Five year results of radical mastectomy for breast cancer,by a sternal splitting,intrapleuralen bloc resection of the internal mammary lymph nodes

A new operative method of extended radical mastectomy enables complete resection of the axillary and internal mammary lymph nodes. In this paper, we present the histological analysis of the internal mammary involvement, and the estimated 5 year survival rate, of 100 patients with breast cancer of Stage I, II or III, who underwent this operation. The incidences of axillary and internal mammary involvements were 41 per cent and 17 per cent, respectively. The metastases in the internal mammary lymph node chain were located from just below the supraclavicular vein to the third intercostal space along the internal mammary vessels. The types of lymphatic invasion observed in the internal mammary chain were lymph node metastases in 88 per cent, metastatic lesion in the lymphoid tissue in 29 per cent and cancer cell emboli in the lymphatic channel in 71 per cent. The overall estimated 5 year survival rate was 90.5 per cent. Where there was internal mammary involvement, the estimated 5 year survival rates for those with no axillary lymph node metastasis, those with fewer than 3 metastatic axillary lymph nodes, and those with more than 4 metastatic axillary lymph nodes were 100 per cent, 80 per cent and 31.2 per cent, respectively. Although the assumption that more aggressive surgical removal of the primary lesion and the regional lymphatic spread gives a higher cure rate has not been proved, this extended radical mastectomy with adjuvant chemoendocrine therapy seems to give a higher 5 year survival rate for patients with internal mammary involvement.     

The significance of regional lymph node dissection in the surgical management of breast cancer

The results of an analysis done on the regional lymph node metastases of 300 patients with operable breast cancer, who were treated in the Department of Surgery (II), Kanazawa University Hospital from 1973 to early 1988 are reported herein. It was found that the metastases of the axillary and internal mammary lymph nodes were closely related to the survival of patients, but they were hardly diagnosed before the operation. Only the dissection of these lymph nodes proved useful for providing the prognostic information. Moreover, in a retrospective study comparing the en bloc extended radical mastectomy versus the other types of mastectomy, the extended radical mastectomy was seen to greatly improve the survival of patients with 3 or less than 3 metastatic axillary lymph nodes. Thus, the extended radical mastectomy provides the maximum diagnostic and prognostic information, and gives the best chance of loco-regional control of the disease. The anterior chest deformity created by the extended radical mastectomy, however, should be avoided in those patients without internal mammary involvement. We therefore propose the modified extended mastectomy as a staging operation.     

The significance of regional lymph node dissection in the surgical management of breast cancer

The results of an analysis done on the regional lymph node metastases of 300 patients with operable breast cancer, who were treated in the Department of Surgery (II), Kanazawa University Hospital from 1973 to early 1988 are reported herein. It was found that the metastases of the axillary and internal mammary lymph nodes were closely related to the survival of patients, but they were hardly diagnosed before the operation. Only the dissection of these lymph nodes proved useful for providing the prognostic information. Moreover, in a retrospective study comparing theen bloc extended radical mastectomyversus the other types of mastectomy, the extended radical mastectomy was seen to greatly improve the survival of patients with 3 or less than 3 metastatic axillary lymph nodes. Thus, the extended radical mastectomy provides the maximum diagnostic and prognostic information, and gives the best chance of loco-regional control of the disease. The anterior chest deformity created by the extended radical mastectomy, however, should be avoided in those patients without internal mammary involvement. We therefore propose the modified extended mastectomy as a staging operation.     

Breast cancer and regional lymph node dissections

Regional lymph node metastases were evaluated in 289 patients with operable breast cancer. The metastases of the axillary and internal mammary lymph node were shown to be closely related to the survival of patients, but the status of these nodes was shown to be impossible to estimate before the operation. Thus, axillary and internal mammary node dissections seem to be very important in order to attain an acceptable amount of information for staging of certain breast cancer patients. Due to the radicality of operations including internal mammary node dissection, the use of modified extended mastectomy is proposed as the staging operation. In this manner, the anterior chest deformity created by an extended radical mastectomy can be avoided and the pectoralis major muscle spared in patients without internal mammary lymph node involvement. Also found in this study, was some evidence of the beneficial use of en bloc extended radical mastectomy for the survival of a selected group of patients.     

Radical mastectomy with parasternal node dissection or radiation to the parasternal region for breast cancer of medial or central location

In order to establish a therapeutic approach for primary breast cancer of medial and central origin, we reviewed 183 patients who had been treated by one of the following three modalities at the Second Department of Surgery, Osaka University Medical School between January, 1965 and December, 1980. Group A (n=70): standard radical mastectomy alone; Group B (n=34): standard radical mastectomy followed by postoperative irradiation to the parasternal and supraclavicular regions, and; Group C (n=62): extended radical mastectomy that included removal of the parasternal lymph nodes. The background factors of the three groups were not significantly different. The overall survival five and ten years following surgery in the three groups were 91 per cent and 79 per cent in group A, 82 per cent and 67 per cent in group B, and 82 per cent and 70 per cent in group C, respectively, showing no significant difference in overall survival among the three groups. When the patients were classified according to the extent of axillary lymph node involvement, there was no difference in survival among the three treatments in patients who had less than three lymph node metastases in the axilla. However, treatment of the parasternal lymph nodes improved survival in the patients who had more than four lymph node metastases in the axilla. Parasternal lymph node involvement definitely worsened the prognosis, showing it to be a good prognostic factor. Thus, extended radical mastectomy should be considered for patients with breast cancer of medial or central location, when extended axillary lymph node involvement is found.     

Lymphatic tumor burden negatively impacts the ability to detect the sentinel lymph node in breast cancer

Sentinel lymph node (SLN) biopsy is the preferred method of nodal breast cancer staging. Techniques of SLN biopsy rely on transport of interstitial molecules through mammary lymphatics. Lymphatic flow may be disrupted by tumor emboli. Increased lymphatic tumor burden may be responsible for failure to identify the sentinel lymph node in patients with breast cancer. A prospective database of 110 patients who had SLN biopsy between January 2001 and December 2002 was analyzed. The number of metastatic axillary lymph nodes was used as a measure of lymphatic tumor burden. SLN was found in 94 per cent of cases. It was not found in seven patients; five of them had extensive axillary metastases (71%) compared to 23 per cent when SLN was found (P = 0.001). The average number of metastatic lymph nodes was larger when SLN was not found compared to when SLN was found (12.8 vs. 3.9, respectively, P = 0.002). Increasing numbers of metastatic nodes correlated with decreasing success in SLN biopsy (P = 0.075). The incidence of axillary metastases is higher in patients in whom the sentinel node is not found. High lymphatic tumor burden may have a causative role in SLN biopsy technical failure. Axillary dissection should be performed if SLN is not found, regardless of the tumor size or histology.     

The modified extended mastectomy using the trap-door method as a staging operation

The choice of operation for breast cancer must be directed towards giving the best chance of local control of the disease. Extended radical mastectomy may be beneficial for patients with internal mammary lymph node metastases, although it has remained controversial. The anterior chest defect created by extended radical mastectomy should be avoided in patients with no metastasis in the internal mammary lymph nodes. This paper, proposes a new technique of modified extended mastectomy using the trap-door method as a staging operation and an intermediate operation between modified radical mastectomy and extended radical mastectomy. In this operation, the axillary dissection could be performed by reflecting the pectoralis major muscle and the internal mammary lymph nodes could be dissected by reflecting the parasternal chest wall in trap-door fashion. In cases in which the metastasis is histologically found in the internal mammary content, extended radical mastectomy by sternal splitting is preferred.     

Reevaluation of parasternal lymph node dissection in the treatment of mammary cancer

One hundred and forty one patients with mammary cancer underwent the extended radical mastectomy with parasternal lymph nodes dissection between January, 1966 and December, 1974. From the basis of the present report involvement of parasternal lymph node chain was evaluated retrospectively with respect to the stage, location, size, histological type of cancer, metastasis to axillary and subclavicular lymph nodes, and the five-year survival rate. The parasternal as well as subclavicular and axillary lymph node involvements were not found in non-infiltrating cancer. The more the stage of cancer advanced, the more frequently the parasternal lymph nodes were involved regardless of the location of cancer in the breast. The parasternal lymph node chain alone was rarely involved, but frequently affected along with the axillary lymph nodes. When the parasternal lymph nodes were involved, the five-year survival rate was extremely poor, even after their surgical removal. Subsequently, addition of parasternal lymph node dissection does not seem to be beneficial.     

Reevaluation of parasternal lymph node dissection in the treatment of mammary cancer.

One hundred and forty one patients with mammary cancer underwent the extended radical mastectomy with parasternal lymph nodes dissection between January, 1966 and December, 1974. From the basis of the present report involvement of parasternaly lymph node chain was evaluated retrospectively with respect to the stage, location, size, histological type of cancer, metastasis to axillary and subclavicular lymph nodes, and the five-year survival rate. The parasternal as well as subclavicular and axillary lymph node involvements were not found in non-infiltrating cancer. The more the stage of cancer advanced, the more frequently the parasternal lymph nodes were involved regardless of the location of cancer in the breast. The parasternal lymph node chain alone was rarely involved, but frequently affected along with the axillary lymph nodes. When the parasternal lymph nodes were involved, the five-year survival rate was extremely poor, even after their surgical removal. Subsequently, addition of parasternal lymph node dissection does not seem to be beneficial.     

Radiation after mastectomy in high-risk patients: is it necessary?

A retrospective review of cases from 1988 through 1992 was performed examining high-risk breast cancer patients treated with modified radical mastectomy without postoperative radiation at a single institution. Locoregional recurrence, distant metastases, overall survival, and number of lymph nodes removed were examined. This was compared with recent Danish and Canadian studies. Thirty-three premenopausal node-positive breast cancer patients had a 9 per cent locoregional recurrence rate. In the Danish and Canadian studies the locoregional recurrence rates were 32 and 21 per cent. These were reduced to 9 per cent and 10 per cent respectively in the radiated arms. Our locoregional recurrence in nonradiated patients was similar to that in the radiated arms of the studies and improved when compared with recurrence in their non-radiated controls. The adequacy of the axillary lymph node dissection was examined. In the current study a median of 18 lymph nodes were recovered with only 3 per cent containing less than 12 nodes. In the Danish study a median of seven lymph nodes were removed. Similarly in the Canadian trial a median of 11 nodes were removed. With complete axillary dissection results equivalent to those of postoperative adjuvant radiation is achieved. Further randomized controlled studies with standard axillary dissections are needed before the recommendation of routine postoperative radiotherapy.     

The relationship between lymph node metastases and DNA-ploidy status as prognostic factors in invasive breast cancer

We evaluated the relationship between the regional lymph node metastases and the DNA ploidy status in 207 patients with invasive breast cancer, as well as their prognostic values in estimating the prognosis of breast cancer. A significantly higher incidence of aneuploidy was found in patients with a large T3 or T4 tumor, a positive axillary lymph node status, more than 4 positive axillary lymph nodes or positive internal mammary lymph nodes. In a univariate study, the overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. In the multivariate analysis, however, only axillary and internal mammary lymph node metastases were recognized as important independent prognostic factors on survival. In this series, the DNA ploidy status did not appear to be an independent prognostic factor either in the entire series or in negative axillary node patients, since it was closely correlated with the axillary or internal mammary lymph node metastases, and the axillary node negative patients had an extremely favorable prognosis.     

Prognostic significance of internal mammary lymph node metastases in breast cancer patients]

Examination was made of clinical, histological and biological prognostic factors in 207 patients with invasive breast cancer, and determination was made as to whether variable prognostic factors, especially internal mammary lymph node metastases, would serve as a basis for the prognosis of breast cancer. In a univariate study, overall survival was significantly corrected with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases and DNA ploidy status. In a multivariate study, however, only axillary and internal mammary lymph node metastases were recognized as important, and independent prognostic factors on survival. Neither axillary lymph node status nor DNA ploidy status appeared an important prognostic factor. Axillary and internal mammary lymph node metastases could not be predicted from their clinical assessment. Only axillary lymph node dissection and biopsy of first and second intercostal spaces were concluded to be useful for accurately indicating the status of these lymph nodes.     

Halsted Revisited: Internal Mammary Sentinel Lymph Node Biopsy in Breast Cancer

OBJECTIVE: To investigate the feasibility of internal mammary sentinel lymph node biopsy as a method to refine and thereby improve nodal staging in breast cancer. SUMMARY BACKGROUND DATA: The internal mammary lymph node status is a major prognostic factor in breast cancer. If positive, prognosis is less favorable. However, staging this regional nodal basin is not performed routinely, thus discarding additional staging information. METHODS: In a consecutive series of 256 patients with primary breast cancer, sentinel node biopsy was performed based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 10 mCi (370 MBq) (99m)Tc-nanocolloid injected peritumorally and 0.5 to 1.0 mL Patent Blue V injected intradermally. During surgery, whenever possible, both axillary and internal mammary sentinel nodes were sampled. RESULTS: Lymphoscintigraphy showed axillary sentinel nodes in 95% (243/256) and additional internal mammary sentinel nodes in 25.3% (65/256). The overall success rate of axillary sentinel node biopsy was 97% (249/256). Sampling the internal mammary basin, based on the results of lymphoscintigraphy, was successful in 63% (41/65). In three patients a small pleural lesion resulted from staging this basin. This technique revealed internal mammary metastases in 26.8% (11/41). In 7.3% (3/41), internal mammary nodes showed metastatic involvement without accompanying axillary metastases. CONCLUSIONS: Internal mammary sentinel node biopsy is feasible without serious additional complications. It improves nodal staging in breast cancer by identifying higher-risk subgroups with internal mammary nodal metastases, which might benefit from altered adjuvant treatment regimens.     

A multivariate study of the relationship between regional lymph node metastases and prognosis in patients with operable breast cancer

In order to evaluate the prognostic importance of clinical and histological node information, we made univariate and multivariate analyses of regional lymph node metastases in 223 patients with operable breast cancer who were surgically treated from 1973 to 1985. Clinical axillary node status, histological involvement of the axillary lymph nodes, their anatomical levels and numbers, and histological involvement of the internal mammary lymph nodes were selected as evaluating prognostic factors. The histological presence or absence of axillary node involvement, especially at the distal level, proved to be the most important prognostic factor. However, neither the anatomical level nor the number of histologically involved axillary lymph nodes appeared to be an important prognostic factor. On the other hand, histological involvement of the internal mammary nodes appeared to be an important and independent prognostic factor. Therefore, we concluded that axillary lymph node dissection with a biopsy of the internal mammary nodes would provide more accurate information about the prognosis of patients with operable breast cancer.     

A multivariate study of the relationship between regional lymph node metastases and prognosis in patients with operable breast cancer.

In order to evaluate the prognostic importance of clinical and histological node information, we made univariate and multivariate analyses of regional lymph node metastases in 223 patients with operable breast cancer who were surgically treated from 1973 to 1985. Clinical axillary node status, histological involvement of the axillary lymph nodes, their anatomical levels and numbers, and histological involvement of the internal mammary lymph nodes were selected as evaluating prognostic factors. The histological presence or absence of axillary node involvement, especially at the distal level, proved to be the most important prognostic factor. However, neither the anatomical level nor the number of histologically involved axillary lymph nodes appeared to be an important prognostic factor. On the other hand, histological involvement of the internal mammary nodes appeared to be an important and independent prognostic factor. Therefore, we concluded that axillary lymph node dissection with a biopsy of the internal mammary nodes would provide more accurate information about the prognosis of patients with operable breast cancer.     

Relation of tumor size, lymph node status and prognosis in breast cancer]

Tumor size and the extent of axillary lymph node involvement are the two most important prognostic factors for breast cancer, but their relation is not clear. Data on 2189 cases of radical surgery from 1956-1985 showed a linear relation between tumor size and percentage of cases with positive lymph node involvement. A negative relation was noted between tumor size, the extent of lymph node involvement and prognosis. There was a significance difference in survival rate between one group, two group or more lymph nodes involve. The worst prognosis was seen in those patients with level 3 lymph nodes involve. Tumor size and lymph node status were found to be independent but additive prognostic indicators. If there was no lymph node involvement, the survival rate was decreased because of tumor size. In cases of 1-3 and 4-6 lymph nodes involved, the survival rate was not different when tumor size was less than 5 cm, but there was a significant difference when tumor size large than 5 cm. In cases of more than 7 nodes involved, the survival rate decreased regardless of tumor size. Lymph node metastasis was more important than tumor size in prognosis. The relation of different TNM combination with prognosis was investigated, and the importance of the treatment of internal mammary lymph node in breast cancer was emphasized.     

Probability of false negative nodal staging in conjunction with partial axillary dissection in breast cancer

There is a risk of overlooking lymph node metastases and thereby contributing to inaccurate nodal staging when performing partial axillary dissection in conjunction with total mastectomy in female breast cancer. The Danish Breast Cancer Cooperative Group (DBCG) analysed this risk in a prospective nation-wide adjuvant trial dealing with primary operable breast carcinoma. The series comprised 3114 patients, initially found to have lymph node negative axillae, followed for a median of 24 months (quartiles 12-40). It was found that the probability of early ipsilateral axillary relapse of cancer, estimated by means of the life table method, decreased with the number of nodes removed. After 2 years the recurrence rate was 12 per cent for patients with no lymph nodes removed, 7 per cent with one or two nodes removed and 2 per cent with three or more nodes removed. It is concluded that the risk of false negative nodal staging in conjunction with partial axillary dissection is modest, provided at least three lymph nodes are removed and found to be negative on histological examination.     

Prognosis of breast cancer patients after mastectomy and dissection of internal mammary nodes.

The results of the analysis carried out on data on 1119 patients with operable breast cancer treated at the National Cancer Institute of Milan from 1965 to 1979 with enlarged mastectomy are reported. Metastases to internal mammary chain were found to be significantly associated with the maximum diameter of primary (16.1% for tumors less than 2 cm and 24.5% for larger tumors, p = 0.007), the age of the patients (27.6% in patients younger than 40 years, 19.7% in patients between 41-50 years, and 15.6% in patients older than 50 years, p = 0.01). The site of origin of the cancer had no impact on internal mammary node metastases. Patients with positive axillary nodes showed metastases to internal mammary nodes in 29.1% of the cases, while 9.1% of patients with axillary negative nodes had positive retrosternal nodes. Survival was significantly affected by the presence of positive internal mammary nodes: the percentage of 10-year survival varied from 80.4% in patients with axillary and internal mammary negative nodes to 30.0% in patients with both nodal basins involved. Intermediate survival rates (54.6% and 53.0%) were found when one or the other of the nodal stations (axillary and internal mammary) was separately affected. Maximum diameter of the primary significantly affected the survival of each group identified by the status of both axillary and internal mammary nodes. In conclusion, the information on the presence or absence of internal mammary node metastases would be of great importance in formulating the prognosis of breast cancer patients. To obtain this information, a biopsy at the first intercostal space may be reasonable in selected patients (age, maximum diameter, and axillary node involvement being the basis for selection) as long as noninvasive methods of diagnosis are available.     

Do cytokeratin-positive-only sentinel lymph nodes warrant complete axillary lymph node dissection in patients with invasive breast cancer?

The small number of nodes harvested with lymphatic mapping and sentinel lymph node (SLN) biopsy has allowed a more detailed pathologic examination of those nodes. Immunohistochemical stains for cytokeratin (CK-IHC) have been used in an attempt to minimize the false negative rate for SLN mapping. This study examines the value of CK-IHC positivity in predicting further lymph node involvement in the axillary basin. From April 1998 through May 1999, 519 lymphatic mappings and SLN biopsies were performed for invasive breast cancer. SLNs were examined by imprint cytology, hematoxylin and eosin (H&E), and CK-IHC. Patients with evidence of metastatic disease by any of the above techniques were eligible for complete axillary node dissection (CAND). The frequency with which these modalities predicted further lymph node involvement in the axillary basin was compared. Of the 519 lymphatic mappings, 39 patients (7.5%) had a CK-IHC-positive-only SLN. Five (12.8%) of these 39 patients had at least 2 SLNs positive by CK-IHC. Twenty-six of the CK-IHC-positive-only patients underwent CAND. Three of these 26 patients (11.5%) had additional metastases identified after CAND. The sensitivity levels with which each modality detected further axillary lymph node involvement were as follows: CK-IHC, 98 per cent; H&E, 94 per cent; and imprint cytology, 87 per cent. A logistic regression to compare the prognostic value of the three modalities was performed. All were significant, with odds ratios of 19.1 for CK-IHC (P = 0.015), 5.3 for H&E (P = 0.033), and 3.86 for imprint cytology (P = 0.0059). These data validate the enhanced detection of CK-IHC for the evaluation of SLNs. Detection of CK-IHC-positive SLNs appears to warrant CAND in patients with invasive breast cancer. However, the therapeutic value of CAND or adjuvant therapies based on CK-IHC-positive SLNs would be best answered by prospective randomized trials.     

Risk of internal mammary lymph node metastases and its relevance on prognosis of breast cancer patients

The risk of internal mammary chain metastases according to some parameters and its prognostic relevance was evaluated on the basis of the experience collected at the National Cancer Institute of Milan where, from January 1965 to December 1980, 1085 patients were submitted to Halsted mastectomy plus internal mammary chain dissection. A multivariate analysis was carried out, resorting to a multiple linear regression with logistic transformation of the dependent variable. The selection of prognostic factors has been performed with a step-down approach. The frequency of metastases to internal mammary chain nodes was evaluated according to four criteria: age, site and size of primary tumor, and presence of axillary metastases. Data of this series indicate that the frequency of internal mammary node metastases is significantly associated with the age of the patients (younger patients have a higher risk) (p = 0.006) with the size of primary tumor (p = 0.006) with the presence of axillary node metastases (p = 10(-9). Patients with both axillary and internal mammary positive nodes have a very poor prognosis (10-year survival 37.3%) while patients with either axillary metastases only or internal mammary metastases only have an intermediate less grave prognosis (59.6% and 62.4%, respectively). As regards the risk of internal mammary nodes involvement, it appears that knowing the age, the size, and the axillary nodes status, it is possible to calculate with good approximation the probability of their invasion.