Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

Metastasis-directed therapy for oligometastases in breast cancer.

The concept of oligometastases was first proposed to describe a disease state between localized cancer and extensive metastasis. After the emergence of variations in the definition of oligometastasis, in April 2020 the European Society for Radiotherapy and Oncology and the European Organization for Research and Treatment of Cancer defined oligometastases as the presence of one to five metastatic lesions that can be safely treated. However, the pathogenesis of oligometastases remains unknown, and it is uncertain which patients will benefit from metastasis-directed therapy. Breast cancer with oligometastases is generally managed with systemic therapy. Retrospective studies have suggested that the addition of metastasis-directed therapy, such as surgery, radiofrequency ablation and stereotactic body radiation therapy, may increase overall survival in breast cancer patients with oligometastases, but as yet there have been no prospective studies. Phase II trials of stereotactic body radiation therapy or fractionated irradiation for oligometastases of breast cancer have demonstrated impressive rates of local control and overall survival. Although the efficacy of stereotactic body radiation therapy in the SABR-COMET was largely anticipated, it is noteworthy that only 18% of the patient population had breast cancer. For this reason, various trials were planned or are being conducted globally to investigate the efficacy of metastasis-directed therapy for oligometastases of breast cancer. Metastasis-directed therapy for oligometastases has been shown to be effective, and stereotactic body radiation therapy and other therapies are commonly used internationally and are considered to be safe. However, the efficacy of metastasis-directed therapy for oligometastases has not yet been proven. The results of future clinical trials are thus eagerly awaited.

Clinical Utility of Breast Ultrasound Images Synthesized by a Generative Adversarial Network.

BACKGROUND AND OBJECTIVES: This study compares the clinical properties of original breast ultrasound images and those synthesized by a generative adversarial network (GAN) to assess the clinical usefulness of GAN-synthesized images. MATERIALS AND METHODS: We retrospectively collected approximately 200 breast ultrasound images for each of five representative histological tissue types (cyst, fibroadenoma, scirrhous, solid, and tubule-forming invasive ductal carcinomas) as training images. A deep convolutional GAN (DCGAN) image-generation model synthesized images of the five histological types. Two diagnostic radiologists (reader 1 with 13 years of experience and reader 2 with 7 years of experience) were given a reading test consisting of 50 synthesized and 50 original images (≥1-month interval between sets) to assign the perceived histological tissue type. The percentages of correct diagnoses were calculated, and the reader agreement was assessed using the kappa coefficient. RESULTS: The synthetic and original images were indistinguishable. The correct diagnostic rates from the synthetic images for readers 1 and 2 were 86.0% and 78.0% and from the original images were 88.0% and 78.0%, respectively. The kappa values were 0.625 and 0.650 for the synthetic and original images, respectively. The diagnoses made from the DCGAN synthetic images and original images were similar. CONCLUSION: The DCGAN-synthesized images closely resemble the original ultrasound images in clinical characteristics, suggesting their potential utility in clinical education and training, particularly for enhancing diagnostic skills in breast ultrasound imaging.

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.

Clinical Usefulness of Ultrasound-Guided Fine Needle Aspiration and Core Needle Biopsy for Patients with Axillary Lymphadenopathy.

Background and Objectives: It is necessary to properly diagnose and manage axillary lymphadenopathy caused by a variety of diseases. This study aimed to evaluate the utility of ultrasound (US)-guided sampling in patients with axillary lymphadenopathy. Materials and Methods: Patients with axillary lymphadenopathy (excluding patients with newly diagnosed breast cancer) who underwent US-guided fine needle aspiration (FNA) or core needle biopsy (CNB) at a single center between February 2016 and September 2020 were retrospectively examined. The association between US imaging findings and malignancy was investigated and the diagnostic performance of US-guided sampling was assessed. Results: Fifty-five patients (including eight males) were included in the study; of these, 34 patients (61.8%) were finally diagnosed with a malignant lymph node lesion. Twenty-two patients (40.0%) had undergone FNA and 33 (60.0%) had undergone CNB. Larger short and long axis diameters, thicker lymph node cortex, and the absence of fatty hilum on the US were significantly associated with malignancy (p < 0.05). The diagnostic performance of FNA, CNB, and FNA + CNB was excellent (sensitivity, specificity, and accuracy of 0.909, 0.900, and 0.917 for FNA, 0.958, 1.000, and 0.970 for CNB, and 0.941, 0.952, and 0.945 for FNA + CNB, respectively). Conclusions: US-guided FNA and CNB play an important role in the diagnosis and management of patients with axillary lymphadenopathy.

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.

Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types.

BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies. METHODS: Blood samples were collected from gastric (GC), colorectal (CRC), lung (NSCLC), breast (BC), prostate cancer (PC) patients, and a healthy control group. ctRNA was purified from fractionated plasma, and following reverse transcription, levels of PD-L1 expression were analyzed using qPCR. RESULTS: PD-L1 expression was detected in the plasma ctRNA of all cancer types at varying frequencies but no PD-L1 mRNA was detected in cancer-free individuals. The frequencies of PD-L1 expression were significantly different among the various cancer types but the median relative PD-L1 expression values were not significantly different. In 12 cases where plasma and tumor tissue were available from the same patients, there was a high degree of concordance between expression of PD-L1 protein in tumor tissues and PD-L1 gene expression in plasma, and both methods were equally predictive of response to nivolumab. CONCLUSIONS: PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. These results pave the way for further studies aimed at determining whether monitoring the levels of PD-L1 mRNA in blood can identify patients who are most likely to benefit from the conventional treatment.

[A Case of HER2 Positive Occult Breast Cancer Presenting as Swollen Axillary Lymph Nodes].

Occult breast cancer, which develops as a metastatic lesion with no primary tumor detected in the breast, is a rare breast cancer. A 68-year-old female patient particularly complained of the presence of a right axillary mass. The mass in the right axilla was palpable, but no tumor was found in both the breasts on palpation, ultrasound examination, or MRI. Partial breast resection and axillary lymph node dissection were performed following a diagnosis of invasive ductal carcinoma by core needle biopsy. There was no mammary gland tissue present around the tumor due to the pathology of the disease, and the tumor was diagnosed as occult breast cancer. As the cancer was ER negative and HER2 positive, treatment with a combination of FEC, docetaxel, and trastuzumab was initiated. Radiotherapy, which irradiated the right supraclavicular fossa and the right mammary gland, was administered. No disease recurrence and mammary tumor has been reported in the patient till date. Treatment of occult breast cancer generally includes local therapy such as radiation and surgery. However, in the present case, we did not operate upon the breast; instead we treated the right breast and the right supraclavicular fossa with radiation therapy. As the tumor was HER2 positive, we reasoned that local control of disease would be likely if treatment with chemotherapy and trastuzumab was performed effectively.

[A Case of Ipsilateral Breast Tumor Recurrence with Breast Ulcer].

The patient was a 61-year-old woman with a history of treatment for breast cancer. She had undergone left breast-conserving surgery and axillary lymph node dissection followed by radiation therapy for left breast cancer when she was 43 years old and later presented to our hospital with a chief complaint of a left breast ulcer with a messy exudate. Core needle biopsy (CNB)from the ulcer showed no malignancy. PET-CT showed low FDG uptake at the left breast and high FDG uptake at a contralateral axillary lymph node. CNB of a contralateral axillary lymph node showed metastasis of breast cancer. She underwent left mastectomy and right axillary lymph node dissection for local control. Ipsilateral breast tumor recurrence in the left breast and contralateral axillary metastases were identified in the final pathological findings. The patient was treated with FEC 100 and tri-weekly docetaxel and has been recurrence-free for 2 years after surgery.

[A Case of Noninvasive Ductal Carcinoma of the Breast in a Male].

Breast cancer in male is rare, accounting for 1%of all breast cancers.Among male breast cancers, noninvasive carcinoma is extremely rare.We experienced a case of noninvasive carcinoma of the breast in a male.A 72-year-old male was referred to our hospital with a chief complaint of the tumor and blood secretion from the left nipple.Mammography revealed a highdensity mass.Ultrasound examination revealed low echoic mass at the E area, and it measured 1.5 cm.Core needle biopsy failed to provide a definitive diagnosis, and we performed an excisional biopsy of the tumor.The pathological diagnosis was noninvasive ductal carcinoma.He underwent a mastectomy without sentinel lymph node biopsy because the resection margin was positive.The patient received no adjuvant therapy and the patient's postoperative course was uneventful for 1 year.As there have been few reports on male noninvasive ductal carcinoma, we do not have evidence for indication of the sentinel lymph nodes and postoperative adjuvant therapy such as tamoxifen.We may confuse the treatment policy.

Arterial Calcification Disappearance in Breast Imaging: A Key Indicator for Transition to Invasive Ductal Carcinoma.

A woman in her 70s, initially suspected of having fibroadenoma due to a well-defined mass in her breast, underwent regular mammography and ultrasound screenings. Over several years, no appreciable alterations in the mass were observed, maintaining the fibroadenoma diagnosis. However, in the fourth year, an ultrasound indicated slight enlargement and peripheral irregularities in the mass, even though the mammography images at that time showed no alterations. Interestingly, mammography images over time showed the gradual disappearance of previously observed arterial calcification around the mass. Pathological examination eventually identified the mass as invasive ductal carcinoma. Although the patient had breast tissue arterial calcification typical of atherosclerosis, none was present around the tumor-associated arteries. This case highlights the importance of monitoring arterial calcification changes in mammography, suggesting that they are crucial indicators in breast cancer diagnosis, beyond observing size and shape alterations.

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.

[A case of pathologically complete response of local recurrence in the mesorectum after multidisciplinary therapy].

The patient was a 68-year-old man who had undergone sigmoidectomy 1 year previously. Adjuvant therapy with tegafur- uraci(l UFT) and Leucovorin( UZEL) was administered. Seven months later, the carcinoembryonic antigen( CEA) level increased to 7.5 ng/mL. Enhanced computed tomography (CT) revealed a 4-cm mass in the mesorectum, and the patient was diagnosed as having local recurrence. Chemotherapy with oxaliplatin, 5-fluorouracil, and Leucovorin( mFOLFOX6) and radiation therapy( 60 Gy) were administered. As the tumor could not be detected after chemoradiotherapy, abdominoperineal resection was performed. Pathological examination showed no cancer and indicated a complete response. The patients CEA level has not increased and no recurrence has been detected on enhanced CT for 3.5 years. The tumor could be decreased in size by chemoradiotherapy and the operation could be safely performed without resecting other organs. Although surgery is generally performed for local recurrence, multidisciplinary therapy could be useful in performing such surgery safely.

[A case of cardiac tamponade due to breast cancer treated with weekly paclitaxel].

A 44-year-old woman who underwent surgery for left breast cancer 2 years ago presented with dyspnea. Her pathological stage of breast cancer was T2N1M0, ER (3+), PgR (3+), and HER2: 1+. She was treated with tamoxifen only as adjuvant therapy. Pleural effusion in both lungs and pericardial effusion were detected by computed tomography. We aspirated 1,100 mL of the pleural effusion and 700 mL of the pericardial effusion; the cytologies of both were class V. Because her dyspnea disappeared, she was administered weekly paclitaxel. Her pleural effusion and pericardial fluid have not re- emerged. The therapy of choice for pericardial effusion is local chemotherapy or systemic chemotherapy. Systemic chemotherapy after pericardial drainage was effective for this patient. Key words: Breast cancer.

[A long-surviving case of HER2-positive breast cancer with brain metastasis treated by multidisciplinary therapy].

We present a case of a 55-year-old woman who visited our hospital aware of a lump in her right breast. We diagnosed it as bilateral breast cancer [Rt: ABCDE, T3N1M0, ER (-), PgR (-), HER2: 3+, Stage IIIA; Lt: C, T2N0M0, ER (-), PgR (-), HER2: 1+, Stage IIA]. She underwent NAC with EC followed by docetaxel. After cPR, an operation (Rt Bt+Ax, Lt Bp+Ax) was performed. Liver metastases were identified 9 months after the operation, and she was administered weekly paclitaxel+trastuzumab for 12 courses. After cPR, the treatment was changed to trastuzumab only. Because a cerebellar metastasis appeared in postoperative month 19, she underwent an operation using a gamma-knife. Because a new cerebellar metastasis appeared in postoperative month 26, she underwent another gamma-knife operation. Furthermore, liver metastases were diagnosed as PD, and treatment was changed to vinorelbine and trastuzumab. Because third new cerebellar metastasis appeared in postoperative month 45, she underwent another gamma-knife operation. Lung metastases were identified 59 months after the operation, and the therapy was changed to lapatinib and capecitabine. There was no subsequent growth of metastatic tumors, and good control was obtained.

[A case of metastatic breast cancer with bilateral hydronephrosis effectively treated with capecitabine].

A 54-year-old female was diagnosed with invasive ductal carcinoma (pT3N1M0, Stage IIIA, estrogen receptor positive [ER (+)], progesterone receptor positive [PgR (+)], human epidermal growth factor receptor type 2 [HER2] score 0) and was treated by preoperative chemotherapy with weekly paclitaxel followed by 5-fluorouracil(5-FU) plus epirubicin plus cyclophosphamide regimen(FEC). Partial mastectomy with axillary dissection was performed. The pathological examination disclosed that the tumor was scirrhous carcinoma, and a pathological partial response was achieved by chemotherapy. Multiple bone metastases were detected 18 months after the surgery during treatment with letrozole as adjuvant therapy. Retroperitoneal metastases with hydronephrosis and a lung metastasis were detected 28 months after the surgery, even though exemestane and zoledronate were administrated after detection of the bone metastases. Chemotherapy with capecitabine was started and she recovered from hydronephrosis 4 months after the start of treatment. After 32 months from the first treatment with capecitabine, the patient is presently alive without hydronephrosis due to continued chemotherapy.

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.

[A case of scalp metastases from breast cancer successfully treated with letrozole].

A 62-years-old woman visited a dermatology clinic for hard mass at her scalp. Clinicallly, the mass was hard and alopecic. The diameter was 3 cm. A skin biopsy was done and histpathological examination showed adenocarcinoma. Immunehistchemically, estrogen receptor was positive. It was suspected that breast cancer could be metastasized to the scalp, but mammography, ultrasound, and positron emission tomography showed no particular metastases in her breast and other organs. Magnetic resonance imaging showed enhanced lesions in her birateral breast. Needle biopsy was done and pathological findings showed bilateral breast carcinoma and metastases to the scalp. So we started endocrine therapy using letrozole, the mass was shrunk to 1 cm after 6-month. It is rare that breast cancer was metastasized to the scalp. But Conner et al. reported that 84% of metastatic scalp carcinoma was from the breast, so we should examine the breast more carefully.