrence were compared with those with no recurrence. A total of 16 differentially expressed exosomal miRNAs were identified between the patients with pCR and non-pCR by microarray analysis. Of these, a combined signature of four miRNAs (miR-4448, miR-2392, miR-2467-3p and miR-4800-3p) could be used to discriminate between pCR and non-pCR patients with TNBC with an area under the curve value of 0.7652. Furthermore, this study found 43 differentially expressed miRNAs between the patients with non-pCR and recurrence and non-pCR patients without recurrence. In network analysis, 'pathway in cancer', 'focal adhesion' and 'cell cycle' were identified as the crucial pathways in patients with non-pCR who also developed recurrence. Several exosomal miRNAs may be useful biomarkers to predict treatment efficacy for TNBC. The present study identified patients who were resistant to standard chemotherapy and therefore more likely to develop breast cancer recurrence.

APOBEC3B gene expression as a novel predictive factor for pathological complete response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is a gene editing enzyme with cytidine deaminase activity and high expression of its mRNA in breast tumors have been shown to be associated with progressive cases and poor prognosis. In this study, we aimed to examine the relationship between the expression of APOBEC3B and the effect of neoadjuvant chemotherapy (NAC) using pretreatment biopsy tissue, and examined whether the expression of APOBEC3B influenced chemotherapy efficacy. METHODS: We retrospectively selected a total of 274 patients with primary breast cancer who received NAC in more than 4 courses and underwent surgery at our institute. We assessed the expression of APOBEC3B mRNA using pretreatment biopsy specimens of NAC by quantitative real-time PCR (qRT-PCR) and examined the relationship between APOBEC3B mRNA expression and sensitivity to chemotherapy using pathological complete response (pCR) as an indicator. Further, we assessed the prognostic value of APOBEC3B in the patients receiving NAC. RESULTS: APOBEC3B mRNA expression levels were successfully assessed in 173 (63.1%) of the 274 specimens. The total pCR rate was 36.4% (n = 63). An association between APOBEC3B expression levels and pCR was observed (Wilcoxon test, P ≤ 0.0001). The patients were divided into two groups, low (n = 66) and high (n = 107), according to the APOBEC3B expression levels, using the cut-off value calculated by the receiver operating characteristics (ROC) curve for pCR. The rate of pCR was significantly higher among the patients in the high group than among those in the low group (47.7% vs 18.2%, P ≤ 0.0001). High APOBEC3B expression was significantly associated with high nuclear grade (P = 0.0078), high Ki-67 labeling index (P = 0.0087), estrogen receptor (ER) negativity (P ≤ 0.0001) and human epidermal growth factor receptor 2 (HER2) negativity (P = 0.032). Tumor size (P = 0.011), ER (P ≤ 0.0001), HER2 (P = 0.0013) and APOBEC3B expression (P = 0.037) were independent predictive factors for pCR in multivariate analysis. However, there was no association between APOBEC3B expression and prognosis. CONCLUSIONS: Our study showed that APOBEC3B mRNA expression correlated with sensitivity to NAC in breast cancer patients. In contrast to previous studies, APOBEC3B mRNA expression was not associated with breast cancer prognosis in patients receiving NAC.

A case of premenopausal breast cancer with symptomatic cerebellar metastasis successfully treated by systemic endocrine therapy alone: relationship to biological features.

We report a case of premenopausal breast cancer with symptomatic cerebellar metastasis successfully treated by systemic endocrine therapy alone. The patient developed dysarthria, headache, lightheadedness and became difficult to write gradually. The cerebellar tumor was detected by computed tomography (CT) and was suspected hemangioma or hemangioblastoma. The tumor was resected and histologically diagnosed as poorly differentiated adenocarcinoma or squamous cell carcinoma. A whole body CT scan revealed a right thyroid tumor and left breast tumor. Core needle biopsy of the breast tumor histologically diagnosed the tumor as estrogen receptor positive, progesterone receptor positive, human epidermal growth factor receptor-2 negative, and Ki-67 labeling index 5%. After these examinations, histologically, the resected cerebellar tumor showed the same subtype as the breast tumor, so the final diagnosis was metastatic breast cancer with cerebellar metastasis. The patient subsequently received radiotherapy with the CyberKnife and endocrine therapy without resection of the thyroid tumor. Her medical condition has maintained a good response and stable disease for 7.5 years after the start of treatment. Analysis of four ESR1 mutations showed no mutations in the cerebellar metastatic lesion and breast cancer tissue. Our findings show that these tumors have high hormone responsiveness.

High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level.

BACKGROUND: Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level. METHODS: Formalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated. RESULTS: RT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value. CONCLUSIONS: High mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients.