Percutaneous ultrasound-guided cryoablation for early-stage primary breast cancer: a follow-up study in Japan.

BACKGROUND: Ultrasound-guided percutaneous cryoablation (PCA) for early-stage breast cancer (ESBC) can be performed under local anesthesia in an outpatient clinic. This study continues a pilot stage to examine local control, safety, patient quality of life (QoL), satisfaction and cosmetic outcomes of cryoablation for ESBC. METHODS: PCA was performed under local anesthesia for patients with primary ESBC, followed by radiation and endocrine therapies. Oncologic outcomes were examined by imaging (mammography, ultrasound, MRI) at baseline and 1, 6, 12, 24, 36, and 60 months post-cryoablation. EQ-VAS, EQ-5D-5L, subjective satisfaction and Moiré topography were used to measure health-related QoL outcomes. RESULTS: Eighteen patients, mean aged 59.0 ± 9.0 years, mean tumor size 9.8 ± 2.3 mm, ER + , PR + (17/18), HER2-, Ki67 < 20% (15/18), underwent PCA and were followed for a mean of 44.3 months. No serious adverse events were reported, and no patients had local recurrence or distant metastasis in the 5-year follow-up. Cosmetic outcomes, satisfaction level, and QoL all improved post-cryoablation. Five-year average reduction rates of the cryolesion long, short, and depth diameters, on US, were 61.3%, 42.3%, and 22.8%, respectively, compared to the 86.2% volume reduction rate on MRI. The correlation coefficient between MRI and US measurement criteria was highest for the long diameter. During follow-up, calcification of the treated area was observed in 13/18 cases. CONCLUSION: Cryoablation for ESBC is an effective and safe procedure with excellent cosmetic outcomes and improved QoL. This study contributes to the growing evidence supporting cryoablation as a potential standard treatment for ESBC, given compliance to pre-defined patient selection criteria.

Value of adjuvant chemotherapy and informed microscopic examination for occult gynecologic cancer detected upon risk-reducing salpingo-oophorectomy after chemotherapy for BRCA1/2-associated breast cancer: a case report.

BRCA1/2 mutation carriers are at high risk for type II ovarian, fallopian tube or peritoneal cancer. Although risk-reducing salpingo-oophorectomy plays an important role in the prevention of these BRCA1/2-associated gynecological cancers, occult ovarian, fallopian tube, or peritoneal cancer is discovered upon risk-reducing salpingo-oophorectomy in 1-4% of BRCA1/2 mutation carriers. Notably, around 30% of BRCA1/2 mutation carriers who undergo risk-reducing salpingo-oophorectomy have undergone adjuvant chemotherapy for breast cancer. We describe the discovery and treatment of occult cancer at the edge of the left fimbria in a BRCA1 mutation carrier who had, just a short time previously, undergone neoadjuvant paclitaxel plus carboplatin (TC) chemotherapy for triple-negative breast cancer. During subsequent risk-reducing salpingo-oophorectomy, a 5.5-mm nodule was observed at the edge of the left fimbria. Microscopic examination of the tumour tissue revealed high-grade serous carcinoma with degenerate tumour cells and fibrosis. Peritoneal fluid was negative for cancer cells. Two months later, hysterectomy, omentectomy and retroperitoneal lymphadenectomy were performed. The final diagnosis was stage FIGO IA fallopian tube cancer. Adjuvant chemotherapy (TC administered every 3 weeks) was applied, and there has been no evidence of recurrence for 5 years. In applying gynecologic surgery and adjuvant chemotherapy, we followed the general recommendation for stage IA fallopian tube cancer. There is no standard strategy for the treatment of occult fallopian tube cancer detected after chemotherapy for BRCA1-associated triple-negative breast cancer. According to our experience in this case, we believe the clinical value of staging laparotomy in cases of a small occult BRCA1/2-associated gynecological cancer should be further investigated.

[Clinical Significance of the Curative Effect after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer-Correlation to Prognosis].

We investigated factors related to the recurrence and prognosis of patients with triple-negative breast cancer (TNBC)after neoadjuvant chemotherapy(NAC). Of the 545 patients who underwent surgery after NAC between January 2013 and December 2016, 131 patients had TNBC. An analysis of each TNBC case indicated that the presence or absence of clinical lymph node metastasis(cN)before treatment might be a predictive factor of prognosis. There were 57(43.5%)pathological complete response(pCR)(ypT0 or ypTis/N0)cases after NAC. Overall survival(OS)and disease free survival(DFS) were significantly better in pCR cases than in non-pCR cases. However, recurrence was observed in 8 of 57(14%)pCR cases and 29 of 74(39%)non-pCR cases. The factors defining DFS from the univariate analysis of the non-pCR group were cN, ypT, ypN, and vascular invasion. The multivariate analysis of these factors suggested that residual cN and vascular invasion might be independent factors predicting DFS. Residual vascular invasion was found to predict OS, and was considered to be a poor prognostic factor.

Trastuzumab Emtansine (T-DM1) Plus S-1 in Patients with Trastuzumab-Pretreated HER2-Positive Advanced or Metastatic Breast Cancer: A Phase Ib Study.

BACKGROUND: In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer. OBJECTIVES: The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed. METHODS: This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment. RESULTS: Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1. CONCLUSIONS: S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.

Feasibility Study of Weekly Nanoparticle Albumin-Bound Paclitaxel (150 mg/m2) Followed by Fluorouracil, Epirubicin, and Cyclophosphamide Therapy as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer.

BACKGROUND: Although several studies have shown efficacy of nanoparticle albumin-bound (nab) paclitaxel use as a neoadjuvant treatment in breast cancer, dosage and schedules were varied or used in combination and the data are still limited for weekly regimens. We evaluated the feasibility of weekly nab-paclitaxel followed by FEC (5-FU [fluorouracil], epirubicin, and cyclophosphamide) treatment feasibility as neoadjuvant chemotherapy for breast cancer. PATIENTS AND METHODS: Thirty-three patients with no previous chemotherapy were enrolled to receive nab-paclitaxel 150 mg/m2 the first 3 of 4 weeks (3q4w) followed by FEC as neoadjuvant treatment. The trial was powered for analyses of feasibility. RESULTS: Twenty-five patients completed the treatment as per protocol, and the completion rate was 75.8% (95% confidence interval, 59.0-87.2; P = .44). The regimen completion group was younger than those with regimen incompletion (average 45.1 vs. 56.6 years). The pathological complete response (ypT0-is/N0) rate was 30.3% in 33 patients, which was higher in triple-negative patients (58.3%). Grade 3/4 neutropenia was seen in 48.5%, although there was no febrile neutropenia. Grade 3 peripheral neuropathy was seen in 33.3%. CONCLUSION: Our study showed that weekly nab-paclitaxel 150 mg/m2 3q4w followed by FEC as neoadjuvant regimen might be sufficient in efficacy, although with a relatively high severe adverse event occurrence rate.

Clinicopathological Significance of TARBP2, APP, and ZNF395 in Breast Cancer.

The double-stranded RNA-binding protein TARBP2 has been suggested to act as an upstream regulator of breast cancer metastasis by destabilizing transcripts of the possible metastasis suppressors amyloid precursor protein (APP) and ZNF395. We examined this hypothesis by immunostaining of TARBP2, APP, and ZNF395 in 200 breast cancer specimens using tissue microarrays and analyzed the relationships between expression levels and clinicopathological parameters and prognosis. Increased TARBP2 overexpression was associated with shorter overall survival and disease-free survival, and increased but not reduced APP expression correlated with lower overall survival and disease-free survival. ZNF395 expression levels had no prognostic value, but reduced expression correlated with reduced lymph node metastasis. There was no significant relationship between TARBP2 overexpression and reduced APP and/or ZNF395 expression. Patients with tumors with higher TARBP2 or APP expression had unfavorable prognoses. Although reduced ZNF395 expression was significantly related to reduced lymph node metastasis, further studies are needed to clarify the role of TARBP2/APP/ZNF395 in breast cancer.

Oncologic outcomes and technical considerations of nipple-sparing mastectomies in breast cancer: experience of 425 cases from a single institution.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an advantageous treatment option, providing a complete cure and good cosmetic results. We tested whether NSM is a surgically and oncologically safe technique. METHODS: We evaluated the oncological outcome of 425 breasts in 413 patients who underwent NSM between January 2000 and March 2013. We retrospectively reviewed patient data and analyzed all patient characteristics as potential risk factors of recurrence at the nipple-areola complex (NAC). To confirm the oncological safety of NSM, we compared outcomes of NSM and conventional total mastectomy. RESULTS: The median follow-up time after surgery was 46.8 months (range 6-158 months). Nipple necrosis was observed in 6 cases (1.4 %). The cumulative local recurrence rate after NSM was 5.8 % (25/425 cases), similar to that of conventional total mastectomy in the same period (5.6 %, 49/878 cases). Furthermore, the cumulative local recurrence rate at the NAC was 2.3 % (10 cases). HER2-enriched tumors and young age (<40 years) were significant risk factors for recurrence at the NAC. In patients with recurrence, the site of recurrence was easily excised, and good cosmetic results were achieved in breast reconstruction cases. CONCLUSION: NSM is safe with a low complication rate. No significant difference was observed in cumulative local recurrence rate, cumulative distant disease recurrence rate, and overall survival between patients who underwent NSM or conventional total mastectomy, confirming that NSM was surgically and oncologically safe.

Positive predictive value for malignancy of pure flat epithelial atypia diagnosis by percutaneous needle biopsy of the breast: management of FEA in ultrasonography.

BACKGROUND: Some reports suggest that the rate of definitive diagnosis of malignant tumors, namely, the final diagnosis being revised to a higher stage, in patients diagnosed as having flat epithelial atypia (FEA) by percutaneous needle biopsy of the breast (PNB) is as low as 0-3 %. However, other reports suggest that the rate is as high as 10 % or more, bringing confusion on this issue. We examined the positive predictive value for malignancy in the patients diagnosed as having pure FEA and the patients' radiolopathological characteristics observed in our hospital. METHODS: Of the patients who underwent PNB in our facility, those who were diagnosed as having pure FEA were recruited as the subjects of this study. RESULTS: Of the 4,197 consecutive patients who underwent PNB, 44 (1.0 %) were diagnosed as having pure FEA following a re-examination. Among 44 cases, 39 cases were selected as the subjects of this study. Among the 39 patients, six patients were diagnosed as having malignant lesions, two of whom had invasive carcinoma of no special type (papillotubular type), one had tubular carcinoma, one had ductal carcinoma in situ (DCIS) of high nuclear grade, one had DCIS of intermediate nuclear grade, and one had DCIS of low nuclear grade. The diameters of 6 malignant lesions were 10-30 mm at ultrasonography (US) examination. Five of the 39 patients had contralateral breast cancer. CONCLUSION: The positive predictive value for malignancy of pure FEA was 15.7 %. The patients with pure FEA may make a follow up without an excisional biopsy when the lesion sizes less than 10 mm on US examination.

Microcalcifications of breast tissue: appearance on synchrotron radiation imaging with 6-microm resolution.

OBJECTIVE: The purpose of this study was to use synchrotron radiation imaging with 6-microm resolution to evaluate amorphous and pleomorphic breast tissue microcalcifications. CONCLUSION: Synchrotron radiation imaging depicted microcalcifications as small as 24 microm. Imaging with this technique revealed that most amorphous and pleomorphic calcifications on conventional mammograms are clusters of fine specks and that in addition to the shape or density of a speck, the distribution density of clustered specks is a factor determining the apparent shape.

[Breast cancer].

In Japan the mortality and incidence rates of breast cancer have been increasing. In 2000, the number of breast cancer deaths in female was 9,171. In 1996, the aged adjusted incidence rate of breast cancer was 38.9, top among all of female cancers and the estimated number of female breast cancer patients was 29,448 in Japan. Therefore, efficient breast cancer screening system is urgently needed. In April 2000, breast screening using biennial mammography in combination with clinical breast examination instead of annual clinical breast examination alone was introduced for women aged 50 and over in Japan. However, the compliance of screening using mammography was less than 1% in the fiscal 2000 year. On the other hand, the compliance of screening with clinical breast examination alone was 6.5% in same period. These compliances were significantly lower than that of about 65% in the USA. Given the importance of the control of quality in screening mammography, a central committee for the quality control of mammographic screening has been established in order to educate doctors and radiographers and to assess image apparatus in each facility. As of April 2002, 1,409 out of 1,978 doctors that participated in the training program had obtained either grade A (instructor level) or grade B (adequate level). Gøtzche and Olsen reassessed previous meta-analyses of screening mammography and concluded that screening for breast cancer with mammography was unjustified. Subsequently, reviews by U. S. Preventive Services Task Forces and the WHO reconfirmed the effectiveness of screening mammography in reducing breast cancer mortality. These controversies show the importance of assessment of screening mammography effectiveness in Japan.

[Breast-conserving surgery: quadrantectomy].

The surgical techniques and clinical results of quadrantectomy as a form of breast-conserving surgery are described. A quadrantectomy is a breast-conserving technique including wide resection and tumorectomy. A quadrantectomy is designed to remove an anatomic segment of breast tissue (duct-lobular system). It has the advantage of greater surgical curability than other conserving techniques in cases with ductal spread, because breast cancer arising in the terminal duct often spreads in the duct-lobular system. However, quadrantectomy poses some cosmetic problems due to the large volume of breast tissue excised. Additionally, quadrantectomy has failed to show better results in local recurrence rates compared with wide resection. Therefore quadrantectomy should be limited to breast cancer with segmental and wide ductal spread. It is important to determine the surgical technique that compromises between local curability and cosmetic results for each patient with breast cancer.