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.

Characteristics, treatment trends, and long-term outcomes of Japanese patients with pregnancy-associated breast cancer (PABC).

PURPOSE: To clarify the characteristics, treatment trends, and long-term outcomes of patients with pregnancy-associated breast cancer (PABC). METHODS: PABC includes breast cancer diagnosed during pregnancy (PBC) and breast cancer diagnosed within 1 year after childbirth or during lactation (LBC). We compared clinical characteristics of 126 patients with LBC and 49 patients with PBC who underwent surgery at our hospital from 1946 to 2018. Survival was compared between patients with LBC and those with PBC in terms of breast cancer-specific disease-free survival (BC-DFS) and overall survival (OS). RESULTS: Patients with LBC were more likely to have family history, lymph node metastasis, lymphatic invasion, and to receive chemotherapy than patients with PBC. Patients with LBC showed poorer BS-DFS and OS than patients with PBC. Among patients with LBC, those treated after 2005 were older at surgery, had a smaller tumor size, received more systemic therapy, and had a more favorable prognosis than patients treated before 2004. Family history, breast cancer within 1 year after childbirth, and surgery before 2004 as well as cStage, lymph node metastasis, and lymphatic invasion were significantly associated with poor prognosis in patients with LBC. In the multivariate analysis for BC-DFS and OS among patients with PABC, LBC vs PBC did not remain as an independent prognostic factor while cStage remained. CONCLUSION: Patients with LBC had a poorer prognosis than those with PBC, most likely due to disease progression rather than biological characteristics. Early detection and optimization of systemic treatments are critical for improving the outcomes of patients with LBC.

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.

Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome.

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.

Physician's knowledge, attitudes and practice pattern for breast cancer diagnosed during pregnancy: a survey among breast care specialists in Japan.

BACKGROUND: Breast cancer diagnosed during pregnancy (BCP) is uncommon, and thus there is limited evidence on its treatment. However, the incidence of BCP is increasing probably due to women having children at an older age. We aimed to clarify the practice patterns and limitations in treatment for BCP in Japan. METHODS: A cross-sectional survey was developed for board-certified Japanese breast cancer specialists (n = 1583) to evaluate their knowledge, attitude, experience, and practice patterns regarding BCP. Survey items also included questions regarding potential barriers of practice toward patients diagnosed during pregnancy and respondents' background. RESULTS: In March 2018, 492 (31.1%) breast oncologists responded to the survey. Among them, 234 (48%) respondents had the experience of treating at least one case of BCP. The accuracy of knowledge about BCP was evaluated by three items regarding BCP treatment from the latest Japanese Breast Cancer Society treatment guideline, and 265 (54%) were categorized to have "appropriate knowledge". Majority of the physicians (89%) have responded that patients should be treated in a center where both a cancer-treating team and obstetrician exist, and 48% responded that treating patients by the collaboration of cancer-treating team and obstetric team in different institutes is an alternative reasonable option. CONCLUSIONS: Interest, knowledge, and awareness of the guidelines appear to influence physician attitude, and thus it is urgently important to lay out educational materials and learning opportunities regarding BCP for breast specialists. A regional network of oncologists, obstetricians, and pediatricians to support the BCP patients should be developed.

Prognostic and predictive impacts of tumor-infiltrating lymphocytes differ between Triple-negative and HER2-positive breast cancers treated with standard systemic therapies.

Tumor-infiltrating lymphocytes (TILs) have potential value for stratifying the treatment of breast cancer (BC), though their precise use remains unclear. We aimed to investigate the utility of TILs using an alternative approach in different settings. We reviewed patients with triple-negative (TN) or human epithelial growth factor receptor 2 (HER2)-positive invasive ductal carcinomas from a single institutional cohort and classified archived hematoxylin-eosin-stained samples in terms of TIL score as low (<10 %), intermediate, and high (>50 %). The prognostic and predictive values of TILs were analyzed retrospectively in both adjuvant and neo-adjuvant settings. In the adjuvant setting, the presence of TILs at primary surgery was a significant favorable prognostic factor among 154 TNBCs [relapse-free survival (RFS): p = 0.015], but not among 183 HER2+ BCs (RFS: p = 0.097). The TNBC low-TIL group tended to relapse earlier. In the neo-adjuvant setting, detection of TILs on biopsy before primary systemic therapy was associated with the ratio of patients achieving pathological complete response among 48 TNBCs (p = 0.024), but not among 58 HER2+ BCs (p = 0.30). The presence of TILs in surgical specimens after systemic therapy had prognostic value in HER2+ BC (RFS: p = 0.007). The impact of TILs differs between patients with TN and HER2+ BC treated with standard therapies. Our three-grade scale for TILs may contribute to our understanding of the importance of the tumor microenvironment in routine practice. TILs after primary systemic therapy may be useful for the further stratification of treatment of HER2+ BC.

Differential impact of fosaprepitant on infusion site adverse events between cisplatin- and anthracycline-based chemotherapy regimens.

BACKGROUND: Fosaprepitant may be associated with infusion site adverse events (AEs), and these adverse events possibly vary according to chemotherapy regimen. PATIENTS AND METHODS: 267 oncology patients who were administered anthracycline- or cisplatin-based regimens were retrospectively studied. Multivariate logistic regression was performed in stratified analyses to evaluate potential regimen-specific effects of fosaprepitant. RESULTS: 41.7% of patients administered fosaprepitant experienced infusion site AEs. On the other hand, only 10.9% of patients administered aprepitant experienced AEs. Multivariate analysis showed a statistically significant overall increased risk of infusion site reaction associated with fosaprepitant (p<0.001), but when evaluated separately according to chemotherapy regimen, this relationship appeared to be largely confined to patients receiving an anthracycline-based regimen (OR=12.95, 95%CI=5.74-29.20). No association was observed among patients on cisplatin-based regimens. A test for interaction was statistically significant (p=0.001). CONCLUSION: Fosaprepitant is associated with an elevated risk of infusion site reaction in patients receiving anthracyclines.

Correlation between hemifield visual field damage and corresponding parapapillary atrophy in normal-tension glaucoma.

PURPOSE: To evaluate the correlation between the superior or inferior half area of parapapillary atrophy (PPA) and the corresponding hemifield visual field damage (VFD) in normal-tension glaucoma. DESIGN: Cross-sectional study. METHODS: patients: One hundred nine eyes of 109 consecutive patients with normal-tension glaucoma. observation procedures: Topography parameters of the optic nerve head and PPA (zone beta) area were obtained with the Heidelberg Retina Tomograph (HRT), and VFD was evaluated with the 30 to 2 program of Humphrey Field Analyzer. The HRT parameters and PPA area were determined separately in superior and inferior half regions. main outcome measures: Partial correlation coefficients of the superior and inferior areas of PPA with refractive error, axial length, HRT parameters, and corresponding hemifield VFD. RESULTS: In simple correlation analyses, significant correlation was found between the inferior PPA area and the superior hemifield VFD (Spearman rank correlation coefficient; Rs = -0.32; P < .001) but not between the superior PPA area and the inferior hemifield VFD (Rs = 0.05; P = .6). Age, refractive error, axial length, and height variation contour were associated significantly with the total, superior, and inferior areas of PPA, respectively (P < .01). Multiple regression analyses showed that the superior PPA area was associated significantly with only axial length (P < .001), and the inferior PPA area was associated significantly with the axial length and the superior hemifield VFD (P < .001). CONCLUSIONS: In patients with normal-tension glaucoma, only the inferior half area of PPA correlated significantly with glaucomatous VFD. Axial length and myopia were associated with both the superior and inferior half areas of PPA.