Detection and Significance of Occult Axillary Metastatic Disease in Breast Cancer Patients

▪ Abstract: After clinical staging, the single most important prognostic factor for patients with newly diagnosed primary breast cancer is the presence or absence of detectable metastases to axillary lymph nodes when examined by conventional light microscopy. More sensitive methods of determination of lymph node status, such as evaluation of serial sections, immunohistochemical staining, and use of molecular biological assays increase the rate of detection of micrometastases. Although the feasibility of enhanced detection of occult axillary metastatic disease is well established, the prognostic significance of such detection is only recently starting to emerge. Furthermore, the enormous recent interest in the application of sentinel lymph node biopsy as an alternative to the evaluation of the entire axilla in patients with breast cancer makes the first-time detailed evaluation for micrometastases practically feasible. In this review the different methods of detecting micrometastatic disease in the axilla and the significance of such findings are discussed. ▪     

Supraclavicular and Contralateral Axillary Lymph Node Involvement in Breast Cancer Patients

Annals of Surgical Oncology - Ipsilateral supraclavicular disease was reclassified from Stage IV, distant metastatic disease, to Stage IIIC, locally advanced breast cancer 20 years ago. Treatment...     

Axillary Metastasis as the First Manifestation of Occult Breast Cancer in a Male Patient

Summary

Background

The aim of this study was to investigate the clinicopathologic features of male breast cancer.

Case Report

We present the clinicopathologic data of a 72-year-old male patient with occult breast cancer, who was diagnosed and underwent surgery in our hospital. The diagnosis was confirmed by histological examination, and the patient underwent modified radical mastectomy and axillary dissection. The histological examination showed no tumor foci in the resected breast tissue, but 2 of 15 dissected axillary lymph nodes were invaded by infiltrating ductal carcinoma. Immunohistochemistry staining was negative for both estrogen and progesterone receptors, but showed expression of p53 protein (+++), proliferating cell nuclear antigen (PCNA) (+++), Bcl-2 on-coprotein (+++), nm23 protein (++), multidrug resistance protein (MRP) (++), and human epidermal receptor (HER-2) oncoprotein (+++). 24 months after being diagnosed, the patient is alive without any residual or metastatic disease.

Conclusions

Breast cancer is very rare in men, and the occurrence of occult breast cancer is even less common. Axillary metastases can present as the first manifestation of breast cancer in a male.Key Words: Male breast cancer, Metastasis, Pathology, Hereditary nonpolyposis colorectal cancer, HNPCC     

Retrospective Study of Women Presenting with Axillary Metastases from Occult Breast Carcinoma

Although palpable axillary lymphadenopathy is most often related to benign disorders, it may be a harbinger of an underlying advanced malignancy. Fewer than 1% of patients diagnosed with breast cancer initially present with axillary metastases as their only clinical manifestation. This study represents the Mayo Clinic experience with women with occult breast cancer who presented with axillary metastases. Among a group of 44 women undergoing axillary biopsy for a palpable mass, 35 had histologic evidence of a metastatic carcinoma of primary breast cancer origin. Our retrospective analysis focused on the workup, identification, treatment, and outcome of these 35 women. All 35 women had a palpable axillary nodule, no dominant breast mass, and normal mammograms and chest radiographs. Histologic analysis of the axillary node revealed a probable breast cancer in all patients. Long-term follow-up was available for 33 patients (mean 71.5 months, range 4–252 months). Mastectomy was performed as part of the primary treatment in 18 patients (51%), and among them a primary breast tumor was found in 6 (33%). Of the women who underwent mastectomy (n = 18) and for whom follow-up data were available (n = 17), six developed tumor recurrence (35%), and four died of their disease (24%). Among the patients who did not undergo mastectomy (n = 17) as their primary treatment, follow-up revealed that 12 (of 16) patients developed recurrent disease (75%), and 11 patients died of breast carcinoma (69%). Despite extensive clinical and radiologic evaluation, a primary tumor was not initially located in any of the 35 women with axillary metastases from a presumed occult breast carcinoma. As a consequence of aggressive surgical intervention, six primary breast cancers were located in mastectomy specimens, and those 17 patients followed after mastectomy fared significantly better than the 16 patients without mastectomy (p = 0.047).     

The Incidence of Occult Nipple-Areola Complex Involvement in Breast Cancer Patients Receiving a Skin-Sparing Mastectomy

Background: Surgical treatment of breast cancer traditionally has included resection of the nipple-areola complex (NAC), in the belief that this area had a significant probability of containing occult tumors. The purpose of this study was to investigate the true incidence of NAC involvement in patients who underwent a skin-sparing mastectomy (SSM) and to determine associated risk factors.Methods: A retrospective chart review was conducted of 326 patients who had a SSM at our institution from 1990 to 1993. NAC involvement was reviewed in 286 mastectomy specimens. The charts were analyzed for tumor size, site, histology, grade, nodal status, recurrence, survival, and NAC involvement.Results: Occult tumor involvement in the NAC was found in 5.6% of mastectomy specimens (16 patients). Four patients would have had NAC involvement identified on frozen section if they had been undergoing a skin-sparing mastectomy with preservation of the NAC. There were no significant differences between NAC-positive (NAC+) and NAC-negative (NAC-) patients in median tumor size, nuclear grade, histologic subtype of the primary tumor, or receptor status. There were significant differences in location of the primary tumor (subareolar or multicentric vs. peripheral) and positive axillary lymph node status. NAC involvement was not a marker for increased recurrence or decreased survival.Conclusions: Occult NAC involvement occurred in only a small percentage of patients undergoing skin-sparing mastectomies. NAC preservation would be appropriate in axillary node-negative patients with small, solitary tumors located on the periphery of the breast.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Axillary Ultrasound in the Management of the Newly Diagnosed Breast Cancer Patient

Axillary lymph node status remains an important prognostic factor in patients with breast cancer. Axillary ultrasound (AUS) is an important tool in the workup of patients with newly diagnosed breast cancer and also has an emerging role evaluating the axilla after neoadjuvant chemotherapy. This review discusses the value of AUS in the workup and management of patients with newly diagnosed breast cancer and describes its role given the recent changes in axillary management.     

Axillary Lymph Node Status in Multicentric Breast Tumors and Breast Tumors with Nipple Involvement

Background

Axillary lymph node dissection plays an important role in breast cancer management in terms of staging, prediction of prognosis, determination of adjuvant therapy, and local control of the primary tumor. The objective of this study was to evaluate the axillary lymph node involvement in multicentric breast tumors and breast tumors with nipple involvement in comparison with unifocal tumors.

Patients and Methods

We reviewed the records of 267 patients with stage I or IIA disease. The rates of axillary lymph node metastasis (ALNM) in patients with unifocal tumors, multicentric tumors, or nipple involvement were compared.

Results

209 (78%) patients had unifocal tumors, 24 (8%) had multicentric tumors, and 34 (12%) had nipple involvement. The incidence of ALNM was 9.76% in patients with unifocal tumors, 24.84% in patients with multicentric tumors, and 36.71% in patients with nipple involvement. Hence, the incidence of ALNM was significantly higher in patients with nipple involvement or multicentric tumors than in patients with unifocal tumors.

Conclusion

Our data suggest that compared to unifocal tumors, breast tumors with nipple involvement or multiple foci show a significantly higher incidence of ALNM which is a predictor of a poor prognosis.     

隐匿性乳腺癌的诊治(附30例报告)

目的 总结隐匿性乳腺确（occult breast cancer，OBC）的诊治经验。方法 回顾性分析30例OBC的临床资料，均以腋下肿块为首发症状，并行手术治疗。结果 本组行乳腺癌根治术16例，改良根治术9例，腋下肿块切除加单纯乳房切除3例，腋下肿块切除术2例。术后14例予辅助化疗加放疗，10例予化疗。随访27例，平均6．8（0．5～12）年，5、10年生存率分别为75．5％和56．8％。结论 对女性腋窝肿块同时排除全身其他部位癌转移者应高度考虑OBC的可能。腋下肿块病检对诊断较有帮助，治疗可采用手术辅以放疗和（／或）化疗及内分泌治疗等综合手段。     

Favorable Outcome of Secondary Axillary Dissection in Breast Cancer Patients with Axillary Nodal Relapse

Purpose

Little evidence can be found about the long-term outcome of breast cancer patients after axillary lymph node recurrence (ALNR) and its survival benefit after different kinds of management. The present study intends to evaluate the risk factors associated with axillary recurrence after definite surgery for primary breast cancer. The prognosis after ALNR and particularly outcome of different management methods also were studied.

Methods

We retrospectively reviewed data from 4,473 patients who were diagnosed with primary breast cancer and received surgical intervention in a single institute from January 1990 to December 2002. Medical files were reviewed and data on survival were updated annually. Risk factors and prognosis of patients with axillary recurrence were analyzed. Breast–cancer-specific survival of patients with ALNR and outcomes after different management methods also were studied.

Results

After a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of patients. Factors associated with ALNR included: age younger than 40 years, medial tumor location, no initial standard level I &; II axillary dissection, and not receiving hormonal therapy. The 5-year breast–cancer-specific survival after ALNR was 57.9%. For patients who received further axillary dissection, the 5-year survival rate was 82.5% compared with 44.9% for patients who did not receive further dissection.

Conclusions

ALNR is a rare event in treating breast cancer. Young age at diagnosis and medially located tumor are associated with higher risk, but standardized initial axillary dissection to level II and adjuvant hormonal therapy is protective against ALNR. In patients with ALNR, the outcome is not dismal and survival may be improved if further axillary dissection is given.     

隐匿性乳腺癌的诊断与治疗

以腋窝淋巴结转移癌为首发症状的乳腺癌被称为隐匿性乳腺癌。现代影像学技术的发展让乳腺中微小的原发病灶愈加难以遁形。但为何这小小病灶可以发挥巨大能量，在腋窝淋巴结处蓬勃发展，让我们来揭开它的神秘面纱，一探究竟。     

Management of Contralateral Axillary Sentinel Lymph Nodes Detected on Lymphoscintigraphy for Breast Cancer

Background

Detection of a contralateral axillary sentinel lymph node (SLN) during lymphoscintigraphy for breast cancer is rare, and its significance and management are unclear. The purpose of this study was to review our experience and analyze our results together with similar patients in the literature to identify common characteristics and propose a management strategy.

Methods

A PubMed search was performed for articles describing patients in whom contralateral axillary drainage was identified on lymphoscintigraphy. Additionally, a chart review was performed of all patients who had lymphoscintigraphy for breast cancer at our institution.

Results

At our institution, two of 988 (0.3 %) consecutive patients were identified with contralateral axillary drainage on lymphoscintigraphy. Twenty-seven publications describing 105 patients with contralateral axillary drainage were found. This comprised our study group of 107 patients. Lymphoscintigraphy patterns varied depending on the history and type of prior surgery. A history of chest/axillary surgery was significantly associated with absence of an ipsilateral SLN (p < 0.05). This was observed in 84.2 % of patients with prior axillary lymph node dissection versus 33.3 % with prior SLN. Contralateral SLN biopsy was attempted in 85 patients (79.4 %); 22 (20.6 %) were positive for tumor. In 17 patients (15.9 %), the contralateral node was the only positive SLN.

Conclusions

These findings suggest that contralateral uptake on lymphoscintigraphy, though rare (0.2 %), is clinically significant and such nodes should undergo excision. Because contralateral uptake is significantly associated with prior chest/axillary surgery, routine lymphoscintigraphy should be considered in this group, as it has potential to change disease stage and management.     

Magnetic Resonance Imaging Facilitates Breast Conservation for Occult Breast Cancer

Introduction: Occult primary breast cancer, i.e., isolated axillary adenocarcinoma without detectable tumor in the breast by either physical exam or mammography, represents up to 1% of operable breast cancer. Modified radical mastectomy (MRM) is generally the accepted treatment for this condition although tumor is identified in only two-thirds of mastectomy specimens. Breast magnetic resonance imaging (MRI) can identify occult breast carcinoma and may direct therapy. This study examined the ability of breast MRI to detect occult breast cancer and to facilitate breast conservation therapy.Methods: Forty women with biopsy-proven metastatic adenocarcinoma to an axillary lymph node and no evidence of primary cancer were studied. All patients had a physical examination, mammography, and MRI of the breast. Using a dedicated breast coil, MRI imaging was performed with and without gadolinium enhancement. Positive MRI scans were compared with histopathologic findings at the time of operation (n 5 21).Results: MRI identified the primary breast lesion in 28 of 40 women (70%). Of these 28 patients, 11 had MRM, 11 had lumpectomy/axillary lymph node dissection (ALND)/radiotherapy (XRT), 2 had ALND/XRT alone, and 4 had no local treatment secondary to stage IV disease. Two women initially treated with lumpectomy/ALND subsequently had mastectomy for positive margins. Of the women with positive MRI who had breast surgery, 21 of 22 (95%) had tumor within the surgical specimen. Twelve women had negative MRI of the breast. Five of these 12 underwent MRM, of whom 4 had no tumor in the mastectomy specimen. The remaining 7 patients had ALND and whole breast radiation (ALND/XRT) (n 5 5), or were observed (n 5 2). Overall, 18 of 34 women surgically treated had MRM, while 16 (47%) preserved their breast. Tumor yield for patients having breast surgery was 81%.Conclusions: MRI of the breast can identify occult breast cancer in many patients and may facilitate breast conservation in select women. Negative breast MRI predicts low tumor yield at mastectomy.     

Clinical Benefits of Mastectomy on Treatment of Occult Breast Carcinoma Presenting Axillary Metastases

Abstract: Occult breast carcinoma presenting axillary metastases is uncommon and accounts for less than 1% of newly diagnosed breast carcinoma. However, it continues to be a challenging diagnostic and therapeutic problem. In this study, we analyzed retrospectively on 51 cases of occult breast cancer from 1990 to 2003 in our hospital. All these patients had a palpable axillary nodule, no dominant breast mass, and no abnormal mammograms and breast ultrasonograph. Histological examination of axillary mass revealed metastasis from breast. The positive rate of estrogen receptor, progesterone receptor and the monoclonal antibody M4G3 against human breast cancer showed 62.7%, 66.7%, and 93.1% positive respectively. Among 51 cases, 38 cases received mastectomy whereas 13 cases had no local treatment of the breast. The primary tumors were detected in 28 of 38 cases having mastectomy by pathology. Seventy‐seven percent of patients who had no local treatment of the breast had a tumor recurrence, compared with 26% who had a mastectomy. The mean disease‐free survival was 23 months in patients who had no local treatment of the breast, compared with 76 months in patients who had mastectomy. Eight of the 13 patients who had no treatment with breast died whereas seven of the 38 who had local treatment died, with a mean follow‐up of 73 months. It was found that patients having mastectomy had a better disease‐free survival (p < 0.001) and overall survival (p < 0.001) compared with those having no local treatment of the breast. Once the diagnosis of occult breast carcinoma is clarified, an axillary dissection and the local treatment of breast should be carried out.     

Necessity of Axillary Dissection in Elderly Women with Early Breast Cancer

The need for axillary dissection forstaging and treating early breast cancer has been questioned recently.Can a patient forego axillary dissection, with its associated costs,risks, and morbidity, if it does not affect survival? The studyattempted to find a subset of patients with early breast cancer in whomdisease-free survival was independent of axillary lymph node status. Ifsurvival does not depend on lymph node status, axillary dissectioncould be omitted in the care of these patients. This study included 378women over age 70 with T1 breast cancer diagnosed and treated duringJanuary 1992 to December 1999 at both of our institutions: a largetertiary teaching hospital in Columbus, Ohio and a breast cancertreatment center in West Columbia, South Carolina. We compared thedisease-free survival, using the Kaplan-Meier estimate, in 334node-negative patients and 44 node-positive patients with T1 breastcancer. The 3- and 5-year survival rates of patients with T1N0 tumorswere 86% and 77%, respectively; and the 3- and 5-year survival ratesfor T1 node-positive tumors were 81% and 69%, respectively(p = 0.0673). There was no statistical difference between thenode-negative and node-positive groups. Axillary dissection in womenover 70 years of age with early breast cancer may be unnecessary, asthe presence of lymph node metastases does not appear to affectdisease-free survival rates significantly in this patient group.     

Prognostic Significance of Residual Breast Disease and Axillary Node Involvement for Patients Who Had Primary Induction Chemotherapy for Advanced Breast Cancer

Background We performed this study to determine the prognostic significance of clinical tumor size, pathologic measurement of residual tumor, and number of positive axillary nodes in the surgical specimen relative to overall survival for patients who underwent primary induction chemotherapy for advanced breast cancer. Methods Data, collected prospectively between 1997 and 2002, included clinical tumor-node-metastasis stage, age at diagnosis, hormone receptor status, type of preoperative chemotherapy, histological type, surgical procedure, pathologic measurement in centimeters of residual breast tumor, and the number of positive axillary nodes in the surgical specimen. Univariable correlates of residual breast disease were assessed by using the χ² test. Recursive partitioning analysis was used to determine the prognostic significance of clinical tumor size, residual tumor size, and pathologic node involvement relative to overall survival. Survival was estimated by using the method of Kaplan and Meier and compared by using the log-rank test. A P value of < .05 was considered significant. Results Data were available for 85 patients with advanced breast cancer. Although univariable analysis identified increasing age, clinically involved axillary nodes, and a higher clinical tumor-node-metastasis stage as predictors of an increased risk of residual disease, recursive partitioning analysis identified more than three involved axillary nodes in the surgical specimen, with or without any measurable residual breast disease, as the most significant predictor of decreased survival (P < .001). Conclusions Pathologic axillary node involvement was the most significant predictor of decreased survival for patients who had undergone primary induction chemotherapy for advanced breast cancer.