Primary Neuroendocrine Tumor of the Breast: A Rare Case.

Multidisciplinary considerations in the treatment of triple-negative breast cancer.

A cost-effectiveness analysis of axillary node dissection in postmenopausal woman with estrogen receptor–positive breast cancer and clinically negative axillary nodes

Objective To research the impact of axillary limph node group dissection oriented by sentinel lymph nodes instead of axillary dissection on upper limb lymph edema and disease-free survival(DFS). Methods We designed a randomized controlled research, which included 205 cases of operatable breast cancer(AJCC 7th: stage I or stage IIa)from Jan. 2011 to Jan. 2013. Those cases were separated into 2 groups randomly(random number method): group A underwent mastectomy(or lumpectomy)and axillary group lymphadenectomy oriented by sentinel lymph node biopsy(SLNB)(if positive continued for ALND)while group B underwent mastectomy(or lumpectomy)and axillary lymph node dissection(ALND). All patients underwent SLNB by blue dye method and received adjuvant therapy after surgery according to National Comprehensive Cancer Network(NCCN)guideline and Chinese anti-cancer association guideline. Results There were 101 cases in group A and 104 cases in group B, but 1 case in group A was excluded for false negative of SLN. The midium follow-up was 30 months. There were no significant differences of average age, tumor size, grade, estrogen receptor (ER), progesterone receptor(PR)and human epidermal growth factor receptor 2 (HER2)expression between the 2 groups. Group A had a lower frequency of lymph edema than group B(4.0% vs 17.3%, χ2=9.384, P=0.002), and also a milder degree(mild 2% vs 11.5%, middle 2% vs 3.8%, severe 0% vs 1.9%). There were no significant differences of upper limb sensory disorder(14.0% vs 16.3%, χ2=0.218, P=0.641), neither of DFS(Log-Rank analysis: 3-year average DFS 32.89 months vs 33.72 months, χ2=0.186, P=0.667; Cox risk model analysis: HR=1.395, P=0.495)between the 2 groups. Conclusion Axillary group lymphadenectomy oriented by SLNB can reduce the happening of lymph edema from ALND and has a comparative effect on DFS as ALND. Key words: Breast cancer; Sentinel lymph node; Lymph edema of upper limb

Diminishing morbidity with the increased use of sentinel node biopsy in breast carcinoma

Technical Challenges of Heart Avoidance for Synchronous Breast and Lung Cancers in a Postmenopausal Female: A Planning Case Report From a Safety-Net Hospital

Background. Neo-adjuvant chemotherapy (NAC) is widely used as preoperative systemic therapy for operable breast cancer. However, the use of sentinel-lymph-node biopsy (SNB) following NAC for patients with clinically node positive is controversial, even if they achieve cCR in the axilla. Although preoperative axillary imaging assessment may help to decide axillary management after NAC, few data are available on whether axillary ultrasound (LN-US) is useful to assess axillary response to NAC. Purpose. We investigated the accuracy of axillary node assessment by ultrasound after NAC in clinically node positive patients and analyzed factors related to the accuracy of LN-US. Methods. From January 2012 through December 2016, patients with cT1-4, N1-2, M0 primary breast cancer who had cytologically proven axillary metastasis, and underwent axillary lymph node dissection (ALND) after NAC were retrospectively reviewed. Clinically positive lymph node by LN-US was defined as concentric cortical thickness >3mm, absent fatty hilum, or irregular morphology. Results. A total of 298 patients with clinical stage T1-4, N1-2, M0 primary breast cancer who had cytologically proven axillary metastasis, and underwent surgery with axillary dissection following NAC were enrolled. Of 279 eligible patients, 101 patients (36.2%) showed pathologically node-negative in the axilla (ypN0), and the rate of ypN0 was 20.2% (37/183) in hormone receptor (HR)+/human epidermal growth factor receptor-2 (HER2)-, 71.9% (23/32) in HR+/HER2+, 83.3% (20/24) in HR-/HER2+, and 52.5% (21/40) in HR-/HER2-. Sensitivity and specificity of LN-US were 65.7% and 62.3% respectively. The accurate prediction rate of node-negative status after NAC by LN-US was 49.2% in total, 29.7% in HR+/HER2-, 89.5% in HR+/HER2+, 86.7% in HR-/HER2+, and 68.8% in HR-/HER2- disease. The accuracy was highest in the HER2+, and lowest in HR+/HER2-. The median number of pathologically positive residual nodes at ALND after NAC was 2 (1-16) in total and 2 (1-15) in patients with ycN0. Of 61 patients with ycN0ypN+, 26 (42.6%) had 1 positive lymph node on the pathologic review, 9 (14.8%) had 2 positive lymph nodes, 7 (11.5%) had 3 positive lymph nodes, and 19 (31.1%) had more than 3 positive lymph nodes.The accuracy of node negative status by LN-US varies significantly by tumor subtype (p<0.001) and tumor response as assessed by MRI after completion of NAC (p=0.0003), although there was no significant difference between two groups regarding T category at diagnosis, tumor histology, and the number of positive nodes before NAC as assessed by LN-US. Of 23 patients who achieved ycN0 in LN-US and cCR in the primary lesion in MRI, the accurate prediction rate of ypN0 was 100% in patients with HR±/HER2+ and HR-/HER2- disease. Conclusion. The accuracy of axillary US after NAC depended on subtypes, which was highest in the HER2 disease and the accuracy increased by combing with the tumor response in the breast assessed by MRI. In the point of reducing FNR after NAC by LN-US assessment before surgery, the accuracy of NPV is especially important. We suggest that it is of clinical importance to take account of tumor subtypes and primary tumor response in the breast by MRI in combination with LN-US in selecting patients for SNB after NAC. Citation Format: Yurina Maeshima, Takehiko Sakai, Akiko Ogiya, Yoko Takahashi, Yumi Miyagi, Takayuki Ueno, Shinji Ohno. The accuracy of axillary node assessment of ultrasound after neoadjuvant chemotherapy in clinically node positive patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-19.

Since the pioneering reports of Krag et al. and Giuliano et al. >10 years ago, sentinel lymph node (SLN) biopsy has emerged as a new method for axillary lymph node staging in breast cancer and has become standard care at many institutions in the United States and worldwide. A current meta-analysis of 69 published studies of SLN biopsy validated by a backup axillary lymph node dissection (ALND) confirms an overall success rate of 96%, with the SLN falsely negative in 7.3% of node-positive cases. Observational studies have asked and answered many questions regarding definition, case selection, technique (nuclear medical, surgical, and pathologic), learning curve, and, most importantly, safety. The morbidity of SLN biopsy, although not zero, is less than that of ALND, and axillary local recurrence (LR) after a negative SLN biopsy is both comparable to that of ALND and vanishingly rare, occurring in 0.12% of our own patients at 30 months follow-up. It appears that few false-negative SLN procedures, if any, ever result in axillary LR. Three randomized trials of identical design address the survival equivalence of SLN biopsy and ALND and are almost certain to demonstrate no difference. Finally, two trials, through a physicianand patient-blinded design, promise an answer to the still-controversial subject of prognostic significance in immunohistochemically detected SLN micrometastases. Where do we go from here? Taback et al., in this issue of the Annals, suggest one direction: the application of SLN biopsy in the setting of ipsilateral breast tumor recurrence (IBTR) after breast conservation. Although prior axillary surgery has been anecdotally deemed a contraindication to SLN biopsy, they demonstrate (as we have previously) the feasibility of reoperative SLN biopsy. Among 15 patients (6 with a previous SLN biopsy and 9 with a previous ALND) who developed IBTR, lymphoscintigraphy (LSG) imaged SLNs in 11 (73%). Among 14 patients explored, they identified SLNs in 11 (79%). Their finding that three of four patients with a negative LSG had a previous ALND fits with our observation that the success of reoperative SLN biopsy is inversely related to the number of axillary nodes removed previously. Finally and most importantly, they demonstrate a higher-than-expected rate of lymphatic drainage to nonaxillary sites (including supraclavicular, internal mammary, interpectoral, and contralateral axilla): two of three SLN-positive patients had contralateral axillary disease. We made the same observation in a recent update of our own experience; comparing reoperative SLN biopsy (n = 133) with first-time SLN biopsy (n = 7559), LSG showed nonaxillary drainage in 24% vs. 5% of cases (P < .001; unpublished data). Routine preoperative LSG for SLN biopsy in primary breast cancer is still a matter of debate but may prove particularly useful in the reoperative setting, where prior surgery may have altered the pattern of lymphatic drainage. Their study raises larger issues as well. Over the last 30 years, the management of breast cancer has evolved from an era of clinical detection and a single Received January 24, 2006; accepted February 1, 2006; published online j. Address correspondence and reprint requests to: Hiram S. Cody III, MD; E-mail: codyh@mskcc.org.

Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

A contemporary view of axillary dissection.

Age and Lymph Node Status in Breast Cancer: Not a Straightforward Relationship

Management of the axilla in patients with operable breast cancer is still one of the most controversial areas in clinical oncology. The best procedure to examine the lymph nodes is still standard axillary lymph node dissection; nevertheless, the morbidity associated with this procedure is well known. Based on these considerations, it is important for progress in the treatment of operable breast cancer that strategies are found that permit a less invasive method of axillary sampling which does not impair the patient's quality of life. The technique of sentinel lymph node (SLN) biopsy has recently been proposed for this purpose, with very important results. SLN has now become routine practice in the surgical management of breast cancer, and in many institutions patients with a negative SLN biopsy are spared axillary dissection, while those with a positive SLN biopsy are submitted to axillary node dissection. The good accuracy of SLN biopsy represents a significant advance in the management of primary breast cancer; however, false negative axillary results can occur in a variable percentage of patients, and the contribution of the SLN procedure to the detection of metastases in the internal mammary and supraclavicular lymph nodes is not clear. Among the recently developed imaging modalities, positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has in particular been applied to the study of lymph node metastases in cancer patients. Several clinical studies have been carried out to evaluate the accuracy of PET in the axillary staging of operable primary breast cancer. These studies have sometimes provided conflicting results, either supporting the possibility of using FDG-PET to select patients who need axillary dissection or questioning whether FDG-PET can accurately assess the axillary status in primary breast cancer. All the limitations and the advantages of FDG-PET are discussed in this paper, by examining the performance of scanner technology and the possible causes of the false negative results. In the experience of the authors, comparing FDG-PET with SLN biopsy in the same series of patients, the results seem to indicate that the lower sensitivity of PET is restricted to micrometastases. Of course, this limitation of PET has to be analysed in relation to the importance of such small axillary metastases for the outcome of patients with breast cancer. The added value offered by PET in breast cancer staging in comparison with intraoperative detection of the sentinel node lies in the fact that FDG-PET is a non-invasive procedure that allows, within a single examination, the biological characterisation of breast cancer and viewing of the entire body.

Axillary management varies between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) for patients with clinical N1 (cN1), hormone receptor-positive (HR+), humanepidermal growth factor receptor 2 (HER2)/neu-negative (HER2-), infiltrative ductal carcinoma (IDC) who achieve a complete clinical response (cCR) to neoadjuvant systemic therapy (NAST). This study sought to evaluate clinical practice patterns and survival outcomes of SLNB versus ALND in this patient subset. Patients with cN1, HR+/HER2-, unilateral IDC demonstrating a cCR to NAST were identified from the 2012-2017 National Cancer Database (NCDB) and stratified based on final axillary surgery management (SLNB vs ALND). After propensity score-matching, overall survival (OS) was compared using a Kaplan-Meier analysis, and significant OS predictors were identified using Cox regression. Of the 1676 patients selected for this study, 593 (35.4%) underwent SLNB and 1083 (64.6%) underwent ALND. Use of SLNB increased by 28 % between 2012 and 2017. Among a total of 584 matched patients, 461 matched ypN0 patients, and 108 matched ypN+ patients, mean OS did not differ between SLNB and ALND (all patients [92.1 ± 0.8 vs 90.2 ± 1.0 months; p = 0.157], ypN0 patients [92.4 ± 0.8 vs 89.9 ± 0.9months; p = 0.105], ypN+ patients [83.5 ± 2.3 vs 91.7 ± 2.7 months; p ± 0.963). Cox regression identified age, Charlson score, clinical T stage, and pathologic nodal status as significant predictors of OS. The final surgical management strategy used for cN1, HR+/HER2- IDC patients who achieved a cCR to NAST did not have a significant impact on survival outcomes in this analysis. Potential opportunities for de-escalation of axillary management among this patient subset exist, and validation studies are needed.

Background Axillary staging is important for predicting prognosis, and for local control in early breast cancer. Sentinel lymph node biopsy (SLNB) is a widely accepted method to avoid unnecessary axillary lymph node dissection (ALND). Since the ACOSOG Z0011 trial was published, we have refrained from ALND for selected patients with positive SLNB results. However, some cases have shown regional lymph node recurrences after SLNB without axillary dissection. The purpose of this study is to identify risk factors for recurrences, to ensure a safe axillary surgery. Methods A retrospective review of 1011 patientswho underwent SLNB without ALND between June 2004 and March 2017 was performed. Since October 2012, we have not performed ALND in patients (a) with 1 or 2 positive sentinel lymph nodes (SLNs), (b) with positive SLNs that are unmatted or not gross extra nodal extension, (C) in whom clinical tumor size is &amp;lt;5 cm, and (d) who receive adjuvant endocrine therapy or chemotherapy and radiotherapy. Cases of mastectomy, lumpectomy with a positive margin and additional resection or boost radiotherapy, and bilateral cancer were included. SLNs were identified using technetium sulfur colloid and indigo carmine blue dye, and were bisected in parallel to the long axis of the nodes. The sections were stained with hematoxylin and eosin. Adjuvant systemic and/or radiation treatment was delivered as per the National Comprehensive Cancer Network and the Japanese Breast Cancer Society clinical practice guidelines and was based on the patients' pathological and clinical traits. Results Of the 1011 patients, 969 had negative and 42 had positive SLNs. The median age of patients was 59 years (range 21-88). The median invasive breast tumor size was 15 mm (range 0.05-85), with 1.9% tumors being pathological T3 lesions; 127 patients (12.3%) developed lymphatic vessel invasion. SLNs identification rate was 99.4%. The median number of SLNs removed per patient was 2 (range 1-7). After follow-up of a median 78.5 months, 10 patients (1.0%) had an axillary recurrence and all of them had negative SLN metastasis. The median time to axillary recurrence was 26 months (range 9-94). The hormone receptor (HR) status was significantly related to axillary recurrence (p=0.008). While triple negativity had a tendency to relate (p=0.06), human epidermal growth factor receptor 2 (HER2) status did not correlate with axillary recurrence (p=0.13). Tumor subtypes and axillary recurrence SLNB without ALND (n=1011)Axillary recurrenceP valueHR positive72650.009HR negative1615 HER2 positive12130.13HER2 negative7667 Triple Negative10030.06Not Triple Negative7877 DCIS1240 DCIS: Ductal carcinoma in situ Conclusions As reported previously, the axillary recurrence rate after SLNB was low. Our results show that HR negativity was a significant factor for axillary recurrence. Although the ACOSOG Z0011 trial criteria focused on ALNB positive cases, they do not mention the tumor subtypes. Our findings show that HR negative patients without ALND have to follow up carefully. Citation Format: Sekine C, Nakano S, Mibu A, Otsuka M, Oinuma T. Hormone receptor status is a predictive factor for axillary lymph node recurrence after sentinel lymph node biopsy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-15.

HER2 is overexpressed in 20–25% of breast cancers. Overexpression of HER2 is an adverse prognostic factor and correlates with decreased patient survival. HER2 stimulates breast tumorigenesis via a number of intracellular signaling molecules, including PI3K/AKT and MAPK/ERK.S100A14,one member of the S100 protein family, is significantly associated with outcome of breast cancer patients. Here, for the first time, we show that S100A14 and HER2 are coexpressed in invasive breast cancer specimens,andthere is a significant correlation between the expression levels of the two proteins by immunohistochemistry. S100A14 and HER2 are colocalized in plasma membrane of breast cancer tissue cells and breast cancer cell lines BT474 and SK-BR3. We demonstrate that S100A14 binds directly to HER2 by co-immunoprecipitation and pull-down assays. Further study shows that residues 956–1154 of the HER2 intracellular domain and residue 83 of S100A14 are essential for the two proteins binding.Moreover,we observe a decrease of HER2 phosphorylation, downstream signaling, and HER2-stimulated cell proliferation in S100A14-silenced MCF-7, BT474, and SK-BR3 cells. Our findings suggest that S100A14 functions as a modulator of HER2 signaling and provide mechanistic evidence for its role in breast cancer progression.

Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in patients with early-stage breast cancer. The need for therapeutic ALND is the subject of ongoing debate especially after the publication of the ACOSOG Z0011 trial. In a retrospective trial with univariate and multivariate analyses, factors predictive of sentinel lymph node involvement should be analyzed in order to define tumor characteristics of breast cancer patients, where SLNB should not be spared to receive important indicators for adjuvant treatment decisions (e.g. thoracic wall irradiation after mastectomy with or without reconstruction). Between 2006 and 2010, 1,360 patients with primary breast cancer underwent SLNB with/without ALND with evaluation of tumor localization, multicentricity and multifocality, histological subtype, tumor size, grading, lymphovascular invasion (LVI), and estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status. These characteristics were retrospectively analyzed in univariate and multivariate logistic regression models to define significant predictive factors for sentinel lymph node involvement. The multivariate analysis demonstrated that tumor size and LVI (p<0.001) were independent predictive factors for metastatic sentinel lymph node involvement in patients with early-stage breast cancer. Because of the increased risk for metastatic involvement of axillary sentinel nodes in cases with larger breast cancer or diagnosis of LVI, patients with these breast cancer characteristics should not be spared from SLNB in a clinically node-negative situation in order to avoid false-negative results with a high potential for wrong indication of primary breast reconstruction or wrong non-indication of necessary post-mastectomy radiation therapy. The prognostic impact of avoidance of axillary staging with SLNB is analyzed in the ongoing prospective INSEMA trial.