Periarterial or perivenous invasion is an independent indicator of lymph node metastasis in invasive breast carcinoma of no special type.

Pathological diagnosis of breast cancer often includes cases of lymph node metastases without lymphatic or lymphovascular invasion by the primary tumor. In this study, to resolve this discrepancy, we designed a sensitive method to detect lymphatic invasion and correlate it with lymph node metastasis. Elastica van Gieson (EVG) staining and D2-40 immunohistochemistry revealed the abundant distribution of lymphatic vessels around blood vessels in the mammary tissue in close proximity to the elastic fibers around the arteries and veins. Based on the histological location of the blood and lymphatic vessels, we hypothesized that, in breast cancer, perivascular invasion is similar to lymphatic invasion and correlates with the presence of lymph node metastasis. Using EVG staining, perivascular invasion was histologically classified into periarterial invasion (periA), perivenous invasion (periV), and periarterial or perivenous invasion (periA/V). We tested our method and compared it to other methods commonly used for identifying lymphatic invasion in 105 patients with invasive breast carcinoma of no special type (IBC-NST) who received minimal preoperative therapy. The correlation between perivascular invasion and lymph node metastasis in these patients was statistically analyzed, including findings related to lymphatic invasion, such as retractile artifacts and perineural invasion. PeriA, periV, and periA/V showed significant correlations with lymph node metastasis. PeriA/V had high sensitivity and negative predictive value. The odds ratio (OR) for periV was significantly high in the univariate analysis, while the ORs for periA/V, retraction artifacts, and perineural invasion were significantly high in both the univariate and multivariate analyses. In particular, periA/V revealed a strong correlation with lymph node metastasis (OR: 61.8). These findings indicate that the IBC-NST periA/V ratio is a sensitive pointer of lymphatic invasion and could be an independent and reliable indicator of lymph node metastasis.

Oncoplastic breast surgery to prevent "Bird's beak" deformity in the breast: a comparative retrospective study.

PURPOSES: Breast deformity occurring in the lower pole after breast conserving surgery (BCS) is known as bird's beak (BB) deformity. This retrospective study evaluated the outcomes in breasts reconstructed with a conventional closing procedure (CCP) and a downward-moving procedure (DMP), respectively, after BCS. METHODS: In CCP, the inferomedial and inferolateral portions of breast tissues were reapproximated toward the midline after wide excision to repair the breast defect. In DMP, the retro-areolar breast tissue was detached from the nipple-areolar complex after wide excision, and the upper pole breast tissue was moved downward to refill the breast defect. RESULTS: CCP was performed in 20 patients (Group A), and DMP was performed in 28 patients (Group B). Although retraction of the lower part of the breast was postoperatively observed in 13 (72%) of 18 patients from Group A, it was observed in 7 (28%) of 25 patients in Group B (p < 0.05). The downward pointing of the nipple was observed in 8 (44%) of 18 patients from Group A and in 4 (16%) of 25 patients in Group B (p < 0.05). CONCLUSIONS: DMP is more useful for preventing BB deformity than CCP.

Conservative Axillary Surgery May Prevent Arm Lymphedema without Increasing Axillary Recurrence in the Surgical Management of Breast Cancer.

Axillary lymph node dissection (ALND) has been associated with postoperative morbidities, including arm lymphedema, shoulder dysfunction, and paresthesia. Sentinel lymph node (SLN) biopsy emerged as a method to assess axillary nodal status and possibly obviate the need for ALND in patients with clinically node-negative (cN0) breast cancer. The majority of breast cancer patients are eligible for SLN biopsy only, so ALND can be avoided. However, there are subsets of patients in whom ALND cannot be eliminated. ALND is still needed in patients with three or more positive SLNs or those with gross extranodal or matted nodal disease. Moreover, ALND has conventionally been performed to establish local control in clinically node-positive (cN+) patients with a heavy axillary tumor burden. The sole method to avoid ALND is through neoadjuvant chemotherapy (NAC). Recently, various forms of conservative axillary surgery have been developed in order to minimize arm lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, conventional ALND may not be necessary in either cN0 or cN+ patients. Further studies with a longer follow-up period are needed to determine the safety of conservative axillary surgery.

Axillary Reverse Mapping in Clinically Node-Positive Breast Cancer Patients.

BACKGROUND: Axillary reverse mapping (ARM) nodes are involved in a significant proportion of clinically node-positive (cN+) breast cancer patients. However, neoadjuvant chemotherapy (NAC) is effective at decreasing the incidence of nodal metastases in cN+ patients. PATIENTS AND METHODS: One hundred forty-five cN+ patients with confirmed nodal involvement on ultrasound-guided fine needle aspiration cytology were enrolled in this study: one group underwent axillary lymph node dissection (ALND) without NAC (upfront surgery group), and the other group underwent ALND following NAC (NAC group). The patients underwent 18F-FDG-positron emission tomography/computed tomography (18F-FDG-PET/CT) before surgery, as well as an ARM procedure during ALND. RESULTS: the rates of involvement of ARM nodes in the NAC group were significantly lower than those of the upfront surgery group (36.6% vs. 62.2%, p < 0.01). Notably, involvement was significantly decreased after NAC in non-luminal-type tumors as compared to the luminal-type (18.4% vs. 48.5%: p < 0.01). Moreover, there was a significant difference in ARM node involvement after NAC between patients with or without axillary uptake of 18F-FDG (61.5% vs. 32.5%: p < 0.01). CONCLUSIONS: NAC significantly decreased the risk of ARM node metastases in cN+ patients, but 18F-FDG-PET/CT was not suitable to detect residual metastatic disease of the axilla after NAC.

The involvement of axillary reverse mapping nodes in patients with node-positive breast cancer.

INTRODUCTION: Axillary reverse mapping (ARM) procedure is useful in reducing lymphedema. However, concerns regarding oncologic safety have limited the adoption of the ARM procedure. This study aimed to evaluate the involvement of ARM nodes in node-positive breast cancer patients. MATERIALS AND METHODS: Two hundred twenty-three node-positive patients were enrolled in this study: 90 were clinically node-negative, but had one or more positive sentinel lymph nodes (SLNs) (SLN-positive group); 68 were clinicopathologically node-positive (CpN-positive group); and 65 had confirmed nodal involvement and received neoadjuvant chemotherapy (NAC) (NAC group). All patients underwent axillary lymph node dissection with fluorescent ARM. RESULTS: ARM nodes were involved in 33 (36.7%) patients of the SLN-group. Residual ARM nodes after SLN biopsy were involved in 11 patients (12.2%), including 5 patients (19.2%) with crossover type nodes and 6 patients (9.4%) with non-crossover type nodes. However, the difference in involvement rates between the two types was not high enough to be significant. Of these 11 patients, moreover, four patients had three or more than 3 involved SLNs. On the other hand, the involvement rate of ARM nodes in the NAC group was significantly lower than that of the CpN-positive group (35.4% vs. 64.7%: p < 0.01). Despite lower involvement, the risk of metastases in the ARM nodes was still too high to spare ARM nodes in both the NAC group and CpN-positive group. CONCLUSIONS: Suspicious or involved ARM nodes should be removed even when detected in ARM procedure, particularly in NAC-group and CpN-positive-group patients.

Conservative axillary surgery is emerging in the surgical management of breast cancer.

Axillary lymph node dissection (ALND) has been the standard axillary treatment for breast cancer for a long time. However, ALND is associated with postoperative morbidities, including local sensory dysfunction, reduced shoulder mobility and most notably arm lymphedema. Recently, ALND can be avoided not only in clinically node-negative (cN0) patients with negative sentinel lymph nodes (SLNs), but also in patients with less than 3 positive SLNs receiving breast radiation, axillary radiation, or a combination of the two. Moreover, SLN biopsy has been adopted for use in clinically node-positive (cN +) patients presenting as cN0 after neoadjuvant chemotherapy (NAC); ALND may be avoided in cN + patients who convert to SLN-negative following NAC. Patients who undergo SLN biopsy alone have less postsurgical morbidities than those who undergo ALND. Nevertheless, ALND is still required in a select group of patients. A variety of conservative approaches to ALND have been developed to spare arm lymphatics to minimize arm lymphedema. These conservative procedures seem to decrease the incidence of lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, full conventional ALND removing all microscopic axillary disease may now be unnecessary in both cN0 patients and cN + patients. Regardless, emerging procedures for ALND should still be considered as investigational approaches, as further studies with longer follow-up are necessary to determine the safety of conservative ALND to spare arm lymphatics.

The role of axillary reverse mapping in intraoperative nodal palpation during sentinel lymph node biopsy.

Intraoperative nodal palpation in the axilla is a mandatory part of sentinel lymph node biopsy. However, there is no consensus regarding the definition of suspicious palpable node. The sampling rate and involvement rate of suspicious palpable nodes are inconsistent. We hypothesized that axillary reverse mapping is helpful to select suspicious palpable sentinel lymph nodes more accurately. Patients with clinically negative nodes underwent sentinel lymph node biopsy with intraoperative nodal palpation and axillary reverse mapping. Blue and hot nodes were removed as sentinel lymph nodes. Suspicious palpable nodes that were neither blue nor hot were removed as palpable sentinel lymph nodes. Nodes around blue and hot sentinel lymph node were incidentally removed as para-sentinel lymph nodes. Fluorescent nodes were considered axillary reverse mapping nodes. Patients with positive sentinel lymph node underwent axillary lymph node dissection. Palpable sentinel lymph nodes and para-sentinel lymph nodes were removed in 130 (15%) of 850 patients with clinically negative nodes. Although palpable sentinel lymph nodes and para-sentinel lymph nodes were involved in 19 (15%) of 130 patients, fluorescent palpable sentinel lymph nodes were involved only in 2 patients and fluorescent para-sentinel lymph nodes were not involved. When excluding fluorescent palpable sentinel lymph nodes and para-sentinel lymph nodes, the sampling rate of suspicious palpable nodes significantly decreased (15% vs. 5%, p < 0.01) and the involvement rate of palpable sentinel lymph nodes significantly increased (15% vs. 31%, p < 0.05). Axillary reverse mapping is helpful to avoid an unnecessary removal of palpable nodes without metastases.

Axillary surgery for breast cancer: past, present, and future.

In breast cancer surgery, there has been a major shift toward less invasive local treatment. Although axillary lymph node dissection (ALND) was an integral part of surgical treatment for breast cancer, sentinel lymph node (SLN) biopsy was developed as an accurate method for axillary staging. ALND can be avoided not only in patients with negative SLNs but also in those with one or two positive SLNs receiving breast and/or axillary radiation. On the other hand, ALND has remained the standard treatment for patients with clinically positive nodes. However, axillary reverse mapping (ARM) was developed to map and preserve arm lymphatic drainage during ALND and/or SLN biopsy. This procedure allowed reduction of the rate of arm lymphedema without increasing axillary recurrence, although patients receive postoperative chemotherapy and high-risk patients undergo axillary radiation. Standard ALND may not be necessary even for patients with clinically positive nodes who receive axillary radiation and systemic therapy. Thus, the extent of axillary surgery in breast cancer has been decreased with increased use of systemic and radiation therapy.

A case of recurrent malignant phyllodes tumor undergoing nipple-sparing mastectomy with immediate breast reconstruction.

BACKGROUND: Although the primary treatment for malignant phyllodes tumor (PT) is complete surgical excision with either breast-conserving surgery or total mastectomy, recent technical advances have led to the adoption of nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR). CASE PRESENTATION: A 28-year-old woman noticed a mass in her left breast that was rapidly increasing in size. She underwent tumor excision and a histological diagnosis of marked degenerative and necrotic induration suggested benign PT. One year later, however, she was found to have recurrent masses in the left breast on follow-up mammography and sonography. Needle biopsy was performed and the tumor was diagnosed as borderline or malignant PT. She underwent NSM and sentinel lymph-node biopsy with IBR using a tissue expander. Histological examination of the mastectomy specimen showed multiple fibroepithelial tumors with marked stromal overgrowth, focal necrosis, and hemorrhage. Stromal cells showed pleomorphism and a maximal mitotic rate of approximately 25 per 10 high-power fields. The tumor was diagnosed as malignant PT. She did not receive adjuvant chemotherapy or radiation treatment. At 3-year follow-up, the patient remains free of disease and highly satisfied with the cosmetic results. CONCLUSIONS: NSM with IBR is not a contraindication for malignant PT. It is both curative and can offer an appealing cosmetic option for localized malignant PT.

Axillary reverse mapping in patients undergoing axillary dissection -a short review of the literature.

Axillary lymph node dissection (ALND) can be avoided not only in patients with negative sentinel lymph nodes (SLNs) but also in those with one or two positive SLNs receiving breast or axillary radiation. However, ALND has remained the standard treatment for patients with clinically positive nodes (cN+). Although axillary reverse mapping (ARM) was developed to map and preserve arm lymphatic drainage during ALND, it could not be indicated for cN + patients because metastatic rate of ARM nodes is high. However, a new type of conservative ALND with ARM attempts to preserve ARM lymphatics and nodes except SLNs and other suspicious palpable nodes, including suspicious ARM nodes. This procedure allowed reduction of the rate of arm lymphedema without increasing axillary recurrence, although patients received postoperative chemotherapy and high-risk patients underwent axillary radiation. Thus, a traditional full ALND may not be necessary for cN + patients in the era of effective multimodality therapy.

An autocrine/paracrine circuit of growth differentiation factor (GDF) 15 has a role for maintenance of breast cancer stem-like cells.

Cancer stem cells are thought to be responsible for tumor growth, recurrence, and resistance to conventional cancer therapy. However, it is still unclear how they are maintained in tumor tissues. Here, we show that the growth differentiation factor 15 (GDF15), a member of the TGFß family, may maintain cancer stem-like cells in breast cancer tissues by inducing its own expression in an autocrine/paracrine manner. We found that GDF15, but not TGFß, increased tumor sphere formation in several breast cancer cell lines and patient-derived primary breast cancer cells. As expected, TGFß strongly stimulated the phosphorylation of Smad2. GDF15 also stimulated the phosphorylation of Smad2, but the GDF15-induced tumor sphere forming efficiency was not significantly affected by treatment with SB431542, an inhibitor of the TGFß signaling. Although TGFß transiently activated ERK1/2, GDF15 induced prolonged activation of ERK1/2. Treatment with U0126, an inhibitor of the MEK-ERK1/2 signaling, greatly inhibited the GDF15-induced tumor sphere formation. Moreover, cytokine array experiments revealed that GDF15, but not TGFß, is able to induce its own expression; furthermore, it appears to form an autocrine/paracrine circuit to continuously produce GDF15. In addition, we found heterogeneous expression levels of GDF15 among cancer cells and in human breast cancer tissues using immunohistochemistry. This may reflect a heterogeneous cancer cell population, including cancer stem-like cells and other cancer cells. Our findings suggest that GDF15 induces tumor sphere formation through GDF15-ERK1/2-GDF15 circuits, leading to maintenance of GDF15high cancer stem-like cells. Targeting GDF15 to break these circuits should contribute to the eradication of tumors.

The roles of 18F-FDG-PET/CT and US-guided FNAC in assessment of axillary nodal metastases in breast cancer patients.

BACKGROUND: There is a need for less invasive techniques for preoperative identification of axillary lymph node (ALN) metastases. METHOD: Patients underwent ultrasonography (US) and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT), and then US-guided fine needle aspiration cytology (FNAC) and/or sentinel lymph node (SLN) biopsy were performed based on the US findings of the ALNs. Subsequently, patients with positive FNAC as well as those with positive SLN underwent axillary lymph node dissection (ALND). Postoperatively, removed SLNs and ALNs were examined histologically. RESULTS: Fifty (85 %) of 59 patients with positive 18F-FDG uptake in the axilla had axillary metastases, but 18F-FDG uptake results were false-positive in 9 (15 %) cases. On the other hand, 29 patients with positive FNAC underwent ALND without the need for SLN biopsy, while the remaining 20 patients with negative FNAC as well as 249 patients with negative US findings underwent SLN biopsy. Subsequently, 68 patients with positive SLN underwent ALND. CONCLUSIONS: Positive FDG uptake in the axilla does not always indicate axillary metastasis. US-guided FNAC is useful to avoid unnecessary ALND in patients with positive 18F-FDG uptake. However, SLN biopsy is needed in patients with negative US findings of the ALNs and those with negative FNAC.

The changing role of axillary lymph node dissection for breast cancer.

Currently, it is standard practice that patients with negative sentinel lymph nodes (SLNs) do not undergo axillary lymph node dissection (ALND), whereas ALND is mandated in those with positive SLNs. However, the Z0011 trial showed that ALND could be safely omitted in selected patients with positive SLNs. This article presents a review and discussion of the current role and practice of ALND in the surgical management of breast cancer. A review of the English-language medical literature was performed using the MEDLINE database and cross-referencing major articles on the subject. It may be concluded that ALND can be avoided not only in patients with negative SLNs but also in those with positive SLNs who undergo breast-conserving therapy with whole-breast irradiation and appropriate systemic therapy. However, the omission of ALND would be indicated only in patients with a low axillary tumor burden. On the other hand, ALND remains a standard method of treating regional disease not only in patients with clinically positive nodes but also in other SLN-positive patients who do not meet the above criteria. Although the role of ALND has been limited to the prevention of axillary recurrence, SLN biopsy with whole-breast irradiation and systemic therapy can replace ALND in patients with a low axillary tumor burden.

Nipple- or skin-sparing mastectomy and immediate breast reconstruction by the "moving window" operation.

BACKGROUND: Endoscope-assisted skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) has been developed to minimize the skin incision and to improve the cosmetic outcome of reconstructed breast for patients with breast cancer. However, this procedure can be performed without using endoscopic instruments. METHODS: We have performed SSM or NSM via a small periareolar incision with axillary incision using wound retractors without disposable endoscopic instruments. After the entire breast tissue was removed, immediate breast reconstruction (IBR) using tissue expanders was performed through the axillary incision. RESULTS: Twelve patients (13 cases: 1 patient had synchronous bilateral primary cancer) underwent NSM, and 8 had SSM because of involvement of the nipple-areola complex. IBR was performed with tissue expanders in 18 patients, while 2 patients refused to have IBR because of small breast size. When 3 patients with synchronous or metachronous bilateral breast cancer were excluded, the average length of surgery was 267 min in 15 patients who underwent SSM or NSM followed by IBR with implants, while it was only 120 min in 2 patients who underwent NSM alone. Average blood loss was 135 mL (range 40-350 mL). CONCLUSION: We have described a novel technique using the wound retractor for SSM or NSM followed by IBR in treating breast cancer patients. This technique can minimize skin incisions without using disposable endoscopic instruments and improve the cosmetic outcome of the reconstructed breast.

[A case of port site recurrence after thoracoscopic resection for lung metastasis of cecal cancer].

We experienced a case of port site recurrence after thoracoscopic resection for lung metastasis of cecal cancer. The patient was a 57-year-old woman who underwent right hemicolectomy at the age of 51 following a diagnosis of cecal carcinoma. She underwent video-assisted thoracic surgery for pulmonary metastasis 2 years after the first surgery. She underwent local resection for a retroperitoneal pelvic wall recurrence 3.5 years after the first surgery. Chest wall port site recurrence occurred 5.5 years after the first surgery, and she underwent partial resection of the left lung and chest wall. Subsequent treatment has been performed with adjuvant chemotherapy, and she is healthy with no evidence of recurrence 7 years and 11 months after the initial surgery. In this case, a good prognosis was obtained by frequent local resection and adjuvant chemotherapy for metachronous multiple metastases.

[Recurrent breast cancer obtained long-term survival with local treatment(surgery and stereotactic body radiotherapy)and systemic therapy].

A 52-year-old woman developed right breast cancer and underwent modified radical mastectomy in 1994. Histologically, the tumor was invasive ductal carcinoma. She was positive for estrogen receptor (ER) but negative for progesterone receptor(PgR), while her human epidermal growth factor receptor type 2(HER2) status was not examined. Although she received adjuvant hormone therapy and chemotherapy[cyclophosphamide+doxorubicin+5-fluorouraci(l CAF), 6 courses ], she underwent partial pulmonary resection on both sides with right oophorectomy in 1997. Subsequently, she was treated with weekly doses paclitaxel(12 courses). However, she developed a pulmonary metastasis in the left breast. In 2002, she underwent a partial left pulmonary resection (ER-positive and HER2 3+) and treatment with an aromatase inhibitor. Subsequently, she was treated with trastuzumab because of repeated lung metastasis. A complete response was obtained after the administration of trastuzumab. In 2008, she developed bone metastasis in the sternum and the left seventh rib, and subsequently underwent stereotactic body radiotherapy (SBRT). She was treated with trastuzumab and aromatase inhibitor. At present, she is free of pain and is still living 15 years after breast cancer recurrence. This case suggests that the interaction of local treatment(surgery and SBRT) and systemic therapy(chemotherapy, hormonal therapy, and monoclonal therapy) may improve the survival of patients with recurrent breast cancer.

Axillary reverse mapping using a fluorescence imaging system in breast cancer.

BACKGROUND: The axillary reverse mapping (ARM) procedure is based on the hypothesis that the lymphatic drainage from the upper arm is different from that of the breast. However, the oncologic safety of the procedure has not yet been determined. METHODS: The ARM nodes were identified using a fluorescence imaging system. Axillary lymph node dissection (ALND) was performed in patients with clinically involved nodes, and the ARM nodes were removed separately during ALND. Sentinel lymph node (SLN) biopsy was performed in patients with clinically uninvolved nodes. If the SLN was positive, ALND was performed with removal of ARM nodes. Otherwise, the identified ARM nodes were preserved unless they were the same as the SLN. RESULTS: ARM nodes were identified in 29 (85%) of 34 patients who underwent ALND, and 11 had tumor involvement. The ARM node was identified in 42 (43%) of 97 patients who underwent SLN biopsy, and it was the same as the SLN in 27 patients. However, in 15 patients with a positive SLN who subsequently underwent ALND, ARM nodes were tumor-free when they were not the same as the positive SLN. CONCLUSIONS: It may be feasible to spare ARM nodes during ALND in patients with positive SLN.