Short- and long-term outcomes of immediate breast reconstruction surgery after neoadjuvant chemotherapy.

PURPOSE: Immediate breast reconstruction (IBR) is a standard option for breast cancer patients, although its utility in patients with advanced breast cancer requiring neoadjuvant chemotherapy (NAC) is debatable. We assessed the short-term complications and long-term prognosis of IBR after NAC. METHODS: We retrospectively analyzed 1135 patients with IBR and/or NAC between 2010 and 2018, 43 of whom underwent IBR after NAC. RESULTS: Twenty-five patients underwent reconstruction with a tissue expander (TE) followed by silicon breast implantation, 5 with a latissimus dorsi muscle transfer flap, and 13 with a deep inferior epigastric perforator flap. Complete surgical resection with a free margin confirmed by a pathological assessment was achieved in all patients. The evaluation of the short-term complications indicated no cases of total flap necrosis, two cases of partial flap necrosis, and one case of wound infection. Only one case required postponement of subsequent therapy due to partial flap necrosis. A long-term evaluation indicated no local recurrence, although distant metastasis was observed in 4 cases, 3 patients died, and TE removal after post-mastectomy radiotherapy (PMRT) was performed in 2 of 11 TE cases. CONCLUSION: IBR may be a viable option in patients with advanced breast cancer who achieve complete surgical resection after NAC.

Surgical upstaging rates in patients meeting the eligibility for active surveillance trials.

PURPOSE: Four clinical active surveillance trials including LORIS, COMET, LORD and LORETTA, are being conducted to assess whether women with low-risk ductal carcinoma in situ can safely avoid surgery. The present study aimed to determine the rate of upstaging to invasive cancer among patients with a preoperative diagnosis of ductal carcinoma in situ and to evaluate the incidence of upstaging in patients meeting the eligibility criteria for four active surveillance clinical trials. METHODS: The present study initially enrolled 180 patients with 183 calcifications who received the diagnosis of ductal carcinoma in situ by biopsy. Patients were classified as eligible for four clinical trials according to the respective inclusion criteria. RESULTS: In total, 152 patients with 155 calcifications were analyzed. Of these, 32 (21%) were upstaged to invasive disease based on the final pathological analysis of surgical specimens. Of the 152 patients, 53 (35%), 90 (59%), 24 (16%) and 34 (22%) met the eligibility criteria for the LORIS, COMET, LORD and LORETTA trial, respectively. Among patients with low-risk ductal carcinoma in situ, 10 (19%), 14 (16%), 6 (25%) and 4 (12%) patients were upstaged to invasive disease in LORIS, COMET, LORD and LORETTA, respectively. The upstaging to pT1b or higher rates were 2% (1/53), 3% (3/90), 0% (0/24) and 3% (1/34) in LORIS, COMET, LORD and LORETTA, respectively. CONCLUSIONS: The upstaging rate in patients eligible for the clinical active surveillance trials was 12-25%. Although the rate of upstaging to pT1b or higher was low, further studies are required to determine the rates of upstaging to invasive cancer and the risk factors among patients with low-risk ductal carcinoma in situ.

False-negative ultrasound-guided fine-needle aspiration of axillary lymph nodes in breast cancer patients.

INTRODUCTION: The purpose of this study was to clarify the clinicopathological features of patients with false-negative fine needle aspiration cytology (FNAC) and to determine the factors associated with negative FNAC. METHODS: Patients with negative FNAC from January 2010 to December 2019 were included. The patients with positive sentinel nodes (SN) were divided into two groups: micrometastasis (≤2 mm) group and macrometastasis (>2 mm) group. The clinicopathological characteristics were compared between the two groups using the χ2 test. RESULTS: A total of 165 patients with negative FNAC were included; 52 (31.5%) had positive SNs. Of the 52 patients, 13 (25%) had micrometastasis and the remaining 39 (75%) had macrometastasis. Of the 113 patients with negative SNs, none had metastases found in non-SNs. No significant differences were observed in age, cT stage or subtype, and preoperative ultrasound findings between the two groups. CONCLUSIONS: The false-negative rate of FNAC was high (31.5%). Micrometastatic disease was seen in patients with negative FNAC, and this might be the cause of false-negative FNAC results.

Predictive factors of an axillary pathological complete response of node-positive breast cancer to neoadjuvant chemotherapy.

PURPOSE: The present study aimed to identify the predictive factors of an axillary pathological complete response (Ax-pCR) in patients with node-positive breast cancer who underwent neoadjuvant chemotherapy (NAC). METHODS: The present study included 219 patients who underwent NAC followed by curative surgery, including axillary lymph node dissection (ALND), for 221 breast cancers between January 2010 and April 2018. All patients were clinically and/or pathologically confirmed to be node-positive at the initial diagnosis. The predictive factors of Ax-pCR were analyzed using a chi-square test and multivariate logistic regression models. RESULTS: Ninety-five patients (43%) achieved Ax-pCR after NAC. The odds of achieving Ax-pCR were significantly improved when tumors were high grade (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.00-4.84), estrogen receptor (ER) negative (OR 2.65 95% CI 1.23-5.70), ycN0 on ultrasound (US) imaging (OR 3.89, 95% CI 1.90-7.97), and showed a clinical complete response (CR) at the primary site after NAC (OR 4.22, 95% CI 1.59-11.27). CONCLUSIONS: Ax-pCR was more likely to be achieved in patients who were diagnosed with ER-negative and high-grade breast cancer and those with ycN0 and clinical CR at the primary site after NAC than among others. Among these patients, those with initially cN1/N2 might be good candidates for a deescalated treatment strategy after NAC.

[A Case Report on the Effectiveness of Olaparib in a Patient with Recurrent Breast Cancer with Human Immunodeficiency Virus Infection].

A 43 -year-old woman presented to the hospital with a right breast tumor. She had been treated for human immunodeficiency virus(HIV)infection for 5 years. After being diagnosed with right breast cancer, she underwent total mastectomy and sentinel lymph node biopsy, which indicated T2N1M0 triple-negative breast cancer. She received doxorubicin and cyclophosphamide( AC)followed by docetaxel(AC-T)as postoperative adjuvant chemotherapy. However, 14 months after the adjuvant chemotherapy finished, distant metastasis occurred in the brain, lung, and mediastinum lymph nodes. Treatment for relapse was initiated, with whole brain radiotherapy followed by paclitaxel plus bevacizumab combination therapy(PB); however, new metastatic lesions were found in the bone, liver, and mediastinum lymph node after 2 courses of PB. Given the risk of hereditary breast and ovarian cancer syndrome, a BRCAgene test was performed when the patient received radiotherapy for left recurrent laryngeal nerve paralysis caused by mediastinal lymph nodes; this showed a result positive for a deleterious mutation in BRCA1. Thus, treatment with olaparib, a poly(ADP-ribose)polymerase(PARP)inhibitor, was started. Metastatic lesions, including barky growth, in the liver metastasis were well controlled, as confirmed by CT imaging 4 months after the start of olaparib.

[Toxicity of Palbociclib in Patients Aged 70 Years and Older with Metastatic Breast Cancer].

We aimed to examine palbociclib toxicity in patients aged 70 years and older with metastatic breast cancer(MBC). From December 2017 to August 2018, 32 patients with estrogen receptor(ER)-positive, human epidermal growth factor receptor 2(HER2)-negative MBC were included in this study. The most common adverse event(AE)observed was neutropenia, and comparative rates of grade 3 or 4 AE were identified in the groups of patients aged ≥70 years(n=11)and <70 years(n=21) (91% vs 81%). Febrile neutropenia occurred in one patient. Although dose interruption rate was higher in the older group (≥70 years of age)than in the younger group(<70 years of age)(100% vs 86%, respectively), reduction rates were similar between the two groups(64% vs 62%, respectively). Palbociclib was well-tolerated in Japanese older(≥70 years of age) MBC patients.

Deodorant pad for ulcerated breast cancer: safety and efficacy.

OBJECTIVES: APOLLO study, 'efficacy and safety of the deodorAnt Pad against Odour and uLceration for LOcally advanced breast cancer', aimed to assess the safety and efficacy of wearing a deodorant pad in patients with locally advanced breast cancer (LABC) with an ulceration. METHODS: Komagome Pads were previously developed by Juntendo University and Kao Corporation. In test A, a conventional pad consisting of gauze, a commercially available diaper, pad, etc and the Komagome Pad were compared over 3 days to assess their efficacy and possible improvements for short-term use. In test B, the Komagome Pad was used continuously for 1 month to evaluate its safety during long-term use. RESULTS: This study included 14 patients in test A and nine in test B. In odour evaluation using sensory testing in test A, nine patients reported more significant efficacy in odour suppression with the Komagome Pad. The odour intensity of the Komagome Pad was lower on the gas chromatography-mass spectrometry. The group with a high level of exudation reported significantly higher satisfaction with the Komagome Pad. In test B, no adverse events were observed. CONCLUSIONS: A new deodorant pad for LABC demonstrated high safety and deodorant efficacy.

Germline variant of BRCA1 c.5332G>A has clinical features of hereditary breast and ovarian cancer syndrome.

The proband was a 39-year-old Japanese woman with stage I triple negative breast cancer. Germline BRCA1 and BRCA2 genetic testing revealed the presence of a BRCA1 c.5332G>A (p.Asp1778Asn) variant classified as a VUS in the heterozygous state. She underwent curative surgery and adjuvant chemotherapy for her TNBC, but no intensive follow-up or risk-reducing surgery was performed in contrast to normal practice in a patient with hereditary breast and ovarian cancer syndrome. At postoperative 2 years 6 months, elevation of CA15-3 led to the diagnosis of Stage III high-grade serous ovarian cancer. Studies and information in public databases at the time of the patient's genetic testing showed only VUS results for c.5332G>A; within the next few years, one pathogenic and one likely pathogenic result were confirmed. Thus, according to a joint consensus recommendation of the ACMG/AMP, c.5332G>A is considered 'likely pathogenic'. The public database should be checked regularly for VUS results, and practical management should be considered if reliable likely pathogenic or pathogenic reports were added.

Safety and Effectiveness of Areola-sparing Mastectomy for Breast Cancer With Intraductal Lesions.

BACKGROUND/AIM: Areola-sparing mastectomy (ASM), a conservative mastectomy with nipple hollowing, can be applied to intraductal breast cancer with a tumour-nipple-areola complex (NAC) distance of ≤2 cm. Here, we evaluated the safety and effectiveness of ASM. PATIENTS AND METHODS: We retrospectively reviewed the surgical outcomes of 61 patients (64 breasts) who underwent ASM between 2016 and 2020. RESULTS: Of the 64 breasts, 33 (51.6%) underwent ASM because the tumour-NAC distance on preoperative magnetic resonance imaging was ≤2 cm. Two patients had positive excisional margins but these were at the posterior areola surface therefore additional resection was possible. Over a median postoperative observation period of 16 months (range=3-52 months), one patient developed chest wall recurrence that was resected and did not recur again. CONCLUSION: For breast cancer with an extensive intraductal component, ASM is a good alternative to nipple-sparing mastectomy because it allows safe resection while maintaining aesthetics.

Metastasis of breast cancer to liver through direct lymphatic drainage: a case report.

Breast cancer liver metastasis (BCLM) is considered to occur by hematogenous spread of primary breast cancer cells. We herein present a case of lymphatic BCLM that was confirmed by preoperative imaging for sentinel lymph node biopsy (SLNB). A woman in her early 70s was diagnosed with clinical stage T2N0M0 invasive lobular cancer of the left breast. She underwent mastectomy with SLNB. Preoperative lymphoscintigraphy showed intense accumulation of isotope in the upper abdomen, corresponding to segment IV of the liver on single-photon emission computed tomography/computed tomography (SPECT/CT). However, no abnormalities were detected on magnetic resonance imaging. At 2.5 years postoperatively, the patient's serum CA15-3 concentration was elevated, and positron emission tomography/computed tomography (PET/CT) showed a solitary liver metastasis. The PET/CT findings were similar to the SPECT/CT findings obtained 2.5 years earlier, indicating that the BCLM had developed lymphatically. To the best of our knowledge, this is the first case report of lymphatic BCLM proven by imaging examination.

Application of the Z1071 criteria: classification of axillary lymph nodes on ultrasound after neoadjuvant chemotherapy in initially node-positive breast cancer.

PURPOSE: The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial assessed the accuracy of sentinel lymph node biopsies in clinically node-positive patients who underwent neoadjuvant chemotherapy (NAC). Axillary ultrasound (US) images after NAC were reviewed, and the accuracy of classifying nodes into six types according to the ACOSOG Z1071 trial was determined. METHODS: This study included 69 patients who underwent NAC followed by curative surgery for breast cancer including axillary lymph node dissection between January 2010 and July 2019. All patients were pathologically confirmed as being initially node positive. Lymph nodes were retrospectively classified into one of six types based on the appearance of the nodal cortex and hilum. Types I and II were classified as having normal nodal morphology, whereas types III, IV, V, and VI were classified as having suspicious nodal morphology. These node types on US images after NAC were compared between patients with an axillary complete response (Ax-pCR) and those with residual metastatic lymph nodes (Ax-non-pCR) using Chi-square tests. RESULTS: Twenty-four (35%) of the 69 patients achieved Ax-pCR. Patients with nodes classified as type I or II were more likely to achieve Ax-pCR (83% vs. 36%, p = 0. 0002). CONCLUSION: The classification of six node types was associated with nodal status.

Ultrasound-guided fine-needle aspiration of axillary lymph nodes in breast cancer: Diagnostic accuracy and role in surgical management.

BACKGROUND: The objective of this study was to evaluate the accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes (LN) in breast cancer, to compare the results of FNAC and pathological examination, and to distinguish patients with 1 to 2 metastatic LNs from those with ≥3 metastatic LNs in patients with FNAC-positive patients. PATIENTS AND METHODS: This study included 198 breasts of 196 patients with breast cancer who underwent FNAC and surgery for the primary and axilla without neoadjuvant chemotherapy from January 2010 to August 2016. Axillary nodal status was assessed by ultrasound (US), and whether FNAC-positive had three or more suspicious LNs on US imaging was examined. RESULTS: The results of FNAC were positive in 75 (38%), negative in 97 (49%), suspicious in 2 (1%), indeterminate in 5 (2.5%), and insufficient in 19 patients (9.5%). FNAC sensitivity, specificity, positive predictive value, and negative predictive value were 62.6%, 100%, 100%, and 62.0%, respectively. Whereas 53% (18/34) of patients with false-negative FNAC had one metastatic LN on final pathology, 61% (47/77) patients who were FNAC-positive had three or more metastatic LNs. In the FNAC-positive patients, all patients had ≥3 metastatic LNs if they had ≥3 suspicious LNs on US imaging. CONCLUSION: Patients with positive cytology were more likely to have ≥3 positive LNs compared to false-negative cytology patients. Patients with ≥3 abnormal LNs on US and positive FNAC might require axillary dissection.

Altered expression of heat shock protein 110 family members in mouse hippocampal neurons following trimethyltin treatment in vivo and in vitro.

The heat shock protein (Hsp) 110 family is composed of HSP105, APG-1, and APG-2. As the response of these proteins to neuronal damage is not yet fully understood, in the present study, we assessed their expression in mouse hippocampal neurons following trimethyltin chloride (TMT) treatment in vivo and in vitro. Although each of these three Hsps had a distinct regional distribution within the hippocampus, a low level of all of them was observed in the granule cell layer of the dentate gyrus in naïve animals. TMT was effective in markedly increasing the level of these Hsps in the granule cell layer, at least 16h to 4days after the treatment. In the dentate granule cell layer on day 2 after TMT treatment, HSP105 was expressed mainly in the perikarya of NeuN-positive cells (intact neurons); whereas APG-1 and APG-2 were predominantly found in NeuN-negative cells (damaged neurons as evidenced by signs of cell shrinkage and condensation of chromatin). Assessments using primary cultures of mouse hippocampal neurons exposed to TMT revealed that whereas HSP105 was observed in intact neurons rather than in damaged neurons, APG-1 and APG-2 were detected in both damaged neurons and intact neurons. Taken together, our data suggest that APG-1 and APG-2 may play different roles from HSP105 in neurons damaged by TMT.

Feasibility study of direct fentanyl patch introduction without prior opioid titration.

BACKGROUND: Opioids are key drugs for cancer pain relief, but some patients, especially those who have gastroenterological cancers, suffer from severe opioid-induced bowel dysfunction (OBD), which reduces their quality of life. In order to achieve better pain relief, efforts to minimize OBD are required. METHODS: Between September 2006 and December 2007, 18 patients were enrolled in this feasibility study. All patients had gastroenterological cancer pain. The patients received direct fentanyl patch introduction starting from 12.5 microg/h, with additional opioid treatment for the first 12 h. Adverse events, changes of medications, pain scale, and patients' satisfaction scores were recorded for 9 days after fentanyl patch introduction. RESULTS: All patients completed the protocol treatment without interruption by adverse events. Eight patients (44%) showed adverse events that were presumed to be related to the treatment. However, all events were grade 1 and had a minimal effect on patients' quality of life. According to subjective evaluation on day 9, only 4 patients (22%) mentioned that they had felt adverse events during the treatment course. Seventeen patients (94%) had pain score scale improvements evaluated on day 9. Satisfaction scores on days 9 and day 27 were excellent or good for all but one of the patients. CONCLUSION: This prospective study showed the safety and efficacy of direct fentanyl patch introduction in Japanese gastroenterological cancer patients, and the treatment had good feasibility. This model should help cancer pain management for patients with a high risk of features of OBD such as constipation, subileus, or postabdominal surgery.