Positive Internal Mammary Nodes Research Articles

Radiotherapy for Initial Clinically Positive Internal Mammary Nodes in Breast Cancer

PURPOSE Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. MATERIALS AND METHODS We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. RESULTS The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. CONCLUSION RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.

Radiotherapy for initial clinically positive internal mammary nodes in breast cancer.

PurposeInternal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery.Materials and MethodsWe retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area.ResultsThe median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors.ConclusionRT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.

Internal Mammary Nodes in Breast Cancer: A Review of the Literature and Practical Surgical Recommendations

Background : Involvement of internal mammary lymph nodes with metastatic disease in breast cancer upstages the patient and carries a poorer prognosis. It is the most important prognostic factor after axillary nodal status. Although 75% of the breast lymphatic drainage goes to the axillary lymph nodes, extra-axillary lymph node basins drain the remainder. Extra-axillary recurrences led to the evolution from Halsted’s radical mastectomy to Wangensteen’s “super-radical” and Urban’s “extended-radical” mastectomies, which remove the internal mammary and supra-clavicular lymph nodes in addition to axillary nodes. However, these surgeries failed to improve disease free survival and overall survival and the interest in pursuing extra-nodal metastasis faded away. With the development of the sentinel node techniques, interest in extra-axillary lymph node metastasis was renewed because of identification of drainage to these locations. Several reports from different institutions demonstrate this renewed interest as well as the feasibility of procedures leading to upstaging and changing of treatment plans when metastasis to internal mammary nodes is identified. In this review, the literature addressing internal mammary lymph nodes in breast cancer is examined. Methods : Systematic review of the literature from 1867 to 2015. Conclusion : The techniques and factors that affect the reliability and reproducibility of internal mammary sentinel node biopsy are discussed. In addition, we discuss whether the treatment of positive internal mammary nodes translates into a survival advantage. Finally, we propose a minimally invasive working algorithm to internal mammary lymph node evaluation.

Abstract P2-01-28: Prognosis of metastatic internal mammary sentinel nodes (IMSN) in breast cancer

Abstract Introduction: The presence of positive internal mammary nodes has historically been associated with a significant worse prognosis. Recent studies have also demonstrated a worse prognosis associated with drainage to the internal mammary nodes. Intense search for those nodes, biopsy, appropriate staging and modern treatment for positive IMSN might improve outcome. We sought to study the prognosis of pathologically positive IMSN at our institution. Methods: A retrospective analysis of a prospectively collected database including all breast cancer patients identified with an IMSN that was biopsied between 2005 and 2012 was performed. Demographics, histologic markers, patterns of recurrence as well as survival data were collected. Univariate and multivariate analysis were performed. Results: Thirteen of 82 patients with a biopsied IMSN were metastatic (16%). In 8 of those (62%), the biopsy resulted in a change in staging. In all cases of positive IMSN additional radiation to the internal mammary chain was added. Eighteen percent (18%) of positive nodes did not show drainage to the internal mammary basin during Lymphoscintigraphy. There was no statistical difference in regional and distant recurrences between the patients with positive IMSN and those with negative IMSN. Furthermore there was no difference in disease specific survival. Conclusions: Intense search for IMSN presence and biopsy of those nodes is associated with changes in staging and treatment for metastatic IMSN. In our study, pathologically positive IMSN were associated with a non- inferior prognosis than negative IMSN. Citation Format: Eli Avisar, Shai Libson, Eduardo Perez. Prognosis of metastatic internal mammary sentinel nodes (IMSN) in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-28.

Incidental Internal Mammary Nodes during Recipient Vessel Dissection in Breast Reconstruction

Summary:Internal mammary (IM) lymph nodes may be exposed during recipient vessel preparation in free-flap breast reconstruction, and in rare cases, positivity of these nodes may affect treatment in patients with breast cancer. This systematic review examines the incidence and significance of IM nodes identified by plastic surgeons. Eligibility criteria included free-flap breast reconstruction with concurrent IM node biopsy. Data were analyzed for incidence of IM node biopsy and nodal positivity. Ten studies met inclusion criteria, with a total of 2055 patients and 717 nodes submitted to pathology. Incidence of IM positivity ranged approximately from 1% to 11%, for a calculated gross overall incidence of 2.9%. Of 59 patients with a positive IM node, 50 patients received additional adjuvant therapy, with insufficient data to determine the effect of treatment on survival.

Prognosis of metastatic internal mammary sentinel nodes (IMSN) in breast cancer.

103 Background: The presence of positive internal mammary nodes has historically been associated with a significant worse prognosis. Recent studies have also demonstrated a worse prognosis associated with drainage to the internal mammary nodes. Intense search for those nodes, biopsy, appropriate staging and modern treatment for positive IMSN might improve outcome. We sought to study the prognosis of pathologically positive IMSN at our institution. Methods: A retrospective analysis of a prospectively collected database including all breast cancer patients identified with an IMSN that was biopsied between 2005 and 2012 was performed. Demographics, histologic markers, patterns of recurrence as well as survival data were collected. Univariate and multivariate analysis were performed. Results: Thirteen of 82 patients with a biopsied IMSN were metastatic (16%). In 8 of those (62%), the biopsy resulted in a change in staging. In all cases of positive IMSN additional radiation to the internal mammary chain was added. Eighteen percent (18%) of positive nodes did not show drainage to the internal mammary basin during Lymphoscintigraphy. There was no statistical difference in regional and distant recurrences between the patients with positive IMSN and those with negative IMSN. Furthermore there was no difference in disease specific survival. Conclusions: Intense search for IMSN presence and biopsy of those nodes is associated with changes in staging and treatment for metastatic IMSN. In our study, pathologically positive IMSN were associated with a non- inferior prognosis than negative IMSN.

SU-E-T-66: Characterization of Radiation Dose Associated with Dark Currents During Beam Hold for Respiratory-Gated Electron Therapy

Purpose: The main objective of this study was to estimate the radiation dose contributed by dark currents associated with the respiratory-gated electron therapy during beam hold. The secondary aim was to determine clinical benefits of using respiratory-gated electron therapy for left-sided breast cancer patients with positive internal mammary nodes (IMN). Methods: Measurements of the dark current-induced dose in all electron modes were performed on multiple Siemens and Varian linear accelerators by manually simulating beam-hold during respiratory gating. Dose was quantified at the machine isocenter by comparing the collected charge to the known output for all energies ranging from 6 to 18 MeV for a 10cm × 10cm field at 100 SSD with appropriate solid-water buildup. Using the Eclipse treatment planning system, we compared the additional dose associated with dark current using gated electron fields to the dose uncertainties associated with matching gated photon fields and ungated electron fields. Dose uncertainties were seen as hot and cold spots along the match line of the fields. Results: The magnitude of the dose associated with dark current is highly correlated to the energy of the beam and the amount of time the beam is on hold. For lower energies (6–12 MeV), there wasmore » minimal dark current dose (0.1–1.3 cGy/min). Higher energies (15–18 MeV) showed measurable amount of doses. The dark current associated with the electron beam-hold varied between linear accelerator vendors and depended on dark current suppression and the age of the linear accelerator. Conclusion: For energies up to 12 MeV, the dose associated with the dark current for respiratorygated electron therapy was shown to be negligible, and therefore should be considered an option for treating IMN positive left-sided breast cancer patients. However, at higher energies the benefit of respiratory gating may be outweighed by dose due to the dark current.« less

Internal mammary node biopsy for breast cancer patients: Issues for discussion and our practice.

e22089 Background: The aims of this study was to determine the clinical implications of internal mammary node biopsy as staging, treatment with radiotherapy and systemic treatment and a prognostic factor in patients with breast cancer. Methods: Internal mammary node biopsy via intercostal space was performed in 344 cases of breast cancer. Anatomical location of internal mammary nodes were recorded. Pathological status of internal mammary node were detected by H and E stains. Results: Internal mammary node biopsy was successfully finished in 344 patients.There were 162 cases (48.26%) with positive axillary nodes, while the internal mammary nodes were involved in 72 cases (20.93%).53 patients (32.72%) had regional metastases in both the axillary and internal mammary lymph nodes.19 (5.52%) patients had internal mammary node metastasis but no axillary node metastases. PN stage migration was seen in 72 patients with a positive internal mammary node. There was no statistic relation between internal mammary nodes metastases and tumor location (X2 =0.48, P>0.05). There was no complication such as pneumothorax or haemorrhagia. Conclusions: The approach used is a reliable surgical technique for removing lymph node from intercostal space. Without exploring internal mammary nodes status, pN stage was incomplete. Internal mammary node biopsy enables treatment to be better adjusted to the needs of the individual patient. Using internal mammary node biopsy, patients with a negative internal mammary node can be prevented from radiation to internal mammary nodal areas. This leads to optimization of treatment.

Clinical and Pathological Evaluation of 102 Patients with Internal Mammary Node Metastases in a Single Breast Unit

INTRODUCTION: Although incidence of internal mammary node (IMN) recurrence is only 0.1%, and almost all of these patients have systemic disease, it has an important prognostic value when both axillary and IMN are positive. But routine sentinel node (SN) biopsy of IMN is not standard practice and warrants further investigation of patients who may benefit of this procedure. METHODS: 561 patients with invasive carcinomas who underwent to Patey’s mastectomy (between 1987 and 2004) and skin-sparing mastectomy (after 2004) between 1987 and 2012 in HNSG Breast Unit in Curitiba (Brazil) were included in this study, and underwent to a routine IMN biopsy in the second and third intercostal space, together with complete axillary dissection in 3 Berg’s levels. After 1997 only patients with positive SN underwent to this procedure. RESULTS: 102 patients (18%) in this group had positive IMN. The age ranged from 28 to 85 years, with a median of 52 (sd=12) years. 94 (92%) were invasive ductal carcinomas, 6 (6%) invasive lobular carcinomas, 1 (1%) mucinous invasive carcinoma, and 1 (1%) medullary carcinoma. Most of the tumors were T2 (57%) and T3 (21%), and only 3% were T1. Lymphovascular invasion was found in 99 (97%) in this group. 9 (9%) patients had no positive axillary nodes, and for those with both axillary and IMN positive, median of compromised nodes was 9 (sd=12), 22% of IMN positive had 1-3 compromised axillary nodes, 48% had 4-10, and 31% had more than 10. In the follow-up, 57 (56%) died with disease, 22 (22%) were alive without disease, 5 (5%) were alive with disease, and 22 (22%) lost follow-up. CONCLUSIONS: IMN was positive in more advanced and aggressive tumors. Implication of these results to IMN adjuvant radiotherapy needs further investigation.

Should Internal Mammary Lymph Node Biopsy Be a Routine Step in Recurrent Breast Cancer? Report of Three Cases With Negative Axilla and Positive Internal Mammary Node

Lymph node status is the most important clinicopathological prognostic factor for breast cancer patients and in most breast units it reflects only the axillary lymph nodes. A second often overlooked basin consists of the internal mammary lymph nodes (IMLNs) whose evaluation is not done as a routine step during the staging process. We highlight the need to consider incorporation of IMLNs into a patient’s staging by presenting three cases of recurrent breast cancer with negative axilla and positive IMLN, a finding which altered their final management. We suggest that biopsy of IMLN should be a routine step in recurrent breast cancer when axillary lymphatics are disrupted by previous surgery although further research is required to define the optimal management of node positive cases.

The value of radiotherapy on metastatic internal mammary nodes in breast cancer. Results on a large series

The ‘regional nodal mapping’, is a fundamental step to stage breast carcinoma. In addition to the axillary nodes status, the involvement of internal mammary nodes is an important prognostic factor. Six hundred and sixty-three patients with breast carcinoma, mainly in the inner quadrants, underwent a biopsy of internal mammary nodes. Positive internal mammary nodes were found in 68 out of 663 cases (10.3%) representing 27.2% of all cases with regional node metastases (250). When histologically proven metastases were detected, radiotherapy was administered to the internal mammary nodes chain. In 254 cases, the surgeon's exploration was guided by a gamma probe. Out of these cases, 28 (11.0%) showed metastatic involvement. Out of the other 409 cases, not radioguided, 40 showed positive nodes (9.8%). Patients with internal mammary metastases treated with radiotherapy and appropriate systemic treatment showed an excellent survival (95% at 5 years), a result which is in opposition to the previous experience, which stated that invasion of internal mammary nodes is an ominous prognostic sign. We assume that this excellent result is due to radiotherapy to internal mammary nodes and we propose that exploration of internal mammary nodes should be part of the staging process of carcinomas of the medial part of the breast.

The feasibility of sentinel node biopsy in the previously treated breast

Sentinel lymph node biopsy (SNB) has been a standard technique in early breast cancer. However, it is not clear that the SNB procedure can be applied to second breast cancer or recurrence occurring in the previously treated breast. The purpose of this study was to clarify the feasibility of the SNB procedure in breast cancer occurring in the previously treated breast, and to investigate the factors related to altered lymphatic flow. Between April 2004 and December 2006, 1490 patients underwent the breast SNB procedure. Among them, 31 patients had a history of previous treatments in the same breast. Recent excision biopsy cases were not included in this group. All patients had previous breast-conserving surgery in the same breast. Sixteen patients had axillary dissection, 3 had SNB, and 12 had no axillary treatment. Ten patients had received radiation therapy to the breast and axilla. Visualization of axillary nodes, internal mammary nodes and contralateral axillary nodes was evaluated and compared with pathological results. Axillary nodes were visualized in 23 patients, internal mammary nodes in 7 patients, and contralateral axillary nodes in 7 patients. The patients with previous axillary dissection exhibited altered lymph node distribution, but did not show involvement of contralateral axillary nodes. Visualization of contralateral axillary nodes occurred in 7 of the 10 patients with previous irradiation to breast irrespective of axillary dissection. Twenty-eight patients underwent SNB, 4 of whom showed cancer-positive nodes. Three patients were cancer-positive in non-ipsilateral axillary nodes (one patient showed positive opposite axillary node and two patients showed positive internal mammary nodes). Previous axillary dissection or irradiation to the breast greatly influences lymphatic flow. Irradiation to the breast may be a strong factor for the visualization of contralateral axillary nodes. Despite the frequent alteration of lymphatic flow, SNB seems to be feasible in secondary or recurrent breast cancer patients.

Pathologic Internal Mammary Lymph Nodes in Secondary and Tertiary DIEP Flap Breast Reconstructions

An increasing number of women develop breast cancer and wish for breast reconstruction with DIEP flap(s). Anastomosing DIEP flaps to the internal mammary vessels provides information on part of the internal mammary chain lymph nodes (LN). The purpose of this study was to evaluate whether the current practice of preoperative screening should be changed, in order to find those delayed breast reconstruction patients who have tumor–positive internal mammary nodes or recurrent disease.

Report on a Case of Pure Cribriform Carcinoma of the Breast with Internal Mammary Node Metastasis: Description of the Case and Review of the Literature

Pure ductal invasive carcinoma of the breast is more frequently associated with lymphatic invasion, lymph node involvement and high malignant histological grade than combined forms of breast carcinoma. Internal mammary node metastases are not frequently detected when the axillary nodes are negative. We report our experience of a case of pure cribriform carcinoma, associated with an intraductal cribriform component, in which the sentinel axillary nodes were negative, while nodal and perinodal metastasis was detected in one internal mammary lymph node. Data from the literature show that positive internal mammary nodes are an unusual finding when the axillary sentinel node is negative, especially in cases of cancer with a relatively good prognosis, such as cribriform cases.

Surgical approach to internal mammary lymph node biopsy.

In the management of breast cancer, lymphatic mapping and sentinel lymph node (SLN) biopsy has emerged as an acceptable standard of care for assessing the status of the axilla in selected patients. In studies of SLN biopsy coupled with preoperative lymphoscintigraphy, several authors have reported extraaxillary drainage of tracer, particularly to the internal mammary (IM) chain. Proposed changes to the American Joint Committee on Cancer staging manual will place added emphasis on the status of the IM nodes (IMNs) in the staging of breast cancer. These changes, based on the work of Veronesi and others, demonstrate that a positive IMN has the same influence on prognosis as a positive axillary node, and that when both are positive, the influence on outcomes is additive. These facts suggest that surgeons can likely be faced with removing IMNs, a procedure that has been extremely uncommon in the majority of general surgical practices in recent times. Here we report our technique for biopsy of the IMSLN. This technique was performed in a subset of 142 consecutive patients in whom IM-SLNs were visible on lymphoscintigraphy. In this experience, we noted no increase in morbidity beyond that associated with standard breast cancer procedures.

Utility of internal mammary lymph node removal when noted by intraoperative gamma probe detection.

Lymphatic mapping (LM) for breast cancer has made internal mammary node (IMN) detection practical and dependable. This study demonstrates the necessity of IMN removal when suggested by intraoperative radioguided surgery detection. From April 1998 to July 2000, 1273 patients underwent LM for breast cancer. LM was performed using the combined dye and radiocolloid technique. Patients were scanned operatively with a gamma probe over the IMN area, and most underwent preoperative lymphoscintigraphy. Nodes were removed from patients in whom radioactivity was detected in the internal mammary area. Thirty of the 1273 (2.4%) patients mapped had at least one IMN removed. Twenty-two of 30 (73.3%) had inner quadrant lesions. Five of 30 (16.7%) patients had IMNs that were positive for metastatic disease. Three of these five had no metastatic spread to the axillary sentinel lymph node (SLN). One of thirty (3.3%) patients with IMN localization had neither hot nor blue nodes detected in an SLN procedure. Radioguided SLN detection should be attempted in the IMN basin with all tumors. If an IMN is identified, it should be removed. IMN biopsy is a feasible, low-risk procedure when directed by radioguided LM and provides a guide for radiotherapy for patients with positive IMNs.

Clinical relevance of internal mammary node mapping as a guide to radiation therapy

Background: The surgical management of breast cancer has changed markedly with the development of lymphatic mapping and sentinel lymph node (SLN) biopsy. Lymphatic mapping technique varies with respect to injection method, mapping agent, and surgical technique. The decision to pursue the internal mammary nodes (IMN) is another source of controversy. Methods: From April 1998 to November 2000, 1,470 patients underwent lymphatic mapping for breast cancer and were prospectively entered into the breast database. The combined technique method was used, consisting of both isosulfan blue dye and technetium-99 labeled sulfur colloid. Patients with inner quadrant lesions and suspicion for internal mammary metastasis had preoperative lymphoscintigraphy. Those with internal mammary radioactivity noted by either lymphoscintigraphy or gamma probe underwent removal of the internal mammary sentinel nodes. Results: Thirty-six of the 1,470 (2.4%) patients mapped had at least 1 internal mammary lymph node removed. Inner quadrant lesions were present in 24 of the 36 (67%) IMN mapped patients. Of the 36 patients mapping to the IM area, 5 (14%) had at least 1 IM node positive. Two of the 5 (40%) had only IM metastasis, with 1 of these patients having 5 of 5 IMN positive and no disease detected in her axilla. A total of 2 of the 5 (40%) IM positive patients had more than 1 IMN positive. Twenty-eight of the 36 (78%) IM node harvested patients had preoperative lymphoscintigraphy, with 18 (64%) IMN appearing on imaging. Complications occurred in 3 of the 36 (8%) IMN mapped patients, without clinical significance. Conclusions: Mapping to the IMN basin with the finding of metastasis results in N3 disease by the current staging system. The consequence for these patients is radiation therapy to the IMN basin. It is significant to note that 14% (5 of 36) were upstaged as result of IMN detection and 40% (2 of 5) had multiple positive IMNs. Substantial disease was detected in these 5 patients necessitating additional radiation therapy while avoiding IM radiation and its attendant complications in 86% of patients mapping to the IM basin.

The thoracoscopic approach for internal mammary nodes in breast cancer.

This pilot study was conducted to estimate the use of the thoracoscopic surgery as a new approach for the internal mammary nodes (IMN) in breast cancer. For this study, 21 women with breast cancer who underwent the approach for nodes IMN were enrolled. All the women had suspicious IMN metastasis and no distant metastasis. Thoracoscopic IMN dissection was performed safely for 20 of the women, with an average operative time of 44 min. One woman was excluded from the procedure because of pleural adhesion. The patients were restricted from walking for 1.3 days because of chest drainage, but no patients had severe complication or chest wall deformity after the operation. Six patients had positive IMN outcomes. After surgery, 10 of the 20 patients had a lower tumor node metastases (TNM) staging. Two patients who tested positive for IMN and three who tested negative experienced a relapse, but none had pleural dissemination in a median follow-up period of 24 months. Thoracoscopic surgery may be useful in managing patients with IMN.

The contribution of regional lymph nodes in the resistance against breast cancer: practical implications.

Experimental evidence suggests that regional lymph nodes (RLN) are important in the initiation and possibly the maintenance of tumor immunity. "Negative" nodes denote strong tumor immunity and "positive" nodes low. The latter also serve as markers of systemic disease. From histological and immunological studies, and mostly from recent clinical studies in breast cancer, the following practical recommendations are made: (1) Clinically positive axillary nodes are best eliminated by surgery. (2) Resection of positive internal mammary nodes appears to increase survival of patients with central and inner quadrant lesions; however, destruction of these nodes by irradiation, although improving local disease control, may decrease survival. (3) Negative RLN should be preserved, as they appear to prevent lymph node metastases and stimulate systemic immunity. Only a small fraction of unresected RLN harboring micrometastases will ultimately develop palpable disease, and their elimination at that late phase yields the same results as when these nodes are treated prophylactically.

Selecting variations in extent of surgical procedure for breast cancer.

Most breast cancers arise in multicentric areas of the breast parenc hyma and exist as silent innocuous in-situ entities for many years before the infiltrating stage develops. Most of the lymphatic drainage extends to the axillary lymphatic nodes but some to the internal mammary lymph node chain. Risk of spread to the internal mammary nodes increases as the primary tumor approaches the sternal margin as the size of the primary tumor increases and when axillary nodes are also involved. The primary operation should remove all disease present. Aggressive primary surgery and radiation therapy will salvage those without generalized disease. Systemic therapy should be reserved for those with systemic disease. Uninvolved regional lymph nodes do not add to the immune protective mechanism. Modified radical mastectomy in which axillary nodes are removed is adequate for early cases. Histological study at time of operation is essential. Only patients with negative axillary nodes do well with this less complete operation. More complete axillary dissection is preferable when disease is present in the axilla. Radical mastectomy is best for most infiltrating breast cancers. When metastases are found in the axillary nodes supervoltage radiation therapy is also given because of the risk of spread to the internal mammary lymph chain. Extended radical mastectomy which includes en bloc excision of the internal mammary nodes has been used for patients with a high risk of spread to these nodes. Almost 800 patients have been so treated with an operative mortality of less than .5%. Of these 33% had metastases to these nodes and 47% also had axillary node involvement. Of those with negative axillary involvement 15% had positive internal mammary nodes; this was found highest when the primary tumor was on the inner side of the breast. 5 years after surgery 500 patients 47% with axillary involvement and 30% with internal mammary involvement were evaluated. 72.4% were alive 65.8% were disease-free and 7% had local recurrence. 41% with involvement of both nodal areas were clinically disease free. Of 315 evaluated at 10 years 52% were clinically disease-free. Of 98 patients with internal mammary node metastases 27 were clinically disease-free and 28 survived at 10 years. Palliative mastectomies were done on 37 considered inoperable. With added radiation therapy local control was obtained in 29. In only 5 of 14 treated with radiation alone was local control obtained. Of the total 51 inoperable patients 21% were alive at 5 years and 14% were free of disease. None survived 10 years.