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.

Recurrent malignant phyllodes tumor of the breast: An extremely rare case of recurrence with only rhabdomyosarcoma components.

Rhabdomyosarcoma is a rare disease that typically occurs in children. Rhabdomyosarcoma seldom occurs in the breast, and its diagnosis and treatment have infrequently been reported. The present case is a rare one of a recurrent malignant phyllodes tumor of the breast with only rhabdomyosarcoma components. A 69-year-old woman received a diagnosis of borderline phyllodes tumor of the left breast and underwent partial mastectomy. During follow-up, a left breast mass was found 1 year and 8 months after the previous surgery. Based on examination findings, it was suspected to be recurrent phyllodes tumor, so total left mastectomy was performed in our hospital. After the surgery, immunostaining failed to determine the epithelial component which may be produced by the proliferative part of stromal cells of previous phyllodes tumors. However, we could not exclude the possibility that this was a new tumor. After comparing samples with specimens from the first operation, it was finally determined to be a malignant phyllodes tumor with a rhabdomyosarcoma component. Therefore, chemotherapy was given, and vincristine, actinomycin D, and cyclophosphamide therapy was introduced. At the same time, radiation therapy was planned. Among phyllodes tumors, cases involving rhabdomyosarcoma components are very rare, especially those where the recurrence morphology only shows the same rhabdomyosarcoma components. This was a rare case with unique characteristics and great reference value.

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.

A unique surgical case of giant invasive intracystic carcinoma of the male breast focusing on cytological findings.

A 60-year-old male presented with a history of a relatively hard and cystic right chest mass that had gradually increased in size, with subsequent skin erosion, exudate and hemorrhage. The cytologic specimens from a cyst fluid contained a large number of sheet-like or papillary clusters of atypical cuboidal to columnar epithelial cells with loss of myoepithelial components, in a severely inflammatory background with scattered siderophages. We first interpreted it as a carcinoma, but could not completely exclude out the possibilities of benign. Tumor extirpation was performed, and a gross examination of the neoplasm revealed a giant, cystic and partly solid papillary-projected tumor lesion, with a gray-whitish cut surface, associated focally with skin invasion, measuring approximately 9 × 7 cm with a 6 × 4 cm solid area in diameter. On a microscopic examination, solid parts of the tumor were predominantly composed of the intracystic proliferation of mildly atypical epithelial cells with absence of two-cell patterns in a papillary or papillotubular growth fashion, only partly involving the dermis to epidermis. Immunohistochemistry showed that the carcinoma cells were specifically positive for estrogen and progesterone receptors, whereas negative for p63, S-100 protein and several neuroendocrine markers. Therefore, we finally made a diagnosis of invasive intracystic carcinoma of the male breast. We should be aware that owing to its characteristic cytological features, cytopathologists might be able to make a correct diagnosis of that, based on multiple and adequate samplings, even though a core biopsy would be the absolute minimum assessment.

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.

[Treatment Outcomes of Advanced Gastric Cancer after Neoadjuvant Chemotherapy with S-1 and Cisplatin].

BACKGROUND: The prognosis after neoadjuvant chemotherapy(NAC)is expected to improve in patients with resectable advanced gastric cancer who are at high risk of recurrence or those with unfavorable prognostic factors. PATIENTS AND METHODS: This retrospective study examined treatment outcomes and survival of 25 patients with advanced gastric cancer who received NAC with S-1 and cisplatin(CDDP)between October 2008 and December 2015. RESULTS: Among patients with clinical Stage II (4 patients)and III (21 patients)tumors, 13 had partial response(PR)and 12 had stable disease(SD). Neither complete response(CR)nor progressive disease(PD)was noted. CR of lymph node metastases was observed in 6 patients, PR in 9 patients, and SD in 7 patients. R0 resection was performed in 16 patients, R1 in 3 patients, and R2 in 6 patients. Histologic grades of primary tumors were Grade 0(1 patient), Grade 1a(16 patients), Grade 1b(5 patients), Grade 2(3 patients), and Grade 3(none). The 3-year survival rate after R0 resection was 46%, 3-year progression-free survival rate was 68%, and 3-year recurrence-free survival rate was 69%. Significant differences were observed for pathologic stages ypN0/1, 2, and 3(p=0.04), tumor down-stage(p=0.02), and overall tumor fStage I , II / III , and IV (p<0.01). CONCLUSION: It is conceivable that R0 resection and downstaging after NAC will improve prognosis.

[Clinical Analysis of Esophageal Bypass Surgery with Nutritional Assessment in Patients with Unresectable Esophageal Cancer].

BACKGROUND: Esophageal bypass surgery is palliative surgery for unresectable esophageal cancer with esophageal stenosis, which often leads to poor nutrition. We investigated the clinical characteristics, nutritional status, and outcomes of patients who underwent esophageal bypass surgery. PATIENTS AND METHODS: We reviewed 11 cases of esophageal bypass surgery for unresectable esophageal cancer performed in our hospital between 1992 and 2015, and we examined the surgical outcome along with preoperative nutritional assessment. RESULTS: There were 1, 9, and 1 cases of cStage Ⅲ, Ⅳa, and Ⅳb, respectively. For the bypass, a gastric tube was used in 8 cases and colon reconstruction in 3. Postoperative complications were 1 case of recurrent laryngeal nerve palsy (9%), 4 cases of anastomotic leakage (36%), and 4 cases of pneumonia (36%). The preoperative nutritional status (total protein, albumin, and cholinesterase levels) in the esophageal bypass group (n=11) was significantly worse than that in the esophagectomy group (n=40). The median survival of all patients (n=11) was 5.7 months. Patients receiving induction chemoradiotherapy followed by bypass surgery (n=7) had a median survival of 15.2 months. CONCLUSION: Since patients undergoing esophageal bypass surgery often present with malnutrition, attention to anastomotic leakage and infectious complications is necessary.

[A Successful Case of Treatment of Colonic Metastasis and Peritoneal Recurrence of Type 4 Gastric Cancer by Using Colectomy and Chemotherapy].

We present a successful case of treatment of colonic metastasis and peritoneal recurrence of type 4 gastric cancer by using colectomy and chemotherapy. A 70-year-old woman with a diagnosis of type 4 advanced gastric cancer underwent distal gastrectomy. The final pathological diagnosis was LM, circ, type 4, sig, pT4a (SE), ly1, v1, pN1, M0, P0, CY0, pStage Ⅲa. Adjuvant chemotherapy was conducted with oral administration of S-1, though regrettably the chemotherapy was interrupted because of diarrhea, an adverse effect of S-1. Metastatic recurrence occurred on the transverse colon, for which she underwent transverse colectomy 2.9 years after the initial surgery. Another colonic metastasis in the ascending colon along with peritoneal recurrence was diagnosed 3.11 years after the initial surgery, and the patient underwent a palliative colostomy and received chemotherapy with S-1 plus docetaxel. She was successfully treated up to a clinical CR with chemotherapy, and she died 5.10 years after the initial surgery. In this case, a good prognosis was obtained through the combination of resection of the recurrence sites, palliative surgery for avoiding obstruction, and chemotherapy using S-1 plus docetaxel for metachronous multiple metastases.

[A Case of Gastric and Pancreatic Cancer Resected with Curative Intent while Preserving Organ Function].

A 57-year-old woman was diagnosed with a pancreatic tumor. Abdominal computed tomography showed cStage Ⅳa pancreatic cancer with a 20×16 mm tumor near the base of the celiac artery. Since the tumor contacted the SMA at an angle of 90 degrees, it was judged as a borderline resectable tumor. In addition, cStage ⅠB gastric cancer was found in the corpus ventriculi. Since the patient had a respiratory complication, a distal pancreatectomy with celiac axis resection in combination with a total gastrectomy was considered too aggressive for this patient. Therefore, she received chemoradiotherapy prior to the surgery. Distal pancreatectomy with D2 lymphadenectomy and subtotal gastrectomy with lower left phrenic artery preservation was performed. This case involved a considerable extension of the disease and radical surgery; however, currently the patient's prognosis and QOL are good.

[Evaluation of combination chemotherapy with docetaxel and nedaplatin in patients with advanced or recurrent esophageal cancer].

BACKGROUND: There is no standard regimen after failure of 5-fluorouracil and cisplatin-based first-line chemotherapy in patients with advanced or recurrent esophageal cancer. The feasibility of combination chemotherapy with docetaxel (DOC) and nedaplatin (CDGP) for these patients was retrospectively evaluated. METHODS: Patients received DOC (30 mg/m² intra- venously) and CDGP (30-40 mg/m² intravenously) on days 1 and 15 of each 4-week period. The efficacy and toxicity of combination chemotherapy with DOC and CDGP in 13 patients was analyzed. RESULTS: The patients received a median of 2 cycles of treatment(range, 1-23). The response and disease control rates were 8% and 54%, respectively. Grade 3 or 4 hematological toxicities were neutropenia, anemia, and thrombocytopenia, observed in 4(31%), 11(15%), and 2 patients (15%), respectively. Non-hematological toxicity, anorexia, was detected in only 1 patient(8%). No treatment-related death was observed. The median progression-free survival and overall survival were 3.2 and 11.6 months, respectively. CONCLUSIONS: Combination chemotherapy with DOC and CDGP is considered a feasible regimen for refractory esophageal cancer.

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.