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.

Evaluation of RASSF1A methylation in the lysate of sentinel lymph nodes for detecting breast cancer metastasis: A diagnostic accuracy study.

The restriction enzyme-based digital methylation-specific polymerase chain reaction (RE-dMSP) assay is useful for diagnosing sentinel lymph node (SN) metastasis in patients with breast cancer, by detecting tumor-derived methylated Ras association domain-containing protein 1 (RASSF1A). In addition, this assay has high concordance (95.0%) with one-step nucleic acid amplification (OSNA). The present study aimed to perform RE-dMSP using OSNA lysate from more patients and to re-evaluate its clinical usage. Overall, 418 SNs from 347 patients were evaluated using both OSNA and RE-dMSP. The concordance rate was 83.3% (348/418). RASSF1A methylation of the primary tumors was negative in 36 patients. When these patients were excluded, the concordance rate improved to 88.2% (330/374). Of the 79 OSNA-negative cases, 19 were RE-dMSP-positive, although all were positive for cytokeratin 19 expression in the primary tumor, suggesting that RE-dMSP can detect tumor-derived DNA with a higher sensitivity. The percent of methylated reference of the breast tumors showed a wide variety in the 16 OSNA-positive/RE-dMSP-negative cases, and such variability of methylation could have affected the results in these patients. In conclusion, although RE-dMSP can diagnose SN metastasis with high sensitivity and accuracy, and can be a supplementary tool to OSNA in breast cancer, RE-dMSP showed certain discordance with OSNA and critically depended on the absence or heterogeneity of DNA methylation in breast tumors. Further research is expected to develop an assay targeting other DNA alterations, such as mutations.

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.

Differences in baseline risk estimated by physicians and patients with early breast cancer.

BACKGROUND: Physicians recommend adjuvant therapy to patients based on baseline risk. A common recognition for baseline risk between patients and physicians is critical for successful adjuvant therapy. We prospectively investigated the differences in estimated baseline risk between physicians and patients with early breast cancer. METHODS: This analysis was performed at a single institution in Japan. Early breast cancer patients over 18 years old were enrolled after surgery. After explaining the pathological results, physicians asked each patient about an estimated baseline risk. Differences in estimated baseline risk were defined as the baseline risk estimated by patients minus the baseline risk estimated by physicians. The primary endpoint was that the number of patients who estimate baseline risk higher than physicians was higher than those who estimate a lower baseline risk. The secondary endpoints were differences in estimated baseline risk by stage, subtype and the influence of patient factors to differences in estimated baseline risk. RESULTS: From July 2017 to December 2018, 262 patients were enrolled. Among the 262 patients, 190 estimated a higher baseline risk than physicians, 53 estimated a lower baseline risk and 19 estimated the same. Overall, patients estimated a significantly higher baseline risk than physicians (P < 0.001). Differences in estimated baseline risk was significantly smaller in patients who knew the term 'baseline risk' than patients who did not (P = 0.0037). Differences in estimated baseline risk were also significantly smaller in patients with stage II breast cancer than patients with stage I (P = 0.0239). However, there were no statistically significant differences of differences in estimated baseline risk according to other factors. CONCLUSIONS: Patients with early breast cancer estimated a significantly higher baseline risk than physicians. Physicians should accurately explain baseline risk to patients for shared decision making.

Increased chemosensitivity via BRCA2-independent DNA damage in DSS1- and PCID2-depleted breast carcinomas.

Breast cancer, the most common malignancy among women, is closely associated with mutations in the tumor suppressor gene BRCA. DSS1, a component of the TRanscription-EXport-2 (TREX-2) complex involved in transcription and mRNA nuclear export, stabilizes BRCA2 expression. DSS1 is also related to poor prognosis in patients with breast cancer owing to the induction of chemoresistance. Recently, BRCA2 was shown to be associated with the TREX-2 component PCID2, which prevents DNA:RNA hybrid R-loop formation and transcription-coupled DNA damage. This study aimed to elucidate the involvement of these TREX-2 components and BRCA2 in the chemosensitivity of breast carcinomas. Our results showed that compared with that in normal breast tissues, DSS1 expression was upregulated in human breast carcinoma, whereas PCID2 expression was comparable between normal and malignant tissues. We then compared patient survival time among groups divided by high or low expressions of DSS1, BRCA2, and PCID2. Increased DSS1 expression was significantly correlated with poor prognosis in recurrence-free survival time, whereas no differences were detected in the high and low BRCA2 and PCID2 expression groups. We performed in vitro analyses, including propidium iodide nuclear staining, single-cell gel electrophoresis, and clonogenic survival assays, using breast carcinoma cell lines. The results confirmed that DSS1 depletion significantly increased chemosensitivity, whereas overexpression conferred chemoresistance to breast cancer cell lines; however, BRCA2 expression did not affect chemosensitivity. Similar to DSS1, PCID2 expression was also inversely correlated with chemosensitivity. These results strongly suggest that DSS1 and PCID2 depletion is closely associated with increased chemosensitivity via BRCA2-independent DNA damage. Together with the finding that DSS1 is not highly expressed in normal breast tissues, these results demonstrate that DSS1 depletion confers a druggable trait and may contribute to the development of novel chemotherapeutic strategies to treat DSS1-depleted breast carcinomas independent of BRCA2 mutations.

Mechanisms and anatomical risk factors of pneumothorax after Bevacizumab use: A case report.

BACKGROUND: Bevacizumab is an antiangiogenic agent, and that synergizes with chemotherapeutic drugs. When used in combination therapies, Bevacizumab is associated with adverse events such as hemorrhage, gastrointestinal perforation, delayed wound healing, and pneumothorax. However, the molecular mechanisms underlying these adverse events are not fully understood. CASE SUMMARY: A 45-year-old female with multiple lung metastases that were derived from primary breast cancer, was placed on Bevacizumab + paclitaxel therapy, since this combination has a potent antitumor effect. She reported dyspnea before cycle 3, day 1 and we therefore ran a chest X-ray, which detected a right pneumothorax. The coronal plane computed tomography revealed that one solid mass rapidly necrosed and was replaced by a cavity that passed through the bronchus in the right lower lobe. The cavity eventually ruptured the pleura and made the bronchopleural fistula that led to this pneumothorax. Thoracic cavity drainage using an intercostal catheter was performed. On the 7th day of drainage, the patient was discharged from our hospital on recovery. Recurrence of pneumothorax was not reported, and continuation of chemotherapy was made possible by changing the regimen. CONCLUSION: Patients with lung metastases surrounding the bronchi and on the pleura should be monitored for pneumothorax by Bevacizumab-containing chemotherapies.

Utility of regional nodal irradiation in Japanese patients with breast cancer with 1-3 positive nodes after breast-conserving surgery and axillary lymph-node dissection.

The utility of regional nodal irradiation (RNI) is being considered in cases of 1-3 axillary node metastases after breast-conserving surgery (BCS) with axillary lymph-node dissection (ALND). Therefore, we examined the necessity of RNI by examining the sites of recurrences in cases at our institution. We retrospectively analyzed 5,164 cases of primary breast cancer between January 2000 and December 2014 at the Aichi Cancer Centre, identifying local and distant recurrences in 152 patients with primary breast cancer treated with BCS and ALND and who had 1-3 positive axillary nodes. All patients received whole-breast irradiation (WBI) and adjuvant systemic therapy with either chemotherapy or anti-endocrine therapy with or without anti-human epidermal growth factor receptor 2 therapy. The present study excluded patients with ipsilateral breast tumor recurrence, contralateral breast cancer, neoadjuvant chemotherapy, T4 tumors or N2-3 nodes and distant metastasis. From the database of our institution, we identified 152 cases that met the defined criteria. The median follow-up period was 71 months (1-176). Isolated locoregional recurrences were found in three patients (2.0%) and were recurrent only in the breast. Only one patient had local lymph node recurrence with distant recurrence. The 10-year rates of isolated regional disease-free survival (DFS), DFS, and overall survival were 95.41, 89.50 and 96.75%, respectively, which was better compared with previous studies. We conclude that the addition of RNI to WBI is not necessary for Japanese patients who have 1-3 positive axillary nodes and ALND.

Impact of BMI for clinical outcomes in Japanese breast cancer patients.

OBJECTIVE: The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. METHODS: Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is <18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, >30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. RESULTS: From the database of our institution, we identified 3223 patients. The median follow-up period was 57 months (1-149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38-4.28; P < 0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15-6.44; P = 0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11-3.02; P = 0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15-11.04; P < 0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52-13.34; P < 0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02-4.89; P = 0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. CONCLUSION: Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.

Circulating tumor cells detection in tumor draining vein of breast cancer patients.

Circulating tumor cells (CTCs) in tumor draining vein blood (DB) are potential sources for liquid biopsy. However, the identification of CTCs in DB of breast cancer has not been attempted. In this study, we investigated the feasibility of CTC detection in DB of breast cancer patients using a newly developed filtration-based microfluidic CTC detection device. Samples of peripheral vein blood (PB) and DB drawn from the lateral thoracic vein of the resected breast tissue were collected during the perioperative period. We investigated 41 breast cancer patients who underwent breast surgery with axillary lymph node dissection. DB was successfully collected in 36 patients (87.8%), with a mean amount of 0.85 ml. CTCs were detected in 58.3% of PB samples and 80.6% of DB samples. DB had significant higher number of CTCs compared with PB (p < 0.001). CTCs were detected in 75.0% of DB samples and 50.0% of PB samples from patients achieving pathological complete response after neoadjuvant chemotherapy. These results suggest that abundant CTCs are released into the DB of breast cancer patients, indicating that CTCs in DB would be alternative sources for liquid biopsy and potential indicators for monitoring of treatment response and prognosis in breast cancer patients.

A single-arm, phase 2 study of steroid-containing mouthwash for the prevention of everolimus-associated stomatitis in multiple tumor types.

BACKGROUND: Everolimus is a mammalian target of rapamycin inhibitor used in the treatment of multiple tumor types, and its most common toxicity, stomatitis, can affect patient quality of life. Recent studies in breast cancer have supported the efficacy of steroid mouthwash for the prevention of everolimus-associated stomatitis. However, a few studies have been reported to date, and none have examined this effect in other tumor types. METHODS: This single-arm phase 2 study was designed to evaluate the efficacy of steroid-containing mouthwash for the prevention of stomatitis in patients with multiple tumor types receiving everolimus. The primary outcome was incidence of grade ≥ 2 stomatitis at 8 weeks of everolimus with steroid-containing mouthwash prophylaxis. We also assessed the stability of steroid-containing mouthwash components. RESULTS: Twenty-nine patients were evaluated, of which 76% had breast cancer and 24% had neuroendocrine tumors originating in the lung, gastrointestinal tract, pancreas, or of unknown primary origin. Grade ≥ 2 stomatitis incidence at 8 weeks was 28.1% (90% CI 16.2-46.1); the higher confidence limit exceeded the prespecified threshold of 30%. No patients developed grade ≥ 3 stomatitis. Most stomatitis occurred behind the oral cavity, with no lesions observed on the lips or floor of the mouth. CONCLUSIONS: Our findings did not support a prophylactic effect of steroid-containing mouthwash on everolimus-associated stomatitis. Given the needs of prevention of everolimus-associated stomatitis in various tumor types, further studies in a larger population using a randomized controlled trial design are, therefore, required to confirm the efficacy of steroid-containing mouthwash.

A case of giant cell tumor of the breast, clinically suspected as malignant breast tumor.

BACKGROUND: Giant cell tumor (GCT) of the breast is scarce. We report a case of GCT of the breast which was suspected as a malignant breast tumor. CASE PRESENTATION: A 74-year-old woman noticed a tender lump in her right breast. We suspected a malignant tumor spreading widely with axillary lymph node metastasis on clinical examination and imaging. Histological evaluation of the biopsy tissue revealed a tumor composed the proliferation of oval to spindle-shaped cells and multinucleated giant cells without malignant epithelial cells. The tumor cells stained positively for CD68 and negatively for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The pathological findings suggested GCT, and fine needle aspiration biopsy for the axillary lymph node was negative. However, there was a gap between the clinical presentation, such as a tender mass suggesting rapid growth and multiple lymphadenopathies, and the pathological presentation of biopsy, which made us hesitate to conclude GCT as the final preoperative diagnosis. We could not rule out the possibility of malignant tumors with OGCs before surgery. We performed mastectomy and sentinel lymph node biopsy according to a surgical procedure for node-negative breast cancer with a wide ductal spread. The resected tissue histologically showed the same findings to the biopsy tissue. The definitive diagnosis of GCT of the breast was given, because the tumor lacked epithelial components, marked cellular atypia, and pleomorphism. CONCLUSIONS: GCT of the breast occasionally pretends as breast malignant tumors. Complete tumor resection should be performed for local control and the definitive diagnosis.

The overall survival of breast cancer patients without adjuvant therapy.

PURPOSE: There are little data regarding the overall survival (OS) of patients without adjuvant systemic therapy, because most patients have been subject to standardized systemic therapies. We evaluated the baseline risk to facilitate making decisions about adjuvant therapy. PATIENTS AND METHODS: A total of 1835 breast cancer patients who did not receive adjuvant systemic therapy between 1964 and 1992 were retrospectively evaluated. We investigated the 10-year disease-free survival (DFS) and OS according to the number of metastatic lymph nodes, pathological T classification, stage, and estrogen receptor (ER) status. RESULTS: Survival curves showed that as the number of metastatic lymph nodes, pathological T classification, and staging increased, the 10-year OS and DFS decreased. In univariate and multivariable analyses, the number of metastatic lymph nodes was significantly associated with the DFS and OS, while in a univariate analysis, the pathological T classification and stage were significantly associated with the DFS and OS. ER positivity was a good prognostic factor for the 5-year DFS. However, between 6 and 7 years after surgery, ER negativity was a better prognostic factor than ER positivity. CONCLUSION: We showed survival rates of patients without adjuvant therapy according to TNM classification and ER status. This information can aid in treatment selection for doctors and patients through a shared decision-making approach.

Amyloid tumor of the breast.

BACKGROUND: Amyloid tumor of the breast is a rare disease, which was first reported in 1973. To date, only six cases have been reported in Japan. CASE PRESENTATION: A 45-year-old woman who had a medical history of Sjogren's syndrome presented with a lump of 3 cm in diameter on the outer side of the right breast. Mammography showed no abnormality. Ultrasonography showed a well-defined and rough hypoechoic mass of 32 mm in diameter at the site of the lump. With suspicion of breast cancer, an ultrasound-guided vacuum-assisted breast biopsy was performed. For pathological diagnosis, hematoxylin and eosin staining showed deposits of nonstructural substances in the interstitium. The specimen stained red with Congo red staining and showed green birefringence under a polarizing microscope. Thus, the mass was diagnosed as an amyloid tumor. Since the patient had Sjogren's syndrome, it was considered a breast finding of autoimmune disease. We considered further therapy to be unnecessary, and annual follow-up was recommended. CONCLUSIONS: We diagnosed the mass as an amyloid tumor by an ultrasound-guided vacuum-assisted breast biopsy without resection. The patient had no systemic symptoms suspected systemic amyloidosis, and we diagnosed localized amyloidosis. An amyloid tumor of the breast may show findings suggestive of breast cancer. Pathological diagnosis before surgery is important to avoid excessive invasion. If deposits of nonstructural substances are observed by hematoxylin and eosin staining, Congo red staining should be added.

Prediction of pathological margin status using preoperative contrast-enhanced MRI in patients with early breast cancer who underwent skin-sparing mastectomy.

Skin-sparing mastectomy (SSM) with immediate reconstruction is standard surgical treatment for early breast cancer with widespread ductal carcinoma in situ (DCIS). The local recurrence rate after SSM is up to 7.0%. We investigated prediction of the pathological margin using contrast-enhanced MRI, and evaluated the cut-off point to obtain the safety margin. We performed SSM with immediate reconstruction in 216 early breast cancer patients with widespread DCIS and/or invasive cancer from January 2014 to December 2015. Forty cases were retrospectively reviewed after excluding those with >15 mm between skin and tumor, determined by preoperative contrast-enhanced MRI, or involving reconstructive surgery for local recurrence, immeasurable lesion by preoperative contrast-enhanced MRI, or neoadjuvant chemotherapy. We defined a positive pathological margin as <1 mm from the cancer nest. We reviewed the distance between skin and tumor by MRI and pathological examination. To identify the cut-off for predicting a positive pathological margin, we performed sensitivity analysis using an ROC curve. The margin-positive rate by pathological examination was 27.5% (n = 11/40), with a moderate correlation of MRI margin and pathological margin (r = 0.44). The best cut-off point for margin positivity was 5 mm of MRI margin, with sensitivity and specificity of 54% and 86%, respectively (P = 0.009). This is the first prediction of pathological margin by preoperative contrast-enhanced MRI in early breast cancer patients with SSM. Care is required for SSM if the MRI margin is less than 5 mm due to pathological margin positivity.

A case of radiation-associated angiosarcoma after breast cancer.

BACKGROUND: Radiation-associated angiosarcoma (RAAS) is a rare subtype of secondary angiosarcoma that is characterized by rapid proliferation and extensive tissue infiltration. Although various treatments for RAAS (such as surgery, chemotherapy, and radiation therapy) have been reported, there is no consensus as to which approach is the best. CASE PRESENTATION: A 76-year-old woman presented with right breast cancer (T1N0M0, stage I) 9 years ago. She had undergone breast-conserving surgery and sentinel lymph node biopsy and was receiving adjuvant chemotherapy and radiation therapy for the malignancy. Six years after presenting with the tumor, she developed pigmented skin and was diagnosed with a RAAS; this angiosarcoma recurred three times within 2 years. The angiosarcoma was resected each of the three times, after which adjuvant radiation therapy was performed. At 76 years old, the patient developed a new mass on her chest skin in the vicinity of the scar. Angiosarcoma was diagnosed following a pathology report, which resulted in a second diagnosis of recurrent RAAS again since the diagnostic criteria were met. After extensive resection of the irradiated area, the patient has remained free of angiosarcoma for the last 3 years. CONCLUSION: Resection of the entire irradiated field is critical for successful treatment of RAAS.

The investigation study using a questionnaire about the employment of Japanese breast cancer patients.

BACKGROUND: Breast cancer is the most common cancer among women, and its survival rate has improved. As the number of cancer survivors increases, it is important to support their social comeback during and after treatment. METHODS: Questionnaires were distributed to breast cancer patients treated in Aichi Cancer Center Hospital between June and November 2014. Responders were categorized according to adjuvant therapy (Group A: none, Group B: endocrine therapy, Group C: chemotherapy), or if they had advanced or recurrent breast cancer (Group D). RESULTS: A total of 279 patients returned questionnaires (62, 79, 92 and 46 patients in Groups A, B, C and D, respectively). In adjuvant treatment groups, 43 patients (18.5%) quit their job during or after treatment. Most patients had quit their jobs at the time of diagnosis (7.5%), followed by those undergoing chemotherapy (5.6%) and those at the time of operation (4.9%). Quit rate from the workplace in which patients worked at the time of diagnosis was highest in Group C (30%), followed by Group B (20%) and Group A (13%). At the time of operation, 127 patients (57%) were absent from work. In Group D, 16 patients (35%) quit their job during treatment. Rates for patients currently working who had anxiety were 62, 30, 26 and 9% in Groups D, C, B and A, respectively. CONCLUSIONS: In adjuvant treatment groups, in which quit rate was highest at the time of diagnosis, consultation about working is necessary immediately after diagnosis. Patients treated most heavily had higher quit rates and experienced more anxiety about working.

Assessing residual cancer cells using MRI and US after preoperative chemotherapy in primary breast cancer to omit surgery.

BACKGROUND: Enhanced magnetic resonance imaging (MRI) and ultrasonography (US) are used to assess residual lesions after preoperative chemotherapy before surgery. However, residual lesion assessments based on preoperative imaging often differ from postoperative pathologic diagnoses. We retrospectively reviewed the accuracy of preoperative residual lesion assessments, including ductal carcinoma in situ (DCIS) cases to find criteria for cases in which surgery can be omitted. METHODS: We reviewed 201 patients who received preoperative chemotherapy and surgery in our hospital from January 2013 to November 2016. Presurgical evaluations regarding the possible existence of residual lesions, and clinical Complete Response (cCR) or non-cCR, were compared with postoperative pathological diagnoses. RESULTS: Of the 201 patients, 52 were diagnosed with cCR, and 39 with pathological complete response (pCR). Predictions for residual lesions were 86.4% sensitive, 76.9% specific, and 84.6% accurate. When patients were divided into 4 groups by estrogen receptor (ER) and HER2 status, sensitivity in each group was ER+/HER2-: 91.4%; ER-/HER2-: 94.1%; ER+/HER2+: 78.6%; and ER-/HER2+: 78.5%. Of the 22 patients preoperatively assessed with cCR, but diagnosed with non-pCR, the median invasive residual tumor size was 2 mm (range 0-46 mm); 5 patients (22.7%) had only DCIS. CONCLUSIONS: Predicting residual lesions after preoperative chemotherapy by using MRI and US is a reasonable strategy. However, current methods are inadequate for identifying patients who can omit surgery; therefore, a new strategy for detecting small tumors in these patients is needed.

Feasibility study of contralateral risk-reducing mastectomy with breast reconstruction for breast cancer patients with BRCA mutations in Japan.

BACKGROUND: Contralateral risk-reducing mastectomy (CRRM) for breast cancer patients with BRCA mutations has been reported to not only reduce breast cancer incidence but also to improve survival. The National Comprehensive Cancer Network guidelines recommend providing CRRM to women with BRCA mutations who desire CRRM after risk-reduction counseling. However, in Japan, CRRM cannot be performed generally because it is not covered by health insurance. Thus, we conducted a feasibility study to confirm the safety of CRRM. METHODS: CRRM with bilateral breast reconstructions were performed for breast cancer patients with BRCA mutations. The primary endpoint was early adverse events within 3 months, and secondary endpoints were late adverse events. RESULTS: Between August 2014 and November 2016, ten patients were enrolled. The median age was 37.5 years, and five of the patients had the BRCA1 mutation while five had the BRCA2 mutation. Six patients received neoadjuvant chemotherapy. Eight patients selected silicone breast implants, and two patients selected transverse rectus abdominis myocutaneous flap reconstruction. Pathological findings showed no evidence of occult breast cancers in any of the patients. At a median of 25.5 months follow-up time, CRRM-related early adverse events were hematoma (subsequently removed by re-operation; grade 2, n = 1), wound infection (grade 2, n = 1), skin ulceration (grade 1, n = 2) and wound pain (grade 1, n = 1). Overall, there were no grade 3 or more severe adverse events. CONCLUSION: Our results confirm that CRRM with reconstruction could be performed safely.